Registration Form • Jun 5, 2015
Registration Form
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Public limited company with a capital of 688,276.10 Euros Headquarters: Bâtiment Adénine – 60 Avenue Rockefeller 69008 Lyon Companies and Trades Registry 479 560 013
AUTORITÉ DES MARCHÉS FINANCIERS
In particular application of Article 212-13 of its General Regulations, the French financial market authority (l'Autorité des marchés financiers - "AMF") has assigned this reference document visa no. R.15-048 dated June 4, 2015. This document may only be used in support of a financial transaction if it is completed by a transaction note signed by the AMF. This reference document was written by the issuer and incurs the liability of its signers.
Registration, pursuant to the provisions of article L.621-8-1-I of the Monetary and Financial Code was awarded after the AMF checked to see that "the document is complete and comprehensible, and that the information contained therein is consistent." This implies neither approval of the opportuneness of the transaction nor authentication of the accounting and financial documents presented.
This unapproved English translation of the Registration Document is a free translation of the original which was prepared
in French, submitted to and registered with the Autorité des marchés financiers (AMF) on June 4rd, 2015 in accordance
with Article 212-13 of the AMF General Regulations. It is not a binding document. In the event of any ambiguity or conflict
between corresponding statements or items contained in this English translation and the original French version, the
relevant statements or items of the French version shall prevail. The auditor's reports apply to the French version of the
Management Report and the financial statements.
Copies of this reference document are available at no cost at the headquarters of ERYTECH Pharma, Bâtiment Adénine, 60, Avenue Rockefeller 69008 in LYON, as well as electronically on the ERYTECH Pharma website (www.erytech.com) and the AMF website (www.amf-france.org).Error! Hyperlink reference not valid.
| CONCORDANCE TABLE 8 |
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|---|---|---|---|---|---|
| 1. | RESPONSIBLE PARTIES12 | ||||
| 1.1. | Person responsible for the reference document 12 | ||||
| 1.2. | Certification by the responsible party 12 | ||||
| 1.3. | Persons responsible for the financial information 12 | ||||
| 2. | STATUTORY AUDITORS13 | ||||
| 2.1. | Statutory auditors 13 | ||||
| 2.2. | Deputy auditors 13 | ||||
| 2.3. | Declaration of fees paid to the auditors 14 | ||||
| 3. | SELECTED FINANCIAL INFORMATION 15 |
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| 4. | RISK FACTORS17 | ||||
| 4.1. | Operational risks 17 | ||||
| 4.1.1. | Risks related to product development17 | ||||
| 4.1.2. | Risks relating to the particular nature of the products 18 | ||||
| 4.1.3. | Risk related to the production process19 | ||||
| 4.1.4. | Risks related to production capacity 19 | ||||
| 4.1.5. | Risk of commercial failure 19 | ||||
| 4.1.6. | Risks related to sales, marketing and distribution resources20 | ||||
| 4.1.7. | Risk related to dependence on exclusive distributors of GRASPA® 20 |
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| 4.1.7.1. Teva Group21 |
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| 4.1.7.2. Orphan Europe (Recordati Group)21 |
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| 4.1.8. | Risk related to dependency on its most advanced product: ERY-ASP/GRASPA® | 21 | |||
| 4.1.9. | Risks related to dependence on key scientific partnerships 22 | ||||
| 4.1.10. | Risks of conflict of interest 22 | ||||
| 4.1.11. | Risks of dependence on subcontractors and key raw material suppliers23 | ||||
| 4.1.12. | Risks relating to hygiene, safety and environment 24 | ||||
| 4.2. | Strategic risks 25 | ||||
| 4.2.1. | Risk related to key personnel 25 | ||||
| 4.2.2. | Risks related to key objectives not being reached25 | ||||
| 4.2.3. | Risks related to the management of internal growth 25 | ||||
| 4.2.4. | Risks related to competition26 | ||||
| 4.2.5. | Risks related to confidentiality of Company information and knowledge 27 | ||||
| 4.2.6. | Risks related to the use of information systems27 | ||||
| 4.2.7. | Risk related to industrial espionage 27 | ||||
| 4.2.8. | Specific risks related to the use of technologies owned by third parties28 | ||||
| 4.2.9. | Risks related to intellectual property 28 | ||||
| 4.3. | Legal risks 30 | ||||
| 4.4. | Regulatory risks 30 | ||||
| 4.4.1. | Risks related to the regulatory environment30 | ||||
| 4.4.2. | Risks related to regulations for the collection of human samples31 | ||||
| 4.4.3. | Risks related to changes in health care reimbursement policies31 | ||||
| 4.4.4. | Risks related to the regulatory status of the Company 32 | ||||
| 4.5. | Financial risks 32 | ||||
| 4.5.1. | Risks related to historical and forecast losses32 | ||||
| 4.5.2. | Risks related uncertain additional funding32 | ||||
| 4.5.3. | Risk of major financial crisis33 | ||||
| 4.5.4. | Risk of dilution33 | ||||
| 4.6. | Social and fiscal risks 34 | ||||
| 4.6.1. | Risks related to research tax credit 34 | ||||
| 4.6.2. | Risks related to tax fluctuations for drugs34 | ||||
| 4.6.3. | Risks related to changes in fiscal or labor legislation34 |
| 4.7. | Market risks 36 | |||
|---|---|---|---|---|
| 4.7.1. | Liquidity risk 36 | |||
| 4.7.2. | Exchange rate risk 37 | |||
| 4.7.3. | Interest rate risk 37 | |||
| 4.8. | Volatility risk 37 | |||
| 4.9. | Insurance and risk coverage 38 | |||
| 4.10. | Exceptional events and litigation 40 | |||
| 5. | INFORMATION ABOUT THE COMPANY41 | |||
| 5.1. | History and evolution of the Company 41 | |||
| 5.1.1. | Company name, trade name, and headquarters of the Company 41 | |||
| 5.1.2. | Location and registration number of the Company 41 | |||
| 5.1.3. | Date of formation, duration, and transformation of the Company 41 | |||
| 5.1.4. | Legal form of the Company and applicable laws 41 | |||
| 5.1.5. | Fiscal year41 | |||
| 5.1.6. | History 41 | |||
| 5.2. | Investments 48 | |||
| 5.2.1. | Principal investments made since 2013 48 | |||
| 5.2.2. | Principal investments currently being made 48 | |||
| 5.2.3. | Principal investments planned 48 | |||
| 6. | OVERVIEW OF BUSINESS ACTIVITIES49 |
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| 6.1. | Overview 49 | |||
| 6.2. | Introduction to cancer treatment 53 | |||
| 6.3. | Acute leukemia: A significant unmet medical need 55 | |||
| 6.3.1. | Bone marrow cancer55 | |||
| 6.3.2. | An increasing number of patients worldwide 56 | |||
| 6.3.3. | A lower 5-year survival rate for adults and seniors58 | |||
| 6.4. | L-asparaginase: a decisive drug in the treatment of acute leukemias 59 | |||
| 6.4.1. | Current treatment of patients with acute leukemia59 | |||
| 6.4.2. | L-asparaginase's crucial role in the remission of patients60 | |||
| 6.4.2.1. ALL treatment 62 |
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| 6.4.2.2. AML treatment64 |
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| 6.4.3. | Limitations of direct administration of L-asparaginase 67 | |||
| 6.4.4. | The current market for L-asparaginase68 | |||
| 6.5. | ERY-ASP/GRASPA® : An innovative treatment entering the market in ALL 72 |
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| 6.5.1. | L-asparaginase encapsulated for greater efficacy and improved safety 73 | |||
| 6.5.2. | Clinical results and ongoing clinical programs for acute leukemia 73 | |||
| 6.5.3. | Obtaining orphan drug designation and its benefits83 | |||
| 6.5.4. | Marketing GRASPA® 83 |
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| 6.5.5. | Positioning of GRASPA® on the market83 | |||
| 6.6. | Marketing GRASPA® in Europe and Israel 84 | |||
| 6.7. | Development of ERY-ASP for leukemia in the United States 86 | |||
| 6.8. | Potential new indications for ERY-ASP: Solid tumors 87 | |||
| 6.9. | ERYTECH's encapsulation technology 88 | |||
| 6.9.1. | The innovative approach to encapsulate therapeutic enzymes88 | |||
| 6.9.2. | Automated and strong industrialized encapsulation process 89 | |||
| 6.9.3. | Organized production in the United States for future clinical trials91 | |||
| 6.10. 6.11. |
TEDAC and other projects under development 91 The pharmaceutical industry's interest in orphan drugs 93 |
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| 6.12. | Environmental, social and corporate responsibility policy 94 | |||
| 7. | ORGANIZATION CHART 95 |
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| 8.1. Real estate property 96 |
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|---|---|---|---|---|---|
| 8.2. Environmental constraints that may affect the use of assets 97 |
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| 9. | REVIEW OF EARNINGS AND FINANCIAL POSITION98 | ||||
| 9.1. | Overview 98 | ||||
| 9.2. | Comparison of the last two years 98 | ||||
| 9.2.1. Operating profit breakdown 98 |
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| 9.2.1.1. Sales revenue and other income from activity 98 |
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| 9.2.1.2. Operating expenses 99 |
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| 9.2.1.3. Net income breakdown 102 |
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| 9.2.1.4. Net income and net income per share 102 |
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| 9.3. | Non-deductible expenses 102 | ||||
| 9.4. | Balance sheet analysis 103 | ||||
| 9.4.1.1. Non-current assets103 |
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| 9.4.1.2. Current assets103 |
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| 9.4.1.3. Equity 104 |
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| 9.4.1.4. Non-current liabilities104 |
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| 9.4.1.5. Current liabilities104 |
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| 10. | CAPITAL RESOURCES AND CASH105 | ||||
| 10.1. | Information on the Company's capital, liquidity and capital resources 105 | ||||
| 10.2. | Cash flow 106 | ||||
| 10.3. | Information on the borrowing requirements and funding structure 108 | ||||
| 10.4. | Restriction on the use of capital 108 | ||||
| 10.5. | Sources of financing needed for the future 108 | ||||
| 11. | RESEARCH AND DEVELOPMENT, PATENTS AND LICENSES 109 |
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| 11.1. | Research and development activity 109 | ||||
| 11.2. | Intellectual property 109 11.2.1. Patents109 |
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| 11.2.1.1. In its own name109 | |||||
| 11.2.1.2. Licenses114 | |||||
| 11.2.1.3. Trademarks114 | |||||
| 11.2.2. Domain Names118 |
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| 12. | TREND INFORMATION 119 |
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| 12.1. | Main trends since the end of the last fiscal year 119 | ||||
| 12.2. | Known trends, uncertainties, requests for commitments or reasonable events that could affect | ||||
| the Company's prospects 119 | |||||
| 13. | FORECASTS OR ESTIMATES OF EARNINGS 120 |
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| 14. | ADMINISTRATIVE AND MANAGEMENT BODIES 121 |
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| 14.1. | Executive Officers and Directors 121 | ||||
| 14.1.1. Composition of the Board of Directors121 |
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| 14.1.2. Composition of Senior Management123 |
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| 14.1.3. Other corporate duties124 |
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| 14.1.4. Experience with administrative and managerial bodies 126 |
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| 14.2. | Potential conflicts of interest and agreements 127 | ||||
| 15. | REMUNERATION AND BENEFITS128 | ||||
| 15.1. | Compensation and in-kind benefits allocated to the Company's corporate officers for the last | ||||
| financial year 128 | |||||
| 15.2. | Amounts allocated or identified by the Company for the payment of pensions, retirement, or other benefits 139 |
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|---|---|---|---|---|---|
| 15.3. | Share subscription warrants, founder subscription warrants, and other securities giving access to the capital, assigned to directors and executive officers. 139 |
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| 15.4. | Summary statement of transactions by executive officers and persons mentioned in article | ||||
| L.621-18-2 of the Monetary and Financial Code involving shares of the Company conducted | |||||
| during the past fiscal year 139 | |||||
| 16. | OPERATION OF THE ADMINISTRATIVE AND MANAGEMENT BODIES 141 |
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| 16.1. | Term of office for directors 141 | ||||
| 16.2. | Service agreements binding members of the Board of Directors and Senior Management with | ||||
| 16.3. | the Company 141 Corporate governance, internal audit, and risk management 141 |
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| 16.3.1. | ISO certification142 | ||||
| 16.3.2. | Chairman's report on internal audits 143 | ||||
| 16.4. | Elements capable of having an impact in the event of a public offering 156 | ||||
| 16.4.1. | Capital structure of the Company 156 | ||||
| 16.4.2. | Restrictions resulting from the bylaws respecting the voting rights and transfers of | ||||
| shares or clauses of which the Company has been informed in application of article | |||||
| L.233-11 of the Commercial Code 156 | |||||
| 16.4.3. | Direct or indirect stakes held in the Company's share capital of which it is aware by virtue | ||||
| of articles L.233-7 and L.233-12 of the Commercial Code156 | |||||
| 16.4.4. | Parties holding any securities involving special rights of control and description thereof.156 | ||||
| 16.4.5. | Control mechanisms provided in any system for employee shareholding, when the | ||||
| controller rights are not exercised by the latter156 | |||||
| 16.4.6. | Agreements between shareholders of which the Company is aware and which may result | ||||
| in restrictions to transfers of shares and the exercise of voting rights156 | |||||
| 16.4.7. | Rules applicable to the appointment and replacement of members of the board of | ||||
| directors as well as modification of the bylaws 156 | |||||
| 16.4.8. | Powers of the board of directors, particularly the issuance or redemption of shares156 | ||||
| 16.4.9. | Agreements made by the Company which have been modified or which shall end if there | ||||
| is a change in control of the Company. 156 | |||||
| 16.4.10. Agreements providing for indemnities to members of the board of directors or | |||||
| employees if they resign or are dismissed without real or serious cause or if their employment is terminated due to a public offering157 |
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| 17. | EMPLOYEES158 | ||||
| 17.1. | Personnel 158 | ||||
| 17.1.1. 17.1.2. |
Functional organization chart158 Experience and positions of the principal managers158 |
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| 17.1.3. | Personnel distribution 159 | ||||
| 17.1.4. | Human Resources Management160 | ||||
| 17.1.5. | Organization of work time 160 | ||||
| 17.2. | Stakes held by corporate officers 160 | ||||
| 17.3. | Investment stake held by Company employees who are not corporate officers 161 | ||||
| 17.4. | Incentive agreement 161 | ||||
| 18. | MAJOR SHAREHOLDERS162 | ||||
| 18.1. | Distribution of share capital and voting rights 162 | ||||
| 18.2. | Shareholder voting rights 164 | ||||
| 18.3. | Control of the Company 164 | ||||
| 18.4. | Shareholders' agreement 164 | ||||
| 18.5. | Concerted action 164 | ||||
| 18.6. | Agreements capable of resulting in a change in control 165 | ||||
| 19. | RELATED-PARTY TRANSACTIONS166 | |||||||
|---|---|---|---|---|---|---|---|---|
| 19.1. Intra-group transactions 166 19.2. Related party transactions 167 |
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| 19.2.1. | Special report by the statutory auditor on regulated agreements – Financial year ended December 31, 2014 167 |
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| 19.2.2. | Special report by the statutory auditor on regulated agreements – Fiscal year ending | |||||||
| December 31, 2013 173 | ||||||||
| 20. | FINANCIAL | INFORMATION CONCERNING THE COMPANY'S EQUITY, |
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| FINANCIAL POSITION, AND RESULTS178 | ||||||||
| 20.1. | Financial statements prepared based on IRFS standards for the year ended December 31, 2014 178 |
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| 20.2. | Corporate financial statements prepared (French standards) for the years ended December 31, 2013 and 2014 213 |
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| 20.3. | 31, 2014248 | Auditors' report on the corporate financial statements prepared for the year ended December | ||||||
| 20.4. | Date of last financial information 251 | |||||||
| 20.5. | Table of results for the last five financial years (Erytech Pharma SA, annual financial | |||||||
| statements prepared in accordance with French accounting standards) 251 | ||||||||
| 20.6. | Dividend distribution policy 252 | |||||||
| 20.6.1. | Dividends paid during the last three fiscal years252 | |||||||
| 20.6.2. | Dividend distribution policy252 | |||||||
| 20.7. | Legal and arbitration proceedings 253 | |||||||
| 20.8. | Significant changes in the financial or commercial situation 253 | |||||||
| 20.9. | Report on the economic and financial results (annual financial statements prepared in accordance with French accounting standards) 253 |
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| 20.10. Report on the economic and financial results (financial statements consolidated in accordance | ||||||||
| with IFRS framework) 254 | ||||||||
| 20.11. Allocation of the results 255 | ||||||||
| 20.12. Luxury expenditures and non-deductible expenses 255 | ||||||||
| 20.13. Information on payment timeframes 255 | ||||||||
| 20.14. Regulated agreements 256 | ||||||||
| 21. | ADDITIONAL INFORMATION 257 |
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| 21.1. | Share capital 257 | |||||||
| 21.2. | Acquisition of shareholder equity by the Company 257 | |||||||
| 21.3. | Unissued authorized capital 260 | |||||||
| 21.4. | Securities not representing the capital Erreur ! Signet non défini. | |||||||
| 21.5. | Other securities giving access to the capital Erreur ! Signet non défini. | |||||||
| 21.6. | Company capital forming the object of an option or a conditional or unconditional agreement | |||||||
| stipulating its placement under option 266 | ||||||||
| 21.7. | Evolution of the share capital 267 | |||||||
| 21.8. | Evolution of the shares 268 | |||||||
| 21.9. | Main provisions of the articles of incorporation 269 | |||||||
| 21.9.1. | Corporate purpose (Article 3 of the articles of incorporation) 269 | |||||||
| 21.9.2. | Administration and Senior Management (articles 17 to 24 of the articles of incorporation) 269 |
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| 21.9.3. | Rights, privileges, and restrictions attached to shares (Articles 9 to 16 of the articles of incorporation) 272 |
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| 21.9.4. | General Meetings (articles 26 to 30 of the articles of incorporation) 275 | |||||||
| 21.9.5. | Clauses of the articles of incorporation such as may have an effect on the occurrence of a | |||||||
| change of control 277 | ||||||||
| 21.9.6. | Crossing of thresholds set by the articles of incorporation 277 | |||||||
| 21.9.7. | Special provisions governing modifications to the share capital 277 | |||||||
| 22. | MAJOR CONTRACTS 278 |
| 22.1. Partnership and cooperation agreements 278 22.1.1. Financed agreements278 |
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|---|---|---|---|---|
| 22.1.2. | 22.1.1.1. Erytech/Inserm/Aphp/Diaxonhit 278 Partnership agreements280 22.1.2.1. ERYTECH/Orphan Europe (Recordati Group)281 |
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| 22.2. | License agreement 281 | |||
| 22.2.1. | Erytech/National Institutes of Health (NIH) 281 | |||
| 22.3. | Supply contracts: 282 | |||
| 22.3.1. | Erytech/Établissement Français Du Sang (EFS)282 | |||
| 22.3.2. | Erytech/American Red Cross (ARC) 282 | |||
| 22.3.3. | Erytech/medac 282 | |||
| 22.3.4. | Other supply contracts282 | |||
| 22.4. | Subcontracting agreements 283 | |||
| 22.4.1. | Erytech/American Red Cross (ARC) 283 | |||
| 22.4.2. | Other subcontracting agreements 283 | |||
| 23. | INFORMATION | ORIGINATING FROM THIRD PARTIES, |
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| DECLARATIONS, AND DECLARATIONS OF INTERESTS 284 |
EXPERT | |||
| 24. | DOCUMENTS ACCESSIBLE TO THE PUBLIC 285 |
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| 25. | INFORMATION ON INVESTMENT STAKES286 | |||
| 26. | GLOSSARY287 | |||
| REPORT | APPENDIX 1 – | REPORT BY THE STATUTORY AUDITORS ON THE CHAIRMAN'S 289 |
share capital
The concordance table below makes it possible to identify in this reference document:
| Annual financial report | Reference document |
|---|---|
| 1. Certification by the responsible party | See section 1.2 |
| 2. Company annual financial statements – French standards |
See section 20.4 |
| 3. Company annual financial statements – International Financial Reporting Standards (IFRS) |
See section 20.1 |
| 4. Management report | See index below |
| 5. Chairman's report on internal audit | See chapter 16 |
| 6. Annual information document | See section 5.1.6 |
| 7. Statement pertaining to the statutory auditor's fees | See section 2.3 |
| 8. Statutory auditor's report on the annual financial statements according to French standards and IFRS standards |
See sections 20.2 and 20.5 |
| 9. Report by the statutory auditor about the Chairman's report | See appendix 1 |
| Annual management report | Reference document |
| 1. Condition of the Company and activity during the past fiscal year | See chapters 6 |
| 2. Examination of the financial statements and earnings – Allocation of earnings – Review of dividends distributed – Expenses that are not tax deductible |
See chapter 20 |
| 3. Information about supplier payment deadlines | See chapter 20 |
| 4. Progress made or difficulties encountered | See chapter 6 |
| 5. Primary risks and uncertainties faced by the Company – Use of financial instruments by the Company |
See chapter 4 |
| 6. Research and development activities | See chapters 6 and 11 |
| 7. Forecast and outlooks | See chapters 6 and 12 |
| 8. Significant events that have occurred since the end of the fiscal year | See chapter 20 |
| 9. Employee investment in share capital | See chapter 17 |
| 10. The Company's Senior Management | See chapters 14, 15 and 16 |
| 11. Information about officers and directors | See chapters 14, 15 and 16 |
| 12. Acquisition of significant stakes in companies that have their headquarters in France, or acquisition of control over such companies; sales of such stakes |
See chapters 7 and 25 |
| 13. Activities of subsidiaries and controlled companies | See chapters 7 and 25 |
| 14. Information pertaining to the distribution of capital and cross holding – Share repurchase program |
See sections 18.1 and 21.1.2 |
| 15. Changes that occurred during the fiscal year in the makeup of the | See sections 18.1 and 21.2 |
| 16. Changes in the security – Risk of variation in price |
See sections 4.7 and 21.3 |
|---|---|
| 17. Summary statement of transactions by the executive officers and persons mentioned in article L.621-18-2 of the monetary and financial code involving shares of the Company conducted during the past fiscal |
See section 15.4 |
| year 18. Information required by article L.225-100-3 of the Commercial code |
See section 16.4 |
| 19. Social and environmental information | See section 6.12 and |
| 20. Table of earnings for the last five fiscal years | chapter 17 See section 20.7 |
| 21. Delegations respecting increases in capital | See section 0 |
In this reference document ("the Reference Document"), the terms "ERYTECH" or the "Company" refer to the company ERYTECH Pharma, a public limited company with its head office located at 60 Avenue Rockefeller, Bâtiment Adénine, 69008 Lyon, France, registered with the Lyon Trade and Companies Register under number 479 560 013. The term "Group" refers to the Company and its subsidiary, the company ERYTECH Pharma Inc., which head office is located at 185 Alewife Brook Pkwy Ste 410, CAMBRIDGE MA 02138, United States of America.
The Reference Document notably presents the annual financial statements for the Company, prepared in accordance with accounting standards applicable in France (the "Financial Statements") for the financial year ending December 31, 2014, as well as a set of financial statements for the same year, in accordance with the IFRS accounting standards adopted by the European Union. In application of article 28 of regulation (EC) no. 809/2004 of the Commission, the following are included as references in this Reference Document:
The Base Document may be consulted on ERYTECH Pharma's website (www.erytech.com) and that of the AMF (www.amf-france.org).
Unless stated otherwise, the financial information regarding the Company mentioned in the Reference Document is taken from the IFRS consolidated financial statements. Additionally, the Reference Document contains statements about the Group's objectives, as well as its areas of focus for development. These statements are at times identified by the use of the future tense, the conditional tense, and forward-looking terms such as "consider", "plan", "think", "has as its objective", "expects to", "understand", "must", "strive", "believe", "estimate", "wish", "be able to", or, as applicable, the negative form of these same terms, or even, any other variation or similar terminology. The reader's attention is directed to the fact that these objectives and these directions for development depend on circumstances or facts for which the occurrence or completion is uncertain.
A glossary defining certain technical terms referenced in the Reference Document as well as an index of abbreviations used is found in chapter 26.
The goals and directions for development presented are not historical data and must not be interpreted as being guarantees that the facts and data stated shall occur, that the scenarios have been verified, or that the objectives shall be reached. Inherently, these objectives may not be reached and the statements or information found in the Reference Document could turn out to be erroneous, and the Company shall not be under any obligation in any way whatsoever to provide an update, except as required by applicable regulations and particularly the General Rules of the Autorité des Marchés Financiers ("AMF").
The Reference Document furthermore contains information pertaining to the Group's activities, as well as the market and industry in which it operates. Some of this information originates from sources external to the Group and has not been verified independently by the Group.
Investors are invited to carefully weigh the risk factors described in chapter 4 -"Risk factors" - of this Reference Document before making their investment decision. The occurrence of all or part of these risks may have a negative impact on the Group's activities, circumstances, financial results, or the achievement of its objectives. Additionally, other risks that have not yet been identified or considered by the Group to be significant could have the same negative effect and investors could thus lose all or part of their investment.
Mr.Gil Beyen Chairman and Chief Executive Officer
"I hereby declare, after having taken all reasonable measures to this effect, that, to my knowledge, the information contained in this Reference Document conforms to reality and does not contain any omissions such as may alter its nature or intent.
We have obtained a certification letter from the statutory auditors, in which they declare that they have performed an audit of the information in the financial statement and the accounts reported in this Reference Document, and have read the entire Reference Document.
The historical financial information presented in the present Reference Document is reported in the statutory auditors' reports provided in Chapters 19 and 20."
June 3, 2015
Mr.Gil Beyen
Mr. Gil Beyen Chairman and Chief Executive Officer
Tel.: +33 4 78 74 44 38 Fax: +33 4 78 75 56 29 e-mail: i[email protected]
KPMG Audit Rhône Alpes Auvergne, a simplified limited company, Lyon Trade and Companies Registry 512 802 828, 51, rue de Saint Cyr - 69338 Lyon Cedex 9.
Date of first appointment: June 11, 2010.
Expiration date for term of office: The general shareholders' meeting voting on the financial statements for the year ending December 31, 2015.
KPMG SA was the statutory auditor for the period from initial establishment of the Company and up to its replacement by KPMG Audit Rhône Alpes Auvergne on June 11, 2010, upon expiry of its term.
RSM CCI CONSEILS, LYON Trade and Companies Register 398 384 198, 2 bis, rue Tête d'Or, Lyon 6
Date of first appointment: June 17, 2014
Expiration date for term of office: The general shareholders' meeting voting on the financial statements for the year ending December 31, 2019.
KPMG Audit Sud Est, a simplified limited company, Marseille Trade and Companies Register 512 802 729, 480, avenue du Prado 13269 Marseille Cedex 08.
Date of first appointment: June 11, 2010.
Expiration date for term of office: The general shareholders' meeting voting on the financial statements for the year ending December 31, 2015.
The deputy statutory auditor from establishment of the Company and up to the expiry of his term on June 11, 2010, was Mr. Pierre Duranel, acting in his own name.
Pierre-Michel MONNERET, 2 bis, rue Tête d'Or, 69006 LYON
Date of first appointment: June 17, 2014
Expiration date for term of office: The general shareholders' meeting voting on the financial statements for the year ending December 31, 2019.
The table below presents the auditor fees sustained by the Company in the first three years:
| In Euros (before tax) | KPMG SA, then KPMG Rhône Alpes Auvergne | RSM-CCI Conseils | ||||||
|---|---|---|---|---|---|---|---|---|
| 2014 | % | 2013 | % | 2012 | % | |||
| Audit: | ||||||||
| Audit engagement, certification, examination of individual accounts |
95 000 | 69 750 | 15 300 | |||||
| Directly associated due diligence reviews |
12 000 | 1 800 | 11 390 | |||||
| Subtotal | 107 000 | 100% | 71 550 | 100% | 26 690 | 100% | ||
| Other services: | ||||||||
| Legal, fiscal, social security | None | None | None | |||||
| Internal audit | ||||||||
| Other | ||||||||
| Subtotal | ||||||||
| Total | 107 000 | 100% | 71 550 | 100% | 26 690 | 100% |
The other diligence activities and services directly associated with the auditor's assignment include:
The main financial information presented below is extracted from the consolidated financial statements of the ERYTECH PHARMA Group, in accordance with IFRS standards, for the financial years ended December 31, 2013 and December 31, 2014, as provided in Section 20.1 of the present Reference Document.
The historical legal financial statements for the parent company, prepared in accordance with French standards, are included in Chapter 20.
This main accounting and operational data should be read alongside the information contained in Chapters 9 "Examination of the Company's financial position and results", 10 "Cash position and capital", and 20 "Financial information concerning the Company's equity, financial position, and results".
| as of Dec. 31 in thousands of € | 2 013 | 2 014 |
|---|---|---|
| NON-CURRENT ASSETS | 910 | 1 080 |
| intangible assets | 14 | 31 |
| tangible fixed assets | 813 | 967 |
| non-current financial assets | 83 | 82 |
| deferred tax assets | - | - |
| CURRENT ASSETS | 17 039 | 39 526 |
| cash and cash equivalents | 15 113 | 36 988 |
| TOTAL ASSETS | 17 949 | 40 607 |
| SHAREHOLDERS' EQUITY | 13 587 | 35 824 |
| NON-CURRENT LIABILITIES | 848 | 525 |
| CURRENT LIABILITIES | 3 515 | 4 258 |
| TOTAL LIABILITIES AND SHAREHOLDERS | 17 949 | 40 607 |
| EQUITY Simplified income statement |
||
| as of Dec. 31 in thousands of € | 2 013 | 2 014 |
| Total income from activities | 1 802 | 2 026 |
| sales revenue | - | - |
| Operating results | (7,085) | (8,948) |
| Financial results | (1,100) | 68 |
| Net income | (8,145) | (8,860) |
| as of Dec. 31 in thousands of € | 2 013 | 2 014 |
|---|---|---|
| Internal financing capacity before financial results and tax | (7,965) | (9,113) |
| Changes in working capital needs related to business activities | 1 492 | 1 874 |
| Net cash flow generated by business activities | (6,473) | (7,239) |
| Net cash flow generated by investment operations | (289) | (420) |
| Net cash flow generated by financing operations | 13 999 | 29 535 |
| capital increase performed in cash, net of costs | 14 537 | 29 173 |
| Variation in net cash position | 7 237 | 21 876 |
At March 31, 2015, cash and cash equivalents totaled 33.5 million Euros, compared to 37 million Euros at the end of 2014.
During the first quarter of 2015, the Group did not record any revenue from activities.
Investors are invited to review all information contained in this Reference Document, including the risk factors described in this section. The Company has performed a review of the risks that could have a significant negative effect on its activities, its financial position, or its results (or on its ability to achieve its objectives), and considers that no significant risks exist other than those presented in this chapter. At the time of filing this Reference Document, those risks are those that the Company believes could have a significant material adverse effect on the Company or its activity, financial position, results or growth.
To obtain the regulatory approval required to bring a candidate drug to market, the Company must conduct preclinical and clinical studies to show safety and efficacy. These studies entail high costs. The trend for these costs could be on the rise with the growth of the Company and increase in products it develops. If the results of these studies are unsatisfactory or inconclusive, the Company may have to choose between abandoning the program, leading to loss of investment in time and money, or its pursuit, with no guarantee that the additional costs that this would entail would lead to completion.
The Company may choose, or regulatory authorities may force the Company, to suspend or end clinical trials if the patients are or have been exposed to unexpected and serious risks or to clinical ineffectiveness (loss of opportunity) or request additional scientific information/validations. Deaths and other adverse events could occur during a clinical trial as a result of medical problems that may or may not be related to the treatment under study, and force the Company to delay or interrupt the trial. In light of trial results, the Company could also decide to abandon development projects that it initially believed held promise.
Other factors can have a significant material adverse effect on the Company's activities, prospects, financial position, results and growth:
1 The GRASPA® brand was licensed to Orphan Europe (Recordati Group) in order to market the product in ALL and AML in Europe and to the Teva Group in Israel.
– In the event of serious tolerance or toxicity problems, the trials must be interrupted.
Finally, no guarantee can be made as to positive preclinical and clinical results. Favorable results during preclinical studies and preliminary clinical trials are not always confirmed during future clinical trials. In addition, clinical trials can produce safety and efficacy results that, while positive, are not sufficient to obtain marketing approval. Positive results in a clinical trial and/or the grant of marketing approval of a product with a given indication does not presume the efficacy, safe use and marketing approval (MA) for another indication, even if the latter may be related or linked by scientific rational.
ERY-ASP/GRASPA® must be intravenously injected in the patient in accordance with the rules for administering red blood cells (transfusion) and the notably the compatibility of the donor (blood type). The red blood cells used during the manufacture of ERY-ASP/GRASPA® originate from blood donations prepared and tested by blood banks, notably the Établissement Français du Sang (French national blood service - EFS), known for their high standards of quality and safety.
However, ERY-ASP/GRASPA® could present certain risks that exist in relation to blood transfusions. These risks, while rare, are possible despite having never been observed with ERY-ASP/GRASPA® at the time of filing of the Reference Document:
In addition, the blood banks follow a strict red blood cell preparation process, approved by health authorities, to detect and reduce possible risks for contamination by infectious agents.
Risks related to molecules encapsulated in red blood cells could be varied and depend on their known or unknown toxicity. For example, enzymatic biological molecules (such as asparaginase) are immunogenic in humans and promote development of antibodies and allergic reactions, which could lead to anaphylactic shock and death in the patient. The level of knowledge of the risks inherent in encapsulated molecules is greater with a molecule that has already been approved for the market in France or another country than for a new molecule that has never been used in humans. ERY-ASP/GRASPA® uses asparaginase, a product used in Europe since the '70s, the toxicity of which is well known and documented.
ERYTECH manufactures according to manufacturing best practices applicable to drugs for clinical trials and to specifications approved by the regulatory authority. Only products that meet the standards are released for administration to patients. If a product is found to be non-compliant, ERYTECH would be required to manufacture again, which would entail additional costs and may prevent delivery of the product to patients on time.
Other risks may have the same effect, such as:
These risks, should they occur, could have a material adverse effect on the activities, financial position, results, reputation or growth of the Company.
Moreover, a rise in direct/indirect energy rates may increase product manufacturing and logistical costs, therefore having a negative impact on the activities, financial position, results or growth of the Company.
The Company's production capacity may prove insufficient in the future to meet the growth of its activity. If the Company must increase production capacity, it could need to make considerable investments that could lead to significant financing needs or to sub-contracting agreements in order to outsource part of the production.
At this time, none of the products developed by the Company has received marketing approval (MA). For the development and marketing of products based on these technologies, the Company is confronted with a high level of risk and uncertainty which could slow or suspend the development efforts for its products and negatively affect its activities. Therefore, even if the Company could obtain and maintain regulatory approvals to market these products, it is possible that:
– The future products of the Company are not marketable due to third party intellectual property rights claims (see also section 4.2 of the Reference Document).
The level of acceptance of each Company product by the market will also depend on the following factors:
These factors could limit or halt product acceptance by the market which would have a significant material adverse effect on the Company's activities, financial position, results and growth.
To date, the Company has not invested in sales, marketing and distribution. The Company will have to develop marketing and sales capability either on its own or with strategic partners.
To market its first product, ERY-ASP/GRASPA®, the Company has entered into a partnership with specialists in the sale of orphan drugs, Orphan Europe (Recordati Group) for Europe and Teva Group for Israel (see also Section 4.1 and Chapter 22 pertaining to major contracts).
For other products and jurisdictions, the Company will choose to market its products:
In the first case, the Company will have to organize its own sales and marketing infrastructure.
In the second case, it is possible that:
Such events may have a significant material adverse effect on the activity, prospects, results, financial position and growth of the Company.
In all cases, it will consequently have to incur additional costs, mobilize management resources, recruit specific personnel, draw on new competencies and take the time required to put in place the appropriate organization and structure to assist the development of the product in accordance with current legislation and, more generally, optimize its marketing efforts.
The Company chose Teva Group as exclusive distributor for GRASPA® in the treatment of ALL in Israel (see also Section 22 of the Reference Document).
A licensing and exclusive distribution agreement has been reached between the parties as of March 28, 2011.
The marketing success of GRASPA® in Israel therefore depends on marketing and commercial efforts deployed by this distributor as well as its capability to sell the treatments developed by the Company. Any failure on the part of Teva Group would have adverse consequences on the Company. The Company has limited these risks by putting in place a steering committee to follow-up on the development and marketing of products developed by the Company.
The Company has chosen Orphan Europe as the exclusive distributor of GRASPA® in the treatment of ALL and AML for 38 countries in Europe, including the European Union (see also Section 22 of the Reference Document).
The risk resulting from this agreement is the risk of dependence where:
ERY-ASP/GRASPA® is, to date, the only company product under clinical development. In fact, the clinical development of ERY-ASP/GRASPA® is not yet complete.
The development of ERY-ASP/GRASPA® has required and will continue to require the mobilization of numerous Company resources. The future of the Company depends on the successful development of its flagship product: ERY-ASP/GRASPA®. Indeed, if the Company does not successfully develop and market ERY-ASP/GRASPA®, and it does not, in parallel, reduce its dependence on this product, its activities, prospects, financial position, results, and growth could be significantly affected.
The Company considers its dependence on ERY-ASP/GRASPA® to be significant.
The Company depends on partnerships and expects to continue to depend on partnerships, namely with public and private research institutions, to conduct an important part of its discovery activities. If one of these partnerships breached or terminated its agreement with the Company or otherwise failed to work efficiently with the Company, the research, development or marketing of products planned as part of this partnership could be delayed or canceled. In the event a partnership agreement entered into by the Company is terminated or the Company is no longer in a position to renew the partnerships in question under acceptable conditions, the Company's activities may be delayed and even penalized.
Directors (see also sections 14 and 16 of the Reference Document)are subject to a regulatory and legal framework, including for conflicts of interest. However, no provision can replace the ethical conduct of a director. In addition, in the event of conflict of interest, a director risks losing his/her intellectual independence or objectivity. The occurrence of this risk could have a significant material adverse effect on the activities, financial position, results, reputation or growth of the Company.
Members of the scientific board (see also section 16 of the Reference Document) contractually declare their interest(s). The Company consequently assesses the risks, but does not verify the truthfulness of these statements. In the event of omission or of false declaration, a member risks losing his/her intellectual independence or objectivity. The occurrence of this risk could have a significant material adverse effect on the activities, financial position, results, reputation or growth of the Company.
The Company is supplied in:
EFS (Établissement Français du Sang [French Blood Facility]) is under contract with ERYTECH to supply the Company for its clinical trials in progress and as part of temporary approval for use. Blood collection and distribution is managed in France by EFS, a public institution with a monopoly position, the only blood transfusion authority responsible for meeting the national need in blood products, which it must supply in sufficient quantity with optimal quality. In the event of a major and/or international crisis impacting blood banks and the practice of blood donation, the Company may not be supplied sufficiently with RBC to satisfy clinical trials and/or the market.
The asparaginase market is a closed one with few international players and multiple marketing exclusivity rights between players and geographical areas. ERYTECH is exclusively supplied by a company with which it has signed a long-term contract to supply asparaginase.
The Company outsources the following:
In the event of failure, bankruptcy or shutdown of, or dispute with these subcontractors and/or key suppliers, the Company could then not be able to enter into new agreements with other contractors under commercially acceptable conditions and therefore could not be able to develop, test, manufacture and market its products in the expected time frame and at an acceptable cost. This could have a significant material adverse effect on the activities, financial position, results or growth of the Company.
In addition, the contracts that the Company entered into with these companies normally contain limitation of liability clauses in their favor meaning that the Company will not have recourse to full compensation of potential losses that it would risk incurring in the event of failure.
To reduce its dependence on these companies, the Company's contracts provide for, when possible, an extended notice period before any cancellation or shutdown of activity in order to have sufficient time to find a new qualified provider, if needed, that can meet the same need.
When possible, the Company also has alternate suppliers as part of its purchasing policy, and undergoes follow-up with its suppliers through audits managed by the Company Quality Assurance department. In addition, the Company suppliers are generally subjected to precise specifications. However, the Company cannot guarantee these suppliers will follow the Company's directives.
If third-party supplied and manufactured products do not comply with regulatory standards, penalties may be imposed on the Company. These penalties may include fines, injunctions, refusal by regulatory authorities to pursue our trials, delays, suspension or withdrawal of approvals, seizure or recall of our products and criminal prosecution, all measures which could have a considerable negative impact on the Company.
In the event the Company must change key suppliers or subcontractors, it will be asked to show that the change has had no impact on the quality of the manufactured products. This verification could be costly, time consuming and could require the attention of the most qualified personnel. In order to show absence of impact due to the change, the Company could be required to conduct animal studies or other clinical studies. Some changes are subject to approval by regulatory authorities. If the change is refused, the Company could be constrained in finding another supplier/subcontractor which could delay the production, development or marketing of products and increase the manufacturing costs of these products.
The Company's research and development activities exposes it to chemical and biological risks and forces it to take and follow preventive measures according to current legislation.
During company preclinical research and development programs and tests, the Company uses hazardous materials, such as compressed gases, and biological material, blood from donors, but also from patients (see also the section Risk related to the particular nature of products from technology in the Reference Document), solvents and other chemical products that could be genotoxic.
There are therefore health risks related to the handling of these hazardous materials by the Company employees and/or subcontractors. Consequently, the Company is subject to environmental and safety legislation and regulations governing use, storage, handling, emission and hazardous materials disposal, including of chemical and biological products. While the Company considers that the safety measures meet the standards set out by current legislation and regulations and allow its employees and subcontractors to work under good conditions, the risk of accidental contamination or of occupational diseases related to hazardous material handling cannot be completely eliminated.
Although the company doesn't identify major environmental risks related to its activity, as well as in the event of an accident, the company could be held responsible for all resulting damages and the incurred liability could exceed the limits of the insurances the Company subscribes to and even not be covered by them.
Moreover, conforming to environmental, health and safety regulations imposes on the Company additional costs, and it could have to incur significant expenses to conform to future environmental legislation and regulations.
The Company's success depends in large part on the actions and efforts by its executive officers and personnel in key positions. In the event that the Company is not able to keep its executive officers and scientists, its research and development (preclinical as well as clinical) could be delayed, and the implementation of its strategy could be negatively affected. As the Company progresses in its programs and extends the scope of its activities, it could have to recruit new employees with competencies in areas such as clinical trials, regulatory matters, reimbursement procedures, sales and marketing. As part of recruiting and retaining qualified personnel, the Company is confronted with intense competition from other companies in the sector, universities, public and private research institutions, as well as other organizations. Under these circumstances, the Company cannot guarantee its ability to recruit and/or retain its qualified personnel under conditions that are acceptable from an economic point of view. The delay in recruiting or the loss of a key employee could prevent the Company from reaching its overall objectives and consequently have a negative impact on its activities, results, financial position and its prospects.
Moreover, the loss or disability of one or more members of the board could lead to significant negative effects on activities, financial position and overall growth of the Company. While the Company benefits from a "Key Persons" insurance policy (described in Section 4.9 of the Reference Document) for Gil Beyen and Yann Godfrin, this policy could prove insufficient to compensate for any damages suffered.
The Company is bound to academic and commercial partnerships through financial agreements for research programs or by commercial development agreements. These agreements are contingent upon royalties, public funds, achievement of commercial, industrial, proof of concept or other objectives.
Consequently, if the Company does not reach these objectives, this will have a significant material adverse effect on its activities, financial position, results or growth.
As part of its growth strategy, the Company will need to recruit additional personnel and develop its operational capabilities, which could excessively mobilize its internal resources. To do so, the Company will need:
If the Company does not manage its growth or if it encounters unexpected difficulties during its growth, this could have a significant material adverse effect on its activities, financial situation, results or growth.
The markets in which the Company is involved in are well defined and very competitive and progress rapidly. The Company competes with larger companies that have more industrial and commercial experience and access to distinctly superior resources.
Consequently, the Company cannot guarantee that its drugs will:
Finally, the Company cannot guarantee that its partners and/or employees will not choose, in the more or less long term, to join or work for competitors.
Such events could have a significant material adverse effect on the activity, results, financial position and growth prospects of the Company.
It is likely that new developments will continue in the pharmaceutical industry and in public and private research institutions. As well as developing safer, more effective and less expensive products than those developed by the Company, its competitors could manufacture and market their products under better conditions. As such, the Company cannot exclude the possibility that companies and other public and private organizations that are currently competing in the same space merge or enter into partnerships or other types of alliances, consequently becoming more aggressive competitors. In addition, rapid technological developments by these competitors could render the Company's drugs or its potential products obsolete before being able to recuperate the research, development and marketing costs for its products.
To the Company's knowledge, new forms of asparaginase are under development as well as other products that could be used in the treatment of acute leukemia (see also section 6.4, The L-asparaginase market).
Even if the Company's products are marketed successfully, market recognition could be delayed and the Company could not be able to offset its costs with its potential revenues. In order to gain market acceptance for its products over existing ones, the Company will have to commit significant marketing as well as investment efforts. To date, the Company has not undertaken significant marketing activity and disposes of few financial and human resources to this effect.
As part of partnership agreements, current and future, between the Company and natural persons as well as other public or private entities, subcontractors or third parties, information and/or products could be provided in order to conduct tests or other services. In these instances, the Company requires the signing of a confidentiality agreement. In fact, the proprietary non patented and/or non patentable technology, processes, knowledge and data are considered trade secrets that the Company attempts to protect through such confidentiality agreements.
It cannot be guaranteed that confidentiality agreements are not infringed or ensure the sought after protection, that the Company has appropriate solutions against such infringements, or that its trade secrets are not disclosed to or developed by its competitors.
More specifically, the Company has no control over the conditions under which third parties, with which it has agreements, have recourse themselves to third parties, and protect its confidential information.
The occurrence of this risk could have a significant material adverse effect on the activity, prospects, financial position, results and growth of the Company.
In order to safeguard the information systems and their users, the Company standardized rules governing their use (information technology charter, internal control procedures) to outline the main precautions and guidelines of use that each user must follow when using Company information systems.
However, the Company cannot guarantee that the users will follow these rules and that these rules are sufficient to avoid cyber attacks, loss of sensitive data, discontinuity of operations and claims against the Company. These risks, should they occur, could have a material adverse effect on the activities, financial position, results, reputation or growth of the Company.
Given its highly technological and innovative activity and advanced research and development projects that could confer it a competitive advantage in its market, the Company is exposed to an industrial espionage risk.
Disclosure or theft of its scientific research content would deprive the Company of potential revenue sources and affect its activity.
Such a situation, should it occur, is susceptible to have a negative impact on the Company, its activity, financial position, results or growth.
The Company entered into agreements with researchers working for public and/or private entities (see Section 22 of the Reference Document). The agreements entered into with these entities contain specifications pertaining to intellectual property rights and confidentiality commitments.
It cannot be guaranteed that these agreements will ensure the protection sought or are followed by the Company's co-contracting parties. The Company also relies on the commercial licensing terms which it will obtain, if applicable, for the results of the experiments covered by such agreements.
Finally, the Company cannot guarantee that entities with which it has agreements have at their disposal all the rights to use the technologies and that they will be able to grant the Company licenses for such rights.
When the Company is granted a patent license from third parties (see Section 22 of the Reference Document), the Company undertakes to comply with certain conditions to maintain its rights on the patent. In addition, the Company relies on the patent being protected and enforced.
The conditions for maintaining rights on the technology could include elements such as carrying out development efforts to transform the patent into a commercial product, payment of licensing fees while carrying out predefined steps and payment of annual licensing fees based on sales revenue generated as a result of the patent.
Any failure on the part of the Company could lead to loss of patent exclusivity. If the Company loses its rights to the patent obtained under license or if it cannot obtain new similar rights under reasonable terms, this could constitute an obstacle to development, manufacture and sale of its products.
The protection offered by patents and other intellectual property rights is uncertain. The Company may not be able to maintain adequate protection of its intellectual property rights and thereby lose its technological and competitive advantage. Part of the Company's activity could depend on or infringe upon patents and/or other intellectual property rights owned by third parties. The exclusive nature conferred by intellectual property rights could be circumvented by the Company's third parties/competitors.
The Company's success depends on its ability to obtain, maintain and enforce its patents and other intellectual property rights. If one or more brands or patents covering a technology, the manufacturing process or a product were to be invalidated or found unenforceable, the development and marketing of such a technology or product could be directly affected or interrupted.
In the pharmaceutical industry in which the Company operates, patent law varies according to the country and is in constant evolution. There is therefore much uncertainty in this area. Consequently, the Company cannot guarantee that:
– third parties will not be granted or will not file patent applications or use any other intellectual property rights that, even if they don't infringe on those of the Company, limit its growth.
Intellectual property litigation is often long, costly and complex. Some of the Company's competitors have access to greater resources and could be more able to conduct such proceedings. A court judgment against the Company could seriously affect its ability to continue its activity and, more particularly, could force the Company:
Patent applications in Europe and in the United States are not generally published until 18 months after the priority date on the application and, moreover, in the United States, some applications are not published before the patent is granted. In addition, in the United States, if the legislation has changed, the notion of the right to the patent for all patent applications before March 2013 is related to the notion of first-to-invent which is based on the date the invention was conceived, while in other countries, the right to the patent is attributed to the first to file the patent application. The new legislation in the United States provides that the right henceforth belongs to the first inventor to file under the new rules. As a result, the Company cannot guarantee that third parties will not be in a position to be considered as first inventor or first inventor to file an invention covered by its patents and its pending patent applications in the United States. In such circumstances, the Company could have to enter into licensing agreements with third parties (provided that these licenses are available), modify some of its activities or manufacturing processes, or develop or acquire different technologies.
The Company is confronted with similar risks for its trademarks.
The Company also relies on its technology, manufacturing processes, knowledge and non-patented confidential data that it protects through confidentiality agreements signed by its employees, consultants and some of its subcontractors. The Company cannot guarantee that these agreements will always be followed, that the Company has recourse in the event of a breach of such agreements or that the confidential information in question will not be disclosed to third parties or independently developed by competitors. The Company also cannot guarantee that, despite the implementation of measures, a consultant or employee will not claim rights on an invention discovered as part of a Company project.
The occurrence of any one of these situations regarding any patent or intellectual property right of the Company could have a significant negative effect on the activities, financial position, results or development of the Company.
The use or misuse of the Company's products during feasibility studies and clinical trials, as well as the sale, promotion, or use of future related products risk exposing the Company and/or its subsidiary to liability actions.
Complaints could be filed and legal action taken against the Company and/or its subsidiary by patients, regulatory authorities, pharmaceutical companies, or other third parties using or selling the Company's products. The Company cannot guarantee that its current insurance policies are sufficient to protect the Company and/or its subsidiary against such proceedings. If the Company and/or its subsidiary, its subcontractors, or its other partners are found liable (even in the case of proceedings that do not lead to conviction) or if it is impossible to obtain or maintain appropriate insurance policies at an acceptable price or to obtain other protection, this could significantly affect the development and, in the future, the marketing of the Company's products and have a significant negative effect on the activities, financial position, results, reputation, and growth of the Company.
At this time, no Company product, including its most advanced product, ERY-ASP/GRASPA®, has received marketing approval from any regulatory authority. The Company cannot be assured that it will receive the necessary approvals to market any of its products. The Company as well as its products are subject to extensive and very stringent legislation and regulations and to controls from regulatory authorities such as the Agence Nationale de Sécurite du Médicament et des Produits de Santé [National Agency for the Safety of Drug and Healthcare Products] (ANSM) in France, the Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) in Europe. The applicable regulatory requirements are known, but subject to change. Any failure to comply with these requirements can lead to sanctions including fines, rulings, civil penalties, refusal of marketing approval, delays, suspension or withdrawal of approvals, seizure or recall of products, restriction of use and legal proceedings.
To obtain marketing approval for any of its products, the Company must show, through many long and costly clinical trials with uncertain outcomes, that use of its products is safe and effective in humans. If the Company was not in a position to follow its development schedule or if it cannot conduct clinical trials for its products within expected time limits, its activities, financial position, results and growth could be significantly negatively affected.
The Company's ability to obtain marketing approval for its products will depend on many factors, including the following:
the Company cannot submit to the regulatory authority of a jurisdiction the results of clinical trials conducted in another jurisdiction or for other candidate drugs;
the Company is forced to conduct additional clinical trials requested by regulatory authorities;
In addition, the Company's products that have already been approved could prove unsafe and be withdrawn from the market, or produce effects over time other than those expected, which could limit or render impossible their commercialization.
To obtain marketing approval for its products in a given jurisdiction, the Company must show that they meet the quality, safety and efficacy criteria defined by the relevant authorities for the intended indications.
If the Company is not granted marketing approval of a product in a given jurisdiction, it will not be able to sell the product in question for the intended indication in that jurisdiction. In addition, a refusal of marketing approval in one of the Company's key jurisdictions could have a negative influence on the authority in charge of granting marketing approvals in another key jurisdiction.
As such, if the Company is not granted marketing approval for its products in a given jurisdiction, this will have a significant material adverse effect on its activities, financial position, results or growth.
ERYTECH and its partners comply with the regulations on the collection of human samples. These regulations require, in some cases, patient consent, confidentiality of his/her identity, approval of clinical tests by (hospital) ethics boards and/or other supervisory boards and, in some cases, grant of certain regulatory approvals.
If ERYTECH and its partners failed in its obligation to comply with these regulations or if the regulations in question were to be amended unfavorably, research projects and activities and the growth at ERYTECH as well as its related schedule could be penalized.
The commercial success of the Company will depend, in part, on the level of reimbursement of its products by public health associations, private insurers and managed healthcare organizations or any other organization.
No guarantee exists relative to the terms of reimbursement which will be applied on the Company's products or if the reimbursement will be sufficient.
If the Company's products are not granted a reasonable level of reimbursement, their market acceptance could be negatively affected.
Moreover, the legislative and regulatory measures to control or reduce health costs or to reform healthcare programs could mean lower sale prices for Company tests and products. A low price for the relevant products will limit the Company's ability to generate sales revenues in line with expectations, as currently estimated by the Company.
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To date, the Company holds the designation of "Pharmaceutical Manufacturing Facility" and of "Pharmaceutical Operating Facility." The Company cannot be assured that it or its partners will retain these statuses to manufacture and market any of its products. The Company as well as its products are subject to extensive and very stringent legislation and regulations and to controls from regulatory authorities such as the Agence Nationale de Sécurite du Médicament et des produits de santé (ANSM), the FDA and EMA. The applicable regulatory requirements are known, but subject to change. The Company must show that it meets the quality and safety criteria defined by relevant authorities.
Any failure to comply with these requirements can lead to sanctions including fines, rulings, civil penalties, refusal of marketing approval, delays, suspension or withdrawal of approvals, seizure or recall of products, restriction of use and legal proceedings.
If the Company or its partners do not maintain these statuses, it or they will not be able to manufacture and/or sell the product in question in the jurisdiction concerned; this would have a significant material adverse effect on its activities, financial position, results or growth.
The Group has recorded accounting and fiscal losses since the start of its operations in 2004. At December 31, 2014, accumulated losses totaled 37.3 million Euros according to IFRS accounting standards. These operational losses are principally accounted to investments in research expenditures and development costs for conducting preclinical studies and clinical trials. The Group anticipates substantial new operating losses for the coming years as its research and development activities, pre-clinical studies, and clinical trials are pursued. At the time of filing of this Reference Document, neither ERY-ASP/GRASPA® nor any other of its products have generated sales revenue.
The Group's profitability will depend on its ability to successfully develop, produce, and market its products. The Group's own financial resources will come, in the near future, from the first sales of ERY-ASP/GRASPA® and from payments made by partners within the context of established distribution or licensing agreements related to the development of new products and/or use of the research platform.
Additional funding through public subsidies or from private associations are also possible. The Group does not anticipate revenue from the sale of products other than ERY-ASP/GRASPA® in the medium term. In the event of the absence or delay of marketing approval for this product, the Company may not sell any product in the short, medium or long term.
Refer to Section 20 of this Reference Document.
As the final phases of product development in the biotechnology and biopharmaceutical industry require increasing investments, the financial needs of the Group will continue to increase as the Group invests in developing existing and new products. However, the Group considers that its internal financing capacities will be sufficient to cover its financial needs in the medium term, that is until 2016, at which point revenue from the Group will be sufficient to provide for its activities. These financial needs, other than structural costs, concern clinical trials that the Group has planned to conduct (please refer to Sections 6.5, 6.7, and 6.8) as well as expenses involved in research programs assisted by Oséo (please refer to Section 9.3). However, the Group may be required to raise additional funds sooner, by reason of various factors, such as:
The Group had a free cash flow of 37 million Euros at the end of December 2014, which will cover its needs for more than one year.
The Group could be linked to major events, in the background and external to its activity or existence. A systemic financial risk with a non negligible probability of major disruption can cause serious deterioration if not paralysis - of the financial system as a whole for an entire economic sector, over a vast geographical area or even on a global scale.
A crisis of this magnitude would have a significant negative effect on its financial position, results, and growth.
As part of its incentive policy for its executive officers, directors and employees, the Group has issued or allocated share subscription warrants. In the future, the Group could proceed with the issue or allocation of new financial instruments giving access to Group capital.
Any additional allocation or issue of shares or other financial instruments giving access to capital would lead to potentially significant dilution for the Group's shareholders (See Section 21.1.5 herein).
The Group benefits from public funding to which all innovative companies have access, in particular the research tax credit (crédit d'impôt-recherche - "CIR"). The research expenditures that are eligible for the research tax credit include wages and salaries, consumer goods, services subcontracted to approved research organizations (public or private) and intellectual property costs.
The claim on the national treasury that the research tax credit represents is submitted during the first quarter of the next fiscal year.
Only the research projects (and related expenses) that meet the eligibility criteria for the research tax credit in accordance with provisions of article 244c of the General Tax Code are entitled to the research tax credit scheme.
Due to its very nature, its corporate purpose, and its pipeline of pre-clinical and clinical projects, the Group is confident in its eligibility for the research tax credit program. Moreover, in 2013, the Group's authorization from the French Ministry of Research and Higher Education was renewed.
Lastly, the Group has been audited by the tax authorities with respect to the research tax credit for 2010, 2011, and 2012, the risk being thus extinguished for these years, as well as for previous years, due to lapse of the limitation period.
The Group considers that any financial consequences of future tax audits could jeopardize and/or halt the growth of the Group.
The deficit of certain national drug cost-sharing and coverage programs has lead to and could lead to governments in certain countries to impose taxes on drug company activities. The introduction of such taxes or their increase could have a negative impact on the activities and profitability of the Group.
There are multiple sources of fiscal risks. If the risk of deliberate violation of a tax law (legal or illegality risk) is ruled out, the risks could be current or long term; they could originate externally or internally, and could be related to persons, operating processes, technology, or business tax management procedures.
Taxation also constitutes an aspect of market risk as an element of cost and pricing.
The French – US tax authorities and/or tax agreements could jeopardize the agreements between the Group and its subsidiary. The Group, however, is not specifically concerned by this risk, in the absence of any special new tax aspects existing at the present time.
Each transaction is met with taxation. The more a transaction is complex, the more fiscal uncertainty it could generate and, consequently, fiscal risks. The more the transaction is uncommon or unusual, the more it exposes to specific risks.
The Group, however, is currently not specifically concerned by this risk with regard to the present situation.
Fiscal risk depends on its impact and its probability of occurrence. The probability of occurrence depends on the action or reaction of tax administration in response to a situation. As such, this probability is high when a company finds itself in certain situations attracting in its own right a tax audit such as a company generating VAT (Value-Added Tax) and CIT tax credits namely during the first requests for restitution.
The Group, however, is not specifically concerned by this risk, in the absence of any special new tax aspects existing at the present time.
Generally, repetitive operations do not tolerate uncertainty since uncertainty that relies on common activities can have consequences in terms of high risks. Operational risks involve all departments and persons concerned with tax aspects, and not only its corporate tax department (supply, transportation, inventory records, personnel, treasury and finances, commercial, invoicing, delivery, shipping, investment, accounting, etc.). The Group does not consider itself to be concerned by this risk, as it monitors the proper training of and documentation by persons involved and good communication between the parties involved in operations
having a direct fiscal impact.
A good fiscal compliance strategy involves staying informed and taking into account the administrative doctrine or, even better, obtaining authorization or approval for fiscal administration on the chosen approach for the resolution of a tax problem. The risk is even greater since fiscal as well as social legislation could be retroactive and incur additional costs for the Group (for example, tax aspects relating to the BSPCEs). The Group does not consider that its current tax situation is particularly subject to a risk of assessed back taxes.
Accounting, as a consolidation, synthesis and tax base instrument, constitutes the main foundation for tax audits and, consequently, for tax litigation. Accounting also embodies the choices of the directors that have a fiscal consequence (allocation theory, tax credit, choice of accounting policies, etc...). Accounting therefore appears to be the tool for formalizing the options deemed to offer an opportunity for the company. Efficient processes for entry and allocation, analysis and cost accounting and accounting-tax alignment are to reduce fiscal accounting risks. The Group does not consider that its accounting structure bears any risk at the present time, aside from the work performed by the audit committee.
Few companies document and formalize their management of fiscal risk. In this case, the main risk lies in the fact that fiscal risk management is the responsibility of the executive officers in charge of it. If these persons leave the company, there is the risk of a difficult succession and especially loss of the ability to seize opportunities during the search for successors. Recourse to external advisers as well as internal expertise offer a certain level of stability and continuity and, at least, assistance for an easier succession.
However, the Group is not specifically concerned by this risk at the present time, in light of the stability of its management and its external advisors.
A serious fiscal failure can affect the reputation of a company, its executive officers, its personnel and its auditors.
Given the aforementioned aspects of risk exposure, the Group does not believe that it is exposed to any particular risk to its reputation at the present time.
The Group has been structurally loss-generating since its creation. The net cash flows associated with the Group's operating activities were respectively -6.5 million Euros at December 31, 2013 and -7.2 million Euros at December 31, 2014.
Historically, the Group has financed its growth by strengthening its shareholders' equity in the form of capital increases and the issue of convertible bonds. The increase in capital as a result of its stock market listing in May 2013 and the funds raised in October 2014 enable the Group to ensure its business continuity over a number of years. Likewise, the 2015 budget voted by the Board of Directors in January 2015 provides for an outlook over more than one year of activity.
The remaining contractual maturities of financial liabilities are broken down as follows (including interest payments):
| in euros | 2014 | ||||
|---|---|---|---|---|---|
| Contractual cash flows | |||||
| Book value | Total | Less than 1 | 1 to 5 years | ||
| Loans | |||||
| Conditional advances | 549,161 | (580,107) | (257,500) | (322,607) | |
| Financial debts related to | |||||
| lease agreements | 220,376 | (230,183) | (80,702) | (149,481) | |
| Convertible bonds | |||||
| Bank overdrafts | |||||
| Trade payables and related | |||||
| accounts | 2,084,546 | (2,084,546) | (2,084,546) | ||
| Total | 2,854,083 | (2,894,836) | (2,422,748) | (472,088) |
| in euros | 2013 | ||||
|---|---|---|---|---|---|
| Contractual cash flows | |||||
| Book value | Total | Less than 1 | 1 to 5 years | ||
| Loans | 15,000 | (15,499) | (15,499) | - | |
| Conditional advances | 693,669 | (763,607) | (183,500) | (580,107) | |
| Debt associated with leases | |||||
| Convertible bonds | 303,217 | (319,826) | (89,643) | (230,183) | |
| Bank overdrafts | - | - | - | - | |
| Trade payables and related | - | - | - | - | |
| accounts | |||||
| 1,421,436 | (1,421,436) | (1,421,436) | |||
| Total | 2,433,322 | (2,520,368) | (1,710,078) | (810,290) |
The Company has conducted a specific review of its liquidity risk and considers that it is capable of meeting its upcoming payment deadlines. The net cash available at March 31, 2015 totals 33.5 million Euros.
The Group uses the Euro as its reference currency within the scope of its disclosures and financial communications. However, a significant portion, in the amount of 10% of its operating expenses, is denominated in US dollars (agency office in Philadelphia, collaborations relating to the production of clinical batches with the American Red Cross, business development consultants, consultants for the development of clinical trials in the United States, and various collaborations around tests and clinical projects in the United States).
To date, the Group has not opted to use active hedging techniques, and has not made recourse to derivative instruments to this end. Unfavorable exchange rate fluctuations between the euro and the dollar that are difficult to predict could affect the financial position of the Company.
This dependency will increase, as the Group will perform clinical trials in the USA and, in the longer term, sell on this market. The Group will opt to use exchange rate hedging techniques.
Expenses in US Dollars totaled \$949,232 during the 2014 financial year. The counter-values recorded in the accounts totaled €714,807 in relation to the receipt of invoices and price fluctuations. This represents an average annual rate of \$1.328 per €1 (\$1.324/€ on average in 2013).
However, the EUR/USD rate fell considerably at the period end, reaching \$1.2141 per €1 at December 31, 2014.
The Group purchased 1 million dollars at the rate of \$1.2197 per €1 during December 2014. The exchange rate differences are not significant for the periods presented.
The Group's exposure to interest rate risk primarily involves cash equivalents and securities.
These are only comprised of term accounts. Interest rate variations have a direct impact on the remuneration rate of these investments at time of renewal, as well as on cash flow. These financial instruments are convertible at maturity of at most one month.
During the course of 2014, a variation of 10 basis points in interest rate would not have had a significant effect on the year's results.
The price of the Company's shares could be affected by significant volatility. Aside from occurrence of the risks described in this section, the market price of the Company's shares could be significantly affected by a number of factors that would impact the Group, its competitors, or general economic conditions and the biotechnology sector.
The following factors could have a significant influence on the share price:
changes in international political, economic, and monetary context and notably unfavorable changes in the regulatory environment applicable in the countries or to the markets specific to the Group's sector of activity or to the Group itself;
announcements regarding changes in Group's ownership structure;
Furthermore, stock markets have seen significant fluctuations that have not always been due to the results and outlook of the companies whose shares are traded on them. Such market fluctuations as well as economic environment could therefore also significantly affect the market price of the Company's shares.
The Company has implemented a coverage policy of main insurable risks that it considers compatible with its cash flow requirements and activities.
The total premiums paid for all the Company's insurance policies amounted to 45,818 Euros for the financial year ended December 31, 2014 and 79,893 Euros for the financial year ended December 31, 2013.
Policy Insurer Risks covered Main characteristics Expiry Key person April Death, permanent total disability for Yann Godfrin Death for Mr. Gil Beyen. Limit of liability of €500,000 per person. Renewable by tacit agreement on January 1st of every year. Premises and liability Chubb Insured activities: - Development of a new generation of drugs for serious diseases, orphan indications or patient subpopulations in areas of hematology, cancer and metabolic diseases. - Encapsulation of therapeutic molecules in red blood cells - Development of a therapeutic pipeline of innovative solutions based on its proprietary technology and its expertise in the physical properties of erythrocytes All damages including physical injury: €7,500,000 per claim with sub-limits outlined in the contract Criminal Defense - Recourse: €30,000 per dispute Renewable by tacit agreement on January 1st of every year. Property and Casualty Business COVEA RISKS Address of risk: 60 Avenue Rockefeller 69008 Lyon Fire and related risks Water damage: Equipment - furniture personal belongings: guaranteed up to 2,016,198 Euros Natural disasters Electrical damage Recovery by neighbors and third parties Broken glass Theft Equipment breakdown Renewable by tacit agreement on January 1st of every year.
The Company has subscribed to several insurance policies, including the following:
Page | 38 of 302
| Policy | Insurer | Risks covered | Main characteristics | Expiry |
|---|---|---|---|---|
| Computer and office automation all risks |
||||
| Other events cover Automatic insurance on investment Resulting costs and losses Business interruption/material damage, equipment breakdown and electrical damage Inaccessibility |
||||
| Civil Liability for Executive Officers and Corporate Officers |
Chubb | Civil liability for executive officers. |
Extensions: Claim of misconduct Claim against legal entity Crisis management costs |
Renewable by tacit agreement on January 1st of every year. |
| Maximum aggregate amount per insurance period: 5,000,000 euros with sub-limits set out in contract |
||||
| Territory covered: Global coverage |
||||
| Transported Goods |
Chubb | Merchandise consists of: ERY-ASP/GRASPA® - ENHOXY® - Guaranteed worldwide Excluding shipments to/from the following countries: Afghanistan, Birma, Irak, Iran, Cuba, North Korea, Sudan and any country at war |
Ground and air transport Additional guarantees: Packing and packaging Loading and unloading Undelivered packages Merchandise return and reshipment Controlled temperature Disposal |
Renewable by tacit agreement on January 1st of every year. |
| Exclusions: rust, oxidation, various scratches, disturbed content |
||||
| Automobile | COVEA FLEET |
All employees on assignments for a total of 3,000 km maximum per year. |
Automobile liability Criminal defense and claim All accidental damages, theft and attempted theft, fire Broken glass Luggage and personal belongings Physical injury - driver |
Renewable by tacit agreement on January 1st of every year. |
| Business travel | Chubb | Travel by 5 employees on behalf of the subscriber. |
Personal injury Assistance Business travel Personal safety |
Renewable by tacit agreement on January 1st of every year. |
| Clinical trials | HDI Gerling |
Covers liability of the Company as a sponsor of biomedical research in the United States. The amount of guarantees subscribed for the |
Fixed amount per patient and per protocol based on each clinical trial program. |
–– |
Page | 39 of 302
Translated from French for convenience purposes only
| of trials, their location and the number of patients involved in the trial. |
||||
|---|---|---|---|---|
| Clinical trials | CHUBB | Covers liability of the Company as a sponsor of biomedical research in the United States |
Maximum aggregate per insurance \$10,000,000 |
amount __ period: |
Given that the Company has no sales revenues, it has not yet subscribed to insurance policies covering risks of operating losses.
The Company cannot guarantee that it will always be in a position to maintain, and in some cases, obtain similar insurance coverage at an acceptable price, which could lead it to accept more expensive insurance policies and to assume a higher level of risk particularly as the Company grows. Moreover, the occurrence of one or more important disasters, even if they are covered by these insurance policies, can seriously affect the activity of the Company and its financial position due to the interruption of its activities, which could result from such a disaster, reimbursement delays from the insurance companies in the event policy limits are exceeded and finally due to increased premiums that would result.
The occurrence of one or more of these risks could have a significant material adverse effect on the activity, outlook, financial position, results or growth of the Company.
Given the Company's outlook, namely current and future activities in the United States, as described in Section 6.7of the Reference Document, the Company anticipates that its insurance premiums could increase while remaining insignificant compared to its research and development expenses, its annual losses and the value of its assets.
In the course of its normal activities, the Group is not involved in any legal proceedings.
To the Group's knowledge, there is no litigation or arbitration or pre-litigation having recently had or that will have in the future a significant influence on the financial position, results, activity and capital of the Group.
The corporate name of the Company is ERYTECH Pharma S.A.
The company's headquarters is located at Bâtiment Adénine, 60 Avenue Rockefeller, 69008 LYON
The Company's telephone number is 04.78.74.44.38
The Company's website can be found at the following address: www.ERYTECH.com
The Company is registered with the Trades and Companies Registry of Lyon under number 479 560 013.
The Company's professional activity code (APE) is 7211Z and its computerized identification code (SIRET) is 479560013000 19.
ERYTECH was constituted in the form of a simplified French limited company, following a private deed in Lyon dated October 26, 2004. ERYTECH was transformed into a French corporation with an executive board and a board of supervisors following a decision by the Company's extraordinary General Meeting of September 29, 2005. At the General Meeting of April 2, 2013 the Company amended its mode of governance, so as to implement a Board of directors instead of the Executive Board and the Board of supervisors, subject to the condition precedent of the Company's initial public offering.
The term of the Company was set at 99 years from the date of its registration with the Trade and Companies Register, except in case of early dissolution or extension.
The Company is a French corporation subject to the provisions of the Commercial Code.
The fiscal year, having a term of 12 months, begins on January 1 and ends on December 31 of each year.
ERYTECH's two co-founders, Dr. Yann Godfrin (Biomedical Engineer from the University of Compiègne, Doctorate in Life and Health Sciences from the University of Nantes, Master's degree in Strategy and Methods for Clinical Development – University of Lyon) and Mr. Pierre-Olivier Goineau (Master's and DEA [Advanced Studies Degree] in Management Sciences, Master's in Management for Pharmaceutical Industries – IAE Lyon), met in 2003, through the Lyon biotechnology entrepreneurs' network, BioTuesday.
At that time, Dr. Yann Godfrin was Chairman and R&D Director of Hemoxymed Europe, a subsidiary of Hemoxymed Inc based in the United States, a company developing technologies involving red blood cells. He had previously worked as a consultant with BioAlliance (FR0010095596 – BIO) and as a Development Engineer at Hémosystem (systems for detecting contamination in blood products).
Mr. Pierre-Olivier Goineau was, at the same time, a senior consultant for strategy at KPMG Enterprises, the national standard-setter in the "health and life sciences" sector. Previously, he had been the majority partner in his own finance and development consulting company targeting international projects.
Both wished to create a company specialized in the development of therapeutic profits for orphan indications.
Convinced of their complementary nature, they decided to combine their skills and abilities in biology, technology, preclinical and clinical development for Dr. Yann Godfrin, and management, strategic positioning and marketing, public and private finance for Mr. Pierre-Olivier.
ERYTECH began activity in March as part of the Créalys incubator, one of the best-known in the domain of life sciences in France, with the financial support of Conseil Régional Rhône-Alpes. An initial R&D collaboration was entered into with Centre Léon Bérard in Lyon, a reputable cancer-fighting research centre in Europe. The "ERYTECH Pharma" project was awarded a prize by the French Ministry of Research in the category of Creation and received a 40,000 Euro grant. In August, the Company filed its first patent involving encapsulation technology.
ERYTECH was established in October and started operations in the BioParc Lyon-Laennec business incubator. The co-founders made initial rounds with Business Angels. The Company also has surrounded itself with external scientific experts.
ERYTECH obtained the status of Young Innovative Company.
ERYTECH was a Laureate of the Prize from the Ministry of Research in the "Development" category and received a €450,000 stipend. Additionally, it obtained significant initial financial support from the Agence Nationale de la Recherche [National Agency for Research] and from the Cancéropole Lyon Rhône-Alpes Auvergne [Cancer Center of Rhône-Alpes Auvergne].
In October, the AFSSAPS (which later became the ANSM - the French National Agency of Medicine and Health Product Safety) authorized the conducting of ERYTECH's first clinical trial: a phase I/II trial involving the treatment of Acute Lymphoblastic Leukemia with GRASPA®.
Emboldened by this initial success, the Company raised €750,000 from its shareholders, Cap Décisif, Amorçage Rhône Alpes, and two new business angels from the health sector.
Two new patents associated with new candidate-products were filed.
ERYTECH began opening clinical investigation centers to conduct its first trial involving leukemia: more than 20 centers would be opened throughout France bringing together most of the French opinion makers treating children and adult patients suffering from acute lymphoblastic leukemia.
The European Medicines Agency (EMA) classified ERYTECH's medicinal product ("Medicinal Product") GRASPA ® as its first Orphan Drug Designation (ODD) in the treatment of acute lymphoblastic leukemia and gave it "SME" status.
ERYTECH received a significant stipend of €450,000 from Oséo to finance the development of GRASPA®.
The Company accelerated its development by raising €12 million in funds from its historic shareholders, AGF Private Equity (which became IDInvest Partners), Auriga Partners, and Axa Private Equity.
2007 was a year of structuring, organization, and team building to prepare for future challenges:
The Company acquired space in a new building in the Bioparc Laennec site in Lyon and started work on its production unit in order to master its technology on an industrial scale and its production costs.
The team was enriched with a Medical Director, a Regulatory Director, a Quality Assurance Director, and increased its number of researchers; at the end of the year it would have 14 people.
The Belgian health authorities gave approval to treat patients in Belgium as part of the phase I/II trial already authorized in France.
At the same time, the work by the R&D department was allowing new candidate products to be identified.
At the start of the year, ERYTECH included its last patient in the phase I/II clinical trial started in 2006.
The Lyon production unit was completed at the end of the year and complete with the most demanding regulatory criteria. This unit is capable of production for both clinical trials and commercial uses.
The Company received new support from the Agence Nationale de la Recherche and the Cancéropôle Lyon Rhône Alpes (CLARA). Oséoalso confirmed its commitment to the company through a repayable aid of €735,000 to finance the clinical phase I for GRASPA® in pancreatic cancer.
Very promising results from the study were presented orally at the American Society of Hematology's (ASH) Annual Meeting in San Francisco. ERYTECH presented its scientific results in New York and Las Vegas.
ERYTECH's production unit, after an audit and inspection by AFSSAPS (which became ANSM), the classification as a "Pharmaceutical Facility" validating its level of health safety in accordance with the EMA rules.
Shortly afterward, ISO 9001:2008 certification was delivered by SGS to ERYTECH, validating the quality control organization implemented in all departments in accordance with the policy of excellence sought by the executive officers.
The results from the phase I/II clinical trial allowed ERYTECH to pursue its clinical development and obtain the authorizations to start to new clinical phases from the AFSSAPS (now the ANSM) for the treatment of acute lymphoblastic leukemia (ALL)
A phase II clinical trial for first-line treatment of adult patients over 55 years of age,
A phase II/III clinical trial for treatment of child and adult patients under 55 years of age who have relapsed.
Page | 43 of 302
ERYTECH also obtained authorization from the AFSSAPS to begin a phase I clinical trial to test GRASPA® among patients suffering from pancreatic cancer. The European Medicines Agency granted a second Orphan Drug Designation to GRASPA® for pancreatic cancer.
The Ministry of Research granted new financial assistance to the Company in the form of a grant awarded by the ANR.
ERYTECH filed its 10th patent.
ERYTECH found space within the Philadelphia Science Center one of the largest health clusters in the United States. Shortly thereafter, the Company signed two agreements with the American Red Cross which is the largest blood bank in the world:
an agreement to provide Red Blood Cells coming from American donors;
A subcontracting agreement providing that premises of cGMP based in Philadelphia would be provided, in accordance with FDA regulations and personnel dedicated to produce GRASPA® in the United States.
This major step prepared the way for conducting clinical trials in the United States and considerably strengthened the visibility of ERYTECH's actions among American companies.
ERYTECH continued its three clinical trials in parallel. The Company finished the year ahead of schedule, the recruitment of the last patient for its phase II trial with treatment by GRASPA® of patients older than 55 years of age suffering from acute lymphoblastic leukemia.
The Company employed 36 people at the end of 2010.
The FDA granted Orphan Drug Designation status to GRASPA® for the treatment of acute lymphoblastic leukemia, offering advantages comparable to the European designation on American soil.
The Company signed an R&D partnership agreement with the MD Anderson Cancer Center in Houston to develop a companion test that would make it possible to detect patients suffering from cancer who could be treated with GRASPA®.
ERYTECH recruited its last phase I patient for pancreatic cancer.
The Company formed a Joint Venture with the Teva Group (a NASDAQ-listed company as TLV:TEVA) to market GRASPA® in Israel (see also chapters 6 and 22 of the Reference Document).
ERYTECH signed a long-term contract to provide aspariginase with the German pharmaceutical laboratory medac GmbH.
ERYTECH was selected by several international Conferences on Hematology to orally present promising preclinical results from a new proposed product for the treatment of sickle cell anemia.
ERYTECH filed an IND application with the FDA to start a phase I clinical trial with the GRASPA® to provide therapy as first-line treatment of adult patients, over 40 years of age, suffering from Acute Lymphoblastic Leukemia, in which the principal investigator was Professor Richard Larson (Chicago), Chairman of the Adult Leukemia group within the CALGB (the largest cooperative group treating leukemia and cancer in the United States).
Gil Beyen became a consultant to the Company then Chairman of the Supervisory Board in August. Gil Beyen was the co-founder and CEO of TiGenix N.V. (NYSE Euronext Brussels: TIG), a European cellular therapy company with an approved product and advanced clinical trials.
The Company has received assistance totaling 7 million Euros, including 4.9 million Euros in repayable advances and 2.1 million Euros in grants (refer to Section 22.1 for the terms of this contract), which shall be paid progressively between 2012 and 2019 in keeping with development within the context of the TEDAC project, a research and development project focused on developing therapies for radiation/chemotherapyresistant cancers, in association with other companies and entities (Diaxonhit, Inserm, University of Paris-Diderot, and the AP-HP [Public Assistance-Paris Hospitals]).
Over time, the goal is to offer a solution including a test predicting response to treatment, one or more suitable enzyme therapies, as well as a test to monitor therapeutic efficacy.
ERYTECH's production unit obtained the designation of "Operating Facility."
The Company received a favorable opinion from the Committee for Orphan Medicinal Products of the EMA (European Medicines Agency) concerning the orphan drug designation of its experimental product ENHOXY® for the treatment of sickle cell anemia.
The Company signed a partnership agreement with Orphan Europe (Recordati group) for the development and marketing of GRASPA® in 38 European countries for the treatment of children and adults suffering from acute lymphoblastic leukemia and acute myeloid leukemia (AML) (see also chapters 6 and 22 of the Reference Document).
Dialog with the FDA continued for the purpose of starting a clinical trial involving acute lymphoblastic leukemia and ERY-ASP.
On April 30, 2013, the Company became listed on the regulated market NYSE Euronext Paris, compartment C, raising €17.7 M.
On May 6, 2013, the Company changed its method of governance, with a view to establishing a board of directors in place of the executive board and supervisory board, and appointed Gil Beyen as Chief Executive Officer, formerly Chairman of the Supervisory Board.
The committee of independent experts (the Data Safety Monitoring Board or DSMB) in charge of monitoring the Phase II/III clinical study of ERY-ASP/GRASPA® in adults and children experiencing a relapse of ALL met and delivered a favorable opinion concerning the conduct of this Phase III clinical trial following the original protocol with a total pool of 80 patients.
The European Union granted ERY-ASP/GRASPA® orphan drug designation for AML.
The ANSM (Agence nationale de sécurité du médicament et des produits de santé [French National Agency of Medicine and Health Product Safety]) granted ERYTECH the right to begin a Phase IIb in AML. ERYTECH recruited its first patient in March.
The DSMB in charge of monitoring the Phase IIb clinical study of ERY-ASP/GRASPA® in AML delivered a favorable opinion concerning the conduct of this clinical trial following an evaluation of the product's tolerance in 30 initial patients.
The FDA granted ERYTECH the right to start a Phase Ib with ERY-ASP in ALL.
The USPTO (United States Patent and Trademark Office) delivered the patent protecting ERYTECH's technology, granting it exclusivity until 2029 with the potential for extension into 2034.
Internationally, the company filed two new patent applications.
The Company launched a Phase II study of pancreatic cancer with its product ERY-ASP.
ERYTECH obtained the authorization of numerous European countries for its AML study, enabling it to broaden the recruitment of its patients, and obtained a second positive DSMB opinion.
The Company announced the addition of a new candidate drug to its oncology portfolio: "Affameur de tumeurs" [Tumor starvation inducer] ERY-MET.
The Company announced the positive Phase III results on its clinical study with ERY-ASP/GRASPA® in the treatment of ALL.
The company received notice of the issue, by the European Patent Office, of a key patent covering the use of ERY-ASP in the treatment of pancreatic cancer.
The main centers for the recruitment of patients for the Phase I study opened (Chicago, Duke, Colombus), and the first patients were treated.
The Company has obtained the issue of a new patent in the United States, in the area of asparaginase.
Page | 46 of 302
The Company announced the issue, in India, of its main encapsulation patent entitled "Lysis/Resealing Process for Preparing Erythrocytes".
On the financial level, the Company:
On January 9, 2015, the Company established a Level 1 American Depositary Receipt ("ADR") program on the American over-the-counter ("OTC") market, for which the Bank of New York Mellon is the custodian. Each American Depositary Share represents one ERYTECH Pharma share as traded on Euronext Paris.
The Company has strengthened its patent portfolio in the United States:
The Company has announced the positive opinion of the DSMB relating to its Expanded Access Program in acute lymphoblastic leukemia.
The Company presented the complete results of the Phase III pivotal study of ERY-ASP/GRASPA® in ALL and a poster on the design of the Phase IIb study in progress on AML at the annual meeting of the American Society of Clinical Oncology ("ASCO") taking place from May 29 to June 2, 2015 and at the annual congress of the European Hematology Association ("EHA") taking place from June 11 to 14, 2015.
The Company will outline its activities for investors at the Jefferies 2015 HealthCare Conference, which will take place in New York on June 4, 2015 at 9:00 A.M. EST (3:00 P.M. CET).
Because all clinical research and development costs are booked as charges until obtaining marketing approval, the principal investments in the first two fiscal years essentially pertain to the current production site, the Pharmaceutical Facility, and the R&D laboratory, and to a lesser degree, office and computer equipment.
| as of Dec. 31 in thousands of € | 2 013 | 2 014 |
|---|---|---|
| Purchase of fixed assets | ||
| - Intangible assets | (9) | (26) |
| - Tangible fixed assets | (418) | (521) |
| - Investments | (3) | (0) |
| Disposal of fixed assets | ||
| - Intangible assets | - | - |
| - Tangible fixed assets | 142 | 126 |
| - Investments | - | 1 |
| Grants cashed | - | - |
| Effects of changes in perimeter | - | - |
| Net cash flow generated by investment operations | (289) | (420) |
Since the start of the 2015 financial year, investments performed have decreased by €10k, as compared to 2014.
The Company is not currently planning to make any significant investments in forthcoming years for which the Company's oversight bodies have made firm commitments.
ERYTECH was founded in 2004 to develop and market innovative therapies for acute leukemia and other cancers for which medical needs remain unmet. The innovative approach by ERYTECH consists of acting on the tumor's environment and "starving" it, so that the cancerous cells no longer have access to the growth factors that are necessary for them to live and proliferate.
The core product of ERYTECH, ERY-ASP/GRASPA®2 , is used in the treatment of acute leukemias, a cancer of the blood and bone marrow that proliferates rapidly and requires urgent treatment. The two most common forms are acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), depending on the cells at the origin of the disease. Each year, approximately 50,000 patients are diagnosed with acute leukemia in Europe and the United States.
ERY-ASP/GRASPA® shows convincing clinical results obtained in several clinical trials and is in the final phase of clinical development in Europe with a view to obtaining a marketing authorization (AMM) in Europe for ALL. Based on these results, ERYTECH forged two distribution partnerships for the European and Israeli markets with international companies Orphan Europe (Recordati Group) and the Teva Group.
ERY-ASP/GRASPA®, developed based on ERYTECH proprietary technology, consists of an enzyme, Lasparaginase, encapsulated in the red blood cells. L-asparaginase is an essential weapon in the treatment of acute leukemia. This enzyme has the property of being able to remove the supply of asparagine, a naturally occurring substance in the blood that is essential for their growth, from leukemic cells. This L-asparaginase treatment, resulting in the death of cancer cells, has demonstrated efficacy in children with ALL, who almost all enter remission and have a high probability of full recovery. However, its usage is considerably limited by its significant side effects (allergic reactions and immune response, bleeding disorders, and pancreatitis, for example). Clinicians cannot administer it to most adult and senior patients, as they cannot tolerate free-form asparaginase.
Sales of existing treatments based on L-asparaginase are estimated at approximately €250 M3 in Europe and in the United States, but represent only a fraction of a much larger market, still underdeveloped and which could represent a billion4 Euros. Over 80% of current L-asparaginase sales are for children with ALL. Other leukemia patients, namely adults and seniors with ALL and all AML patients (more than 80% of patients with acute leukemia), have little or no access to these drugs because the patients are too fragile to tolerate them.
Through the encapsulation of asparaginase in the red blood cells using ERYTECH proprietary technology, ERY-ASP/GRASPA® is uniquely positioned to provide a solution to the significant unsatisfied medical needs of these fragile patients. The red cell membrane prevents interactions between the body and L-asparaginase, thereby protecting the body from the side effects of L-asparaginase and simultaneously preventing the immune system from eliminating L-asparaginase, thus reducing its efficacy. Encapsulated L-asparaginase fully achieves its goal of destroying asparagine circulating in the blood because it is absorbed inside the red blood cell through a natural phenomenon. The red blood cell acts as a bioreactor circulating in the blood and destroys asparagine, which could feed leukemic cells.
ERY-ASP/GRASPA® has the potential to become a reference medicine in the treatment of acute leukemias: ERY-ASP/GRASPA® allows fragile patients who currently do not have the possibility, due to their state of general health and side effects experienced, to be treated with L-asparaginase, and who have smaller chances of survival because of this. For patients who are unable to receive the current treatments based on L-
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2 The GRASPA® brand has been licensed to Orphan Europe (Recordati Group) for placement of the product on the market in the treatment of ALL and AML in Europe; ERY-ASP is the code name used outside Europe and excluding acute leukemias.
3 Source: Jazz Pharmaceuticals and ERYTECH
4 Refer to the following sections:
- The pharmaceutical industry's strong and growing interest in orphan drugs
- ERY-ASP/GRASPA®: An innovative treatment entering the market
asparaginase, ERY-ASP/GRASPA® offers an effective alternative with a considerably improved tolerance profile.
ERYTECH is in the final stages of clinical studies for GRASPA® for ALL and has compelling results in terms of efficacy and tolerance in: (a) the results of a Phase I/II study in children and adults with a relapse of ALL, (b) the results of a Phase II study performed on patients more than 55 years of age who are affected by ALL, and (c) the positive results of a Phase II/III study (in adults and children in relapse). In time, these studies will underpin the need for a Marketing Approval (MA) at the European level.
In November 2012, ERYTECH signed a marketing agreement with Orphan Europe, an orphan drug specialist subsidiary of the Recordati Group, a leading European pharmaceutical group, to distribute GRASPA® in 38 European countries. With the establishment of this partnership, GRASPA® may be sold efficiently as soon as the necessary approvals are obtained in all European countries and ERYTECH will receive a substantial part of the profits under the agreement. ERYTECH also signed a partnership agreement with the Teva Group, a world leading pharmaceutical company, to distribute GRASPA® in Israel.
The Company has a production unit based in Lyon with the qualifications of "Pharmaceutical Facility" and "Operating Facility", which makes it possible to serve the European and Israeli markets.
ERYTECH is developing possible new indications for ERY-ASP outside the area of leukemias. Initial preclinical and clinical results suggest that ERY-ASP could also be effective against certain solid tumors for which therapeutic options are currently reduced. ERYTECH launched a Phase II study of pancreatic cancer in 2014.
Further, the Company has a pipeline of potential products targeting orphan diseases that constitute medium and long-term sources of growth for the company and/or partnership options. In the longer term, the ERYTECH technology can encapsulate various molecules or active ingredients inside red blood cells and could help develop new drugs, particularly in cancer treatment, with much better efficacy and toxicity profiles, consequently improving the patients' survival and quality of life.
ERYTECH has what it takes to establish itself as a mature biotechnology company with revenues from partnership agreements for the distribution of a drug at the doors to the market and a pipeline of promising products and indications:
Treatments that affect the supply of oxygen or nutrients to tumor cells are one of the weapons to effectively fight cancer and are complementary to approaches that can potentially target cancer cells directly. These drugs cause tumor cells to die by asphyxiation or nutrient deprivation. ERYTECH develops innovative new enzyme therapies able to starve tumors and treat cancers that do not respond to radiation or chemotherapy. In particular, L-asparaginase treatment deprives leukemic cells of asparagine, an amino acid essential to their growth and survival. Removing this amino acid from the metabolic environment is a key issue in the fight against leukemia but also certain other cancers.
ERYTECH is positioned as a treatment for acute leukemia, which are most forms of leukemia, and it accounts for about 50,000 new cases diagnosed per year in Europe and the United States. Medical needs are considerable given this cancer's very poor prognosis for most patients. Children with ALL, which accounts for approximately 12% of new cases of acute leukemia, have over a 5-year survival rate of 90% due to Lasparaginase treatment. All other patients, adults and seniors, and relapsed patients typically cannot tolerate this treatment, despite efforts over dozens of years to adapt it. Adult and senior patients with ALL have a 5 year survival rate of between 10% and 30%, the lowest rate of all cancers combined. Existing asparaginasebased treatments generate sales estimated at approximately €250 M, largely relating to children, but the potential market is estimated at more than one billion Euros in Europe and the United States.
ERYTECH anticipates filing an application for authorization with the European Medicines Agency (EMA) for the placement of GRASPA® on the market for ALL in mid-2015, based on three studies (including one Phase I/II and one Phase II/III study) in adult and pediatric patients with ALL in relapse and one study performed on patients more than 55 years of age. The first study, in children and adults with ALL in relapse, demonstrated the safety of the product and identified the best dose. It also demonstrated that one injection of GRASPA® can result in the same depletion of asparagine as up to 8 injections of free-form L-asparaginase. It was followed by a Phase II/III study in the same type of patients. Analysis of the data from the GRASPIVOTALL clinical trial (GRASPALL 2009-06), after one year of monitoring, demonstrates that the study convincingly achieved its primary objectives, and its secondary objectives confirm a favorable profile for the clinical efficacy of GRASPA®. The study also shows favorable results in patients with histories of allergies to L-asparaginase. The third study is a Phase II study in patients greater than 55 years of age with ALL. This study showed that, in the category of fragile patients who often cannot be treated with L-asparaginase at induction, GRASPA® was well tolerated and resulted in complete remission for 77% of patients completing their induction.
In 2013, ERYTECH began a Phase IIb clinical study of AML, the results of which, if positive, will allow the indication of GRASPA® to be extended to these patients once the drug is on the market, an Expanded Access Program (EAP) for ALL in France, and a Phase Ib study, again on ALL, in the United States.
ERYTECH has entered into two major partnerships for the commercialization of GRASPA® in 38 European countries with Orphan Europe (Recordati Group) and in Israel with the Teva Group. Due to the innovative nature of GRASPA®, its ability to satisfy unmet medical needs, and its progress in clinical development, ERYTECH has been able to obtain favorable terms, particularly with regard to the sharing of future profits (representing up to 45% of the net sale price). Both partners have recognized trade capacities and can effectively promote GRASPA® in their respective territories. In particular, through its subsidiary Orphan Europe, Recordati is a specialist in orphan diseases and will work with ERYTECH on the regulatory approach to optimize the marketing of GRASPA®. The agreement with Orphan Europe (Recordati Group) notably provides for a payment of €5M upon signature, sharing in the development costs for GRASPA® in AML, and future payments of up to €37.5M, subject to achieving regulatory and commercial objectives. ERYTECH will receive a payment for product delivered, and royalties on the sales performed by Orphan Europe (Recordati Group) with GRASPA®, for a total of up to 45% of the net sale price.
Separately, another Recordati Group company has purchased bonds that were converted into an investment in ERYTECH equity worth €5 million at the time of the initial public offering.
ERY-ASP/GRASPA® has obtained orphan drug status in ALL, AML, and pancreatic cancer in Europe and in the United States. ERYTECH can therefore benefit from a marketing procedure with shorter lead times and reduced costs, and benefit from exclusive marketing after obtaining the marketing authorization for the product for 7 and 10 years, in the United States and Europe respectively. L-asparaginase treatment has been included in almost all European and American chemotherapy protocols since the 1970s for pediatric ALL patients. ERYASP™/GRASPA® will be incorporated in or be added to the existing medical practice. Therefore, ERYTECH anticipates a rapid adoption of ERY-ASP/GRASPA®. Moreover, they are the same clinicians who treat AML patients and, for this indication, ERY-ASP/GRASPA® will capitalize on the clinical experience of these prescribers. The placement of ERY-ASP/GRASPA® on the market will require reasonable promotional and commercial resources, given the specialized position of the drug (clearly identified and relatively few prescribers, hospital treatment or specialist care center).
ERYTECH's encapsulation technology is internationally protected by 12 patent families filed both on the processes and on the products. ERYTECH has successfully developed a process to produce loaded erythrocytes in a reproducible, reliable and economical way on a large scale, regardless of the initial characteristic and origin of the red cells used. More than 400 bags of ERY-ASP/GRASPA® have already been produced and transfused in five clinical trials conducted by ERYTECH. ERYTECH's production unit operates according to the highest standards of pharmaceutical production, quality and traceability. The Company has obtained the status of "Pharmaceutical Facility" and "Operating Facility" from ANSM to produce GRASPA® for the European and Israeli markets. The current production capacity is sufficient to meet the needs of the various clinical trials scheduled and the initial years of sales. The gross margin for ERY-ASP/GRASPA® is in line with pharmaceutical industry standards.
The US market is virtually equivalent to that of Europe in terms of number of patients with acute leukemia and is the natural progression in the development of ERY-ASP. A Phase Ib clinical trial in adult patients greater than 40 years of age with ALL is in progress, after obtaining authorization for a Phase Ib study from the "Food and Drug Administration" (FDA). The Company is relying on studies already underway in Europe. ERYTECH believes that the development of ERY-ASP in the United States could allow it to anticipate placement on the market within the 2019 horizon, and it will evaluate partnership opportunities at various key stages of the clinical development program for ALL and AML. ERYTECH has established a close partnership with the American Red Cross of Pennsylvania (Philadelphia, USA) to produce, under the Company's supervision, the lots needed for clinical studies.
Asparagine has been shown to also be a growth factor for several other types of cancer. In partnership with the MD Anderson Cancer Center (Houston, USA), one of the most recognized hospitals in the world for the treatment of cancer, ERYTECH analyzed various types of solid tumors and determined that asparaginase could effectively help combat solid tumors. The first milestone for developing ERY-ASP for solid tumors was achieved with a positive Phase I study, which demonstrated good tolerance of the product even at high doses. The next step is the initiation of a Phase II study, for which the first patients were recruited in 2014. In addition, ERYTECH's technology platform is versatile and opens up many possibilities for developing new drugs. The effectiveness of the technology has been demonstrated mainly with L-asparaginase, but it is possible to encapsulate other enzymes, molecules or proteins in red blood cells. The TEDAC program has made it possible to identify a new drug candidate: ERY-MET.
With its scientific and medical board, ERYTECH is surrounded by world-renowned American and European experts, particularly in the fields of oncology and leukemia. In addition to their active role in optimizing ERYTECH's strategy, their opinion in the scientific and medical communities will help promote the adoption of ERY-ASP/GRASPA® in hospitals and specialized care centers.
ERYTECH is directed by Gil Beyen, Chief Executive Officer of the Company, with strong expertise in international development and pharmaceutical partnerships, and by one of his co-founders, Yann Godfrin, Delegated Managing Director, Scientific Director, biologist and scientific expert in the development of health products and the industrialization of processes. The Company relies on a talented team of 45 professionals with diverse, complementary backgrounds and skills totally in line with the ERYTECH's development objectives.
The interest of pharmaceutical companies in orphan and rare diseases has grown steadily since the mid-2000s and the last decade has been the most productive for the development of these drugs. Several major international pharmaceutical companies such as Pfizer, GSK and Sanofi, and many mid-size pharmaceutical groups such as, Recordati, Swedish Orphan Biovitrum and Shire have created specialized divisions for orphan and rare diseases and/or made them a major strategic focus. Consequently, transactions in this area, in the form of acquisitions or partnership agreements have multiplied. In particular, there were 3 operations in the Lasparaginase market: the acquisition of OPI (France) by EUSA (UK) for €100 million in 2007, the acquisition of a portfolio of products from Enzon (US) by Sigma Tau (Italy) for \$327 million in 2009, and the acquisition of EUSA by Jazz Pharmaceuticals (US) for \$700 million in 2012. In this context, ERYTECH has created significant strategic value with ERY-ASP/GRASPA® and its technology platform.
| Product | Indication | Pre clinical |
Phase I | Phase II | Pivot | Registration | Market |
|---|---|---|---|---|---|---|---|
| Acute lymphoblastic leukemia EU |
|||||||
| GRASPA®/ | Acute lymphoblastic leukemia US |
||||||
| ERY-ASP | Acute myeloid leukemia EU |
||||||
| Non-Hodgkins lymphoma |
|||||||
| Pancreatic cancer |
|||||||
| ERY-MET | Tumor starvation |
||||||
| ERY-VAX | Cancer immunotherapy |
||||||
| ERY-TOL | Tolerance induction |
Cancer treatment is mainly based on surgery, radiotherapy and medical treatment, including chemotherapy. Each cancer is unique and the techniques used depend on the type of cancer, the stage at which it was discovered and the patient and his/her general health. They can also be combined to yield better results.
Surgery and radiation are effective as local treatment and loco-regional treatment. Medical treatments can reduce the volume of the primitive tumor and/or tackle the cells spread throughout the body but also reduce the risk of relapse after loco-regional treatment.
Chemotherapy is a mainstay cancer treatment and involves the use of a set of several drugs with different mechanisms of action that are combined and managed in a coordinated manner to effectively fight cancer cells. The drugs and doses used depend on a number of parameters including the type of cancer and the patient profile.
These drugs act by altering the reproductive mechanism of the cancer cell. Indeed, cancer cells reproduce continuously and uncontrollably and can be destroyed by selective medications, acting at different stages of the cells' reproductive cycle. However, in a course of chemotherapy, some normal cells (skin cells, mucous membranes, blood, etc.) which are also reproducing, are affected. This is the reason these treatments are associated with significant side effects.
In chemotherapy cocktails, "targeted" therapies, developed thanks to advances in research, particularly in understanding the operating mechanisms of the cancer cell, have played an increasingly significant role. These drugs produce a targeted action that saves healthy cells and are therefore potentially more effective and less toxic. They can be classified into 3 main categories:
– Drugs acting at a specific stage of the tumor cell's development, for example in the transduction of the signals telling the cell to multiply or by ordering the death of cancer cell (apoptosis).
– Treatments that stimulate and direct the body's immune response against cancer cells to destroy them (e.g., "therapeutic" vaccines).
Treatments that act on the tumor cells' supply of oxygen or nutrients. These drugs suffocate or starve tumors.
ERYTECH is positioned in the last treatment category and is developing innovative new enzyme therapies able to starve tumors and treat cancers that do not respond to radiation or chemotherapy. In particular, Lasparaginase treatment deprives leukemic cells of asparagine, an amino acid essential to their growth and survival. Removing this amino acid from the metabolic environment is a key issue in the fight against leukemia but also certain other cancers.
Leukemia is a cancer of the bone marrow cells, sometimes called cancer of the blood. Leukemia is characterized by an abnormal and excessive proliferation of white blood cell precursors which, in the absence of treatment, invade the bone marrow and then the blood.
Leukemias are categorized according to their speed of development and the type of cells that proliferate:
By combining these two criteria as shown in the diagram below, there are four types of leukemia and ERYTECH is focused exclusively on acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), which are quickly life-threatening for patients.
type
Acute leukemias account for about 60% of cases of leukemia and 40% of chronic leukemia as shown in the following chart.
Source: PETRI Study
Each year, approximately 50,000 patients are diagnosed with acute leukemia in Europe and the United States.
Approximately 10,000 new cases of patients suffering from ALL are diagnosed in Europe5 (EU27) per year and 6,000 in the United States6 , which corresponds to an age-adjusted incidence estimated to be approximately 2 new cases per year out of 100,000 persons7 .
5 Rodrigues-Abreu et al., Annals of Oncology, 2007
6 Siegel et al., CA Cancer J Clin, 2013
7 Dores et al, Blood 2010; SEER Cancer Statistics
AML has an age-adjusted incidence approximately twice as high, with about 4 new cases per year per 100,000 people, representing approximately 19,000 new cases in Europe8 and 15,000 in the United States9 .
As shown in the following diagram, the majority of ALL patients are children. The remaining ALL patients are divided evenly between adults (18-55 years old) and seniors (>55 years old).
AML is, however, a form of leukemia that affects mainly adults and seniors, and marginally children as shown in the following chart. The median age at diagnosis is 67. Because of their age and often multiple pathologies, these patients are particularly difficult for clinicians to treat.
Source: U.S. NIH – NCI - SEER Cancer Statistics Source: SEER Cancer Statistics 1975-2007
8 Rodrigues-Abreu et al., Annals of Oncology, 2007
9 Siegel et al., CA Cancer J Clin, 2013
Source: SEER-17, 2001 to 2007 Source: Source: SEER (Surveillance, Epidemiology and End Results) Cancer Statistics Review, 1975-2008. National Cancer Institute; 2011.
The exact causes of leukemia have not been completely identified, but various studies have shown10 that the following conditions increase the risks for it:
The incidence of the disease is relatively stable and tends to increase with the aging of the population.
With the development of new drugs and new therapies, the prognosis for some of these cancers has dramatically improved, such as breast and prostate cancer, as well as ALL in children or thyroid cancer. There is still a large number of cancers with a poor prognosis, such as pancreatic, liver, esophageal or even lung cancer. Among the cancers with the worst prognoses are ALL and AML in adults and seniors.
* NHML: Non-Hodgkin malignant lymphoma Source: INCA 2012 & ERYTECH
The 5-year survival rate for ALL varies considerably between young subjects (children and young adults), who currently have about a 90% 5-year survival rate11 and older subjects (adults and seniors) who have a low 5 year survival rate (10 to 30%).
The evolution of treatment protocols and new drugs has led to steady improvement in the remission rate and chance of long-term survival. The protocols and drugs used successfully in children, in particular Lasparaginase, are often not transposable in older subjects due to their difficulty tolerating intensive chemotherapy because of their general health. For these priority patients, clinicians have a great need for new treatments with a better safety profile. ERYTECH is developing a new product, ERY-ASP/GRASPA® to meet this need.
For AML, without effective treatment, the 5-year survival rate is estimated at 23% and around 13%12 for patients over 50 years of age suffering from AML.
The current treatment of patients with leukemia is based on chemotherapy combining several drugs according to various regimens as is the case for the vast majority of cancers.
11 Source: Cancer Statistics Review 1975–2005
12 Source: SEER (2004 data; US)
Treatment protocols for ALL are clearly established in all European countries and the United States depending on the patient's age, medical history and the specific characteristics of the disease. For AML, despite a generally similar approach, treatment protocols may differ considerably from one country to another and may also change depending on clinical or scientific advances.
Generally, after a diagnosis and preparation stage, chemotherapy protocols include several phases: induction of complete remission, remission consolidation, delayed intensification to prevent recurrence of leukemia and maintenance treatment:
Asparagine is an amino acid naturally produced by healthy cells for their own use in protein synthesis. Too much of this amino acid produced by healthy cells is found in the bloodstream. Cancer cells also need it to grow and survive but they do not produce it. Therefore they use circulating asparagine.
The principle of the treatment is to remove circulating asparagine using a specific enzyme: L-asparaginase. This enzyme is capable of destroying asparagine and deprives cancer cells of a key nutrient, causing them to die.
The history of L-asparaginase as an antitumor agent began with the first observations of a cytotoxic effect in 1953 and the confirmation of these results in the early 1960s. A bit later, L-asparaginase was purified from bacteria (E. coli) and it was demonstrated to have an effect on acute leukemia.
Introduction of L-asparaginase to standard ALL treatment in the 1970s. Its use has revolutionized pediatric protocols by improving complete remission rates and the duration thereof. It experienced a significant therapeutic decline both with regard to its efficacy and its tolerance13
Asparaginase gradually established itself as a pillar of anti-leukemia chemotherapy. Clinicians place it at the center of the therapy, along with other cytotoxic molecules and have extended its use to young adults and adults when they can tolerate this therapy.
The objective of clinicians is for the patient to go into complete remission of the disease (i.e., disappearance of the tumor cells) for as long as possible. Their current clinical practices are based on systems of intensive use of L-asparaginase (the more doses given, the sooner and longer the remission). Indeed, it has been shown that the longer the deprivation of asparagine, the higher the chances of complete remission, maintaining this remission, and having it remain sustainable.14
As the study presented below shows, the patients in whom the level of asparagine was reduced have considerably higher chances of remission and survival than those in whom it was not possible. The graph shows the survival of 63 adult patients with ALL who obtained a good level of asparaginase activity following treatment with asparaginase, as compared to a group of 22 patients for whom asparaginase activity was not sufficiently suppressed (depleted) during treatment.
Source: Wetzler M et al. CALGB. Blood 2007;109: 4164
For AML, L-asparaginase is currently only partially used. It has received a marketing authorization for AML in some countries only (e.g., Canada), and is used in certain treatment protocols.
As illustrated in the diagram below, the relevance of L-asparaginase treatment and its efficacy for AML have been demonstrated. In 1988, a study of 195 patients with AML demonstrated the efficacy of L-asparaginase15 as adjunct therapy to the standard cytarabine-based therapy.
The significant risk of side effects for this population of often elderly patients in fragile health is a major obstacle to the use of L-asparaginase.
| Refractory | Relapsed | ||||
|---|---|---|---|---|---|
| Age | High-dose High-dose cytarabine and cytarabine asparaginase |
High-dose cytarabine and asparaginase |
High-dose cytarabine |
||
| < 60 years old | 54% | 18% | 37% | 33% | |
| > 60 years | 31% | 0% | 43% | 21% |
Source: Capizzi & White, The Yale Journal of Biology and Medicine, 1988
In addition, in vitro experiments have demonstrated the efficacy of L-asparaginase on over 70% of several biological samples from different AML subtypes (M0, M1, M4 and M5), comparable to the results obtained on biological samples of ALL. Approximately 50%-60% of patients are estimated to be potential responders to L-asparaginase treatment16 .
In the case of ALL, the choice of drugs involved in the successive phases of chemotherapy depends on a genetic specificity, the presence or absence of the Philadelphia chromosome. This anomaly is present in approximately 10% of ALL cases in children and about 20% to 40% of ALL cases in adults. Its frequency increases with age.
ALL patients with the Philadelphia chromosome (called Ph+ "Phi positive") are primarily treated with monoclonal antibodies and in particular tyrosine kinase inhibitors (BCR-ABL) such as imatinib, marketed by Novartis under the name Gleevec®/Glivec®, and dasitinib marketed by BMS under the name Sprycel®. However, clinical trials have demonstrated the lack of efficacy of imatinib and dasitinib on ALL patients without the Philadelphia chromosome.
The remaining ALL patients, i.e., the majority of patients (~ 80%) do not have the Philadelphia chromosome (called Ph- "Phi-negative"). These patients' lymphoblasts respond to L-asparaginase. Therefore, Lasparaginase treatment has been included in almost all European and American chemotherapy protocols since the 1970s for this type of patient.
The following diagram provides an overview of the key molecules that can be used in chemotherapy cocktails depending on the different phases of treatment.
| Induction | Consolidation | Intensification | Maintenance | |
|---|---|---|---|---|
| Possible treatments |
Cytarabine Methotrexate (MTX) Prednisolone Vincristine (VCR) Doxorubicin Dexamenthasone Asparaginase |
Cytarabine VCR Cyclophosphamide 6-Mercaptopturine(6- MP) Asparaginase |
Cytarabine MTX VCR Dexamethasone Doxorubicin Cyclophosphamide Thioguanine Asparaginase |
MTX VCR Dexamethasone Cyclophosphamide 6-MP Thioguanine |
| Duration of treatment |
~ 1 to 2 months | 3 to 9 months | ~ 1 to 2 months | 2 - 3 years |
L-asparaginase is the only drug of those used for treating ALL without the Philadelphia chromosome to affect asparagine and thus to be able to deprive tumor cells of this demonstrated growth factor.
The following figure shows an example of a treatment protocol for relapsed patients (COPRALL protocol - France). After a preparation phase, the patient receives intensive treatment with up to 32 injections of Lasparaginase in the induction and consolidation phases.
Acute myelogenous leukemia (AML) is a form of cancer that affects bone marrow cells that produce the blood components (red cells, white cells and platelets). Without treatment, it is rapidly fatal because of the risk of infection and bleeding. It is potentially curable with intensive chemotherapy courses, and the risk of relapse is lower if a bone marrow transplantation can be done, but at the cost of transplant-related mortality that increases with age. The chances of remission and relapse risks vary according to age and abnormalities of the karyotypes of leukemic cells.
There are several categories of AML based on the appearance of leukemic cells viewed by microscope (cytology) and the analysis of leukemic cell chromosomes. Numerous treatment protocols have been developed taking this variety of subtypes into account.
| Type of AML | Particular aspects | Frequency |
|---|---|---|
| AML0-M2 | Myeloid, very little differentiation | 50% |
| AML3 | Promyelocytic (bundles of Auer Rods), with bleeding disorders |
10% |
| AML4 | Myelomonocytic: dystrophic monocytes in the blood, bone marrow myeloblasts |
25% |
| AML5A and B | Monoblasts somewhat differentiated | frequency of dermal and gingival involvement) 10% |
| AML6 | Erythroblastic | 4% |
| AML7 | Megakaryocytic | 1% |
FAB (French-American-British) international classification is the most commonly used and the following table
provides the frequency and particular aspects of each.
Classification of M0 to M7 does not reflect the severity of the disease. Treatment is essentially the same for all leukemia subtypes except for AML-M3, which has an effective treatment of transretinoic acid. Without treatment, AML causes rapid death by infection, bleeding or respiratory and brain disorders by significant increase in white blood cells. The goal of treatment is for abnormal blasts to disappear from bone marrow and increase neutrophils, platelets and hemoglobin in the blood. This condition is called "complete remission." Without further treatment, relapse (recurrence of blasts in bone marrow) is most often observed.
Apart from a minority subtype (AML3) requiring a more specific drug, the molecule all-trans retinoic acid or ATRA which is proven to be effective for this subtype, the treatment is essentially the same for all types of AML.
The choice of treatment depends on the patient's pre-treatment assessment (cardiac, kidney, liver function) and the physiological age of the patient. AML in children is differentiated from that in subjects under 60 years old and that in subjects > 60 years old.
For AML in children, the therapeutic strategy after obtaining complete remission is a bone marrow allograft from an intra-family donor (75% disease-free 5-year survival rate) or treatment intensification with high-dose cytarabine and maintenance treatment with subcutaneous cytarabine and 6-thioguanine (55% disease-free survival).
For AML patients 18 to 60 years old, intensive chemotherapy may be offered with several phases: an induction phase, a consolidation phase and finally maintenance treatment including either autograft, marrow allograft or further courses of chemotherapy.
Remission maintenance treatment (4-12 months) can then be given as appropriate.
Approach to the treatment of AML
In patients over the age of 60, there is no standard treatment. Intensive chemotherapy treatments cannot be given and conventional bone marrow allografts are not possible. Induction treatment will consist of a treatment similar to that for young subjects but with a lower dose of cytarabine. Post-induction treatment may involve a sequence of high-dose cytarabine if the patient's physiological condition permits. It is similar to the case for young subjects associated with anthracycline that is different from that used in induction, novantrone or the use of another interposing treatment such amsacrine. Hematopoietic growth factors could reduce the toxicity of the treatment. Maintenance treatment following completion of consolidation treatment. Patients not eligible for intensive chemotherapy may also be offered supportive care by transfusions, anti-infectious agents and
| NEUROMENINGEAL PROPHYLAXIS |
achieved | support allowing for complete remission to be | CATCH-UP in the event of a setback |
|
|---|---|---|---|---|
| POST-INDUCTION TREATMENT Depends on initial prognosis factors and response to induction |
109 leukemia cells if complete remission after induction |
|||
| CONSOLIDATION RE-INDUCTION INTENSIFICATION Autologous transplant Allogenic transplant |
MAINTENA NCE In patients over the age of 60, there is no standard treatment. Intensive chemotherapy treatments cannot be given and conventional bone marrow allografts are not possible. Induction treatment will consist of a treatment similar to that for young subjects but with a lower dose of cytarabine. Post-induction treatment may involve a |
<105 cells if cured |
||
| sequence of high-dose cytarabine if the patient's physiological condition permits. It is similar to the case for | young subjects associated with anthracycline that is different from that used in induction, novantrone or the use of another interposing treatment such amsacrine. Hematopoietic growth factors could reduce the toxicity of the treatment. Maintenance treatment following completion of consolidation treatment. Patients not eligible for intensive chemotherapy may also be offered supportive care by transfusions, anti-infectious agents and palliative chemotherapy, with the goal being quality of life, and/or participation in a clinical trial. |
|||
| INDUCTION | Principles of treatment protocols for AML CONSOLIDATION |
INTENSIFICATION | MAINTENANC E (RESERVED |
|
| SUBJECT < 18 YEARS OLD |
ARACYTINE MITOXANTRONE |
HIGH DOSE ARACYTINE AMSACRINE VP16 DAUNORUBICIN ASPARAGINASE ALLOGENIC TRANSPLANT |
OR HIGH DOSE CYTARABINE (HIDAC) |
FOR AML 3) |
| SUBJECT 18-60 YEARS OLD |
STANDARD 7+3 CYTARABINE + IDARBUCIN OR DAUNORUBICIN |
HIGH DOSE CYTARABINE (HIDAC) STEM CELL TRANSPLANT |
- | |
| SUBJECT > 60 YEARS OLD |
LOW DOSE 7+3 | HIGH DOSE CYTARABINE (HIDAC) NOVANTRONE AMSACRINE |
- |
Like lymphoblasts for ALL cases, most myeloblasts need circulating asparagine to grow and multiply. The
L-asparaginase is used in some pediatric treatment protocols: for example, in France in the ELAM 02 protocol, in the USA in the COG or St. Jude protocols), or in Canada, where it has marketing approval.
However, its toxicity profile prevents its widespread use in fragile children and especially in adult patients, or it is rarely used.
In clinical practice, ERYTECH estimates that one third of ALL patients – mostly elderly and relapsed patients – and the majority of adult AML patients are intolerant to L-asparaginase treatment. These patients are considered fragile.
Other patients, mostly children and young adults with ALL, receive L-asparaginase treatment which enables them to achieve remission of the disease and improves survival. Nevertheless, the use of L-asparaginase in these patients may also cause severe side effects including hypersensitivity reactions (anaphylactic shock), pancreatitis and bleeding disorders.
Severe toxic effects of L-asparaginase include:
Clinicians consider that the risk of serious intolerance has been identified in adult and senior patients with ALL and in patients in relapse. There is indeed an increased risk of liver, pancreatic, and nervous system toxicity, as well as hypersensitivity and bleeding disorders in these fragile patients.
Relapsed ALL patients representing approximately 15% of children and 40% of adults with the illness (totaling approximately 20% of these patient groups) have a demonstrated risk of severe intolerance.
ERYTECH believes that the current market for the various forms of aspariginase is approximately 250 million Euros 17for Europe and the United States, and that less than 20% of patients suffering from acute leukemia are treated with aspariginase. The potential market for other patients, including adult and elderly patients with ALL and all AML patients is not being exploited and could represent more than one billion Euros.
* Europe and the United States Source: Company
The diagram below shows that over 80% of current sales of L-asparaginase are from children with ALL and approximately 15% from adults and primarily young adults (under 40 years old) with ALL who are still able to tolerate it. However, older patients are only marginally treated with L-asparaginase.
Use of L-asparaginase for ALL by age group
* The survival rate 5 years after diagnosis varies depending on the patient's age. For example, patients under 29 years old have a 5-year survival rate of 54% and patients 30 to 54 years old have a 5-year survival rate of 28%.
The current market for L-asparaginase mainly includes 3 products, "native" L-asparaginase (Kidrolase®, Leunase®, Asparaginase Medac®), Oncaspar®, and Erwinase®, which correspond to different formulations and/or different production processes. As a result, these products have separate profiles, particularly in terms of activity duration, frequency of injections, and side effects.
The native form (Kidrolase®, Leunase®, or Asparaginase Medac®) is the first L-asparaginase. Sales of it began in France in 1971. Erwinase® and Oncaspar® were sold for the first time in 1985 and 1994 respectively. These products are indicated for the treatment of ALL, but are not or are very rarely used in patients with AML.
Themain L-asparaginase drugs are described briefly below:
The introduction of native L-asparaginase to the standard treatment of ALL in children and then adults dates back to the 1970s. This L-asparaginase was purified from E. coli bacteria.
Native L-asparaginase remains the first-line treatment for ALL in children in many European countries. Because of its general toxicity, this native form is rarely or not used in fragile patients. Its market is in steady decline, faced with competition from other more recent formulations.
Native L-asparaginase is mainly produced by the Japanese company Kyowa and distributed in Europe by Jazz Pharmaceuticals (following the acquisition of Eusa Pharma, formerly OPI, in June 2012) under the brand Kidrolase® and by the German company medac under the brand asparaginase medac®.
In the United States, the native form (Elspar®) was recently taken off the market because of production problems and the competition of the pegylated form (Oncaspar®).
PEG-asparaginase
PEG-asparaginase is an L-asparaginase from E. coli, pegylated (attachment of a polyethylene glycol group to the enzyme) so as to reduce its toxicity, including immune and allergic reactions, and to prolong its duration of action (half-life).
PEG-asparaginase is typically administered in patients with an allergic reaction to native L-asparaginase. In some countries (United States, United Kingdom), it has almost completely replaced native L-asparaginase in children. PEG-asparaginase has been the subject of numerous publications in pediatrics but comparatively few studies in relapsed patients or adults. In practice, incorporating PEG-asparaginase in chemotherapy for adults is still uncommon because of the side effects feared by clinicians.
The only form of PEG-asparaginase allowed on the market is Oncaspar®. This injectable drug is registered in the United States, Germany, and Poland, and is available in other countries through special approvals. It was developed by Enzon, a company acquired by Sigma Tau in November 2009. Oncaspar® was previously distributed in Europe by medac; Sigma Tau resumed direct sales in August 2012.
ERYTECH estimates that about one third of current sales of L-asparaginase are related to the use of PEGasparaginase.
L-asparaginase produced by E. chrysanthemi bacteria is marketed by Jazz Pharmaceuticals (previously by EUSA Pharma) in Europe and in the United States under the brands Erwinase® and Erwinaze® respectively. The product has been present in some European countries since 1985 and in the United States where it was approved again in November 2011.
Worldwide sales revenue of Erwinase® published by Jazz Pharmaceuticals for 2014 was \$199.7 million.
This product is positioned as second-line treatment in cases of hypersensitivity reactions to L-asparaginase derived from E. coli (the native form or the pegylated form). Immune reactions (allergies and antibodies) that a patient develops against the form produced with E. coli are specific to that form in particular, and do not target L-asparaginase derived from Erwinia chrysanthemi. However, treatment with Erwinase® can generate a specific immune reaction with the development of antibodies against Erwinase.
The differences between the half-life for the various preparations were therefore that Erwinase® is administered more frequently than the form derived from E. coli.
The following table shows the use of each L-asparaginase according to patient category. For ALL, the strategy adopted by clinicians' over time has been to attempt to adapt treatment protocols that have achieved high remission rates in children for use in older subjects (adolescents and young adults). L-asparaginase treatment is not used for ALL patients over about 55 years old and AML patients too fragile to receive it.
| ALL | AML | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Children | Adults | Senior | All | |||||||
| 1st line | 2nd line |
Relapse d |
1st line | 2nd line |
Relapse d |
1st line | s 2nd line |
Relapse d |
populations | |
| Native | ||||||||||
| PEG | ||||||||||
| Erwinia chrysanth emi |
||||||||||
| Native | ||||||||||
| PEG | ||||||||||
| Erwinia chrysant hemi |
Commonly used
Rarely used
Not used
To the Company's knowledge, the following new forms of asparaginase are under development:
There have been three major transactions in the market for L-asparaginase that are part of a broader trend in the interest of pharmaceutical groups in rare and orphan diseases. ERYTECH believes that these transactions were performed based on particularly attractive valuations:
To the Company's knowledge, the more advanced products under development that may be able to treat ALL without the Philadelphia chromosome or AML are:
18 Borghorst et al., Pediatric Hematology and Oncology, 2012
ERYTECH believes that these products can be used with GRASPA®.
Recognizing a real need for a new L-asparaginase drug, ERYTECH developed the product ERY-ASP/GRASPA®. ERY-ASP/GRASPA® consists of an L-asparaginase encapsulated in a red blood cell. Encapsulation allows L-asparaginase to destroy asparagine within the red blood cell, without causing allergic reactions and reducing other side effects. ERY-ASP/GRASPA® offers a treatment with extended efficacy relative to the other forms and a significantly improved safety profile, making it possible to treat fragile patients.
Since 2006, ERYTECH has conducted 5 clinical trials, including 4 involving ALL, to establish the safety and efficacy of ERY-ASP/GRASPA®. The following table summarizes the main findings of these ALL studies. The results of the Phase I pancreatic cancer study are presented in Section 3.4.6 on solid tumors.
| Indication | Study | N | Status | Key findings | |
|---|---|---|---|---|---|
| Phase I/II | 24 Completed |
GRASPA® is well tolerated even at the highest dose and shows depletion similar to 8 injections of Kidrolase® |
|||
| Relapsed ALL in children and adults |
Phase II/III | 80 | Completed | Primary objectives achieved and secondary objectives confirm a favorable profile for the clinical efficacy of GRASPA®; the study also shows favorable results in patients with histories of allergies to L-asparaginase. |
|
| ALL patients > 55 years old |
Phase II | 30 | Completed | GRASPA® is well tolerated in this highly fragile population and has shown a remission rate of approximately 70% |
Synopsis of ALL clinical data
Based on completed or ongoing clinical studies, ERYTECH expects to be able to file an application for marketing approval through the centralized procedure for Europe in 2015 for ALL.
In the meantime, ERYTECH has launched a study within the Expanded Access Program (EAP), treating patients who are allergic to all current forms of asparaginase; within this program, the 1st DSMB recommended continuing the recruitment of patients into the program, with no modifications to the study.
The European Medicines Agency (EMA) and the American Food and Drug Administration (FDA) have granted ERY-ASP/GRASPA® orphan drug designation for ALL, offering it exclusive marketing upon obtaining marketing approval for the product for 7 and 10 years in the United States and Europe respectively.
ERY-ASP/GRASPA® involves the encapsulation of the enzyme L-asparaginase. The red cell membrane protects the L-asparaginase from the antibodies that are present in patients' blood and would likely substantially lessen or completely neutralize the enzyme activity or cause a hypersensitivity reaction. Thus, L-asparaginase remains active within the red blood cell without causing immune or allergic reactions in the patient. The enzyme can remain active and effective in the red blood cell as long as it is in the bloodstream and it has been demonstrated that the encapsulation process does not significantly alter the red blood cell's life span (29 days on average).
The encapsulation of L-asparaginase therefore not only significantly improves the drug's safety profile but also maintains the therapeutic efficacy of the enzyme over a long period compared to directly administering it to the patient. For this reason,, ERY-ASP/GRASPA® may be administered to fragile patients who cannot receive current forms of L-asparaginase and offer all patients an effective treatment with fewer injections and fewer side effects.
As illustrated in the following diagram, asparagine is an amino acid that naturally enters the red blood cell and ERYTECH's technology does not interfere with this natural mechanism.19 The enzyme encapsulated in the cell, L-asparaginase, can then break down asparagine into L-aspartic acid and ammonia. The concentration of asparagine in the patient's blood decreases and leukemic and cancer cells are deprived of the asparagine they need to live, grow and develop.
Mode of action
Clinical development program for acute leukemias
| Clinical study | Status | Number of patients included in the study |
|---|---|---|
| Phase I/II study in adults and children with relapsed ALL (Europe) |
Completed | 24 |
| Phase II study in patients over the age of 55 for first-line treatment (Europe) |
Completed | 30 |
| Phase II/III study in adults and children with relapsed ALL (Europe) |
Completed | 80 |
| Phase I/II study in adults over the age of 40 with ALL (in the United States) |
Ongoing | 12 |
| Phase IIb study in patients over the age of 65 with AML (Europe) |
Ongoing | 123 |
| Expanded Access Program for ALL in children and adults not eligible for other forms of asparaginase (France) |
Ongoing | N/A |
| Total | 269 |
This section presents the protocols for these completed and ongoing clinical studies, and provides a breakdown of the results:
Between 2006 and 2009, ERYTECH performed a Phase I/II multicenter, randomized clinical trial (in France and Belgium) of GRASPA®, comparing it to the standard treatment (free L-asparaginase - Kidrolase®) in adults and children with relapsed ALL. The study has demonstrated the safety of GRASPA®, its efficacy over time in reducing the level of plasma asparagine in a single injection by an amount equivalent to that observed after 8 injections of free L-asparaginase (standard treatment), as well as fewer side effects associated with Lasparaginase (high-grade allergic reaction and cases of reduced coagulation disorders).
The main objective of this comparative study was to determine the relationship between the dose of GRASPA® (three doses tested: 50, 100 and 150 IU/kg) administered and the period during which plasma asparagine was reduced (depletion) in the sick patient. The trial was also designed to evaluate the efficacy of GRASPA® compared to the standard treatment through the duration of plasma asparaginase depletion, and the tolerance of the product by examining the side effects associated with GRASPA® encapsulated L-asparaginase.
The protocol for the clinical trial involved treating some adult or pediatric patients with relapsed ALL, according to the standard treatment, namely chemotherapy in combination with Kidrolase® free asparaginase, and the remaining patients with chemotherapy in combination with GRASPA®. Patients were randomly distributed into 4 groups of 6 people: 3 groups received three gradual doses of GRASPA® (50, 100 and 150) in parallel and on a double-blind basis in addition to chemotherapy; the 4th control group received only the free asparaginase standard treatment (Kidrolase®) in combination with chemotherapy.
This Phase I/II study showed that GRASPA® produced an average asparagine plasma depletion duration of 18.6 days after the first injection of a 150 dose, a period equivalent to the average depletion observed in the control group treated with Kidrolase® (which has an average depletion duration of 20.6 days after 8 injections of a 10,000 IU/m² dose administered every three days).
A reduction in side effects was also observed for GRASPA®, particularly with regard to the occurrence of allergies, pancreatitis or coagulation disorders regardless of the dose of the product administered.
The table below presents the main clinical results of the Phase I/II study in adults and children with relapsed ALL during the first treatment cycle.
| Kidrolase® (standard L asparaginase) (n=6) |
GRASPA® (n=18) | |
|---|---|---|
| N (%) | N (%) | |
| Allergic reaction | 3 (50%) | 0 (0%) |
| including high grade (3 or 4) | 2 (33%) | 0 (0%) |
| Clinical pancreatitis | 0 (0%) | 0 (0%) |
| Pancreatic enzyme elevation | 1 (17%) | 3 (16%) |
| Liver problems | 3 (50%) | 7 (38%) |
| Hypoalbuminemia | 2 (33%) | 0 (0%) |
| Coagulation disorder | 4 (67%) | 3 (16%) |
| including clinical thrombosis | 1 (17%) | 0 (0%) |
| Clinical results of the Phase I/II study in adults and children with relapsed ALL | ||||
|---|---|---|---|---|
| ----------------------------------------------------------------------------------- | -- | -- | -- | -- |
Source: Domenech e.a, BJH 2010
In 2008, ERYTECH conducted a Phase II, dose-escalation clinical trial on GRASPA® as first-line treatment in 30 patients over the age of 55 with ALL and without the Philadelphia chromosome (Ph- ALL). These clinical trials confirmed a favorable tolerance profile for GRASPA® in a particularly fragile population of senior patients, and an absence of clinical allergies and absence of pancreatitis. Moreover, this trial showed that GRASPA® (100 IU/kg) resulted in complete remission for 77% of patients with a median survival improved by 6 months compared to historical data.
The study's main objective was to determine the maximum tolerated and effective dose of GRASPA® (among the three doses of 50, 100 and 150) in combination with chemotherapy, in the population studied. This clinical trial also aimed to evaluate the side effects related to the investigational drug in combination with chemotherapy, its pharmacokinetic and pharmacodynamic parameters and the rate of complete remission after treatment.
The study was open-label with a 3-patient cohort and included escalating doses of GRASPA® (50 IU/kg, 100 IU/kg and 150 IU/kg). After administration and review of the clinical response of the first cohort to the lower dose of GRASPA®, an independent monitoring board approved the transition to the higher dose. Patients were monitored every 3 to 4 weeks and then every 2 to 3 months to collect data pertaining to patient survival.
The following table presents the main results of the Phase II clinical trial by dose of GRASPA® administered:
| GRASPA® 50 (n=3) | GRASPA® 100 (n=13) | GRASPA® 150 (n=14) | |
|---|---|---|---|
| N (%) | N (%) | N (%) | |
| Clinical allergies | 0 (0%) | 0 (0%) | 0 (0%) |
| Clinical pancreatitis | 0 (0%) | 0 (0%) | 0 (0%) |
| Pancreatic enzyme elevation |
1 (33%) | 2 (15%) | 3 (21%) |
| Thrombosis / attack | 1 (33%) | 1 (8%) | 2 (14%) |
| Reduction of ATIII | 2 (67%) | 3 (23%) | 7 (50%) |
| Complete remission | 2/3 (67%) | 10/13 (77%) | 9/14 (64%) |
| Median survival | - | 15.6 months | 9.5 months |
Source: Hunault – Berger e.a., ASH abstract #1473, 2012
The GRASPIVOTALL study (GRASPALL 2009-06) is a controlled, multi-center Phase II/III clinical study performed on 80 children and adults with relapsed or refractory acute lymphoblastic leukemia (ALL). This study is broken down into three arms. The first two compare GRASPA® with native E. Coli L-asparaginase, both in association with standard chemotherapy (COOPRALL), in a randomized study with a proportion of one to one in patients without a history of allergy to L-asparaginase. The third arm is an open study evaluating GRASPA® in patients who have had allergic reactions to L-asparaginase during first-line treatments.
Analysis of the data from the GRASPIVOTALL clinical trial, after one year of monitoring, demonstrates that the study convincingly achieved its primary objectives, and its secondary objectives confirm a favorable profile for the clinical efficacy of GRASPA®. The study also shows favorable results in patients with histories of allergies to L-asparaginase.
The main evaluation criteria for this study involves two objectives, in accordance with the opinion of the CHMP20 : a) a higher tolerance, seen in a significant reduction in the incidence of allergic reactions to GRASPA® as compared to the control group, and b) a duration not less than that of the asparaginase activity, beyond the threshold of 100 IU/l, during the induction phase in non-allergic patients. The two criteria needed to be satisfied for the study to be considered positive. The main secondary objectives of efficacy involved complete remission (CR), minimal residual disease (MRD), progression-free survival (PFS), and overall survival (OS).
The primary objectives achieved are as follows:
The secondary objectives confirm a favorable profile for the clinical efficacy of GRASPA®. At the end of the induction phase, 15 patients (65%) in the GRASPA arm showed complete remission, as compared to 11 patients (39%) in the control arm.
Equally promising results were seen in patients with histories of allergies to L-asparaginase. A favorable clinical profile was found in patients with histories of allergies to L-asparaginase. Only three patients had slight allergic reactions.
These results confirm the previous observations obtained with GRASPA® in a Phase I/II randomized, doseescalating study of 24 patients with a relapse of ALL, and a Phase II study in patients older than 55 years of age with ALL and receiving first-line treatment.
20 Based on the scientific opinion obtained by the Scientific Advice Working Party (SAWP)/Commission for Human Medicinal Products (CHMP) at the European Medicines Agency (EMA)
| Randomized arms | HypSen arm | |||
|---|---|---|---|---|
| ERY001 | L-ASP | ERY001 | ||
| N=26 | N=28 | N=26 | ||
| Primary objectives | ||||
| Duration with asparaginase activity > 100 IU/l (days)* |
20.5 ± 5.2 | 9.4 ± 7.4 | p < 0.001 | 18.6 ± 6.3 |
| Hypersensitivity to asparaginase |
||||
| All grades | 0 (0%) | 12 (43%) | p < 0.001 | 3 (12%) |
| Grade ≥ 3 | 0 (0%) | 7 (25%) | 0 (0%) | |
| Main secondary objectives | ||||
| Complete remission** | 17 (65%) | 11 (39%) | p < 0.05 | 14 (54%) |
| MRD < 10-3** | 9 (35%) | 7 (25%) | 6 (23%) | |
| Overall Survival at 6 months | 92.3% | 78.6% | 73.1% | |
| Overall Survival at 12 months | 76.9% | 67.9% | 50.0% | |
| Event Free Survival at 6 months |
75.7% | 60.7% | 60.4% | |
| Event Free Survival at 12 months |
64.9% | 48.6% | 50.3% |
Table summarizing the results of the Phase III clinical study of GRASPIVOTALL with ERY-ASP/ GRASPA® :
*measured in whole blood **at the end of induction
Lyon (France), June 1, 2015 – ERYTECH Pharma (Euronext Paris - ERYP; OTC US - EYRYY), the French biopharmaceutical company that develops innovative 'tumor starvation' treatments for acute leukemia and other oncology indications with unmet medical needs, reported complete Phase III results of its pivotal program with GRASPA® in Acute Lymphoblastic Leukemia (ALL) and presented the design of the ongoing Phase IIb study in Acute Myeloid Leukemia (AML) at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO). During an investigator meeting ERYTECH also presented the progress and plans on other development programs.
On Saturday, May 30, Prof. Dr. Yves Bertrand, oncologist at the Institute for Pediatric Hematology and Oncology in Lyon, France, presented full Phase III results of the GRASPIVOTALL trial in a plenary session in a packed Arie Crown theatre (4250 seats).
The title of his presentation was:
Clinical activity of ERY001 (erythrocyte encapsulated l-asparaginase) and native l-asparaginase (L-ASP) in combination with COOPRALL regimen in Phase III randomized trial in patients with relapsed acute lymphoblastic leukemia (ALL)
The GRASPIVOTALL is a controlled, randomized, multicenter Phase II/III trial comparing GRASPA® (development name: ERY001) to native L-asparaginase (L-ASP) in children and adults suffering from relapsing or refractory ALL. Positive top line data were made available end of last year and demonstrated that the trial met both of its primary endpoints.
The main conclusions of the study, as presented by Prof. Bertrand, are:
The presentation will be available on the ASCO website (http//am.asco.org).
On Sunday, May 31, Dr. Xavier Thomas, hemato-oncologist at Hospital Lyon South, presented a poster on the design of the ongoing Phase IIb study in Acute Myeloid Leukemia entitled:
GRASPA-AML 2012-01 study: A multicenter, open, randomized Phase 2b trial evaluating ERY001 (Lasparaginase encapsulated in red blood cells) plus low-dose cytarabine vs low-dose cytarabine alone, in treatment with newly diagnosed acute myeloid leukemia (AML) elderly patients, unfit for intensive chemotherapy
The poster has been made available in the company's website.
The GRASPA-AML study was launched mid 2013. Today, close to three quarters of the 123 patients to be enrolled in the study have been treated. Two DSMB reviews, one on 30 patients and one on 60 patients, have been performed. A third DSMB review with a futility analysis was originally planned when 60 patients would have experienced an event (progression of the disease or death). The 60 events have recently been reached, later than expected. Given the very advanced stage of patient recruitment in the study, and in order to save statistical power for the final analysis of the study (limit 'α-spending') it was decided not to perform the futility analysis. Futility analyses are typically performed early in a study to avoid unnecessary burden to patients and costs to the sponsor. A safety data review continues to be foreseen and results are expected towards the end of Q3 2015. Full enrolment in the study is expected by the end of the year.
21 Percentage of patients with at least one drug-related event during the induction phase
During investigator meeting organized by ERYTECH on May 31, the company and five distinguished Key Opinion Leaders provided an update on the use of asparaginase products and on the ongoing programs with GRASPA, both in hemato-oncology and solid tumors.
Dr. Ching-Hon Pui, MD, St. Jude Children Hospital, Memphis, presented an overview of the experience with the use of asparaginases in pediatric ALL. He highlighted the contribution asparaginase has made in improving the prognosis for children affected by ALL, but he also pointed at the need for safer formulations to be able to target the more fragile patient populations, such as children in relapse and high risk patients.
Prof. Dr. Larson, MD, PhD, University of Chicago, continued by presenting how the asparaginase was introduced into adult protocols based on pediatric inspired regimens. He continued by describing how important the completion of the planned dose is (25 weeks and more) and how sustained asparaginase activity effect correlated with of survival outcome, compared to the patients who did not completed their treatment, for multiple reasons, including asparaginase related toxicities.
Prof. Dr. Yves Bertrand, MD, PhD, IHOP Lyon, presented the highlights of the clinical evidence with GRASPA in ALL obtained so far, including the Phase III results he communicated the day before in an oral presentation at the ASCO conference
Dr. Phil Lorenzi, PhD, MD Anderson Cancer Center, Houston, USA, presented a summary of most recent work done around L-asparaginase and supporting its utility exploring in solid tumors as well as using ASNS as a predictive biomarker.
Prof Dr. Pascal Hammel, oncologist at Hospital Bichat-Beaujon in Paris continued with a presentation of the ongoing Phase II study with ERY-ASP22 in pancreatic carcinoma.
ERYTECH Pharma subsequently gave an overview of the other current development programs with GRASPA, notably the Phase IIb study in AML and the preparations of a Phase II study in NH lymphoma and a Phase I study with ERY-MET (methioninase in red blood cells).
ASCO, the American Society of Clinical Oncology, is a professional oncology society committed to conquering cancer through research, education, prevention and delivery of high-quality patient care. ASCO's Annual Meeting is the world largest event on clinical oncology which annually gathers more than 30,000 specialists interested in the latest achievements in the field of cancer treatment.
Founded in Lyon in 2004, ERYTECH is a French biopharmaceutical company providing new prospects for cancer patients, particularly those with acute leukemia and selected solid tumors. By encapsulating the asparaginase enzyme in red blood cells, ERYTECH has developed ERY-ASP/GRASPA®, an original treatment that targets cancer cells through "tumor starvation" while significantly reducing the side effects for patients. ERY-ASP/GRASPA® has recently announced positive Phase III data in Acute Lymphoblastic Leukemia (ALL) and is in Phase IIb clinical trial in Acute Myeloid Leukemia (AML) in Europe. The product is also in Phase I/II clinical development in ALL in the USA.
Every year about 50,000 patients are diagnosed with Acute Lymphoblastic Leukemia (ALL) or Acute Myeloid Leukemia (AML), the two forms of acute leukemia. Today, for about 80% of these patients, mainly adults and relapsing patients, current forms of asparaginase cannot be used due to their toxicity. With a presumed improved safety profile, ERY-ASP/GRASPA® is being developed to allow all leukemia patients to be treated, even the most fragile ones, representing a market opportunity of more than EUR 1 billion.
The company is also developing other indications in solid tumors and certain orphan indications outside oncology. A Phase II study in pancreas cancer is ongoing and the company is exploring other solid tumor indications for ERY-ASP.
ERYTECH has obtained orphan drug designations for ERY-ASP/GRASPA® in ALL, AML and pancreas cancer, both in Europe and the USA, and has its own GMP-approved and operational manufacturing site in Lyon (France), and a site for clinical production in Philadelphia (USA). The company has concluded licensing and distribution partnership agreements for ALL and AML in Europe with Orphan Europe (Recordati Group), and for ALL with TEVA in Israel.
ERYTECH is listed on Euronext regulated market in Paris (ISIN code: FR0011471135, ticker: ERYP) and is part of the CAC Healthcare, CAC Pharma & Bio, CAC Mid & Small, CAC All Tradable, EnterNext PEA-PME 150 and Next Biotech indexes. ERYTECH is also listed in the US under an ADR level 1 program (OTC, ticker EYRYY).
22 ERY-ASP is the codename for GRASPA outside the field of acute leukemia and outside Europe. The GRASPA® brandname has been licensed for use in acute leukemia in Europe to Orphan Europe (Recordati), ERYTECH's European commercial partner in Europe.
ERYTECH Gil Beyen Chairman and CEO Tel: +33 4 78 74 44 38 [email protected] NewCap Julien Perez / Emmanuel Huynh Investor relations Nicolas Merigeau Press relations Tel: +33 1 44 71 98 52 [email protected]
This document may contain forward-looking statements and estimates with respect to the financial situation, the results of operations, the strategy, the project and to the anticipated future performance of ERYTECH and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, "believes", "anticipates", "expects", "intends", "plans", "seeks", "estimates", "may", "will" and "continue" and similar expressions. They include all matters that are not historical facts. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond the Company's control. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results, the financial condition, performance or achievements of ERYTECH, or industry results, may turn out to be materially different from any future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Documents filed by ERYTECH Pharma with the French Autorité des Marchés Financiers (www.amf-france.org), also available on our website (www.erytech.com) describe such risks and uncertainties. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of the publication of this document. ERYTECH disclaims any obligation to update any such forward-looking statement. Readers are cautioned not to place undue reliance on any of these forward-looking statements. ERYTECH disclaims any obligation to update any such forwardlooking statement, forecast or estimates to reflect any change in the Company's expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based, except to the extent required by French law.
On May 30, 2015, the Company presented the complete results of its Phase III pivot study of GRASPA® in acute lymphoblastic leukemia (ALL) at the 51st annual meeting of the American Society of Clinical Oncology (ASCO).
The presentation was entitled:
"Clinical activity of ERY001 (erythrocyte encapsulated l-asparaginase) and native l-asparaginase (L-ASP) in combination with COOPRALL regimen in Phase III randomized trial in patients with relapsed acute lymphoblastic leukemia (ALL)".
GRASPIVOTALL is a controlled, multi-center Phase II/III randomized study comparing GRASPA® (development code: ERY001) with native l-asparaginase (L-ASP) in children and adults with relapsed or refractory acute lymphoblastic leukemia. The first positive results of the study were published at the end of last year, demonstrating that the two primary objectives had been achieved.
The main findings of the study are as follows:
The treatment was generally well tolerated, with a low risk of major incidents such as coagulation disorders (35% as compared to 82%21), pancreatic toxicity (27% as compared to 50%21), and liver toxicity (19% as compared to 43%21).
The favorable safety and efficacy profile of GRASPA offers effective alternative options for patients who have previously been treated with asparaginase, notably those who have already developed a hypersensitivity to E-coli derived asparaginase.
A Phase IIb, multi-center clinical study is currently under way in newly diagnosed patients with AML over 65 years of age and unable to receive intensive chemotherapy. Generally, L-asparaginase is very rarely used for this indication. Although the efficacy of this treatment has been demonstrated for AML, the risk of side effects for this fragile population of often elderly patients is too great to justify the administration. The primary objective of this study is to evaluate the efficacy of GRASPA® when added to the standard product (low-dose cytarabine). To accomplish this, progression-free survival will be analyzed between patients receiving GRASPA® in combination with low-dose cytarabine, and patients receiving only low-dose cytarabine. This study plans to recruit 123 patients, 2/3 of whom will be treated with GRASPA® . The study protocol includes monitoring patients for 24 months, an analysis of the first 30 and 60 patients to analyze tolerance by a Data Safety Monitoring Board (DSMB), and a third interim analysis where sixty patients have experienced a progression of their disease.
The first analysis by the DSMB was performed in November 2013, and the second in August 2014. The committee of independent experts has issued two favorable opinions with regard to the continuation of this clinical trial after evaluation of the product's safety in the first 30 and 60 patients treated. The results at one year from the study are expected in the first half of 2017.
On May 31, 2015, the Company presented a poster on the design of the Phase IIb study in progress on acute myeloid leukemia, entitled:
"GRASPA-AML 2012-01 study: A multicenter, open, randomized Phase 2b trial evaluating ERY001 (Lasparaginase encapsulated in red blood cells) plus low-dose cytarabine vs low-dose cytaragine alone, in treatment with newly diagnosed acute myeloid leukemia (AML) elderly patients, unfit for intensive chemotherapy".
The GRASPA-AML study was launched in mid-2013. On June 1st, 2015, nearly three-quarters of the 123 patients scheduled for recruitment into the study had been treated. Two reviews have been performed by the DSMB (committee of independent experts) on 30 and 60 patients respectively. A third DSMB review, accompanied by a futility analysis, was initially planned when 60 patients had experienced an incident (progression of the illness or death). This 60-incidencesreview trigger recently occurred, later than anticipated. Considering the now considerably advanced recruitment of patients into the study, and to retain statistical strength for final analysis of the study ('α-spending' limit), it was decided that the futility analysis would not be performed. Futility analyses are generally performed at the start of a study to avoid useless treatments for patients and costs for the company conducting the study. A study of the tolerance data is nevertheless planned, the results of which are expected toward the end of Q3 2015. Full recruitment to the study, in turn, should be completed by the end of this year.
Regulatory authorities in Europe and the United States have established marketing approval and specific reimbursement procedures for drugs to treat orphan diseases in order to encourage development efforts and innovation in connection with these diseases that affect very few patients. In particular, requirements for the necessary clinical studies are adjusted to take into account the small patient population and procedures for obtaining Marketing Approval (MA) are often facilitated and accelerated to meet public health needs.
The major advantage of this legislation is to allow manufacturing pharmaceutical companies selling products with orphan drug designation to take advantage of exclusive marketing after obtaining an MA for the product for 7 and 10 years, in the United States and Europe respectively.
The EMA and the FDA have granted Orphan Drug Designation to ERY-ASP/GRASPA® for ALL, AML, and pancreatic cancer.
Based on the results from the phase II/III clinical study in adults and children with relapsed ALL, and based on previous studies, ERYTECH will be able to file an AMM marketing approval application through the European centralized procedure in 2015.
The Company will request, from the health authorities, the broadest possible indication for its AMM. It will then be up to these authorities to accept or not, and to specify whether additional studies are necessary in order to obtain the AMM (see Section 4.4.1 and Chapter 6.1).
Indicative timetable
| ALL: Phase II/III results in relapsed adult or pediatric patients | Q3 2014 |
|---|---|
| ALL: Submission of the MA application to the EMA | 2015 |
| ALL: European MA through the centralized procedure | 2016 |
| AML: Results at one year from the Phase IIb study | S1 2017 |
GRASPA® will be marketed by Orphan Europe (Recordati Group) in 38 European countries and by the Teva Group in Israel. The product's positioning in terms of marketing strategy will be developed in consultation with ERYTECH.
For ALL, ERYTECH anticipates that the dynamics of adopting the product will begin with the fragile populations, first with senior and older adult patients who cannot receive the current forms of L-asparaginase, and then with relapsed or refractory adult and pediatric patients who also cannot be treated with Lasparaginase. GRASPA®'s use can naturally be extended to other patients with the clinical experience acquired by oncologist-hematologists by capitalizing on GRASPA® 's proven safety.
Based on the advantages that GRASPA® could have compared to other forms of L-asparaginase and unmet medical needs, ERYTECH believes that GRASPA® could potentially be the preferred L-asparaginase treatment for one in three ALL patients or approximately 5,000 newly diagnosed patients per year (3,000 in Europe and 2,000 in the United States).
The lack of an L-asparaginase treatment that is approved and/or used in AML may allow GRASPA® to be positioned as the first-line treatment for these patients. Clinicians have expressed a strong interest in using Lasparaginase to treat AML, and ERYTECH intends to meet this demand with GRASPA®. GRASPA®'s primary target for AML represents more than 11,000 patients with AML (more than a third of new cases each year in Europe and the United States). These are patients whose type of AML is particularly sensitive to the removal of asparaginase (about 70%) and whose general health is particularly fragile (about 2 in 3 patients).
The following table illustrates the treatment costs associated with the major L-asparaginase drugs currently on the market for one round of chemotherapy (about 1 month) – considering that a given patient usually requires several. Taking into account the innovative nature of GRASPA®, its medical value and its target position in the treatment of acute leukemia, ERYTECH expects to target a price position similar to Erwinase®. It is important to remember that the pricing and reimbursement of GRASPA® will need to be determined according to the regulations and practices in force in the various countries and the health and drug delisting policies will gradually become more rigorous.
| Product | One-month treatment cycle | |
|---|---|---|
| Injections | Cost | |
| Oncaspar® | 2 | Europe price: 2,400 – 4,800 Euros US Price23: \$11,200 – 23,000 |
| Erwinase® | 12 | Europe price: 17,000 – 42,000 Euros US Price7 : \$86,400 – 216,000 |
The estimated cost of treatment with the major L-asparaginase drugs
Source: ERYTECH
ERYTECH has entered into two major partnerships for the commercialization of GRASPA® in 38 European countries with Orphan Europe (Recordati Group) and in Israel with the Teva Group. Thanks to the innovative nature of GRASPA®, its ability to satisfy unmet medical needs and its progress in clinical development, ERYTECH was able to obtain favorable terms, particularly with regard to the sharing of future profits. Both partners have recognized trade capacities and can effectively promote GRASPA® in their respective territories.
Furthermore, it should be noted that there are relatively few potential prescribers of GRASPA® in each country, mainly hematologist-oncologists, who are clearly identified. Therefore, awareness of specialized products such as GRASPA® and adoption of the drug can occur very quickly. In addition, GRASPA® does not require existing ALL treatment protocols to be modified since L-asparaginase is already included in them. For specialty products like GRASPA®, the commercial and promotional resources required are modest compared to other drugs in general practice for example, thereby making high margins possible.
On November 23, 2012, ERYTECH signed a marketing agreement with Orphan Europe, a company specialized in the development, production, and marketing of drugs for orphan diseases. Orphan Europe is a subsidiary of Recordati, a major pharmaceutical group in Europe.
Orphan Europe holds a portfolio of orphan drugs already on the market in different areas, such as neonatology, pediatrics, and metabolic disorders. Orphan Europe is a leading player in the field of orphan diseases and has the medical, clinical, regulatory and commercial expertise to market and effectively sell GRASPA® in Europe. Orphan Europe is a strategic business for Recordati, which acquired the company in 2007 for €135 million and built it up further with the acquisition of a portfolio of rare and orphan disease drugs in the United States for \$100 million.
Orphan Europe will market GRASPA® in 38 European countries, including all the countries in the European Union for the treatment of ALL and AML. The parties have the opportunity to discuss the extension of this agreement to other areas around Europe and other indications.
ERYTECH is keeping the production of GRASPA® at its Lyon site and will supply Orphan Europe in the various European countries where the drug will be sold.
Under this agreement, Orphan Europe contributed €5 million upon signing. Orphan Europe will have to pay ERYTECH up to €37.5 million in future payments based on various clinical, regulatory and sales events, and Orphan Europe will participate in the costs of the clinical development of GRASPA® in AML. ERYTECH will receive a price for product delivered, and royalties on the sales performed by Orphan Europe with GRASPA®, for a total of up to 45% of the net sale price.
Separately, another Recordati Group company has purchased bonds that were converted into an investment in ERYTECH equity worth €5 million at the time of the initial public offering in April 2013.
On March 28, 2011, ERYTECH signed a partnership agreement with the Teva Group, a global player in the pharmaceutical industry based in Israel, to distribute GRASPA® in that country. The Teva Group is a diversified pharmaceutical group with a strong strategy in innovative specialized products and particularly in therapeutic areas such as the central nervous and respiratory systems, women's health, oncology, and pain.
In accordance with the terms of the agreement, the Teva Group will submit the request for approval of the drug for ALL in Israel and ensure marketing and distribution in the long term in this country. The Teva Group will pay interim payments and share net earnings of product sales in Israel.
ERYTECH retains all rights to ERY-ASP outside the 38 European countries covered by the partnership with Orphan Europe (Recordati Group) for ALL and AML, and in Israel with the Teva Group for ALL. In particular, ERYTECH owns all rights for ERY-ASP in the United States and for other indications such as, for example, solid tumors.
ERYTECH aims to secure distribution agreements in countries surrounding Europe, and particularly key markets such as Russia and Turkey. In some of these countries, Orphan Europe (Recordati Group) has a right of first negotiation.
The Company has a production unit with enough capacity to cover the needs of the European market for 2-3 years after initial placement on the market. This unit meets the highest requirements of ANSM and has "Operating Pharmaceutical Facility" status.
The company has secured its supply for the main raw materials needed to manufacture ERY-ASP/ GRASPA®:
L-asparaginase: ERYTECH Pharma and Medac have signed two worldwide exclusive long-term agreements according to which Medac supplies ERYTECH with two forms of asparaginase that ERYTECH uses for the production of ERY-ASP/GRASPA®, for clinical trials and for the sale of ERY-ASP/GRASPA®, for the therapeutic indications defined by ERYTECH. Medac is a German pharmaceutical company based near Hamburg and selling L-asparaginase (see also Chapter 22 of the Reference Document).
Red blood cells: ERYTECH signed two supply contracts with the Établissement Français du Sang [French Blood Facility] and the American Red Cross, two well-known blood banks, for transfusion quality human red blood cells.
ERYTECH's goal is to develop ERY-ASP in the United States, which represents a significant potential market for ALL and AML.
ERYTECH plans to capitalize on the clinical studies already completed or underway in Europe and replicate the clinical development of ERY-ASP in the United States. On March 21, 2013 ERYTECH obtained approval from the FDA (Investigational New Drug or IND) to begin a Phase Ib clinical trial in ALL, and began recruiting its first patients in the third quarter of 2014. The estimated cost of this Phase Ib clinical study is approximately 4 million Euros, and the Group intends to finance it with funds raised from the initial public offering. This study will also make it possible to pursue clinical development for ALL and AML alone or in a partnership. Further clinical development may include Phase II/III studies for ALL and AML and could make it possible to file an authorization for placement on the market within the 2018/2019 horizon.
ERYTECH has established a close partnership with the American Red Cross in Philadelphia. Under this agreement, the American Red Cross will provide red blood cells, a classified production area and staff trained by ERYTECH, under the supervision of an ERYTECH representative sent to Philadelphia.
In April 2014, ERYTECH created a subsidiary in the United States (Cambridge) under the name of ERYTECH Pharma Inc., 100% held by the parent company, ERYTECH Pharma.
| Indication | 2012 | 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | |
|---|---|---|---|---|---|---|---|---|
| ALL in the United States | = | Phase II/III | ||||||
| AML in the United States | Phase II/III | |||||||
| Phase Ib |
In 2013, ERYTECH launched a Phase Ib clinical study in the United States for patients greater than 40 years of age without the Philadelphia chromosome as first-line treatment in ALL, in combination with the standard chemotherapy (CALGB chemotherapy in the United States), in a sample of 12 to 18 patients with escalating doses (50 to 150 IU/kg).
This multicenter, non-randomized clinical trial strictly in the United States aims primarily to validate the toxicity, safety and efficacy profile of ERY-ASP, in combination with standard chemotherapy. This phase Ib study is the first clinical trial conducted by ERYTECH in the United States. As a toxicity study, the results will also be used in the Phase I AML study.
As for leukemia, the rationale for treating tumor cells deprived of asparagine synthetase (see figure 1 in Section 6. Illustration of the "Starving tumor" concept) is also applicable to solid tumors as long as they do not produce asparagine synthetase and need to consume asparagine contained in plasma. Thus, ERYTECH conducted a study in collaboration with the MD Anderson Cancer Center to assess the proportion of tumors potentially sensitive to asparaginase, i.e., tumors that produce little or no asparagine synthetase.
Source: Dufour et al., "Pancreatic Tumor Sensitivity to Plasma L-Asparagine Starvation," Pancreas, 2012
ERYTECH also validated an immunohistochemistry test using tumor tissue to detect whether the tumor produces asparagine synthetase and therefore whether it is resistant or sensitive to asparaginase.
Moreover, the Company entered into an exclusive license agreement with the NIH to develop a companion test to determine tumor sensitivity to asparaginase. This test could be used in clinical studies and be commercially developed with an industrial partner.
ERYTECH has conducted a Phase I study on pancreatic cancer to demonstrate the safety of ERY-ASP. This clinical trial demonstrated that ERY-ASP was well tolerated even at high doses. With these initial clinical results for solid tumors, ERYTECH plans to continue to develop ERY-ASP for pancreatic cancer and expand this development to other solid tumors of interest.
ERYTECH is developing possible new indications for ERY-ASP outside the area of leukemias and pancreatic cancer. Initial pre-clinical and clinical results suggest that ERY-ASP could also be effective against certain solid tumors for which therapeutic options are currently reduced. ERYTECH is preparing for the launch of a Phase II study on non-Hodgkin lymphoma.
From 2009 to 2010 (12 months), ERYTECH conducted a Phase I, non-randomized, dose-escalation clinical trial on 12 patients in France. This clinical trial demonstrated that ERY-ASP is well tolerated in this highly fragile population, even at the highest dose (150 IU/kg).
Based on these initial clinical results with solid tumors, ERYTECH has continued the development of ERY-ASP in pancreatic cancer in a Phase II study in patients as a second-line treatment.
The Phase II study involves a total of 90 patients randomized 2 to 1 between the standard treatment (Gemcitabine or Folfox) with or without ERY-ASP.
| Clinical study | Status | Number of patients included in the study |
|---|---|---|
| Phase I study on pancreatic cancer (France) |
Completed | 12 |
| Phase II study on pancreatic cancer (France) |
Ongoing | 90 |
| TOTAL | 102 |
ERYTECH's proprietary technology is based on the encapsulation of therapeutic molecules in red blood cells also called erythrocytes. The administration of red blood cells is completely managed and controlled by the hospital staff. In addition, it is a biocompatible carrier with a long half-life in the body of about one month and its elimination by the cells of the reticuloendothelial system is well known.
Because the red cell membrane protects its contents from the external environment, i.e., the body, and vice versa:
This results in an increase of the therapeutic index (toxicity offset by efficacy). For example, in the case of asparaginase, for a given level of efficacy, patients receive a dose 10 times lower when it is encapsulated using ERYTECH's technology.
ERYTECH's technology can transform the red blood cell into a cellular bioreactor. The red blood cell has the natural property of being able to absorb certain amino acids freely circulating in the blood. The therapeutic enzyme encapsulated in the red blood cell can interact and break down the amino acid in question.
The process of encapsulation inside red blood cells is based on a concept of reversible hypotonic lysis as shown in the diagram below:
Red blood cells are subjected to a low-ionic strength medium (hypotonic medium) and swell until they reach a critical volume when the membrane is distended to the point of becoming permeable to macromolecules.
Pores form on the surface of the membrane allowing molecules to enter the erythrocyte.
Restoration of the isotonicity of the suspension medium results in the closing of the pores, rendering the membrane impermeable to macromolecules. Only permeability to very small elements (less than 200 Daltons) is retained. The molecule is thus permanently encapsulated.
The osmotic fragility of one sample of red blood cells to another varies. Thus, the membrane distension capacity and therefore the encapsulation capacity varies. However, osmotic fragility variation may be offset by hypotonic lysis parameters. Thus, variations in the amount of the product encapsulated are reduced. This is the heart of ERYTECH's process patent (see Section 11 on Intellectual Property).
ERYTECH has successfully developed this encapsulation process to produce loaded erythrocytes in a reproducible, reliable and economical way on a large scale, regardless of the initial characteristic and origin of the red cells used. More than 300 bags of ERY-ASP/GRASPA® have already been produced and transfused in five clinical trials conducted by ERYTECH.
An automated and industrialized encapsulation process
Specifically, the major competitive advantages of the production process are:
its stability: 72 hours to deliver the drug (at a temperature of 2-8°C),
reproducibility: consistent quality loaded erythrocytes are produced, regardless of the initial characteristics and the origin of the red blood cells used. Various control steps ensure the quality of the product before release by the head pharmacist,
ERYTECH's production unit is based in Lyon and the production staff includes 6 people. Production meets the highest pharmaceutical production standards (cGMP) and is ISO 9001 certified. In particular, product batches are fully traceable from blood collection and separation of red blood cells performed by the blood banks that supply ERYTECH to the patient. The Company has "Pharmaceutical Company" and "Operating Company" status, which allows it to operate on the European market.
In anticipation of clinical trials in the United States, ERYTECH deployed a qualified production unit in Philadelphia in partnership with the American Red Cross (ARC). The American Red Cross (ARC) is the leading blood bank in the world. It is a federal agency located in all states in the United States of America and its primary activity is collecting, classifying and distributing bags of red blood cells for transfusion.
The ARC is the service provider for the production of GMP (Good Manufacturing Practice) batches of ERY-ASP for clinical trials. The ARC also provides the raw material, the bag of red blood cells. Since ERYTECH's analytical method and process were the subject of an industrial transfer, the operations performed at the U.S. site are similar to those at the French site in compliance with FDA regulations. ERYTECH oversees production and controls for this unit jointly with the ARC.
This agreement with the ARC does not include any transfer of rights to technology or to ERY-ASP, and allows ERYTECH to produce the quantities needed for clinical trials planned in the United States.
ERYTECH's technology platform is versatile and opens up many possibilities for developing new drugs. The efficacy of the technology has been demonstrated mainly with L-asparaginase, but it is possible to encapsulate other enzymes, molecules or proteins in red blood cells.
TEDAC is a research and development project meant to treat cancers resistant to radiation/chemotherapy conducted by ERYTECH in association with other companies and organizations: Diaxonhit, Inserm, Université Paris-Diderot [Paris-Diderot University] and AP-HP [Public Assistance - Hospitals of Paris].
The purpose of this project is to develop innovative enzyme therapies targeting the metabolic environment of tumors, provide individual care to patients with chemotherapy or radiation-resistant cancer thanks to the development of screening, and monitoring tests. This project will also enable the Group to develop a new range of therapeutic solutions by combining anti-cancer enzymes efficiently and safely by acting on the complete metabolic environment of the tumor. Over time, the goal is to offer a solution including a test predicting response to treatment, one or more suitable enzyme therapies, as well as a test to monitor therapeutic efficacy.
This project has a total cost of 22.6 million Euros (14.3 million Euros for which ERYTECH shall be responsible) and will take place over 8 years; €10.7 million is being provided by Oséo (BPI) to fund it under the "Strategic and Industrial Innovation" program, of which €7 million will be paid to ERYTECH (i.e., 48% of the project amount for which ERYTECH is responsible). €2.1 million in grants and €4.9 million in repayable advances.
This made it possible to identify a new drug candidate, ERY-MET, composed of methionine-γ-lyase (MGL) encapsulated in red blood cells. MGL breaks down methionine, an amino acid, and may thus starve very many types of tumors sensitive to the elimination of this amino acid.
In its natural form, MGL has a very short half-life and is highly dependent on a co-factor to be effective. However, this co-factor has the special characteristic of being naturally present within red blood cells. With its exclusive encapsulation technology, ERYTECH demonstrated good stability of MGL in red blood cells, and the increase in its half-life to several days compared to some hours in its free-form.
On the basis of these promising pre-clinical results, the Company is continuing its pre-clinical development for the purpose of performing a clinical trial. The production industrialization phase has been launched with a view to providing for the launch of a Phase I study in humans at the end of 2015/start of 2016.
This is the development of a new anti-tumor vaccine using the Vaccin'ERY System® technology by intraerythrocyte encapsulation of tumor antigens and adjuvant(s) to enable in situ activation of immune cells and generate an immune response.
The use of red blood cells as tumor-specific antigen carriers makes it possible for them to be delivered specifically and simultaneously to dendritic cells, immune cells. Red blood cells are processed to direct themselves toward dendritic cells which will capture them, the phagocytes, and thus incorporating the antigens associated with the tumor cells. This results in a classic immune response, i.e., the immune cells introduce these antigens to lymphocytes which are stimulated to specifically become cells responsible for destroying the tumor.
Furthermore, this technology also makes it possible to consider the encapsulation of adjuvants in order to optimize the efficacy of the vaccination.
Red blood cells can be modified to more specifically target "tolerogenic" cells, i.e., that induce tolerance such as Kupffer cells in the liver. Thus, the tolerogenic cells phagocytose the loaded red blood cells in one immunogenic protein and will generate a tolerogenic response vis-à-vis the immunogenic protein. The purpose is to give the body the ability to make proteins normally not well tolerated tolerable and can induce immune reactions (allergy). ERYTECH Pharma has already achieved very encouraging results for its innovative strategy of inducing immune tolerance (patent pending). This technology is also applicable to autoimmune diseases.
ENHOXY® could be a product able to quickly and effectively improve tissue oxygenation to avoid or significantly reduce sickle deformation, and thus heal and prevent the crisis. It consists in the encapsulation of a molecule that will make it possible to allow a greater salting out of oxygen in the presence of the hypoxic cells or tissues, compared to a normal red blood cell. Preclinical results in the study were presented at different international conferences and resulted in strong interest.
However, and due to its prioritization decisions, the Company has decided to suspend this research program for an undetermined period.
The market for orphan disease therapies was estimated at \$50 billion in 2011, or about 6% of the global pharmaceutical market. Over the 2001-2010 period, this market grew rapidly with an estimated 26% CAGR, compared to 20% for other drugs (source: Thomson Reuters).
Rare or orphan diseases are characterized by having a low incidence rate. In the United States, the definition used by the FDA includes diseases affecting fewer than 200,000 people and in Europe, those affecting fewer than 5 patients per 10,000 persons (EMA definition). Approximately 6,800 orphan diseases have been identified24 and each year, several hundred new orphan diseases are discovered.
Although the orphan drug designation has been established since 1983 by the FDA in the United States (Orphan Drug Act) and since 2000 by the EMEA [sic: EMA] in Europe, only in the last decade have applications for orphan drug designation and the interest in this market segment increased sharply. The number of drugs that have obtained orphan drug designation in the United States has more than doubled over the past 10 years, from 208 in 2000-2002 to 425 in 2006-2008. (Source: Tufts Center for the Study of Drug Development study). Since 1983, more than 2,000 drugs have received this designation and 350 were approved. These figures confirm clear success in the implementation of this specific regulation, which has since been adopted in Japan, South Korea, China and Singapore.
The interest of large pharmaceutical groups has grown steadily since the mid-2000s and the last decade has been the most productive for the development of orphan drugs. The number of transactions, in the form of acquisitions or partnership agreements involving pharmaceutical groups, has clearly increased since 2010. For example, following a licensing agreement with Protalix Therapeutics on a treatment for Gaucher's disease signed in December 2009, Pfizer decided to make orphan drugs one of the group's development focus points and created an R&D division specialized in the study of rare diseases in June 2010. Similarly, after signing a strategic agreement with Isis Pharmaceuticals in April 2010 and an exclusive partnership agreement with Prosensa, including the marketing of a treatment for Duchenne muscular dystrophy in October 2009, GlaxoSmithKline created a dedicated division called GSK Rare Diseases. Finally, Sanofi accessed this market in February 2011 with the acquisition of Genzyme, one of the first companies to have organized its business model around orphan diseases, selling in particular Cerezyme and Fabrazyme.
| Date | Purchaser | Target | Amount |
|---|---|---|---|
| Dec. 2007 | Recordati | Orphan Europe | \$193 million |
| Jan. 2010 | Sigma-Tau | Enzon Pharmaceuticals | \$327 million |
| Jan. 2010 | Biovitrum | Swedish Orphan | \$500 million |
| Sept. 2010 | Pfizer | FoldRx | \$200 million |
| Oct. 2010 | GSK | Amicus Therapeutics (20%) | \$260 million |
| April 2011 | Sanofi | Genzyme | \$19.5 billion |
24 Source: Cliff Mintz, PhD, "Orphan Drugs: Big Pharma's Next Act?" Life Science Leader, October 2010
| Mar. 2012 | Shire | FerroKin Biosciences | \$325 million |
|---|---|---|---|
| June 2012 | Jazz Pharmaceuticals | EUSA Pharma | \$700 million |
| Dec. 2012 | Recordati | Portfolio of 10 Lundbeck U.S. products | \$100 million |
| August 2013 | Amgen | Onyx Pharmaceuticals | \$10.4 billion |
| Nov. 2013 | Shire | ViroPharma | \$4.2 billion |
| Jan. 2014 | Jazz Pharmaceuticals | Gentium | \$1.0 billion |
| March 2015 | Teva Pharmaceuticals Industry |
Auspex Pharmaceuticals Inc | \$3.5 billion |
Source: Mergermarket, press
Orphan diseases represent a promising segment of the pharmaceutical industry given the significant unmet medical needs. In addition, the business model for these drugs has strong appeal for pharmaceutical companies of all sizes, particularly thanks to easy market access, a period of market exclusivity and data protection, high prices and reduced sales and promotional efforts. A number of biotechnology companies such as Genzyme have also successfully developed around this orphan disease model.
See appendix 2 of the Reference Document
As of the date of this document, the Company does not have any branches or secondary facilities. It wholly owns the subsidiary "ERYTECH Pharma, Inc.", created in Delaware (US) on April 9, 2014. The purpose of the subsidiary is to:
Its directors are Mr. Gil BEYEN (President) and Pierre-Olivier GOINEAU (Treasurer and Secretary).
Its share capital is one dollar.
The Group's consolidation perimeter is presented in the IFRS consolidated financial statements under Chapter 20.1, Section 5.5.
The Company leases the premises located at Bâtiment Adénine – 60 avenue Rockefeller – 69008 Lyon. It does not own any real estate.
The items pertaining to these leases are summarized in the table below:
| Address | Nature of the premises |
Lease date of effect |
Term | Rent |
|---|---|---|---|---|
| Bâtiment Adénine 60 Avenue Rockefeller 69008 Lyon |
Commercial (Laboratories and Offices) |
24/09/2007 | 23/09/2016 | €396,292 excluding tax, for rent and rental charges |
| France | Re-invoicing share of property tax |
In addition, the Company owns the following significant assets:
| type of equipment | year of acquisition |
Before-tax value |
|---|---|---|
| 2010 | 50,587.53 | |
| Electronic document management | 2014 | 8,000.00 |
| 2004 | 19,000.00 | |
| 2006 | 22,125.00 | |
| Equipment dedicated to production | 2007 | 39,535.00 |
| 2008 | 63,589.60 | |
| 2009 | 28,000.00 | |
| 2014 | 372,264.00 | |
| 2007 | 42,599.92 | |
| General systems & layout | 2008 | 47,098.01 |
| 2008 | 615,413.56 | |
| Systems at production sites | 2009 | 130,329.70 |
| IT systems | 2013 | 47,298.42 |
| Total | 1,485,840.74 |
The Company also uses a significant amount of equipment located at the production or pre-clinical research site financed through leasing-purchase agreements or "lease-backs":
| type of equipment | year of acquisition |
Before-tax value |
|---|---|---|
| 2010 | 110,104.49 | |
| Equipment dedicated to production | 2011 | 40,000.00 |
| 2013 | 240,413.00 | |
| Total | 390,517.49 |
With the exception of the risks described in Section 4.2 "Risks related to health, safety and the environment", the Company has no environmental impact that could affect the use of its tangible assets (see also Annex 2 of the Reference Document "Environmental, Social, and Corporate Responsibility Policy").
The Group's main activity is research and development in the areas of treatment of acute leukemias and other orphan diseases.
Since its creation, the Group has concentrated its efforts:
The Group's business model is to develop its products up to the point of obtaining authorization for their placement on the market in Europe and then in the United States. Commercial partnerships established by Erytech will allow for the distribution of ERY-ASP to be ensured first in Europe and then in the United States and in the rest of the world. Erytech has the capacity to ensure the supply of Graspa® for the first years of its sale in Europe, through its production unit in Lyon.
Comparison of the last two fiscal years below concerns the financial statements presented following IFRS. The financial statements prepared in accordance with French standards are commented on in Chapter 20.
The other income from activities is composed of the following elements:
| as of Dec. 31 in thousands of € | 2013 | 2014 |
|---|---|---|
| Sales revenue | - | - |
| Other earnings | 1,802 | 2,026 |
| Research tax credit | 1,367 | 1,524 |
| Earnings from ongoing activities | 1,802 | 2,026 |
The other income was primarily generated by the research tax credit and the grants associated with the pre-clinical research programs in partnership with BPI France.
The "Other income" totaled €230,769 in 2014, representing the sum of the internal costs sustained by the Group within the scope of the AML study, and re-invoiced to the company Orphan Europe to this end. The other external costs associated with this clinical trial were re-invoiced to Orphan Europe with no margin, and do not appear under income from activities, but rather deducted from the associated expenses.
At December 31, 2014, no cost of sales existed relative to the manufacture of batches of GRASPA®. Costs related to the manufacture of ERY-ASP within the context of pre-clinical studies or clinical trials are included in the fees for R&D and clinical studies.
In accordance with IAS 38, "Intangible Assets," research expenditures are accounted for in the period during which they are incurred.
An intangible asset internally generated relating to a development project is booked as an asset if, and only if, the following criteria are met:
The initial assessment of the development asset is the sum of expenditures incurred from the date on which the development project meets the criteria above. When these criteria are not met, development expenditures are accounted for in the period in which they are incurred.
According to IAS 38, "Intangible Assets," development costs must be accounted for as intangible assets when specific conditions relating to technical feasibility, marketability and profitability are met. Considering the strong uncertainty associated with the development projects performed by the Group, these conditions will only be met when the regulatory procedures necessary for placement of the products on the market have been finalized. Most of the expenditures being incurred before that stage, the development costs, are accounted for in the period in which they are incurred.
Over the periods presented, the total amount of expenditures for research and development increased sharply from €5,328 k in 2013 to €6,613 k in 2014. Research and development efforts have focused primarily on the TEDAC program, Phase II/III clinical studies on ALL in pediatric and adult patients, the launching of a Phase II study on ALL in the USA, as well as a Phase II study on solid tumors in France.
Research and development expenses during the periods presented are listed by type as follows:
| as of Dec. 31 in thousands of € | 2013 | 2014 |
|---|---|---|
| R&D costs | 2,503 | 2,244 |
| personnel costs | 1,332 | 1,351 |
| Clinical studies | 2,462 | 3,875 |
| personnel costs | 815 | 1,017 |
| Intellectual property costs | 363 | 493 |
| personnel costs | 98 | 75 |
| Total research costs | 5,328 | 6,613 |
R&D costs mainly include costs related to preclinical studies and fees for consultants and scientists. These costs fell considerably in 2014, due to a general refocusing of the department on the TEDAC program.
Costs related to clinical studies primarily include costs of raw materials related to the purchase of supplies necessary for the production of clinical batches of GRASPA®, the staff dedicated to ERYTECH's clinical studies, as well as the outsourcing of monitoring and other services.
This table shows the significant increase in the clinical trials item from 2013 to 2014, due to the high level of clinical activity as mentioned above.
Costs associated with intellectual property likewise experienced a significant increase from 2013 to 2014, due to an increase in subcontracting through Cabinet Lavoix for the protection of its intellectual property.
General expenses primarily include the costs of administrative staff, overhead costs for the head office, external expenses such as accounting, legal, human resources, marketing and communications expenses, as well as travel expenses (excluding scientific conferences).
They totaled €3,587 k and €4,361 k for the financial years ending December 31, 2013 and 2014.
| as of Dec. 31 in thousands of € | 2013 | 2014 |
|---|---|---|
| Overhead and general costs | 3,587 | 4,361 |
| personnel costs | 1,840 | 2,368 |
The Company recorded a significant increase in its structural costs and general expenses, notably associated with the development of its strategy in the USA, as well as the performance of its capital increase on Euronext in October 2014.
Share options were allocated to the directors, to certain employees, as well as to members of the board of directors in the form of Share Warrants ("BSA") or Founder's Warrants ("BSPCE") during the extraordinary general meeting of 05/21/2012. The exercise price for the warrants allocated is equal to the market price of the shares at the date of authorization to issue the warrants.
These warrants may only be effectively exercised where a triggering event occurs (such as a M&A or IPO). Since the Company has been listed on NYSE Euronext since May 6, 2013, the warrants may, in fact, be exercised at any time.
The BSAs and BSPCEs allocated in 2014 are acquired immediately, hence the accounting treatment representing their full market value posted as an expense for the financial year (no spreading out over an acquisition period).
On January 22, 2014, the Board of Directors moreover used the delegation granted by the mixed general shareholders' meeting of April 2, 2013, in its twenty-fifth resolution, to decide on a plan for the free allocation of 22,500 founder share subscription warrants (hereinafter entitled BSPCE2014) to the benefit of Erytech directors (12,000 warrants) and to a category of "employees with management status" not yet identified by name (10,500 warrants).
Concerning the directors and in accordance with IFRS 2, it was considered that the entirety of the 12,000 warrants were assigned on January 22, 2014. The fact that the directors can only subscribe to one third of these warrants each year constitutes a condition of service. In other words, these warrants form the object of a gradual 3-year acquisition period.
Moreover, the board of directors' meeting of December 4, 2014 transformed 3,000 BSPCE2014 into 3,000 BSA2014 for a Medical Director at the subsidiary ERYECH PHARMA INC., in accordance with Annex IV-BSA2014 Regulations, as recorded in the minutes. This allocation is conditional upon the recruitment of a person to this position. As this suspensive clause has not yet been lifted, these BSA2014 had no accounting effect on the 2014 financial year.
The net financial results showed a profit of €68 k for 2014, as compared to a loss of €1,100 k in 2013.
Net cost of debt includes interest charges on financial liabilities (cost of gross financial liabilities integrating financial costs, issue costs on financial liabilities) consisting of loans and other financial liabilities (including overdrafts and liabilities on finance leases), less income from cash and cash equivalents. Other financial income and expenses consist of other fees paid to banks for financial transactions, and the impact on the income from marketable securities.
The breakdown of the item is shown in the table below:
| as of Dec. 31 in thousands of € | 2013 | 2014 |
|---|---|---|
| Interest on leasing | (5) | (7) |
| Interest on bonds | (1,059) | |
| Financial charges | (56) | (43) |
| Net cost of debt | (1,120) | (50) |
| Earnings (losses) from disposal of VMP | 20 | 141 |
| Other Financial Income | 3 | 1 |
| Other Financial Charges | (3) | (23) |
| Other income & financial charges | 20 | 118 |
| Total Income (Loss) | (1,100) | 68 |
This table primarily shows that, for the periods presented:
Given the deficits over the past 3 financial years, the Company has not recorded corporate tax expenses, nor taxable income associated with activation of the loss that can be carried forward.
The loss per share issued (weighted average number of shares in circulation during the financial year) amounted respectively to 1.74 Euros for the financial year ending in 2013 (taking into account the division of the nominal value of shares decided in the general meeting of April 2, 2013) and 1.51 Euros for the financial year ending in 2014.
The Company has made the following tax add-backs to its earnings:
Net non-current assets amounted to €910 k at December 31, 2013 and €1,080 k at December 31, 2014 respectively.
Non-current assets include tangible and intangible assets (concessions, patents, licenses, software), non-current financial assets (deposits and sureties), and deferred taxes.
| as of Dec. 31 in thousands of € | 2013 | 2014 |
|---|---|---|
| NON-CURRENT ASSETS | ||
| intangible assets | 14 | 31 |
| tangible fixed assets | 813 | 967 |
| non-current financial assets | 83 | 82 |
| deferred tax assets | - | - |
| TOTAL NON-CURRENT ASSETS | 910 | 1,080 |
In 2014, there was an increase in tangible assets, primarily dedicated to the production site.
Moreover, non-current financial assets primarily consisting of deposits and sureties have remained relatively stable over the last two financial years.
Loss carry forwards were capitalized only up to the amount of deferred tax liabilities; the amounts capitalized were not significant.
Net current assets amounted to €17,039 k and €39,526 k in 2013 and 2014 respectively.
In 2014, the amount of net current assets increased significantly due to the fact that the capital increase strengthened the Group's cash flow, and due to the increase in the research tax credit as a result of the very significant increase in research activity.
| as of Dec. 31 in thousands of € | 2013 | 2014 |
|---|---|---|
| CURRENT ASSETS | ||
| Inventories | 138 | 198 |
| Clients & associated accounts | 87 | 105 |
| Other current assets | 1,701 | 2,235 |
| Research tax credit | 1,367 | 1,524 |
| tax receivables & other receivables | 204 | 494 |
| prepaid expenses | 101 | 217 |
| other grants receivable | 29 | - |
| Cash & cash equivalents | 15,113 | 36,988 |
| TOTAL CURRENT ASSETS | 17,039 | 39,526 |
Equity was mainly affected by:
This is essentially the non-current portion of lease commitments, repayable advances received and, to a lesser degree, pension commitments in accordance with IAS 19.
| as of Dec. 31 in thousands of € | 2 013 | 2 014 |
|---|---|---|
| NON-CURRENT LIABILITIES | ||
| Provisions, portion at greater than one year | 117 | 89 |
| Financial liabilities - Non-current portion | 731 | 436 |
| repayable advances | 511 | 292 |
| leases | 220 | 144 |
| Deferred tax liabilities | - | - |
| Other non-current liabilities | - | - |
| TOTAL NON-CURRENT LIABILITIES | 848 | 525 |
This balance sheet item primarily includes short-term liabilities relating to supplier debts, tax and social security debts (employees and social security entities), the non-current portion of sums related to repayable advances granted by OSEO (see point 7.9.1 of the annex, section 20.1) and, lastly, deferred income.
| as of Dec. 31 in thousands of € | 2013 | 2014 |
|---|---|---|
| CURRENT LIABILITIES | ||
| Provisions, portion at less than one year | - | - |
| Financial liabilities - Current portion | 281 | 334 |
| Trade payables & related accounts | 1,421 | 2,085 |
| Other current liabilities | 1,812 | 1,840 |
| tax & social security debts | 816 | 971 |
| deferred income | 649 | 368 |
| TOTAL CURRENT LIABILITIES | 3,514 | 4,258 |
Total current liabilities increased significantly from 2013 to 2014, essentially due to the increase in supplier debts.
Also refer to the notes accompanying the financial statements prepared according to the IFRS standards contained in Chapter 20 of the Reference Document. At December 31, 2014, the amount of cash and cash equivalents held by the Group amounted to €36,988 k, as compared to €15,113 k at December 31, 2013.
Cash and cash equivalents include liquid assets and current financial instruments held by the Group (exclusively money-market mutual funds and non-interest bearing short-term bank deposits). These liquid assets will serve to fund the Group's business activities, notably its expenses for research and development and clinical study programs.
Moreover, the Group also retains the potential use of the liquidity contract, for which the management envelope totaled €200 k at December 31, 2014.
Between its establishment in 2004 and December 31, 2014, the Company has received the following sources of funding:
The financial status is presented below:
| as of Dec. 31 in thousands of € | 2013 | 2014 |
|---|---|---|
| Cash and cash equivalents (a) | 15,113 | 36,988 |
| Current financial liabilities (b) | 281 | 334 |
| Non-current financial liabilities (b) | 731 | 436 |
| Financial debt (b+c) | 1,012 | 770 |
| Net financial debt (b) + (c) - (a) | (14,101) | (36,219) |
| Net financial position | 14,101 | 36,219 |
At December 31, 2014, the Company had received a total of 64 million Euros during successive rounds of financing and following the Company's initial public offering.
Financing by repayable advances
The Group did not undertake any bank loans in the 2 financial years presented. However, during 2011, 2012, and 2013, it received €878 k out of a total of €5,711 k granted as conditional advances forming the object of three contracts relating to repayable advances for innovation projects with Oséo/BPI France.
The Group received no new payments in the year 2014: only one contract is still ongoing (TEDAC) and thus in a phase of assistance payments, but the corresponding expenses allowing for new drawdowns on funds have not been reached. However, the Group is clearly within the anticipated schedule with regard to the scientific progress of the TEDAC project. The expenses incurred are lesser than planned in the initially submitted budget, as, in the end it was not necessary to go beyond that in order to achieve the initial steps of the project.
Financing by research tax credit
The Group benefits from the provisions of Articles 244 quater B and 49 septies F of the French General Tax Code pertaining to the research tax credit (French CIR). Since the Group has not initiated any R&D expenditures up to granting of the marketing approval for treatments identified through clinical developments, the CIR is fully accounted for under other operating income.
Cash consumption associated with operating activities for the financial years ending December 31, 2013 and 2014 amounted to a negative flow of €6,473 k and a negative flow of €7,239 k respectively.
The table below shows the net cash flows generated by Group activities over the past two financial years:
| as of Dec. 31 in thousands of € | 2013 | 2014 |
|---|---|---|
| Net income | (8,145) | (8,860) |
| Expenses (income) not affecting cash | - | |
| - Depreciation (write backs) and provisions of non-current assets | 287 | 277 |
| - Depreciation (write backs) and provisions of current assets | (107) | - |
| - Expenses (income) as share-based payments | 581 | 1,236 |
| - Investment grants written back to income | - | - |
| - Gains and losses on disposals | - | - |
| Operating subsidies | (1,661) | (1,795) |
| Cost of net financial debt | 1,120 | 50 |
| Income tax expense (current and deferred) | (40) | (20) |
| Internal financing capacity before financial results and tax | (7,965) | (9,113) |
| Taxes paid | - | - |
| Changes in working capital needs related to business activities | 1,492 | 1,874 |
| Net cash flow generated by business activities | (6,473) | (7,239) |
The working capital requirements for business activities increased significantly in 2014 due to the Group's increased activity in both pre-clinical and clinical research.
Cash consumption associated with investment activities for the financial years ended December 31, 2013 and 2014 amounted respectively to €289 k in 2013 and €420 k in 2014. The table below shows the net cash flows over the past two fiscal years:
| 2014 – Reference Document | ERYTECH | |
|---|---|---|
| as of Dec. 31 in thousands of € | 2013 | 2014 |
| Purchase of fixed assets | ||
| - Intangible assets | (9) | (26) |
| - Tangible fixed assets | (418) | (521) |
| - Investments | (3) | (0) |
| Disposal of fixed assets | ||
| - Intangible assets | - | - |
| - Tangible fixed assets | 142 | 126 |
| - Investments | - | 1 |
| Grants cashed | - | - |
| Effects of changes in perimeter | - | - |
| Net cash flow generated by investment operations | (289) | (420) |
Cash consumption associated with financing activities for the financial years ending December 31, 2013 and 2014 amounted respectively to a positive flow of €13,999 k in 2013 and a negative flow of €29,535 k in 2014.
The table below shows the net cash flows over the past two fiscal years:
| as of Dec. 31 in thousands of € | 2013 | 2014 |
|---|---|---|
| Increase in cash capital | 16,551 | 30,731 |
| Costs of cash capital increase | (2,014) | (1,558) |
| Loan issue | 193 | - |
| Costs of loan issue | - | - |
| Bond redemptions | (130) | (281) |
| Treasury shares | (600) | 651 |
| Interest paid | (2) | (7) |
| Net cash flow generated by financing operations | 13,999 | 29,535 |
The net flows associated with financing activities result from the introduction of the Company on the stock market in 2013, as well as the new round of fund raising on the market in 2014.
The structure of financing received by the Group between its establishment and December 31, 2014 is summarized in paragraph 10.1 above.
The main conditions of the repayable advances that had been granted to the Group at December 31, 2014 are described in the annex to the IFRS financial statements inserted under Chapter 20, Part I of the Prospectus.
The Group faces no restrictions on the availability of its capital.
The Group had a free cash flow of 33.5 million Euros at the end of March 2015, which will cover its needs for more than one year. Other than the anticipated 2015 payments relative to reimbursement of the 2014 CIR, which should represent an additional resource of €1.5 million, the Company has not received any new funding.
See Sections 6.5 and 6.7 of the Reference Document for clinical development.
See Sections 6.5 and 6.10 for Research & Development (R&D) activity.
See Section 5.7 of the IFRS annexes for the R&D costs.
Patents and other intellectual property rights are of the utmost importance in the Group's business sector and constitute the main barrier to entry for competitors. The Group also relies on industrial secrets, and confidentiality agreements are signed to protect its products, technologies, and manufacturing process. Without prejudice to the statements made in Section 4.2 (Risks related to intellectual property), the Group's intellectual property is not, to its knowledge at the date of this Reference Document, subject to any challenge by a third party.
At April 20, 2015, ERYTECH Pharma's patent portfolio consisted of 12 patent families held in its own name.
| Technology/products | Family | Title | Filing date | Status |
|---|---|---|---|---|
| Lysis/resealing process and device for incorporating an active ingredient in erythrocytes |
08/05/2004 | Issued in Japan Issued in Europe Issued in Australia Issued in China Issued in the United States Issued in Korea Issued in India Issued in Canada |
||
| Production process 2 |
Process for stabilizing suspensions of erythrocytes encapsulating the active ingredient, suspensions obtained |
05/07/2013 | PCT application filed National applications filed |
|
| ERY-ASP/GRASPA® | 3 | Medication for the treatment of pancreatic cancer |
12/24/2007 | Issued in Europe Issued in the United States Issued in Israel Issued in Australia Issued in Singapore National/regional phases for other territories |
| Test for predicting neutralization of asparaginase activity |
11/07/2008 | Issued in Europe Issued in the United States Issued in Australia Issued in Singapore National/regional phases for other territories |
| Technology/products | Family | Title | Filing date | Status |
|---|---|---|---|---|
| Medication for the | 03/21/2012 | National/regional phases initiated | ||
| treatment of acute | ||||
| myeloid leukemia | ||||
| Erythrocytes | 04/25/2005 | Issued in Europe, Japan, China, | ||
| containing | Canada, Korea, and Australia | |||
| Arginine | Review phase under way in the | |||
| deiminase | United States | |||
| TEDAC | 2 | Pharmaceutical | 02/12/2014 | PCT application filed |
| composition | National applications filed | |||
| comprising | ||||
| erythrocytes | ||||
| encapsulating an | ||||
| enzyme | ||||
| Composition to | 10/27/2009 | Issued in Australia | ||
| induce specific | Issued in Singapore | |||
| Immune Tolerance | National/regional phases for | |||
| other territories | ||||
| Immune modulation | 2 | Composition and therapeutic anti |
08/08/2007 | Issued in France Issued in China Issued in |
| platform | tumor vaccine | Australia | ||
| Issued in Singapore | ||||
| Issued in Israel | ||||
| National/regional phases for | ||||
| other territories | ||||
| Formulation and | 02/13/2008 | Issued in Europe | ||
| method for the | Issued in Israel | |||
| prevention and | Other national/regional phases | |||
| treatment of | ||||
| skeletal | ||||
| manifestation of Gaucher's disease |
||||
| Formulation and | 03/10/2008 | Issued in France | ||
| Other earnings | 3 | method for the | Issued in China | |
| prevention and | Issued in Australia | |||
| treatment of bone | Issued in Hong Kong | |||
| metastases and other bone diseases |
National/regional phases for other territories |
|||
| Composition of | 02/10/2013 | PCT application filed | ||
| erythrocytes | ||||
| encapsulating | ||||
| phenylalanine | ||||
| hydroxylase and | ||||
| therapeutic use | ||||
| thereof |
The Company's intellectual property strategy aims to secure and perpetuate its exclusive use by filing and obtaining patents on its production process, its products and/or their therapeutic uses as well as diagnostic tests or assay methods directly related to the use of its products.
Prior to each filing, a detailed analysis of the prior art is done in order to satisfy the patentability criteria while seeking a robust and broad scope, in connection with the proposed use.
So-called "main" patents are those that protect the Company's key products and technologies, while the others are considered "secondary."
The "main" patents and the current stage of their process are discussed below:
This is the Company's main patent covering its technology for the encapsulation of therapeutic molecules. The innovation developed by ERYTECH is based on taking into account key physiological parameters of erythrocytes to obtain a reproducible product. The initial application covers both the production process, the device for its implementation as well as all directly resulting products.
This patent was issued in France, Japan, Australia, South Korea, India, and China without any significant changes being made to the claims. In Europe, the process claims had to be separated from the device claims due to inventive unit reasons. An initial European patent was thus issued for the claims covering the production process and the directly resulting products. It currently covers more than 20 countries of the European Patent Organization. The claims covering the device for the implementation of the process were included in a divisional application currently under review by the European Patent Office.
In the United States, the process claims also had to be separated from the device claims. An initial American patent has been issued for claims covering the production process, in accordance with American law and the Patent Term Adjustment. The term of this patent has been extended by an additional five years, which means that it is protected in the United States until April 2030. The claims covering the device for the implementation of the process were included in a divisional application currently under review by the United States Patent Office.
In Canada, a patent has also been issued for claims covering the process.
This patent was licensed by the Company to Orphan Europe as part of an exclusive license and distribution contract (see also chapter 22 of the Reference Document) for the development and distribution of GRASPA® in the EU-27. This contract covers the indications of ALL and AML.
The European patent issued formed the object of opposition proceedings with the European Patent Office. Following withdrawal by the adverse claimant, the European Patent Office concluded the opposition proceedings and upheld the patent in force without any changes to the claims (See also Section 4.2(9) of the Reference Document). This decision was made known to ERYTECH on February 7, 2014.
This patent application covers an improvement in ERYTECH Pharma's encapsulation process to improve the stability of the erythrocytes suspensions obtained. The application was extended through the PCT process in addition to several direct national filings.
This patent covers erythrocytes encapsulating the enzyme arginine deiminase and any related pharmaceutical compositions. Arginine deiminase encapsulated in erythrocytes is an enzyme therapy developed under the TEDAC project. This enzyme is capable of breaking down arginine and thus acting on the metabolism of certain tumor cells by depriving them of a nutrient that is essential for them.
This patent was issued in Europe, Japan, China, Canada, Korea, and Australia without significant changes to the claims. The scope obtained is therefore broad, since product claims not restricted to a particular therapeutic use are included in the claims issued. This patent is under review in the United States.
This patent, filed within the context of the TEDAC project, formed the object of a priority filing in France on 02/10/2014 and has been extended internationally by the PCT and various direct national filings.
This patent covers the use of ERY-ASP for the treatment of pancreatic cancer. This patent has been issued in Europe, the United States, Israel, Australia, and Singapore, and is under review in other territories (Japan and Canada in particular).
This patent covers the use of GRASPA® for the treatment of acute myeloid leukemia. It was the subject of a priority application filed in the United States and it was extended by the PCT, plus some direct national filings.
This patent was licensed by the Company to Orphan Europe as part of an exclusive license and distribution contract (see also chapter 22 of the Reference Document) for the development and distribution of GRASPA® in the EU-27. This contract covers the particular indication of AML.
This patent application covers the technology to induce a specific immune tolerance developed by ERYTECH. The proposed scope is broad, because the application covers both a composition capable of inducing immune tolerance with respect to a therapeutic protein or peptide and a composition capable of inducing immune tolerance with respect to an autoantigen. This patent has been issued in Australia and Singapore; the application is in national/regional phases for other territories.
This patent covers a composition of erythrocytes incorporating a tumor antigen and/or adjuvant and its use as a therapeutic cancer vaccine. The proposed scope is broad because it is not limited by the nature of the antigen, the adjuvant, or their combination.
This patent has been issued in France, Australia, Israel, China, and Singapore, and is under review in other territories (Europe, Japan, USA, and Canada in particular).
* * *
The duration of a patent is 20 years from its filing date. However, in the pharmaceutical field, supplementary protection certificates may be granted in the major industrialized countries, generally extending protection for a non-renewable term of up to five years.
The Company has a policy of regularly filing patent applications to protect its technologies, products and production process.
The Company's strategy is, in fact, to systematically file priority applications in France and/or the United States. For other countries, the Company uses a procedure known as "Patent Cooperation Treaty" (PCT) that makes it possible to validly file for more than 100 countries: PCT filing is done one year after the priority filing. This PCT application is subsequently converted into national or regional filings to cover countries or groups of countries selected according to the desired geographic coverage. Some countries not accessible by PCT may be subject to direct national filings.
With regard to intellectual property, the objective of the Company's strategy is to strengthen its leading position in the use of red blood cells for therapeutic purposes. Its portfolio of filed patents covers 12 different patent families. Of these 12 patent families, 8 are already protected by at least one issued patent.
The inventions of the Company's employees are governed by employment contracts. Upon discovery of a patentable invention, each employee agrees to reveal and recognize that this invention or discovery, as part of its mission, is the property of ERYTECH, which holds all rights. A supplemental remuneration policy for each additional invention was implemented and a confidentiality clause is contained in the employment contracts. Inventions of non-salaried consultants are governed by specific contractual provisions, as the consultants are systematically bound by confidentiality clauses and generally include waiving all rights they might have to the inventions in which they may participate.
An internal procedure ensures the proper use of laboratory notebooks so that ERYTECH's intellectual property rights can be justified if necessary and in the event there is an invention. These laboratory notebooks are regularly signed and dated by a bailiff, then stored on the Company's premises.
Scientific and technological monitoring has also been implemented at ERYTECH in order to monitor:
The NIH (National Institutes of Health) has granted an exclusive license to ERYTECH on intellectual property covering a diagnostic method for predicting the efficacy of L-asparaginase in a patient (see also chapter 22 on major contracts in the Reference Document). This intellectual property based on developments of the National Cancer Institute includes an issued U.S. patent (U.S. 7,985,548) and a patent application under review at the USPTO.
The Company filed the following trademarks:
| TRADEMARK | DESIGNATED COUNTRIES | No. | DATE | |
|---|---|---|---|---|
| France | 03 3 264 900 | December 26, 2003 (Renewed) |
||
| European Community | 00 3 921 319 |
July 5, 2004 | ||
| Albania | ||||
| Bosnia and Herzegovina | ||||
| China | ||||
| Croatia | ||||
| Former Yugoslav Republic of Macedonia |
||||
| Liechtenstein | ||||
| Monaco | November 26, 2007 | |||
| Serbia | ||||
| Switzerland | ||||
| Australia | ||||
| United States | ||||
| Iceland | ||||
| 1 | ERYtech Pharma |
Japan | 947 762 | |
| Turkey | ||||
| Singapore | May 14, 2008 | |||
| Belarus | ||||
| Algeria | ||||
| Egypt | ||||
| Georgia | ||||
| Russia | ||||
| Ukraine | December 18, 2013 | |||
| Montenegro | ||||
| Norway | ||||
| Iran | ||||
| Republic of Korea | ||||
| Morocco | ||||
| Israel | 226 985 | February 3, 2010 | ||
| Canada | 1 387 023 | March 12, 2008 |
| TRADEMARK | DESIGNATED COUNTRIES | No. | DATE | |
|---|---|---|---|---|
| Kosovo | KS/M/2013/ 1211 |
December 17, 2013 | ||
| France | 39 11 751 | April 10, 2012 | ||
| European Union | ||||
| Australia | ||||
| South Korea | ||||
| United States | ||||
| Israel | ||||
| Iceland | June 20, 2012 | |||
| 2 | Monaco | 1127934 | ||
| Russia | ||||
| Singapore | ||||
| Switzerland | ||||
| Turkey | ||||
| Montenegro | ||||
| Norway | October 26, 2012 | |||
| France | 06 3 421 435 | April 6, 2006 | ||
| Albania | November 26, 2007 | |||
| Bosnia and Herzegovina | ||||
| China | ||||
| Croatia | ||||
| Former Yugoslav Republic of Macedonia |
||||
| Liechtenstein | ||||
| Monaco | ||||
| Serbia | ||||
| Switzerland | ||||
| Australia | ||||
| 3 | GRASPA | European Community | ||
| United States | 947 759 | |||
| Iceland | ||||
| Japan | ||||
| Republic of Korea | ||||
| Turkey | ||||
| Singapore | May 14, 2008 | |||
| Russia | June 20, 2012 | |||
| Montenegro | ||||
| Norway | October 26, 2012 | |||
| Belarus | ||||
| Egypt | December 18, 2013 | |||
| Georgia |
| TRADEMARK | DESIGNATED COUNTRIES | No. | DATE | |
|---|---|---|---|---|
| Morocco | ||||
| Ukraine | ||||
| Israel | 226992 226993 226994 |
February 3, 2010 | ||
| Canada | 1 387 024 | March 12, 2008 | ||
| Kosovo | KS/M/2013/ 1212 |
December 17, 2013 | ||
| 4 | ERYASP | France | 13 397 6584 |
January 23, 2013 |
| France | 06 3 402 981 | January 12, 2006 | ||
| 5 | Cleav'ERY System | European Community | 947760 | |
| Switzerland | November 26, 2007 | |||
| United States | ||||
| France | 06 3 402 941 | January 12, 2006 | ||
| 6 | Oxygen'ERY System | European Community | ||
| Switzerland | 947 761 | November 26, 2007 | ||
| United States | ||||
| France | 07 3 533 090 | October 22, 2007 | ||
| 7 | Vaccin'ERY System | European Community | ||
| Switzerland | 967450 | May 14, 2008 | ||
| U.S. | ||||
| France | 07 3 546 157 | December 21, 2007 | ||
| 8 | ERYCAPS | European Community | 972 047 | July 8, 2008 |
| Switzerland | ||||
| United States | ||||
| 9 | Deliv'ERY System | France | 06 3 402 968 | January 12, 2006 |
| 10 | EryDexone | France | 06 3 459 689 | October 26, 2006 |
| 11 | ERYTECH Pharma Deliv'ERY System |
France | 07 3 543 340 | December 10, 2007 |
| France | 11 3 819 125 |
March 23, 2011 | ||
| European Union | ||||
| United States | ||||
| China | ||||
| Switzerland | ||||
| 12 | ENHOXY | Australia | ||
| Iceland | 1,110,463 | 10 February 2012 | ||
| Japan | ||||
| Republic of Korea | ||||
| Turkey | ||||
| Israel | ||||
| Singapore |
| TRADEMARK | DESIGNATED COUNTRIES | No. | DATE | |
|---|---|---|---|---|
| Russia Monaco |
June 20, 2012 | |||
| 13 | KYTASPAR | France | 14 4 103 802 |
July 8, 2014 |
| France | 14 4 103 800 |
July 8, 2014 | ||
| European Union | 013 466 123 |
November 17, 2014 | ||
| 14 | ASPACELL | International: - Albania - Armenia - Azerbaijan - Belarus - Bosnia and Herzegovina - Iceland - Kazakhstan - Kyrgyzstan - Liechtenstein - Macedonia - Moldova - Montenegro - Norway - Uzbekistan - Russia - Serbia - Switzerland - Tajikistan - Turkmenistan - Turkey - Ukraine |
1 235 383 |
December 3, 2014 |
| Kosovo | KS/M/2014 109 |
November 19, 2014 |
None of the Company's trademarks above are subject to a third party trademark license, except under distribution agreements with the Teva Group and Orphan Europe, for the trademark GRASPA® (see also Chapter 22 "Major Contracts" of the Reference Document).
The Company has established global monitoring of its main trademarks, namely ERYTECH Pharma® and GRASPA®. .
The Company filed the following domain names:
| Domain Name | Expiry |
|---|---|
| erytech.com | July 20, 2017 |
| erytech.fr | May 5, 2017 |
| erytech.eu | September 30, 2015 |
| graspa.fr | September 23, 2015 |
| graspa.bio | September 23, 2015 |
| graspa.biz | September 23, 2015 |
| graspa.eu | September 23, 2015 |
| graspa.de | September 23, 2015 |
| graspa.uk | September 23, 2015 |
| graspa.info | September 23, 2015 |
See the year 2015 in Section 5.1 of the Reference Document.
It should be noted that, as of March 31, 2015, cash and cash equivalents totaled 33.5 million Euros, as compared to 37 million Euros at the end of 2014. This increase in expenses is the result of an acceleration of activities following the capital increase performed in October 2014 and activities associated with submission of the file to obtain marketing approval, notably related to the use of consultants.
During the first quarter of 2015, ERYTECH did not record any revenue from activities.
None.
The Company does not wish to report on forecasts of earnings because the assumptions on which these forecasts would be built would include elements that are too vague as of the preparation date of this document.
A summary description of the primary stipulations of the Company's bylaws and rules of procedure concerning specialized committees is found respectively in sections 21.4 and 16.5 of the Reference document.
Please note that the Company was in the form of a corporation with an Executive Board and a Board of Supervisors starting on September 29, 2005. In a general meeting on April 2, 2013, the Company modified its mode of governance to the current one, that being a corporation with a Board of Directors.
The Company has the following directors:
Rollebaan 85
| Last name, first name, age | Term of office | Position |
|---|---|---|
| Gil Beyen 53 years old |
st appointed: The General meeting of April 2, 1 2013 (he had been chairman of the Board of Supervisors since 2012) Term expires: The ordinary general meeting of 2016 voting on the financial statements for the |
Chairman of the Board of Directors and Chief Executive Officer |
| fiscal year ending December 31, 2015. | ||
| Yann Godfrin 43 years old |
st appointed: The general meeting of April 2, 1 2013 (he had been a member of the Executive Board since 2005, Chairman of the Executive board from 2005 to 2010, and Chief Executive Officer since 2010). |
Director and Chief Operating Officer |
| Term expires: The Ordinary General Meeting of 2016 voting on the financial statements for the fiscal year ending December 31, 2015. |
||
| Galenos SPRL, represented by Sven Andreasson, 62 years old 25 rue Jean-Baptiste Meunier, B 1050 Ixelles, Belgium |
st appointed: The Board of Directors' meeting 1 of April 2, 2013 (Chairman of the Supervisory Board from 2009 to 2011, Deputy Chairman of the Supervisory Board since 2011) Term expires: The general meeting of 2016 |
Director |
| Independent director(1) | voting on the financial statements for the fiscal year ending December 31, 2015. |
|
| Philippe Archinard 54 years old 47 rue Professeur Deperet, 69160 Tassin-la-Demi-Lune. |
st appointed: The General meeting of April 2, 1 2013 (member of the Board of Supervisors since 2005) Term expires: The general meeting of 2016 |
Director |
| Independent director (1) | voting on the financial statements for the fiscal year ending December 31, 2015. |
|
| Martine Ortin George 66 years old 9 Southern Hills Drive 08558 Skillman NJ United States of America Independent director (1) |
st appointed: AGM of June 17, 2014 1 Term expires: The general meeting of 2016 voting on the financial statements for the fiscal year ending December 31, 2015. |
Director |
| Hilde Windels 49 years old |
st appointed: AGM of June 17, 2014 1 |
Director |
| Last name, first name, age | Term of office | Position |
|---|---|---|
| 9860 MOORTSELE | Term expires: The general meeting of 2016 | |
| Belgium | voting on the financial statements for the fiscal year ending December 31, 2015. |
|
| Independent director (1) | ||
| Luc Dochez | st appointed: Co-optation, in the Board of 1 Directors' meeting of March 26, 2015, following the resignation of Pierre-Olivier GOINEAU |
Director |
| Term expires: The general meeting voting in 2016 on the financial statements for the year ending December 31, 2015 |
(1) Independent member as understood by the Middlenext Corporate Governance Code for small and mid-caps of December 2009.
The Chief Executive Officer, Gil Beyen, and the Delegated Managing Director, Yann Godfrin, have as their professional address the Company's head office , 60 avenue Rockefeller – 69008 Lyon.
The professional addresses of the other directors are those shown on the table above.
There are no family relationships between the persons listed above.
None of these people, over the course of the last five years:
During the financial year ended December 31, 2014, the following modifications took place concerning the Board of Directors:
Since the financial year ended December 31, 2014, the following modifications have taken place concerning the Board of Directors:
who resigned. The mandate of Luc DOCHEZ will be discontinued at the end of the ordinary general shareholders' meeting to be held in 2017 to rule on the financial statements for the year ended December 31, 2016.
The Chairman and Chief Executive Officer of the Company is Mr. Gil Beyen.
The Company has two Delegated Managing Directors, Yann Godfrin and Jérôme Bailly, the Head Pharmacist.
Together, these people form the Company's Senior Management.
The biographies of the officers are presented below in section 14.1.4.
The Company's current executive officers and directors have also acted as officers and/or occupied the following positions:
| Other duties performed as executive officers or other positions outside of the Company over the |
|||
|---|---|---|---|
| Other mandates and positions held by corporate officers during the financial year ended December 31, |
last five years and which have ceased as of this |
||
| Last name | 2014 | day | |
| Gil Beyen | Manager of Gil Beyen BVBA Manager of AXXIS V&C BVBA Director at Novadip SA Director at Waterleau NV Chairman of ERYTECH Pharma Inc. |
Director at BIO.be | |
| Pierre-Olivier Goineau1 | Chairman of France Biotech Manager of SCI du Grand Tambour (a real estate company) Secretary and Chief Financial Officer of ERYTECH Pharma, Inc. |
N/A | |
| Yann Godfrin | Member of the Board of Supervisors for the NODEA MEDICAL company |
N/A | |
| Galenos SPRL, represented by Sven Andréasson |
Director of Immunicum Director at Cellastra Chairman of Cantargia AB |
Chairman and CEO of Beta-Cell NV Chairman of Unibioscreen SA Board Member of TiGenix NV Chairman of XImmune AB |
|
| Kurma Partners SA2 |
represented by Vanessa Malier until July 17, 2014 |
Director of SafeOrthopaedics3 (as of 11/24/2014) Director at Umecrine Mood Director at Xeltis Director at Step Pharma |
Member of the Board of Directors of Theradiag Member of the Blink Board of Directors Observer at ABM Medical Member of the Board of Cellectis Member of the Board of Novagali Member of the Board of Vivacta Director of Vivalis Chairman of the Strategy Committee at PathoQuest Member of the Board of Directors of Prosensa Member of the Board of Directors of Adocia Member of the Board of Directors of Integragen Member of the Board of Directors of Indigix Member of the Board of Directors of Zealand Pharma Member of the Board of Directors of Auris |
| Other duties performed as executive officers or other positions outside of the Company over the |
|||
|---|---|---|---|
| Last name | Other mandates and positions held by corporate officers during the financial year ended December 31, 2014 |
last five years and which have ceased as of this day |
|
| Director at Hybrigenics Member of the Supervision Committee at PathoQuest Director and Chairman of the Supervision Committee at Key Neurosciences Member of the Board of Directors of AM Pharma Member of the Bioalliance Pharma board Member of the Strategy Committee at ABM Medical Director and Member of the Board of Supervisors of Meiogenics Member of the Genticel Board of Directors Director at STAT Diagnostica Member of the Board of directors of Domain Therapeutics |
|||
| represented by Alain Munoz until January 22, 2014 |
Director at AURIS3 , Director at GENTICEL3 , Director at HYBRIGENICS3 , Director at VALNEVA3 , Director at ZEALAND3 |
N/A | |
| Philippe Archinard | Director and Chief Executive Officer of Transgene3 TSGH's permanent representative on the board of ABL Inc Chief Executive Officer of TSGH Permanent representative on the Board of Directors of Synergie Lyon Cancer for Lyonbiopôle Director at Biomérieux3 Chairman of Lyonbiopôle Director of CPE Lyon, representative of FPUL |
Permanent representative to the Finovi Board of Directors for Lyonbiopôle |
| Last name | Other mandates and positions held by corporate officers during the financial year ended December 31, 2014 President of BioAster |
Other duties performed as executive officers or other positions outside of the Company over the last five years and which have ceased as of this day |
|---|---|---|
| Jérôme BAILLY | Manager of GELFRUIT SARL (France) | |
| Martine Ortin George | Vice President of Pfizer Inc.3 | - Vice President of Pfizer Inc. (United States) - Senior Vice President, GPC Biotech Inc. (United States) - Director, Cytomics Inc. (France) |
| Hilde WINDELS | - Director, VIB3 - Director, Flanders Bio - Director and Chief Operating Officer at BioCartis |
- Director, MDX Health, - Administrative and Financial Director, Pronota - Administrative and Financial Director, Seps Pharma |
| Luc DOCHEZ | Managing Director Primix Bioventures BVBA Executive Director Tusk Therapeutics NV |
Managing Director/Business Director Prosensa Holding NV Director Ovizio SA Director Arcarios BV |
Pierre-Olivier GOINEAU resigned from his positions at ERYTECH Pharma on January 11, 2015. KURMA PARTNERS SA resigned from its positions at ERYTECH Pharma on July 17, 2014. The resignation of KURMA PARTNERS S.A. was acknowledged by the Board of Directors on August 29, 2014. Companies listed on a regulated market
The experience of each of the Company's executive officers and directors is described below.
Gil was the Co-founder and Chief Executive Officer (CEO) of TiGenix (NYSE Euronext: TIG BB) for 12 years. Before creating TiGenix, he had directed the Life Sciences division at Arthur D. Little in Brussels. He holds a masters in bioengineering from the University of Louvain (Belgium) and an MBA from the University of Chicago (USA).
Before co-founding the company, Yann was the R&D director at Hemoxymed Europe. He was also an industrial development consultant for BioAlliance Pharma and Hemosystem. Yann holds a Doctor in Life and Health Sciences from the University of Nantes, a Degree in Biomedical Engineering from the Université de Technologie de Compiegne, and a Master's Degree in Clinical Development of Health Products from the University of Lyon, France. He is the inventor of numerous patents and the co-author of numerous scientific publications. He is a member of several scientific societies.
Before joining the company in 2007, Jérôme was the Director of QA/Production at Skyepharma and Laboratoire Aguettant. Jérôme holds a Doctor in Pharmacy and a Degree in Chemical Engineering, specializing in Biopharmaceutical Engineering and Cellular Production from École Polytechnique de Montréal.
Sven is the Director of Business Affairs at Novavax (United States) and former Chairman and Chief Executive Officer of Isconova AB (Uppsalam SuèdeBeta-Cell NV (Brussels), Active Biotech AB (Lund, Sweden), and several companies in the Pharmacia group. He has much experience in international biotechnology companies and in the pharmaceutical industry.
Sven holds a Bachelor of Science and Business Administration and Finance from the Stockholm School of Economics and Business Administration.
Philippe was appointed General Manager of Transgene on December 7, 2004, after spending 15 years with Biomérieux in various positions including directing the American subsidiary. Philippe has been CEO of the Innogenetics company since March 2000. He is a chemical engineer and holds a PhD in biochemistry from the University of Lyon completed by the Harvard Business School's Program of Management PMD.
A doctor of medicine, Martine George has a broad experience in the United States in clinical research, medical affairs, and regulatory matters, acquired within large and small companies specialized in oncology. Until recently, Dr. George was Vice President in charge of Global Medical Affairs for Oncology at Pfizer in New York. Previously, she held the positions of Medical Director at GPC Biotech at Princeton and Head of the Oncology Department at Johnson & Johnson in New Jersey. Martine George is a qualified gynecologist and oncologist, trained in France and in Montreal. She began her career as the Department Head at the Institut Gustave Roussy in France, and was invited to the Memorial Sloan Kettering Cancer Center of New York as a professor.
Hilde Windels has more than 20 years of experience in corporate financing, capital markets, and strategic initiatives. She is the Managing Director and Director at Biocartis, a molecular diagnosis and immunodiagnostic solutions company based in Belgium and in Switzerland. Hilde Windels was previously the Financial Director at Devgen (Euronext: DEVG) from 1999 to the end of 2008, and member of the Devgen Board of Directors from 2001 to the end of 2008. Between the start of 2009 and mid-2011, she worked as an independent financial director for various private companies specialized in biotechnologies, and sat on the board of directors of MDX Health (Euronext: MDXH) from June 2010 to the end of August 2011. Previously, she was a corporate banking services manager at ING for a region of Belgium. She received her degree in economics from the Université de Louvain (Belgium).
Luc Dochez was Chief Business Officer and Senior Vice-President of Business Development at the Netherlands company Prosensa (NASDAQ: RNA) until its recent acquisition by Biomarin. In this position, he played a key role in establishing a partnership with GSK valued at more than €500 M; he was likewise actively involved in the successful introduction of the company on Nasdaq and managed acquisition of the company by Biomarin for an amount of \$860 M. Before Prosensa, Luc was Vice President of Business Development at TiGenix (Euronext: TIG), Director Business Development at Methexis Genomics, and a consultant at Arthur D. Little.
Related agreements are described in Sections 16.2 and 19.2 of the Reference Document.
To the company's knowledge, there are no current or potential conflicts of interest between the duties, for the Company, and the private interests and/or duties of persons comprising the administrative, management, and senior management bodies, as referenced in section 14.1 "Officers and directors" supra.
In accordance with the law of July 3, 2008, this information is established with reference to the corporate governance code for small and medium-sized companies, as published in December 2009 by MiddleNext. All the tables (from 1 to 10) of the "AMF Guidelines - Guide to preparing reference documents" are presented below.
The positions held at this date by the below-indicated persons are outlined in detail in Chapter 14 - Administrative, Management, and Supervisory Bodies of this Reference Document.
The changes in remunerations paid are notably related to:
| Summary table of compensation and BSPCE (founder subscription warrants) allocated to each executive corporate officer | ||||
|---|---|---|---|---|
| 2014 Financial Year | 2013 Financial Year | |||
| Gil Beyen – Chairman & CEO | ||||
| Remuneration due in relation to the fiscal year (details in table 2) | €372,268 | €342,700 | ||
| Valuation of options allocated during the fiscal year (details in table 4) |
€513,960 | €239,811 | ||
| Valuation of performance shares allocated during the fiscal year (details in table 6) |
||||
| TOTAL | €886,228 | €582,511 | ||
| Pierre-Olivier GOINEAU – Deputy Chairman & Delegated Managing Director |
||||
| Remuneration due in relation to the fiscal year (details in table 2) | €275,422 | €243,507 | ||
| Valuation of options allocated during the fiscal year (details in table 4) |
€220,482 | €107,089 | ||
| Valuation of performance shares allocated during the fiscal year (details in table 6) |
||||
| TOTAL | €495,904 | €350,596 | ||
| Yann GODFRIN – Delegated Managing Director | ||||
| Remuneration due in relation to the fiscal year (details in table 2) | €275,268 | €243,610 |
| Valuation of options allocated during the fiscal year (details in table 4) |
€234,127 | €107,089 |
|---|---|---|
| Valuation of performance shares allocated during the fiscal year (details in table 6) |
||
| TOTAL | €509,395 | €350,699 |
| Jérôme BAILLY – Delegated Managing Director | ||
| Remuneration due in relation to the fiscal year (details in table 2) | €70,085 | €62,816 |
| Valuation of options allocated during the fiscal year (details in table 4) |
€39,166 | €21,929 |
| Valuation of performance shares allocated during the fiscal year (details in table 6) |
||
| TOTAL | €109,251 | €84,745 |
Note: the remunerations owing to Gil Beyen in the 2013 financial year are calculated pro rata temporis on a base annual salary of €342,700.
| Summary table of the compensation package for each executive corporate officer: | ||||||
|---|---|---|---|---|---|---|
| 2014 Financial Year | 2013 Financial Year | |||||
| Gil Beyen | Amounts due | Amounts paid | Amounts paid | |||
| Fixed remuneration (1) | €244,000 | €244,000 | €251,500 | €251,200 | ||
| Variable remuneration (1) (2) | €125,600 | €91,500 | €91,500 | |||
| Special remuneration | ||||||
| Attendance fees | ||||||
| Benefits in kind (3) | €2,668 | €2,668 | ||||
| TOTAL | €372,268 | €338,168 | €342,700 | €251,200 | ||
| 2014 Financial Year | 2013 Financial Year | |||||
| Pierre-Olivier Goineau | Amounts due | Amounts paid | Amounts due Amounts paid |
|||
| Fixed remuneration (1) | €175,783 | €175,783 | €165,771 | €165,771 | ||
| Variable remuneration (1) (2) | €90,000 | €67,500 | €67,500 | €75,000 | ||
| Special remuneration | ||||||
| Attendance fees | ||||||
| Benefits in kind (3) | €9,639 | €9,639 | €10,236 | €10,236 | ||
| TOTAL | €275,422 | €252,922 | €243,507 | €251,007 | ||
| 2014 Financial Year | 2013 Financial Year | |||||
| Yann Godfrin | Amounts due | Amounts paid | Amounts due | Amounts paid |
| Variable remuneration (1) (2) | €90,000 | €67,500 | €67,500 | €75,000 | |
|---|---|---|---|---|---|
| Special remuneration | |||||
| Attendance fees | |||||
| Benefits in kind (3) | €9,718 | €9,718 | €11,114 | €11,114 | |
| TOTAL | €275,268 | €252,768 | €243,610 | €251,110 | |
| 2014 Financial Year | 2013 Financial Year | ||||
| Jérôme Bailly | |||||
| Amounts due | Amounts paid | Amounts due | Amounts paid | ||
| Fixed remuneration (1) | €60,755 | €60,755 | €55,293 | €55,293 | |
| Variable remuneration (1) (2) | €6,000 | €5,172 | €5,172 | €5,000 | |
| Special remuneration | |||||
| Attendance fees | |||||
| Benefits in kind (4) | €3,331 | €3,331 | €2,351 | €2,351 |
Note: the fixed remuneration owing to Gil Beyen in the 2013 financial year is calculated pro rata temporis on a base annual salary of €251,520.
(1) Components of gross remuneration before taxes
The variable compensation is for objective-based bonuses The goals correspond to the Company's strategic goals. This strategy consists, in the medium term, of the success of the GRASPA®/ERY-ASP project. The goals are thus directly associated with:
| Table of attendance fees and other compensation received by non-executive corporate officers | ||||
|---|---|---|---|---|
| Non-executive corporate officers | Amounts paid during the 2014 financial year |
Amounts paid during the 2013 financial year |
||
| Sven Andreasson | ||||
| Attendance fees | €1,000 | €12,958 | ||
| Other remuneration (1) (2) | €5,250 | |||
| GALENOS SPRl | ||||
| Attendance fees | €19,476 | |||
| Other compensation (1) | ||||
| Philippe ARCHINARD | ||||
| Attendance fees | €20,476 | €13,083 |
| Other remuneration | ||
|---|---|---|
| Martine ORTIN GEORGE | ||
| Attendance fees | €10,024 | |
| Other compensation (1) | ||
| Hilde WINDELS | ||
| Attendance fees | €9,024 | |
| Other compensation (1) | ||
| Alain MAIORE | ||
| Attendance fees | €7,875 | |
| Other compensation (1) | ||
| Gil BEYEN | ||
| Attendance fees | ||
| Other compensation (1) | €87,500 | |
| Marc BEER | ||
| Attendance fees | €8,333 | |
| Other compensation (1) | ||
| TOTAL | €60,000 | €134,999 |
(1) The amounts corresponding to fees and out-of-pocket expenses, paid by the Company.
(2) Amounts paid to GALENOS SPR, a company controlled by Sven Andreasson
Share subscription or share call options and other financial instruments giving access to the capital, allocated during the financial year to each executive corporate officer by the issuer and by any group company
| Name of executive corporate officer |
Plan no. and date Type of option (call or subscription) |
Valuation of options according to the method adopted for IFRS accounts |
Number of options allocated during the fiscal year |
Exercise price for each new subscribed share* |
Period of exercise | |
|---|---|---|---|---|---|---|
| Gil Beyen | BSPCE2012 05/21/2012 |
Subscription | Fair value (Black & Scholes) IFRS 7 |
5,631 | €7.362 | Lapses on 05/20/2020 |
| Pierre-Olivier Goineau |
BSPCE2012 05/21/2012 |
Subscription | Fair value (Black & Scholes) IFRS 7 |
2,515 | €7.362 | Lapses on 05/20/2020 |
| Yann Godfrin | BSPCE2012 05/21/2012 |
Subscription | Fair value (Black & Scholes) IFRS 7 |
2,515 | €7.362 | Lapses on 05/20/2020 |
| Jérôme Bailly | BSPCE2012 05/21/2012 |
Subscription | Fair value (Black & Scholes) IFRS 7 |
515 in 2014 |
€7.362 | Lapses on 05/20/2020 |
* Pursuant to the decision to divide by 10:1 at the nominal share value (decision of the general shareholders' meeting of April 2, 2013), the terms and conditions of the warrants were modified to take this modification into account. As such, the exercise price, previously €73.62, is now set at €7,362.
| Share subscription or call options exercised during the fiscal year by each executive corporate officer |
||||
|---|---|---|---|---|
| Name of executive corporate officer |
Plan no. and date |
Number of options exercised during the fiscal year |
Exercise price | |
| n/a | n/a | n/a | n/a | |
| TOTAL | n/a | n/a | n/a |
| Performance shares allocated to each corporate officer | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Performance shares allocated by the general shareholders' meeting during the fiscal year to each corporate officer by the issuer and by any group company (list of names) |
Plan no. and date |
Number of shares allocated during the fiscal year |
Valuation of shares according to the method adopted for the consolidated financial statements |
Date of acquisition Date of availability | Performance conditions |
||||
| n/a | n/a | n/a | n/a | n/a | n/a | n/a | |||
| TOTAL | n/a | n/a | n/a | n/a | n/a | n/a |
| Performance shares that became available for each corporate officer |
Plan no. and date | Number of shares that became available during the fiscal year |
Conditions for acquisition |
|---|---|---|---|
| n/a | n/a | n/a | n/a |
| TOTAL | n/a | n/a | n/a |
| HISTORICAL ALLOCATION OF SHARE SUBSCRIPTION OR CALL OPTIONS | ||||
|---|---|---|---|---|
| INFORMATION ON THE SUBSCRIPTION OR CALL OPTIONS | ||||
| Date of general shareholders' meeting | (1) General BSPCE2012 Meeting of 05/21/2012 |
BSPCE2014 General Meeting of 04/02/2013 |
BSA2012 General Meeting of 05/21/2012 |
BSA2014 General Meeting of 04/02/2013 |
| Date of board of directors' meeting or executive board meeting, where applicable |
Executive Board meeting of 05/31/2012 Board of Director's meeting of 07/18/2013 Board of Directors' meeting of 07/17/2014 |
Board of Directors' meeting of 01/22/2014 |
Executive Board meeting of 05/31/2012 Board of Director's meeting of 07/18/2013 Board of Directors' meeting of 07/17/2014 Board of Directors' meeting of 04/29/2015 |
Board of Directors' meeting of 01/22/2014(4) Board of Directors' meeting of 12/04/2014(4) |
| Total number of shares that can be subscribed or called up(2) , the number of which can be subscribed or called up by: |
337,870 shares can be subscribed, representing a total of 33,787 warrants |
195,000 shares can be subscribed, representing a total of 19,500 warrants |
112,630 shares can be subscribed, representing a total of 11,263 warrants(5) |
30,000 shares can be subscribed, representing a total of 3,000 warrants |
| The corporate officers | 277,370 shares 27,737 warrants |
70,000 shares 7,000 warrants |
||
| Gil BEYEN | 112,630 shares 11,263 warrants |
60,000 shares 6,000 warrants |
n/a | n/a |
| Pierre-Olivier GOINEAU | 75,080 shares 7,508 warrants |
10,000 shares 1,000 warrants |
n/a | n/a |
| Yann GODFRIN | 75,080 shares 7,508 warrants |
30,000 shares 3,000 warrants |
n/a | n/a |
| Jérôme BAILLY | 14,580 shares 1,458 warrants |
Undetermined(5) | n/a | n/a |
| GALENOS | n/a | n/a | Undetermined(5) | n/a |
| Philippe ARCHINARD | n/a | n/a | Undetermined(5) | n/a |
| Hilde WINDELS | n/a | n/a | Undetermined(5) | n/a |
| Martine GEORGE | n/a | n/a | Undetermined(5) | n/a |
| Luc DOCHEZ | n/a | n/a | Undetermined(5) | n/a |
| Starting point for exercise of options | 05/06/2013 (day of listing of the Company's shares for trading on a regulated market) and/or immediately after subscription |
Immeidately after subscription |
05/06/2013 (day of listing of the Company's shares for trading on a regulated market) and/or immediately after subscription |
Immediately after subscription |
| Expiry date | 05/20/2020 | 01/22/2024 | 05/20/2020 | 01/22/2024 |
| Subscription or call price | €7.362 per share €73.62 per warrant |
€12.25 per share €122.50 per warrant |
€7.362 per share €73.62 per warrant |
€12.25 per share €122.50 per warrant |
| Methods of exercise (where the plan includes multiple tranches) |
1 warrant = 10 shares Bearers must exercise a minimum of 50 warrants per exercise or the entirety where they hold less than this amount. Each bearer is limited to excercising warrants four times per year. |
1 warrant = 10 shares Bearers must exercise a minimum of 50 warrants per exercise or the entirety where they hold less than this amount. Each bearer is limited to excercising warrants four times per year. |
1 warrant = 10 shares Bearers must exercise a minimum of 50 warrants per exercise or the entirety where they hold less than this amount. Each bearer is limited to excercising warrants four times per year. |
1 warrant = 10 shares Bearers must exercise a minimum of 50 warrants per exercise or the entirety where they hold less than this amount. Each bearer is limited to excercising warrants four times per year. |
| Number of shares subscribed at 04/20/2015 |
73,750 shares subscribed, i.e., 7,375 warrants |
0 | 50,250 shares subscribed, i.e., 5,025 warrants |
0 |
| Cumulative number of share subscription or call options canceled or lapsed |
0 | 3,000(4) | 0 | 0 |
| Share subscription or call options remaining at year end |
264,120 shares 26,412 warrants |
195,000 shares 19,500 warrants |
62,380 shares 6,238 warrants |
30,000 shares 3,000 warrants |
Page | 135 of 302
(1) The General Meeting of May 21, 2012 cancelled the BSPCECadre2006, which had been partially subscribed. The BSPCECadre2006 were replaced by the BSPCE2012.
(2) Whether or not the related options had been exercised
(3) At December 31, 2014
(4) 3,000 BSPCE2014 of the 22,500 BSPCE2014 issued by the Board of Directors' meeting of January 22, 2014 were transformed into 3,000 BSA2014 by decision of the Board of Directors' meeting of December 4, 2014.
(5) Undetermined means that the total number of shares that could be subscribed by persons is undetermined, but that these people have already subscribed to options.
| SHARE SUBSCRIPTION OR CALL OPTIONS AND Founder's share warrants (BSPCEs) GRANTED TO THE TOP TEN BENEFICIARY NON-CORPORATE-OFFICER EMPLOYEES, AND OPTIONS EXERCISED BY THESE PERSONS |
Total number of options allocated/ of shares subscribed or called up |
Average weighted price |
Plan no. 1 (1) |
Plan no. 2 (2) |
|---|---|---|---|---|
| Options granted, during the fiscal year, by the issuer and any company included within the option assignment perimeter, to the ten employees of the issuer and of any company included within this perimeter, for whom the number of options thus granted is the highest (global information) |
2,515 | n/a | 2,515 | 0 |
| Options held in relation to the issuer and the aforesaid companies, exercised, during the fiscal year, by the ten employees of the issuer and these companies, for whom the number of options thus called up or subscribed is the highest (global information) |
0 | n/a | 0 | 0 |
(1) Founder's share warrants2012
(2) Founder's share warrants (BSPCE)2014
| HISTORICAL ALLOCATION OF FREE SHARES | ||||||||
|---|---|---|---|---|---|---|---|---|
| INFORMATION ON FREE SHARES ALLOCATED | ||||||||
| Date of general shareholders' meeting | Plan no. 1 | Plan no. 2 | Plan no. 3 | Etc. | ||||
| Date of board of directors' meeting or executive board meeting, where applicable |
n/a | n/a | n/a | n/a | ||||
| Total number of shares allocated free of charge, of which the number assigned to: |
n/a | n/a | n/a | n/a | ||||
| The corporate officers | ||||||||
| Gil Beyen | n/a | n/a | n/a | n/a | ||||
| Pierre-Olivier Goineau | n/a | n/a | n/a | n/a | ||||
| Yann Godfrin | n/a | n/a | n/a | n/a | ||||
| Date of share acquisition | n/a | n/a | n/a | n/a | ||||
| End date of retention period | n/a | n/a | n/a | n/a | ||||
| Subscription or call price | n/a | n/a | n/a | n/a | ||||
| Number of shares subscribed at [] (most recent date) | n/a | n/a | n/a | n/a | ||||
| Cumulative number of shares canceled or lapsed | n/a | n/a | n/a | n/a | ||||
| Shares allocated free of charge remaining at year end | n/a | n/a | n/a | n/a |
| Conditions for remuneration and other benefits granted to the executive corporate officers only | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Executive corporate officers |
Employment contract |
Supplementary pension plan |
Indemnities or benefits due or likely to be due because of discontinuation or change of position |
Indemnities pertaining to a non-competition clause |
||||||||
| Yes (1) | Not | Yes (2) | Not | Yes (3) | Not | Yes (4) | Not | |||||
| Gil Beyen Chairman and Chief Executive Officer |
X | X | X | X | ||||||||
| Yann Godfrin Chief Operating Officer |
X | X | X | X | ||||||||
| Jérôme Bailly Chief Operating Officer |
X | X | X | X |
(1) Jérôme Bailly benefited from an employment contract from November 15, 2011 until his initial appointment on December 21, 2012 as a corporate officer. He was considered, by the Board of Supervisors, then by the Board of Directors, to have continued this employment contract after the aforesaid appointments, as this contract covers separate missions under his term as Head Pharmacist, missions pursuant to which he is subject to a subordination relationship.
(2) Subscription to the supplementary pension plan with fixed contributions, within the scope of a collective pension policy stipulated by the Company with AXA. Investment in individual accounts paid for by the 5% pension contribution by employees, gross subject to deductions of 2.50% of costs, on the "Horizon" mutual funds managed by AXA.
(3) Indemnity in an amount equal to one year of pay (see also section 16.4.10 for performance conditions) + GSC policy for Mr. Godfrin only
(4) Indemnity equal to 1/3 of the average monthly wage received during the last three months of presence at the company ERYTECH Pharma over 18 months.
In addition, the executive corporate officers likewise benefit from a supplementary plan for health care and social security expenses (see also Sections 16.2and 19.2 of the Reference Document) and profit-sharing (see also Section 17.4 of the Reference Document).
In its corporate financial statement, the Company has not allocated monies to the payment of pensions, retirement, and other benefits to non-executive corporate officers and/or executive corporate officers who do not moreover benefit (or who have not benefited) from a severance or hiring bonus.
The BSAs (share subscription warrants) and BSCPCEs (founder subscription warrants) granted to nonexecutive or executive corporate officers are outlined in a precise list in Chapter 17.2 of the Reference Document.
During the financial year ended December 31, 2014, the managers and persons indicated in Article L. 621-18- 2 of the French Monetary and Financial Code performed the following operations on Company securities:
Since December 31, 2014, the managers and persons indicated in Article L. 621-18-2 of the Monetary and Financial Code performed the following operations on Company securities:
The Company possesses a Board of Directors, a Management Committee, a Remuneration Committee, an Audit Committee and a Scientific Board.
Refer to section 14.1.1 "Remuneration of the Board of Directors" in this Reference Document.
Refer to section 14.1.2 of this Reference Document.
The Company complies with all provisions of the corporate governance code for small and mid-caps published by Middlenext in 2009 and validated as a coat of reference by the Autorité des Marchés Financiers (the French financial markets regulator).
For the financial year ending December 31, 2014, in addition to the information provided in the present section, the status of application of the guidelines in the Middlenext Code is as follows:
| Guidelines from the MiddleNext Code | Adopted |
|---|---|
| I. Executive power | |
| R 1: Total employment contract and term as officer | X |
| R 2: Definition and transparency in remuneration for executive corporate officers | X |
| R 3: Severance pay | X |
| R 4: Supplemental pension plans | X |
| R 5: Stock options and awards of free shares | X |
| II. The power of "oversight" | |
| R 6: Implementation of rules of procedure for the board | X |
| R 7: Professional ethics for members of the board | X |
| R 8: Composition of the board – Presence of independent members on the board |
X |
| R 9: Selection of board members | X |
| R 10: Term for which board members are elected | X |
| R 11: Notice to board members | X |
| R 12: Implementation of committees | X |
| R 13: Meetings of the Board and of committees | X |
| R 14: Remuneration for directors | X |
| R 15: Implementation of an evaluation of work by the Board | X |
The Company believes that its organization and the procedures implemented (including, namely, the Board of Directors' Rules of Procedure, regularly revised by the directors in order to ensure its relevance and compliance with the Middlenext Code) make it possible to comply with all of the recommendations in the Code.
During its meeting on May 6 ,2013, the Board of Directors adopted rules of procedure which were last updated on April 25, 2014. These rules of procedure may be consulted on the Company's website. They specify the role and composition of the Board, the principles of conduct, and the obligations of the members of the Board of Directors towards the Company and the procedures for the operation of the Board of Directors and the committees, the rules for determining the remuneration of their members. Each member of the Board of Directors agrees to devote the necessary time and attention to his/her duties. He/she shall inform the Board of any situations he/she may find himself in which present a conflict of interest. Furthermore, the rules of procedure incorporate current regulations pertaining to the dissemination and use of privileged information and specify that the members must abstain from engaging in transactions involving the Company's shares when they possess privileged information. Each member of the Board of Directors is required to inform the Company and the AMF of any transactions involving the Company's shares which he/she performs whether directly or indirectly.
After having examined the provisions of the code of corporate governance for listed companies developed by MiddleNext in December 2009, particularly the elements presented in the heading "points of vigilance," the Board of Directors, in its meeting on May 6, 2013, decided to adopt rules of procedure in which it is stated that the Company shall comply with the MiddleNext Code as a corporate code of governance for the Company.
The MiddleNext Code may be viewed at the following website: http://www.middlenext.com/IMG/pdf/Code\_de\_gouvernance\_site.pdf.
The guidelines in the MiddleNext Code have since been applied by the Company as is specified below. It should be noted that the recommendation relative to stock options and the allocation of free shares is not applicable by the Company, as no stock options or free shares have been allocated by the Company to its corporate officers.
During the financial year ended December 31, 2014, the following modifications took place concerning the Board of Directors:
By virtue of legal provisions and those in the bylaws, the Board of directors is composed of no fewer than three directors and no more than eighteen. Directors are appointed, reappointed to their position, or removed by the Company's ordinary general meeting. Their term of office, in accordance with article 17 of the bylaws, is three years.
At December 31, 2014, the Board of Directors was composed of seven members, i.e.:
| Last name | Date of appointment or co-optation |
Expiration of the term on |
|---|---|---|
| Mr. Gil Beyen (Chairman and Chief Executive Officer) |
05/06/2013 | 2016 |
| Mr. Pierre-Olivier Goineau (Vice President and Chief Operating Officer) |
05/06/2013 | 2016 |
| Mr. Yann Godfrin (Chief Operating Officer) | 05/06/2013 | 2016 |
| GALENOS SPRL, represented by Sven ANDREASSON |
01/22/2014 | 2016 |
| Mr. Philippe Archinard | 05/06/2013 | 2016 |
| Martine ORTIN GEORGE | 06/17/2014 | 2017 |
| Hilde WINDELS | 09/17/2014 | 2017 |
We note that the Board of Directors, in its meeting of January 11, 2015, acknowledged the resignation of Pierre-Olivier GOINEAU from his positions as Delegated Managing Director, Deputy Chairman, and Director. These directors were appointed to the Board of Directors because of their knowledge of the Company's activities, their technical and general skills and abilities, as well as their aptitude to fulfill the directors' duties required within that Board.
The Company is aware of the provisions provided in the act of January 27, 2011 pertaining to balanced representation of men and women on boards of directors. At December 31, 2014, the Company's Board of Directors was composed of five men and two women, i.e., a proportion of women greater than 20% of the members of the board of directors, as required by this law at the end of the first ordinary general shareholders' meeting following January 1st, 2014. The law of January 27, 2011 furthermore requires that the proportion of men and women be at least equal to 40% at the end of the first ordinary general shareholders' meeting following January 1st, 2017 or, where the board of directors is not composed of more than eight members, that the difference between the number of members of each gender not be greater than two.
In conformity with the MiddleNext Code, the Board of Directors includes several independent directors, the company GALENOS, Philippe ARCHINARD, Martine Ortin George, and Hilde Windels, who meet the independence criteria defined by the MiddleNext Code.
The criteria specified by the Middlenext Code make it possible to show that the members of the Board are independent, as characterized by the lack of a significant financial, contractual, or familial relationship capable of altering independent judgment, namely:
The list of Company directors, including the positions held in other companies, is shown in paragraph 14.1.2 of the Reference document.
During the Company's mixed general shareholders' meeting of June 17, 2014, the total annual amount of attendance fees allocated to directors is set at 60,000 Euros, and is applicable to the current year.
The Board of Directors' meeting of January 11, 2005 decided on the distribution of attendance fees in function of the regularity of the directors' attendance and of the time that they dedicated to their position during the financial year ended 2014, in conformity with the recommendations of the Compensation Committee, which met on the same day.
Article 19 of the bylaws provides that the Board shall meet as often as required for the interest of the Company.
During the financial year ended December 31, 2014,
– the Board of Directors met twelve times, on January 22, 2014, April 16, 2014, April 25, 2014, May 5, 2014, May 19, 2014, June 9, 2014, July 17, 2014, August 29, 2014, September 16, 2014, September 22, 2014, September 29, 2014, and December 4, 2014.
The number of Board of Directors' meetings held during the financial year ended December 31, 2014 complies with the recommendations of the MiddleNext Code, which requires a minimum of four annual meetings.
A list of agenda items addressed in meetings of the Board of Directors during this financial year is provided below in paragraph A.6.
The attendance rate of members of the Board of Directors during the financial year ended December 31, 2014 was 87% (the rate was 86% during the financial year ended December 31, 2013).
The directors were summoned with reasonable advance notice of meetings pursuant to article 19 of the bylaws.
Pursuant to article L.225-238 of the Commercial Code, the Statutory Auditors were given notice to appear at the meetings of the Board, which examined and approved the interim financial statements (half-yearly financial statements) as well as the annual financial statements.
All documents and information necessary for the directors' mission were provided to them at the same time as the notice of meeting or delivered at the beginning of each meeting of the Board of Directors.
The Board of Directors is assisted by three permanent committees whose powers and procedures are specified in the rules of procedure: the Audit Committee, the Remuneration and Appointments Committee, and the Scientific Board.
The meetings of the Board of Directors occur at the headquarters or at any other location indicated in the notice of meeting, pursuant to article 19 of the bylaws.
During the financial year elapsed, the main subjects listed below were discussed in particular by the Board of Directors:
Minutes of the meetings of the Board of Directors are drawn up following each meeting and immediately sent to all directors. They are approved at the beginning of the following board meeting.
The Chairman, once per year, shall ask the directors for an opinion about the operation and preparation of the work by the Board. During the Board of Directors' meeting of March 26, 2015, the Chairman invited members of the Compensation and Appointments Committee to issue a reasoned opinion on these matters. On the basis of this opinion, the directors shall express themselves during the next Board of Directors meeting.
ERYTECH Pharma pursues an information policy relative to corporate governance and the transparency of compensation of all its primary corporate officers.
Accordingly, in 2007, a Scientific Board was formed and in 2008, an Audit Committee and a Remuneration and Appointments Committee were formed to assist the Board of Supervisors which then became the Board of Directors in its considerations and its decisions. These committees are described in the rules of procedure, which was last updated by the Board of Directors on April 25, 2014.
The Board of Directors establishes the composition and powers of the committees which conduct their activities under its responsibility. These powers may involve delegating powers to a Committee which are expressly allocated to it by law or by the bylaws or by any other shareholder agreement enforceable as against the Company.
These Committees are purely internal to the Company. They do not have any inherent power and particularly no decision-making power. Their role is strictly advisory.
Each Committee reports on its missions to the Board of Directors.
The Board of Directors then has sole discretion to assess any follow-up it intends to make with respect to the findings presented by the Committees. Each director remains free to vote as he or she sees fit, without being bound by studies, investigations, or reports from the Committees, nor any of their recommendations.
Each Committee shall include no fewer than two members and no more than ten members. Members are appointed personally by the Board of Directors based on their experience and may not be represented. The Committees may be composed solely of directors or even include outside persons. The composition of these Committees may be modified at any time by a decision of the Board of Directors.
The term of office for the Committee members coincides with that of their term as directors when they are board members. The term of a Committee member may be renewed at the same time as that of the director. For Committee members who are not part of the Board of Directors, the term of office is set at one (1) year, automatically renewable.
Committee meetings are held at the Company's headquarters or at any other location decided by the Committee Rapporteur. However, Committee meetings may be held, if necessary, by teleconference or videoconference.
For the correct operation of the Committees and their administrative process, the Rapporteur of each Committee:
Within each Committee, the Rapporteur appoints one person who shall be tasked with writing minutes following each meeting. The minutes shall be sent to the Chairman of the Board of Directors. The minutes shall be kept by the Company. The reports on the work and recommendations from each Committee shall be presented by the Rapporteur to the Board of directors.
In its field of competence, each Committee issues recommendations, proposals, and opinions.
Because information communicated to the Committees or to which the Committee members have access for their missions is confidential in nature, Committee members are required to adhere to the strictest confidentiality in matters pertaining to the Board of Directors with regards to any third party and identical to that applicable to directors. This provision also applies to any outside persons who might be invited.
To date, the Audit Committee is composed of three members appointed for the duration of their director mandate.
The Audit Committee must meet at least once per year.
The Audit Committee's mission is to monitor the existence and efficacy of the Company's financial audit and risk control procedures on an ongoing basis. This committee is tasked with:
The Audit Committee may conduct visits or interviews of any directors of operational or functional entities useful to fulfill its mission. It can also hear from the external auditors, including without the presence of corporate officers. It may make use of outside experts with prior approval from the Board of Directors.
Currently, the members of the audit committee are:
The experience of the members of the Audit Committee is presented in section 14.1.3 of the Reference document.
It is hereby specified that these three members hold specific financial and accounting competencies, as a result of their experience of nearly 25 years in the pharmaceutical industry and general management positions that they have held and still hold.
The previous committee members met twice during the financial year ended December 31, 2014.
Among the points discussed during these meetings:
The Remuneration and Appointments Committee is composed of three members, two of whom are independent members, pursuant to the provisions of the rules of procedure:
The experience of the members of the Compensation and Appointments Committee is presented in section 14.1.3 of the Reference document.
This committee hears directors about the evaluation of the Company's performance in light of the defined goals. Additionally, and particularly, this committee performs the following duties:
The committee met once during the financial year ended December 31, 2014.
The members of the Scientific Board were selected because of their scientific expertise in the fields of activity engaged in and developed by the Company.
The Board is thus primarily composed of persons from outside the Company, it meets at least once per year to evaluate, from a scientific point of view, (i) the conduct and evolution in research programs conducted by the Company (ii) the Company's development strategy, particularly given therapeutic needs and market needs and (iii) any risks which might be posed by the research and development programs of the Company's competitors.
The six members of this Board were appointed for a term of one (1) year, automatically renewable (except for the Deputy General Manager in charge of scientific duties and who is the rapporteur and automatically a member).
The members of the Scientific Board as well as their relations with the Company are detailed in the table below:
| Last name | Connection with the Company | Member of the Scientific Board since |
|---|---|---|
| Dr. Yann Godfrin | Chief Operating Officer | 2007 |
| Prof. Eric Raymond | Consultant | 2009 |
| Dr. Philip L. Lorenzi | Consultant | 2010 |
| Dr. Bridget Bax | Consultant | 2012 |
| Prof. Arthur E. Frankel | Consultant | 2012 |
| Dr. Kurt Gunter | Consultant | 2012 |
The experience of Dr. Yann GODFRIN is presented in section 14.1.3 of the Reference document.
Head of the Cancer Treatment Department (SIHC) at the University Hospital of Beaujon-Bichat (Paris), Prof. Raymond is an expert in oncology. He has published more than 100 articles and is a member of several international associations of experts in oncology.
Prof. Raymond holds an advanced Master's degree (DEA) in Biomedical Engineering with a specialization in bio-imaging from the University of Créteil.
Currently, he is the Laboratory and Research Supervisor in the Department of Bioinformatics and Computational Biology at MD Anderson Cancer Center, Houston, Texas, United States. He is an expert in pharmacogenomics, systems pharmacology, and translational research, specializing in the identification of biomarkers associated with the use of L-asparaginase in chemotherapy.
Bridget Bax is an associate professor at London Metropolitan University and conducts her research in the Department of Clinical Development Sciences at the Saint George Hospital. She is an expert in metabolic diseases and enzyme replacement therapy.
Arthur E. Frankel heads the Hematology/Oncology Department of the Scott & White Cancer Institute in Texas and is a professor at the Texas Health Science Center, College of Medicine. He is interested in the involvement of amino acids in cancer and particularly their reduction as a cancer therapy.
Kurt Gunter is chairman of the International Society of Cellular Therapy until 2014 and, since March 2013, has been Chief Medical Officer of Cell Medica (U.K.). Until the end of March 2013, he headed the Department of Regenerative Medicine at the Hospira Inc. in Chicago (USA). He is an expert in the development of medicine and particularly with respect to regulatory aspects. He was Acting Deputy Director at the FDA (Food and Drug administration) of the CBER (Center for Biologics Evaluation and Research).
The Company relies on the AMF's framework of reference (guideline 2010-16) pertaining to risk management and internal control mechanisms, AMF guideline no. 2010-15 of December 7, 2010 pertaining to the AMF's additional report on corporate governance, remuneration of executive officers, and internal controls for small and mid-cap companies referring to the MiddleNext Code, and AMF guideline 2013-17 entitled Chairmen's Reports on Internal Control and Risk Management Procedures – Consolidated presentation of guidelines contained in the annual reports from the AMF.
Goals:
The responsibilities for risk management are held by the Chief Executive Officer, Gil BEYEN.
The risk management mechanism particularly provides:
the Company's assets and reputation.
A risk management procedure (PG-QUAL-017 the last version of which dates from 03/29/2012) encompassing, namely:
Internal control is one of the Company's mechanisms which is intended to ensure:
By contributing to the prevention and governance of risks of not achieving the objectives established by the Company (see also section B.4 below), the internal control mechanism plays a key role in the conduct and steering of its various activities.
However, internal controls cannot provide an absolute guarantee that the Company's objectives shall be reached.
In collaboration particularly with the audit committee (see also Section B.4.4 below), the responsibility for internal controls lies with the Chief Executive Officer, Gil BEYEN.
The internal audit mechanism provides:
The Company has, in particular, implemented the following organization to limit risks in terms of managing finance and bookkeeping matters:
ERYTECH Pharma develops and provides patients, clients, and partners with products that combine safety, quality, and technology.
ERYTECH Pharma, specialty pharma, commercializes drugs and therapeutic solutions intended for the treatment of serious pathologies, orphan indications for fragile patients in the fields of hematology, oncology, and immunology.
These technologies and products represent a new generation of drugs using red blood cells as a vector for therapeutic agents. They seek to:
ERYTECH's management has always sought to offer the best possible service and the best advice in order to fully respond to the needs and requirements of hospital-based healthcare professionals. This orientation allows it to guarantee its development and its continued existence.
The application of this quality policy involves all of the company's department. It is reflected by the establishment and the tracking of shared goals.
The quality objectives of ERYTECH Pharma for 2015 are:
In order to correctly implement this policy, the Company relies on its existing quality system, certified ISO 9001 and described in the Quality Manual.
With the goal of having this policy applied, executive officers personally commit and delegate to the Quality Assurance department (in collaboration with the relevant departments) the implementation and monitoring of the quality system. Directly under management, it must report on the operation of the system. It relies on process managers for efficient management of the quality system.
Management also undertakes to deploy all current resources to personally ensure the implementation and efficacy of the quality system during management reviews and meetings of the Management Committee.
The company's evolution from a research and development structure towards a structure that integrates sales requires modification in the current system to account for new client demands by striving to achieve operational excellence, with collective involvement in this undertaking.
Senior Management is tasked with defining, providing impetus, and overseeing the most appropriate mechanism for the Company's conditions and activity.
In this framework:
Senior Management is responsible for reporting on the essential characteristics of the risk management and internal control mechanism to the Audit Committee.
The members of Senior Management are:
The duties of the Deputy General Managers are specified below in section C.
The members of the Executive Committee are responsible for keeping Senior Management regularly informed of any malfunctions, deficits, and difficulties.
The Executive Committee is composed of Senior Management and Françoise HORAND-PHOTHIRAH, Director of R&D Operations.
In accordance with the internal rules established by the Board of Directors, last updated 04/25/2014, the Audit Committee is responsible for reporting to the Board of Directors on all major risks and/or weaknesses in the internal controls such as may have a significant impact on accounting and financial information.
As needed, the Board may make use of its general powers to engage in any audits and inspections it deems useful or take any other initiative it believes appropriate in the matter.
Pursuant to procedure PG-QUAL-004, the last version of which dates from 02/21/2011, the Company trains and then appoints internal auditors in order to verify whether the procedures and/or processes have been followed and are effective.
Each year, Management defines a program for internal audits, with priority given to: activities having a direct connection to the pharmaceutical facility and patient safety.
Internal auditors are specifically responsible for reporting to the Quality Assurance department any deviation from the procedures and/or processes.
The Quality Assurance department is responsible for reporting to Senior Management, specifically, any significant deviation from the quality policy and/or procedures and/or processes.
Accordingly:
the IOS auditor (http://www.iso.org/iso/home.htmlInternational Organization for Standardization);
the statutory auditors;
participate in risk management through their audits and/or controls.
In 2015, the Company will continue its efforts to improve the monitoring of risk analysis action plans and to better coordinate internal controls with risk management.
Please note that there has been no limitation made to the powers of Mr. Gil Beyen, Chief Executive Officer.
On May 6, 2013, the Board of Directors stated that:
Further, until the date of his resignation, Pierre-Olivier Goineau was especially in charge of the following activities: strategy, organization and management of operations, internal control, finance, administration, legal, human resources, sales and partnerships.
Refer also to section 14.1.2 of the Reference Document, "Composition of Senior Management".
There are no specific procedures pertaining to the shareholder participation in the general meeting of shareholders outside of those provided in article 27 of the bylaws.
The information referenced in article L.225-100-3 of the Commercial Code (concerning elements that may have an impact where there is a public take-over bid for the Company) is shown in the section 16.6 of the Reference Document.
See chapter 18 of the Reference document
None
See chapter 18 of this Reference document.
16.4.4. Parties holding any securities involving special rights of control and description thereof
None
None.
None.
The applicable rules in this matter are found in the bylaws and comply with the law.
The Company's general shareholders' meeting of June 17, 2014 authorized the Board of Directors, on the suspensive condition that the Company's shares be listed on the Euronext Paris market, to implement a buyback program on the Company shares, in conformity with the provisions of Article L. 225-209 and following of the French Code of Commerce and the market practices approved by the Autorité des marchés financiers (see Section 21.1.2 of this Reference Document).
– The characteristics of the share warrants/founder warrants contain procedures for early exercise subject to certain conditions if there is a change in control of the Company (See also section Erreur ! Source du renvoi introuvable. of this Reference document).
– See also Chapter 22 of this Reference document "Significant contracts".
Pursuant to the "TEPA" law and the Middlenext Code of corporate governance, during its meeting of May 24, 2013, the Board of Directors established the terms for severance pay awarded to the company's executive corporate officers (specifically Mr. Gil Beyen, Mr. Pierre-Olivier Goineau, and Mr. Yann Godfrin).
This commitment provided that should the party in question leave the Company, that is to say in the event of:
the party in question may claim an indemnity equal to 12 times the mean monthly remuneration (bonuses included) effectively received over the course of the 12 months preceding the removal decision or the expiration of the term of office (or concerning only Mr. Gil Beyen, the annual fixed remuneration defined by the Board of Directors, should the removal be decided within 12 months following his appointment).
The decision by the Board of Directors on May 24, 2013, made with respect to the procedure for regulated commitments and agreements provided under the "TEPA" act, was published in its entirety on the Company's website. The commitment was approved by the general shareholders' meeting of June 17, 2014 as a specific resolution pertaining to each of the executive corporate officers.
The Board of Directors decided that payment of severance pay is subordinate to the compliance, duly recorded by the Board of Directors at the time of or after the departure from the position, with the conditions associated with the performances of the party in question assessed with regard to those of the Company, defined on this day as being:
See also Annex 2 of the Reference Document "Environmental, Social, and Corporate Responsibility Policy".
The experience and positions of the primary managers are described in section 14.1.4 supra
The Company's workforce included 44 people at March 31, 2015.
– Change in personnel
The average workforce has varied in the following proportions:
| Year | mean personnel | change |
|---|---|---|
| 2004 | 1 | |
| 2005 | 2 | + 100% |
| 2006 | 8 | + 300% |
| 2007 | 14 | + 75% |
| 2008 | 24 | + 71% |
| 2009 | 37 | + 54% |
| 2010 | 41 | + 11% |
| 2011 | 41 | + 0 % |
| 2012 | 38 | - 7% |
| 2013 | 36 | - 5% |
| 2014 | 38 | + 5% |
Source: Tax bundles, table 2058-C "miscellaneous information"
At December 31, 2014, the Company's personnel (including executive officers) was distributed based on the following areas:
| Departments | Personnel |
|---|---|
| Business & Competitive Intelligence | 2 |
| Clinical Affairs | 3 |
| Finance | 2 |
| Legal | 3 |
| Administration | 2 |
| Public Relations/Investors | 1 |
| Production | 12 |
| Quality Assurance | 3 |
| Preclinical | 15 |
| Regulatory | 1 |
| Grand total | 44 |
| Status | Number |
|---|---|
| Management | 23 |
| Non-management | 21 |
| Grand total | 44 |
The management of employees is of great importance for the Company. Indeed, the Company must retain qualified employees who possess strong skills and abilities as ERYTECH's business is, in fact, partially based on the quality and efficacy of its key employees.
The Company believes that it has good relations with its personnel.
The Company's employment contracts are controlled by the national collective-bargaining agreement in the pharmaceutical industry.
The Company has two employee representatives (one elected and one alternate) who meet with management every month.
The large majority of the Company's employees are employed on the basis of permanent contracts; however, the Company does make use of employees on fixed-term contracts, notably to satisfy the demands of periodic increases in business.
Insofar as the remuneration policy is concerned, the employment contracts may provide for, depending on the case, additional remuneration consisting of bonuses determined on the basis of goal attainment.
The organization of work time at ERYTECH complies with all legal and regulatory provisions. The legal length of the workweek is 35 hours for full-time employees.
Senior executives are not covered by the laws respecting hours of work.
Based on the makeup of the share capital and the existing diluting elements as of the date of this document, stakes held by the company's executive corporate officers may be summarized as follows:
| Subscription warrants | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Number of shares |
% capital ** |
% voting right |
Type of warrants |
Creation date |
Number awarded and not exercise d |
Number subscrib ed and not exercise d*** |
Exercise price in € per new share subscribed |
Last date for exercise |
Maximu m number of shares associate d |
Stocks options |
|
| Founder's share warrants2012 |
05/21/12 | 7,863 | 7,863 | 7.362 | 05/20/20 | 78,630 | N/A | ||||
| Gil Beyen* | - | - | - | Founder's share warrants (BSPCE)201 4 |
01/22/14 | 6,000 | 0 | 12.25 | 01/22/24 | 60,000 | N/A |
| Founder's share warrants2012 |
05/21/12 | 7,508 | 7,508 | 7.362 | 05/20/20 | 75,080 | N/A | ||||
| Yann Godfrin * |
142,990 | 2.08% | 3.53% | Founder's share warrants (BSPCE)201 4 |
01/22/14 | 3,000 | 0 | 12.25 | 01/22/24 | 30,000 | N/A |
| Philippe Archinard * |
4,000 | 0.06% | 0.05% | ||||||||
| GALENOS * |
4,500 | 0.07% | 0.06% | Share | 05/20/20 | ||||||
| Martine Ortin George* |
- | - | - | warrants (BSA)2012 |
05/21/12 | 6,238 | 0 | 7.362 | 62,380 | N/A | |
| Hilde Windels* |
- | - | - | ||||||||
| Jérôme Bailly* |
3,000 | 0.04% | 0.04% | Founder's share warrants2012 |
05/21/12 | N/A | 958 | 7.362 | 05/20/20 | 9,580 | N/A |
* See details for positions currently held in Chapter 14– Administrative and management bodies
** Registered shares
*** See also section 21.4.4 of the Reference Document
**** As delegated by the General Meeting
***** one warrant gives rights to 10 new shares
Based on the composition of the capital and dilutive elements existing at the date of financial year end, December 31, 2014, the investment stakes held by non-corporate-officer employees can be summarized as follows:
| Subscription warrants | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Number of shares and voting rights* |
% capital * |
% voting right* |
Type of warrants | Creation date |
Number allocated and not exercised *** |
Number subscribe d and not exercised |
Exercise price in € per new share subscribed |
Last date for exercise |
Maximu m number of shares associate d |
Stocks option s |
|
| Employees who are not | 8 800 | 0.13% | 0.09% | Founder's share warrants2012 |
05/21/2012 | 1,793 | 1,793 | 7.362 | 05/20/2020 | 17,930 | N/A |
| officers or directors | Founder's share warrants (BSPCE)2014 |
01/22/2014 | N/A | 0 | 12.25 | 01/22/2024 | N/A | N/A |
* Registered shares
*** See also section 21.4.4 of the Reference document
*** As delegated by the General Meeting
The Company has implemented a profit-sharing agreement for the years 2014 to 2016, at the end of which a percentage (2.5% in 2014) of the gross annual remuneration at December 31 of each year may be distributed:
In conformity with the provisions of Article L.233-13 of the Code of Commerce, we provide you, below, with the identity of shareholders who hold a stake exceeding the threshold of 5% of the capital and/or 5% of the voting rights. To the Company's knowledge, no other shareholders directly or indirectly, alone or jointly, hold more than 5% of the capital or voting rights.
The Company's shareholder structure at December 31, 2014 is presented as follows, based on information available:
| Last name, first name / Company name | % Share capital | % Voting rights | Number of shares | |
|---|---|---|---|---|
| FCPR AURIGA VENTURES III | 14.79% | 21.46% | 1,018,212 | |
| RECORDATI ORPHAN DRUGS | 6.26% | 5.20% | 431,034 | |
| YANN GODFRIN | 4.26% | 7.07% | 292,990 | |
| PIERRE-OLIVIER GOINEAU | 3.83% | 6.36% | 263,490 | |
| HOLDING ENTREPRISE AND PATRIMOINE1 | 1.24% | 51,530 | ||
| Other nominal shareholders who hold capital less than or equal to 0.5% |
1.66% | 1.85% | 114,513 | |
| BEARER SECURITIES | Held by the Company within the scope of the buyback program2 |
0.07% | 0.00% | 4,500 |
| OTHER BEARER SHARES | 68.38% | 56.77% | 4,706,492 | |
| TOTAL | 100.00% | 100.00% | 6,882,761 |
1 Funds managed by IDINVEST PARTNERS
2 see Section 3.8.9 of the present Annual Financial Report
| Last name, first name / Company name | % Share capital | % Voting rights | Number of shares | |
|---|---|---|---|---|
| FCPR AURIGA VENTURES III | 14,78% | 21,97% | 1,018,212 | |
| RECORDATI ORPHAN DRUGS | 6,26% | 5,32% | 431,034 | |
| GOINEAU Pierre-Olivier | 3.09% | 5,26% | 212,900 | |
| GODFRIN Yann | 2,08% | 3,53% | 142,990 | |
| HOLDING ENTREPRISE ET PATRIMOINE | 0.75% | 1.27% | 51,530 | |
| Registered shareholders who possess no more than 0.5% share capital |
1,16 % | 1.45 % | 79,733 | |
| Held by the Company within the scope of the buyback program2 |
0.04% | 0.00% | 2,500 | |
| BEARER SECURITIES | Other bearer shareholders3 | 71.90% | 61,17% | 4,952,692 |
| TOTAL | 100.00% | 100.00% | 6,888,441 |
1Funds managed by IDINVEST PARTNERS
2 see Section 3.8.9 of the present Annual Financial Report
During the financial year ended December 31, 2014, the Company received information on the following thresholds crossed:
Since December 31, 2014, the Company has received declarations of the following thresholds crossed:
18.2. Major shareholders not represented on the Board of Directors
In the ordinary and extraordinary general meetings of the Company, each share gives the right to one vote, except where there is a right for a double vote.
A double voting right is nevertheless assigned, in accordance with legal conditions, to all shares fully paid up for which evidence is provided, at the latest on the second day prior to the date of the shareholders' meeting, of nominal registration for at least two years in the name of the same shareholder, or in the name of a person holding such rights following a succession, a sharing of the community of property between spouses, or an inter vivos gift granted by a shareholder to his/her spouse or to a relative in the direct line of succession, or following a transfer resulting from a merger or a division of a shareholder company.
In the event of a capital increase through the incorporation of reserves, income, or issue premiums, the double voting right is granted, upon their issue, to nominal shares assigned free of charge to replace the previous shares already receiving such benefit.
The double voting right shall be duly withdrawn from any share having been converted to a bearer share or been subject to a transfer of ownership, except where this transfer results from a succession, a sharing of the community of property between spouses, or an inter vivos gift granted by a shareholder to his/her spouse or to a relative in the direct line of succession, or following a transfer resulting from a merger or a division of a shareholder company.
To the Company's knowledge:
Furthermore, to the Company's knowledge, no shareholder or group of shareholders directly or indirectly holds more than 40% of the voting rights in the Company, capable of creating a presumption of control of the Company with regard to one of the shareholders or a group of shareholders.
The shareholders' agreement dated December 22, 2006 entered into between the Shareholders of the Company, as amended on June 11, 2010, binding as of the registration date for the Reference document, became null and void starting on the day of the first listing of shares of the Company on Euronext Paris.
The shareholders have not indicated an intention to enter into a new shareholders' agreement.
To the Company's knowledge, there is no concerted action among the shareholders.
To the Company's knowledge, there are no agreements in place whose implementation might, at a later date, result in a change in control.
All currently existing regulated agreements are mentioned in the special reports by the statutory auditor presented below.
Since preparation of the special report by the statutory auditor relative to the 2014 financial year;
During the financial year ended December 31, 2014, the Company paid \$100,000 to its subsidiary, ERYTECH Pharma Inc.
Since closure of the financial year ended December 31, 2014, the Company has stipulated a cash management agreement with its subsidiary, ERYTECH Pharma Inc.
Headquarters: Share capital: €688,276.10
Dear Shareholders,
In our capacity as statutory auditor for your company, we hereby present to you our report on regulated agreements and commitments.
Our task is to inform you, on the basis of the information that has been provided to us, of the characteristics and essential mechanisms of those agreements and commitments of which we have been informed or which we uncovered during our assignment, while not discussing their usefulness and their merits, nor searching for the existence of other agreements and commitments. It is your responsibility, in accordance with the terms of Article R.225-58 of the Code of Commerce, to assess the interest presented by the stipulation of these agreements and commitments, with a view to their approval.
Furthermore, our task is, as applicable, to provide you with the information specified in article R.225-31 of the Commercial Code respecting the execution of agreements and commitments already approved by the general meeting over the course of the past fiscal year.
We have conducted the due diligence that we believed necessary in light of the professional doctrine of the Compagnie Nationale des Commissaires aux Comptes pertaining to this mission. This due diligence consisted in verifying that the data provided to us was consistent with the underlying documents from which they came.
In application of articles L. 225-42 et L. 823-12 of the Commercial Code, we hereby inform you that the following agreements and commitments have not been previously authorized by your Board of Directors.
It is our job to inform you of the circumstances due to which the authorization procedure was not followed.
Carré VIP securities management consulting contract for Société Générale Securities Services
Person concerned: Mr. Pierre-Olivier Goineau, Chief Operating Officer of the Company.
Mr. Pierre-Olivier Goineau resigned from his positions as Director and Delegated Managing Director on January 11, 2015.
Carré VIP securities management consulting contract for Société Générale Securities Services
Person concerned: Mr. Yann Godfrin, Chief Operating Officer of the Company.
Carré VIP securities management consulting contract for Société Générale Securities Services
Person concerned: Mr. Gil Beyen, Chairman of the Board of Directors and General Manager of the Company.
Person concerned: Mr. Gil Beyen, Chairman of the Board of Directors and General Manager of the Company.
Your company considers that these agreements fall under Article L.225-39 of the Code of Commerce and, therefore, that the pre-authorization procedure specified in Article L.225-38 of this Code does not apply to them.
In application of article R.225-31 of the Commercial Code, we have been informed that the execution of the following agreements and commitments, already approved by the general meeting during previous fiscal years, were pursued in the past fiscal year.
Person concerned: Mr. Pierre-Olivier Goineau, Chief Operating Officer of the Company.
Mr. Pierre-Olivier Goineau may claim an indemnity equal to twelve times his average monthly remuneration (bonuses included) effectively received during the twelve months prior to the revocation decision or expiry of his term of office.
Payment of this indemnity shall be subject to the finding that the following performance conditions have been met:
Person concerned: Mr. Pierre-Olivier Goineau, Chief Operating Officer of the Company.
Mr. Pierre-Olivier Goineau resigned from his positions as Director and Delegated Managing Director on January 11, 2015.
Person concerned: Mr. Yann Godfrin, Chief Operating Officer of the Company.
Mr. Yann Godfrin may claim an indemnity equal to twelve times his average monthly remuneration (bonuses included) effectively received during the twelve months prior to the revocation decision or expiry of his term of office.
Payment of this indemnity shall be subject to the finding that the following performance conditions have been met:
Person concerned: Mr. Yann Godfrin, Chief Operating Officer of the Company.
Person concerned: Mr. Gil Beyen, Chairman of the Board of Directors and General Manager of the Company.
Nature and purpose: Severance pay, authorized by the Board of Directors on May 24, 2013, in the event of:
Mr. Gil Beyen may claim an indemnity equal to:
Payment of this indemnity shall be subject to the finding that the following performance conditions have been met:
Person concerned: Mr. Gil Beyen, Chairman of the Board of Directors and General Manager of the Company.
Persons concerned: Mr. Gil Beyen, Mr. Pierre Olivier Goineau, Mr. Yann Godfrin, Mr. Jérôme Bailly.
| Charges undertaken in the 2014 fiscal year | Gil Beyen | Jérôme Bailly | Pierre-Olivier Goineau |
Yann Godfrin |
|---|---|---|---|---|
| Contractual professional health insurance APGIS (PRC) | 3,932.16 | 1,394.15 | 3,519.23 | 3,517.89 |
| Additional health insurance (VIVENS) | 1,096.44 | 504.65 | 1,096.44 | 1,096.44 |
| Unemployment insurance (GSC) | 8,562.79 | 8,566.02 | ||
| Additional pension plan (AXA) | 7,509.60 | 3,456.63 | 7,509.60 | 7,509.60 |
| Supply of a company car and fuel paid for | ||||
| -Rents paid during the fiscal year | 17, 185.15 | 6,191.40 | 10, 778.46 | 10, 877.87 |
| -Amount of fuel paid for | 1,874.18 | 1,282.46 | 1,811.20 | 2,066.60 |
| TOTAL | 31, 597.53 | 12, 829.29 | 33, 277.72 | 33, 634.42 |
Mr. Pierre-Olivier Goineau resigned from his positions as Director and Delegated Managing Director on January 11, 2015.
We have been informed of the following commitments which were authorized following the close of the last fiscal year and which were previously authorized by your Board of Directors:
The statutory auditors Lyon, March 30, 2015
For KPMG Audit Rhône Alpes Auvergne For RSM CCI Conseils
Sara RIGHENZI DE VILLERS Gaël DHALLUIN Statutory Auditor Associate
Headquarters: Share capital: €
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In our capacity as statutory auditor for your company, we hereby present to you our report on regulated agreements and commitments.
Our task is to inform you, on the basis of the information that has been provided to us, of the characteristics and essential mechanisms of those agreements of which we have been informed or which we have uncovered during our mission, while not discussing their usefulness and their merits, nor searching for the existence of other agreements and commitments. It is your responsibility, according to the terms of articles R.225-31 and R.225-58 of the Commercial Code to assess the interest presented by the formation of these agreements and commitments in order to approve them.
Furthermore, it is our job, as applicable, to provide you with the information specified in articles R. 225-31 and R.225-58 of the Commercial Code pertaining to the execution of agreements and commitments already approved by the general meeting over the course of the past fiscal year.
We have conducted the due diligence that we believed necessary in light of the professional doctrine of the Compagnie Nationale des Commissaires aux Comptes pertaining to this mission. This due diligence consisted in verifying that the data provided to us was consistent with the underlying documents from which they came.
In application of article L.225-88 and L.225-40 of the Commercial Code, we have been informed of the following agreements and commitments which received prior authorization from your Board of Supervisors and your Board of Directors subsequent to the change in governance approved by the General Meeting on April 2, 2013.
Entity concerned: Auriga Partners, shareholder possessing a fraction of voting rights greater than 10%.
Mr. Pierre-Olivier Goineau may claim an indemnity equal to twelve times his average monthly remuneration (bonuses included) effectively received during the twelve months prior to the revocation decision or expiry of his term of office.
Payment of this indemnity shall be subject to the finding that the following performance conditions have been met:
Mr. Yann Godfrin may claim an indemnity equal to twelve times his average monthly remuneration (bonuses included) effectively received during the twelve months prior to the revocation decision or expiry of his term of office.
Payment of this indemnity shall be subject to the finding that the following performance conditions have been met:
At least one of the two following conditions:
at least one collaboration or licensing agreement underway;
Mr. Gil Beyen may claim an indemnity equal to:
Payment of this indemnity is subject to the finding that the following performance conditions have been met:
| Charge borne in 2013 | Gil Beyen | Jérôme Bailly |
Pierre-Olivier Goineau |
Yann Godfrin |
|---|---|---|---|---|
| Traditional professional health insurance APGIS (PRC) | 2,290 | 1,291 | 3,484 | 3,484 |
| Additional health insurance (GAN) | 971 | 626 | 1,481 | 1,481 |
| Additional pension plan (AXA) | 4,855 | 3,122 | 7,406 | 7,406 |
| Provision of a company vehicle and coverage of | ||||
| fuel expenses | ||||
| - Rents paid during the fiscal year | 5,373 | |||
| - Amount of fuel paid for. | 407 | 1,163 |
We have been informed of the following commitments which were authorized following the close of the last fiscal year and which were previously authorized by your Board of Directors:
In application of articles R.225-30 and R.225-57 of the Commercial Code, we have been informed that the execution of the following agreements and commitments, already approved by the general meeting during previous fiscal years, were pursued in the past fiscal year.
Your company entered into a permanent consultancy agreement with the Gil Beyen BVBA company starting in January 2012. This contract was intended to assist management in the search for financial partners and to contribute its expertise and assistance in the implementation of the company's strategy. In return for the delivery of these services, your company agreed to pay €1,200/day of work by Mr. Gil Beyen, with the average number of days being estimated at 12 per month, although in no case is would it be below or above a range of between 8 and 16 days.
Additional fees were also provided in the contract, particularly in the event that capital was raised, bonds were issued, shareholder loans, payment of advances or firm "milestones" contingent on commercial development (starting from a cumulative payment threshold of €15 million).
If the consultancy agreement was terminated by the Company for any reason other than wrongdoing by the consultant, ERYTECH SA would be required to pay to Gil Beyen BVBA an indemnity equal to three months of normal activity preceding the termination and at least €43,200 if the termination occurred within three months following the signature of the consultancy agreement.
Travel costs were borne by the consultant, except for exceptional travel costs incurred as part of his mission.
Terms:
By virtue of this contract, for fiscal year 2012, your company booked fees in a total amount of €112,763 corresponding to:
Person concerned: Mr. Jérôme Bailly, Chief Operating Officer of the Company.
| Charge borne in 2013 | Pierre-Olivier Goineau |
Yann Godfrin |
Jérôme Bailly |
|---|---|---|---|
| Unemployment insurance policy with the Association pour la Garantie Sociale des Chefs et Dirigeants d'Entreprise |
5,619 | 5,619 | |
| (French GSC - unemployment insurance provider for Provision of a company vehicle and coverage of fuel corporate leaders) |
|||
| expenses | |||
| - Rents paid during the fiscal year | 8,770 | 9,235 | 5,878 |
| - Amount of fuel paid for. | 1,773 | 1,889 |
Lyon, April 28, 2014
KPMG Audit Rhône Alpes Auvergne
Gaël Dhalluin Deputy auditor
| (in euros) | notes | 12.31.2014 (12 months) |
12.31.2013 (12 months) |
|
|---|---|---|---|---|
| Sales revenue | ||||
| Other income from activities | 6.1 | 2,025,687 | 1,802,262 | |
| Income from regular operations | 2,025,687 | 1,802,262 | ||
| Research and development costs | (2,243,971) | (2,502,790) | ||
| Clinical studies | 6.2 to 6.4 | (3,875,421) | (2,461,836) | |
| Intellectual property costs | (493,481) | (363,363) | ||
| Overhead and general costs | (4,361,181) | (3,587,200) | ||
| Regular operating results | (8,948,367) | (7,112,926) | ||
| Other operating income and expenses | 27,776 | |||
| Operating results | (8,948,367) | (7,085,150) | ||
| Net cost of debt | 6.5 | (50,006) | (1,119,787) | |
| Other financial income and expenses | 6.5 | 118,179 | 20,199 | |
| Financial results | 68,173 | (1,099,589) | ||
| Before-tax results | (8,880,194) | (8,184,739) | ||
| Income tax | 6.6 | 20,158 | 40,018 | |
| NET INCOME | (8,860,036) | (8,144,721) | ||
| Elements that may be recycled at a later time as earnings None |
||||
| Elements that may not be recycled at a later time as earnings | ||||
| Reappraisal of liabilities for defined-benefits schemes | 58,547 | 5,755 | ||
| Tax effect | (20,158) | (1,981) | ||
| Other comprehensive income | 38,389 | 3,774 | ||
| COMPREHENSIVE INCOME | (8,821,647) | (8,140,947) | ||
| Basic earnings per share | (1.51) | (1.74) | ||
| Diluted earnings per share | (1.51) | (1.74) |
| ASSETS (in euros) | notes | 12.31.2014 | 12.31.2013 | |
|---|---|---|---|---|
| NON-CURRENT ASSETS | 1,080,239 | 910,132 | ||
| Intangible assets | 7.1 | 30,951 | 14,277 | |
| Tangible fixed assets | 7.2 | 967,474 | 812,947 | |
| Non-current financial assets | 7.3 | 81,814 | 82,908 | |
| Other non-current assets | ||||
| Deferred tax assets | ||||
| CURRENT ASSETS | 39,526,400 | 17,038,828 | ||
| Inventories | 7.4 | 198,356 | 138,238 | |
| Clients and associated accounts | 104,870 | 87,192 | ||
| Other current assets | 7.5 | 2,234,738 | 1,700,874 | |
| Cash and cash equivalents | 7.6 | 36,988,436 | 15,112,523 | |
| TOTAL ASSETS | 40,606,639 | 17,948,960 | ||
| LIABILITIES AND SHAREHOLDERS EQUITY (in | ||||
| 12.31.2014 | 12.31.2013 | |||
| euros) | ||||
| SHAREHOLDERS' EQUITY Capital |
35,824,303 688,276 |
13,586,634 550,602 |
||
| Premiums | 7.7 7.7 |
72,426,817 | 42,741,059 | |
| Reserves | 7.7 | (28,430,754) | (21,560,305) | |
| Net income | (8,860,036) | (8,144,721) | ||
| NON-CURRENT LIABILITIES | 524,629 | 847,689 | ||
| Provisions - Non-current portion | 7.8 | 88,594 | 117,144 | |
| Financial liabilities - Non-current portion | 7.9 | 436,035 | 730,545 | |
| Deferred tax liabilities | ||||
| Other non-current liabilities | ||||
| CURRENT LIABILITIES | 4,257,706 | 3,514,636 | ||
| Provisions - Current portion | ||||
| Financial liabilities - Current portion | 7.9 | 333,502 | 281,341 | |
| Trade payables and related accounts | 2,084,546 | 1,421,436 |
TOTAL LIABILITIES AND SHAREHOLDERS EQUITY 40,606,639 17,948,960
| TABLE OF CHANGES IN SHAREHOLDERS' EQUITY |
Capital | Issue premium | Reserves | Results | Shareholders' |
|---|---|---|---|---|---|
| (in euros) | equity | ||||
| 12/31/2012 | 315,355 | 17,767,715 | (19,938,025) | (2,172,035) | (4,026,990) |
| Issuance of common stock | 240,540 | 240,540 | |||
| Issue premium increase | 25,567,623 | 25,567,623 | |||
| Treasury shares | (5,294) | (594,279) | (34,639) | (634,212) | |
| Allocation of Earnings N-1 | (2,172,035) | 2,172,035 | |||
| Earnings for the period | (8,144,721) | (8,144,721) | |||
| Actuarial gains and losses | 3,773 | 3,773 | |||
| IFRS 2 Charges | 580 621 | 580,621 | |||
| 12/31/2013 | 550,602 | 42,741,059 | (21,560,305) | (8,144,721) | 13,586,634 |
| 12/31/2013 | 550,602 | 42,741,059 | (21,560,305) | (8,144,721) | 13,586,634 |
| Issuance of common stock | 132,381 | 132,381 | |||
| Issue premium increase | 29,040,376 | 29,040,376 | |||
| Treasury shares | 5,294 | 645,382 | 650,675 | ||
| Allocation of Earnings N-1 | (8,144,721) | 8,144,721 | |||
| Earnings for the period | (8,860,036) | (8,860,036) | |||
| Actuarial gains and losses | 38,389 | 38,389 | |||
| IFRS 2 Charges | 1,235,883 | 1,235,883 | |||
| 12/31/2014 | 688,276 | 72,426,817 | (28,430,754) | (8,860,036) | 35,824,303 |
| (in euros) | notes | 12.31.2014 | 12.31.2013 |
|---|---|---|---|
| Net income | (8,860,036) | (8,144,721) | |
| Expenses (income) not affecting cash | |||
| - Depreciation (write backs) and provisions of non-current assets | 276,522 | 286 962 | |
| - Depreciation (write backs) and provisions of current assets | (106,665) | ||
| - Expenses (income) as share-based payments | 1,235,883 | 580,621 | |
| - Investment grants written back to income - Gains and losses on disposals |
- - |
||
| Operating subsidies | (1,794,919) | (1,660,806) | |
| Cost of net financial debt | 50,006 | 1,119,787 | |
| Income tax expense (current and deferred) | (20,158) | (40,018) | |
| Internal financing capacity before financial results and tax | (9,112,701) | (7,964,840) | |
| Taxes paid | - | - | |
| Changes in working capital needs related to business activities | 1,874,169 | 1,491,607 | |
| Net cash flow generated by business activities | (7,238,532) | (6,473,233) | |
| Cash flow related to investment operations | |||
| Purchase of fixed assets | (547,171) | ( 430,638) | |
| - Intangible assets | (25,798) | (9,009) | |
| - Tangible fixed assets | (521,270) | (418,390) | |
| - Investments | (103) | (3,238) | |
| Disposal of fixed assets | 126,826 | 14, 040 | |
| - Intangible assets - Tangible fixed assets |
- 125,629 |
- 142,040 |
|
| - Investments | 1,197 | - | |
| Grants cashed | - | - | |
| Effects of changes in perimeter | - | - | |
| Net cash flow generated by investment operations | (420,345) | (288,598) | |
| Cash flows from financing activities | |||
| Increase in cash capital | 30,731,174 | 16,551,137 | |
| Costs of cash capital increase Loan issue |
(1,558,417) - |
(2,013,989) 193,284 |
|
| Costs of loan issue | - | - | |
| Repayment of loans | (281,341) | (130,000) | |
| Treasury shares | 650,675 | (599,573) | |
| Interest paid | (7,301) | (1,621) | |
| Net cash flow generated by financing operations | 29,534,791 | 13,999,239 | |
| Changes in cash position | 21,875,913 | 7,237,408 | |
| Cash position at year start Cash position at year end |
15,112,523 36,988,436 |
7,875,115 15,112,523 |
|
| Variation in net cash position | 21,875,913 | 7,237,408 |
The present annex forms an integral part of the consolidated financial statements for the year ended December 31, 2014.
The financial statements were issued by the Board of Directors on March 26, 2015.
The Group's main activity is research and development in the areas of treatment of acute leukemias and other orphan diseases.
Since its creation, the Group has concentrated its efforts:
The Group's business model is to develop its products up to the point of obtaining authorization for their placement on the market in Europe and then in the United States. Commercial partnerships established by Erytech will allow for the distribution of ERY-ASP to be ensured first in Europe and then in the United States and in the rest of the world. Erytech has the capacity to ensure the supply of Graspa® for the first years of its sale in Europe, through its production unit in Lyon.
The parent company, ERYTECH PHARMA SA, raised approximately €30 M in October 2014 on Euronext, pertaining to a total of 1,224,489 new shares issued within the scope of a capital increase, with suppression of the preferential subscription right, reserved for investors regularly investing in securities specific to the fields of health care, representing approximately 17.8% of the number of shares in circulation (post-issue).
The issue price was set at 24.50 Euros per share, in compliance with resolution no. 10 of the mixed general shareholders' meeting of June 17, 2014. This price reflects a 3.5% reduction as compared to the weighted average of the parent company's share price in the last five trading sessions prior to establishing the price, i.e., 25.39 Euros. In total, 80% of the issue was performed internationally, with 68% in the United States.
On 09/30/2014, the Group announced the positive Phase III results on its Phase II/III clinical study with GRASPA® in the treatment of ALL. Analysis of the data from the GRASPIVOTALL clinical trial
(GRASPALL2009-06), after one year of monitoring, demonstrates that the study convincingly achieved its primary objectives, and its secondary objectives confirm a favorable profile for the clinical efficacy of GRASPA®. The study also shows favorable results in patients with histories of allergies to L-asparaginase.
During the financial year, the Group also recruited the first patient for its Phase II study on pancreatic cancer in Europe, as well as its first patient for its Phase I/II study in the United States.
The Group announced the positive opinion by its second committee of independent experts (DSMB) for its Phase IIb study on AML. The independent experts analyzed the tolerance data for the first 60 patients treated, and as with the first DSMB committee review on 30 patients, continuation of the study was unanimously confirmed, without requesting any modifications to the study or formulating any particular observations.
The Group likewise obtained Orphan Drug Designation from the FDA for its product ERY-ASP in the treatment of AML in the United States.
The parent company ERYTECH PHARMA SA created the subsidiary "ERYTECH PHARMA Inc." in the USA in April 2014. The Company then proceeded to appoint the firm RSM-CCI Conseils as co-Statutory Auditors in the AGM of June 17, 2014. At June 30, 2014, the Group's financial statements were supplemented, for the first time, by consolidation of the 100% held American subsidiary. This activity had no impact on the financial year.
Pierre-Olivier Goineau, co-founder of the company Erytech Pharma SA and Delegated Managing Director, submitted his resignation to the Group from his positions within ERYTECH PHARMA SA during the parent company's board of directors' meeting of January 11, 2015; Mr. Goineau will remain treasurer and secretary of the American subsidiary ERYTECH PHARMA Inc.
The Group's loss-making situation is explained by the innovative nature of the products developed, therefore involving a multi-year research and development phase. The general accounting conventions were applied in compliance with the principle of prudence, in accordance with the underlying assumptions of:
business continuity,
permanence of accounting methods from one year to the next,
and in conformity with the general rules for the preparation and presentation of consolidated financial statements in accordance with the IFRS.
In application of European regulation 1606/2002 of July 19, 2002, the financial statements for the ERYTECH PHARMA Group are prepared in conformity with the International Financial Reporting Standards (IFRS) published by the International Accounting Standards Board (IASB), as adopted by the European Union at the date of issue of the financial statements by the board of directors, as applicable at December 31, 2014.
This framework is available on the European Commission's website, at the following address: (http://ec.europa.eu/internal\_market/accounting/ias/index\_fr.htm).
The accounting methods outlined below have been applied in a continuous manner to all the periods presented in the Group financial statements, after taking into account or with the exception of the new standards and interpretations described below.
The financial statements are presented in Euros, which is the functional currency of the parent company. All amounts mentioned in this annex to the financial statements are denominated in Euros, save where indicated otherwise.
The accounting principles adopted for their preparation are those applied by the Group at December 31, 2013, with the exception of the following new standards and interpretations applied for the first time as of January 1st, 2014:
These new texts published by the IASB had no significant impact on the Group financial statements.
The Group has not applied in advance any standards and interpretations for which application was not obligatory at January 1st, 2014.
The statement of comprehensive income presents the classification of expenses and income per item, with the exception of other operating income and expenses.
The comparative information is presented using an identical classification.
The cash flow table was prepared according to the indirect method.
The Group closed its annual accounts on December 31, 2014.
The company ERYTECH Pharma SA (head office: 60 avenue Rockefeller, Bâtiment Adénine, 69008 LYON, FRANCE) holds 100% of its subsidiary, ERYTECH Pharma Inc. (head office: 185 Alawife Brook Parkway Ste 410, CAMBRIDGE, MA 02138, UNITED STATES).
The Group's financial statements include consolidation of the American subsidiary.
Preparation of the financial statements in accordance with the rules prescribed by the IFRS requires the use of estimates and the formulation of hypotheses having an impact on the financial statement. These estimates can be revised where the circumstances on which they are based change. The actual results may therefore differ from the estimates initially formulated. The use of estimates and judgment primarily concern the measurement of share-based payments (Note 5.17 and Note 6.3), as well as the estimate of expenses owing relative to clinical trials (Note 9).
Intangible assets generated internally – Research and development costs
In accordance with IAS 38, "Intangible Assets," research expenditures are accounted for in the period during which they are incurred.
An intangible asset internally generated relating to a development project is booked as an asset if, and only if, the following criteria are met:
The initial measurement of the development asset is the sum of expenses sustained starting on the date on which the development project meets the above criteria.
Considering the strong uncertainty associated with the development projects performed by the Group, these conditions will only be met when the regulatory procedures necessary for placement of the products on the market have been finalized. Most of the expenditures being incurred before that stage, the development costs, are accounted for in the period in which they are incurred.
The other intangible assets are recognized at their cost, decreased by the aggregate amortizations and any losses in value. The amortization is calculated on a straight-line basis in function of the duration of the asset's use. The duration of use and the amortization method are reviewed at each year-end. All significant modifications to the anticipated use of the asset are recognized prospectively.
The other intangible assets are primarily composed of computer software and are amortized on a straight-line basis over 1 to 5 years.
An impairment is recorded where the asset's book value is greater than its recoverable value (see Note 7.1).
Fixed assets are recorded in the balance sheet at their purchase cost, composed of their purchase price and all directly associated costs sustained to place the asset in use and in a state of operation according to the usage intended by the company's management.
These assets are amortized according to the straight-line method, in function of their duration of use.
The primary durations of use adopted are as follows:
The duration of use of fixed assets, any residual values, and the amortization method are reviewed at each year-end result and, in the event of a significant change, in a forward-looking revision of the amortization plans.
In compliance with the IFRS, the different components of a single fixed asset having a different duration of use or procuring economic benefits for the company according to a different rhythm are recognized separately.
According to the standard IAS 36, "Impairment of Assets," a loss in value must be recognized where the net book value is lower than the recoverable value. The recoverable value of an asset is the highest value between the fair value less disposal costs and the value in use.
The fair value less disposal costs is the amount that can be obtained from the sale of an asset in a transaction under conditions of normal competition between well-informed, consenting parties, less the disposal costs.
The value in use is the present value of estimated future cash flow anticipated from the ongoing use of an asset. The value in use is determined based on cash flows estimated based on budgets and plans, then discounted by adopting the long-term market rates after taxes that reflect the market estimates of the time value of money and the risks specific to the assets.
Where new events or situations indicate that the book value of certain fixed or intangible assets may not be recoverable, this value is compared to its recoverable value, approached based on the value in use or its market value less disposal costs. Where the recoverable value is less than the net book value of these assets, the latter is changed to its recoverable value and a loss in the asset value is recognized under "provisions for impairment." The new value of the asset thus has a forward-looking amortization based on the new duration of the asset's residual life.
Non-current financial assets are initially recognized at their fair value, increased where applicable by the costs directly ascribable to their purchase, then further measured at the amortized cost. They cannot form the object of a loss in value where an objective indication of impairment exists. The loss in value is recognized in the profit or loss and is reversible where the recoverable value experiences a positive change in the future.
In compliance with the IAS 2 standard for "Inventories," inventories are recognized at their cost or at their net realizable value, where this is lower. In the latter case, the loss in value is recorded under current operating income. Inventories are measured according to the FIFO method.
A lease agreement is considered as being a finance lease where it transfers to the borrower substantially all the risks and benefits inherent in ownership of the asset. The other contracts are considered as being simple lease agreements.
The assets held within the scope of a finance lease are recognized in the balance sheet assets and liabilities under their fair value at the start of the contract or, where this is lower, at the discounted value of the minimum payments on the lease. These assets are then amortized in function of the anticipated duration of the asset's use.
The item "cash and cash equivalents" in the balance sheet includes highly liquid securities for which the initial maturity is equal to or less than three months, considered equivalent to liquid assets. The fair value of these securities is very near their book value, given their short-term maturity.
A provision is recognized where the Group has a current or implicit legal obligation resulting from a prior event, where the obligation can be reliably estimated, and where it is probable that an outflow of resources representing economic benefits will be necessary to discharge the obligation. The portion of a provision estimated as payable in less than one year is recorded under current liabilities, and the balance under noncurrent liabilities. The provisions are discounted where the impact is significant.
Provisions notably include:
Disclosure is made in the detailed notes on any potential assets and liabilities where the impact is significant, except where the probability of occurrence is low.
In compliance with IAS 19, "Employee Benefits," within the scope of defined benefit plans, the postemployment benefits and other long-term benefits are measured every year using the projected unit credit method. According to this method, each service period gives rise to an additional unit of rights to benefits, and each of these units is measured separately to obtain the final obligation. This final obligation is then discounted.
These calculations primarily include:
The primary actuarial assumptions adopted at December 31, 2014 are described in note 7.8.
The positive or negative actuarial differences include the effects, on the commitment, of a change in calculation assumptions as well as adjustments to the obligation linked to experience. In conformity with the standard IAS 19 "Post-employment benefits [employee benefits]", the Group recognizes these actuarial differences under other items of the comprehensive income for post-employment benefits.
The provision showing in the balance sheet under a specific line corresponds to the total commitment at yearend. The cost of prior services associated with a change in the plan are recognized in the statement of comprehensive income.
The expense for the period, composed of the cost of services rendered and the financial expense of accretion, constitutes an operating expense.
The other income from activities involves products pertaining to grants. The grants are initially recognized at their fair value under deferred income, where a reasonable assurance exists that they will be received and the Group will conform with the conditions attached to these grants.
They are then recognized as income, pro rata of costs sustained, in compliance with IAS 20. Due to this, the grants to be received can be recorded in the accounts where the assignment contract is signed but the grants have not yet been received.
In compliance with IAS 20, the "Research Tax Credit" is also presented on the line "Other income from regular operations" in the statement of comprehensive income.
Within the scope of its partnership agreement with Orphan Europe on the development of AML, the Group reinvoices, with no margin, certain clinical costs incurred and invoiced to the Group by external providers.
In application of the standard IAS 18, the Group estimates that, within the scope of this partnership, it acts as agent insofar as concerns external costs re-invoiced, in that:
Consequently, the re-invoicing of these external costs to Orphan Europe is presented as a decrease in corresponding expenses sustained by the Group. For 2014, the amount of external costs re-invoiced within the scope of this partnership totaled 562,000 Euros.
Within the scope of this same agreement, the Group also re-invoiced certain internal clinical costs, such as personnel costs associated with the management of clinical trials, or personnel involved in the production of batches necessary for the AML clinical trial. These re-invoiced internal costs are recognized by the Group as other income from ordinary activities. They total 231,000 Euros for the 2014 financial year.
The regular operating results are formed by income from regular operations less regular operating costs. The regular operating costs primarily include the research and development costs, the clinical studies, the intellectual property costs, the structural and general costs, the net allocations of reversals to amortizations and operating provisions, as well as the costs of share-based payments.
The regular operating results are an indicator used by the Group, enabling it to present "a level of operational performance that can serve as a forward-looking approach to recurring performance" (in conformity with Recommendation CNC2009-R03, relative to the format for corporate financial statements under the international accounting framework). In effect, the regular operating results are a management balance that facilitates an understanding of the Group's performance by excluding the other operating income and expenses defined below.
In compliance with IFRS 2, the benefits granted to certain employees in the form of share-based payments are measured at the fair value of the instruments granted.
This remuneration can take the form of either equity or cash instruments.
Share call and subscription options are granted to directors and to certain employees of the Group.
In compliance with IFRS 2, "Share-Based Payment," the fair value of the options is determined on the grantdate.
To determine their value, the Group uses the Black & Scholes mathematical model. This allows them to take into account the characteristics of the plan (exercise price, period of exercise), the market data at the time of assignment (risk-free rate, volatility, expected dividends), and recipient behavior assumptions. Changes in value subsequent to the grant-date have no effect on this initial measurement.
The value of options is notably a function of their expected lifetime. This value is recorded under personnel expenses using the straight-line method between the grant date and the maturity date (rights acquisition period), with a direct contra-entry in the shareholders' equity.
Loans and other financial liabilities are initially measured at their fair value, and then at the amortized cost, calculated using the effective interest method ("EIM").
The transaction costs directly ascribable to the acquisition or issue of a financial liability decrease this financial liability. These costs are then actuarially amortized on the lifetime of the liability, based on the EIM.
The EIM is the rate that equalizes the flow anticipated from future cash outflows at the current net book value of the financial liability, with a view to deducting its amortized cost.
The liabilities at fair value through profit and loss are measured at their fair value.
The other operating income and expenses correspond to individual, unusual, and infrequent items that the Group presents separately in its statement of comprehensive income to facilitate comprehension of its regular operational performance. These items, where significant, form the object of a precise description, including their amount and nature, in the note "Other operating income and expenses."
In conformity with IFRS 8 "Operating Segments", reporting by operating segment is derived from the internal organization of the Group's activities; it reflects management's viewpoint and is established based on internal reporting used by the chief operating decision maker (the Chairman - CEO) to implement the allocation of resources and to assess performance.
The Group's current reporting has enabled it to define a single operating segment.
The net cost of debt includes:
The other financial income and expenses are composed of:
Considering the level of tax losses that can be carried forward, no tax expense is owing, save for the exceptions established under standard IAS 12.
Deferred taxes are calculated for all the time-based differences between the book value of an asset or a liability and its tax value.
Changes in the tax rates are recorded in the results of the fiscal year during which the rate change is decided.
Deferred tax assets resulting from time-based differences or taxes losses carried forward are limited to the deferred tax liabilities with the same maturity, except where their allocation on future taxable income is probable.
Deferred taxes are calculated in function of the most recent tax rates adopted at the date of each fiscal yearend.
Deferred tax assets and liabilities are not discounted and are classified in the balance sheet under non-current assets and liabilities.
The parent company is subject to the territorial economic contribution (Contribution Economique Territoriale - CET), which combines the corporate real estate contribution (cotisation foncière des entreprises - CFE) and the corporate value added contribution (cotisation sur la valeur ajoutée des entreprises - CVAE):
In conformity with the provisions of IAS 12, qualification of the corporate value added contribution as an income tax leads to the recognition of deferred taxes relative to time-based differences existing at year end, with a contra-entry of a net expense in that year's statement of comprehensive income. Where applicable, this deferred tax expense is presented on the line "taxes." For the moment, the parent company does not pay the CVAE.
The cash flow table is prepared using the indirect method and separately presents the cash flows associated with operating, investment, and financing activities.
Operating activities correspond to the company's primary income-generating activities and all the other activities that do not meet the investment or financing criteria. The Group has decided to classify grants received under this category. The cash flows associated with operating activities are calculated by adjusting the net results of variations in working capital requirements, of items with effects of a non-cash nature (amortization, impairment), of disposal gains, of calculated expenses.
Cash flows associated with investment activities correspond to cash flows associated with the purchase of assets, net of supplier debts on the assets, and with the disposal of assets and other investments.
Financing activities are operations that result in changes in the size and composition of the contributed equity and borrowings of the entity. Capital increases and the obtaining or repayment of loans are classified under this category. The Group has chosen to classify the repayable advances under this category.
The increases in assets and liabilities with non-cash effects are eliminated. As such, the assets financed through a finance lease are not included in the period's investments. The decrease in financial debt associated with leases is therefore included under the period's loan repayments.
The Group presents the basic earnings per share and the diluted earnings per share.
The basic earnings per share are calculated by dividing the Group's net results by the weighted average number of shares in circulation during the financial year.
The diluted earnings per share are calculated by dividing the results by the weighted average number of common shares in circulation, increased by all dilutive potential common shares. The dilutive potential common shares include, in particular, the share subscription warrants.
The Group has defined and implemented monitoring for its off-balance sheet commitments so as to know their nature and object. This monitoring pertains to information relative to the following commitments given:
The other income from activities is composed of the following elements:
| (in euros) | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Research Tax Credit | 1,523 688 | 1,366,656 |
| Grants | 271,231 | 294,150 |
| Other earnings | 230,769 | 141,456 |
| Other income from activities | 2,025,687 | 1,802,262 |
The other income was primarily generated by the research tax credit, the grants associated with the pre-clinical research programs in partnership with BPI France.
The "Other income" totaled €230,769 in 2014, representing the sum of the internal costs sustained by the Group within the scope of the AML study, and re-invoiced to the company Orphan Europe to this end. The other external costs associated with this clinical trial were re-invoiced to Orphan Europe with no margin, and do not appear under income from activities, but rather deducted from the associated expenses.
| 12/31/2014 in € | Research and development costs |
Clinical studies | Intellectual property costs |
Overhead and general |
Grand total |
|---|---|---|---|---|---|
| Consumables | 251,917 | 171,975 | - | costs 28,257 |
452,149 |
| Rental and maintenance | 216,780 | 277,778 | - | 290,508 | 785,066 |
| Services, subcontracting, and fees | 356,144 | 2,186,597 | 416,030 | 1,045,220 | 4,003,990 |
| Employee charges | 1,351,320 | 1,016,651 | 74,835 | 2,367,872 | 4,810,679 |
| Other | 35,375 | 32,682 | 2,616 | 601,259 | 671,931 |
| Net depreciation expense provisions | 32,435 | 189,738 | - | 28,065 | 250,238 |
| Grand total | 2,243,971 | 3,875,421 | 493,481 | 4,361,181 | 10,974,054 |
| 12/31/2013 in € | Research and development costs |
Clinical studies | Intellectual property costs |
Overhead and general costs |
Grand total |
|---|---|---|---|---|---|
| Consumables | 288,280 | 186,997 | - | 31,929 | 507,206 |
| Rental and maintenance | 146,297 | 173,456 | - | 416,265 | 736,018 |
| Services, subcontracting, and fees | 629,890 | 1,060,498 | 265,371 | 449,780 | 2,405,539 |
| Employee charges | 1,331,773 | 814,789 | 97,992 | 1,839,667 | 4,084,221 |
| Other | 25,362 | 84,803 | - | 810,878 | 921,043 |
| Net depreciation expense provisions | 81,187 | 141,293 | - | 38,681 | 261,161 |
| Grand total | 2,502,789 | 2,461,836 | 363,363 | 3,587,200 | 8,915,188 |
The personnel costs are broken down as follows:
| 12/31/2014 in € | Research and development costs |
Clinical studies | Intellectual property costs |
Overhead and general |
Grand total |
|---|---|---|---|---|---|
| Wages and salaries | 732,970 | 631,854 | 43,120 | costs 1,051,374 |
2,459,317 |
| JV Share-based compensation plan | 283,559 | 88,598 | 11,408 | 852,318 | 1,235,883 |
| Social security charges | 334,791 | 296,199 | 20,308 | 464,180 | 1,115,479 |
| Total employee costs | 1,351,320 | 1,016,651 | 74,835 | 2,367,872 | 4,810,679 |
| 12/31/2013 in € | Research and development costs |
Clinical studies | Intellectual property costs |
Overhead and general |
Grand total |
|---|---|---|---|---|---|
| Wages and salaries | 819,239 | 221,068 | 38,708 | costs 1,287,914 |
2,366,928 |
| JV Share-based compensation plan | 135,830 | 397,314 | 40,025 | 7,452 | 580,621 |
| Social security charges | 376,705 | 196,407 | 19,259 | 544,302 | 1,136,673 |
| Total employee costs | 1,331,774 | 814,789 | 97,992 | 1,839,667 | 4,084,222 |
Share options have been allocated to the directors, to certain employees, as well as to members of the Board of Directors in the form of share subscription warrants ("BSA") or founder subscription warrants ("BSPCE").
| Types of securities | Founder's share warrants2012 | Share warrants (BSA)2012 | ||
|---|---|---|---|---|
| Number of warrants authorized for issue | 33,788 | 30,034 | ||
| Number of warrants that the shares authorized to issue, for all types of shares |
45,050 | |||
| Total number of warrants issued |
33,788 11,262 |
|||
| 2012/2013/2014 Total number of warrants Allocated 2012/2013/2014 |
33,788 | 5 025 | ||
| Number of warrants exercised | 6,807 | 5,025 | ||
| Date of General Meeting | May 21, 2012 | |||
| Exercise price per new share subscribed | €7.362 | |||
| Final date for exercising warrants | May 20, 2020 | |||
| Parity | 1 warrant for 10 shares | |||
| General conditions of exercise | Warrant holders can only exercise their subscribed warrants: (i) )only upon the occurrence of a firm, definitive operation involving the initial listing of Company shares for trading on a regulated or unregulated stock market, in France or the European Union, or a foreign securities exchange; (ii) on one single occasion, or (iii) on multiple occasions, within a limit of twice a year and at least 100 warrants. Warrant holders shall only be able to exercise the entirety of their warrants, already subscribed or Allocated but not yet subscribed, in the event that one of the following operations occurs: (i) acceptance, by shareholders representing at least sixty-six point six seven percent (66.67%) of the shares constituting the Company's capital, of a firm, definitive buyback offer pertaining to control of the Company (as pursuant to Article L. 233-3 of the Commercial Code). (ii) the formation of a merger agreement providing for absorption of the Company. The securities to which the warrants give rights are common shares. Each warrant shall give the right to ten (10) shares in the Company's share capital. The new shares resulting from the exercise of founder's share warrants (BSPCEs) shall form the object of periodic requests for admission for trading on the regulated market NYSE Euronext. |
|||
| Maximum number of new shares that can be issued |
332,180 |
Within the scope of the BSA2012 and BSPCE2012plans, the board of directors' meeting of July 17, 2014 defined the additional list of beneficiaries, as well as the number of warrants to which each employee may subscribe within the scope of the BSA2012 and BSPCE2012, in relation to the period of June 1st, 2013 to May 31, 2014. As such, 1,000 additional BSA2012 and 13,176 additional BSPE2012 were allocated to Erytech employees.
In conformity with IFRS 2, Erytech performed a valuation of these instruments, and used the Black & Scholes measurement model to this end.
The primary assumptions used to determine the fair value of these instruments are:
The fair value of warrants allocated in 2014 in relation to the 2012 plan was valued at €1,078,084.80 and was fully reported under income for the 2014 financial year.
At the end of 2014, the subscription warrants for the 2012 plan were broken down as follows:
| BSA / BSPCE (Share warrants/founder's warrants) reference |
Extraordinary shareholder' meeting reference |
Parity | Period of exercise |
Number of warrants issued |
Number of warrants allocated |
fiscal year | Number of warrants remaining to be exercised |
Number of warrants remaining to be allocated |
|---|---|---|---|---|---|---|---|---|
| Founder's share warrants | 21/05/2012 | 1 warrant = 10 | 20/05/2020 | 33,788 | 33,788 | 6,807 | 26,981 | - |
| (BSPCE) 2012 | 21/05/2012 | shares | 20/05/2020 | 11,262 | 5,025 | 5,025 | - | 6,237 |
| Share warrants (BSA) 2012 | 1 warrant = 10 | |||||||
| shares | Total | 45,050 | 38,813 | 11,832 | 26,981 | 6,237 |
On January 22, 2014, the board of directors used the delegation granted by the mixed general shareholders' meeting of April 2, 2013, in its twenty-fifth resolution, to decide on a plan for the free allocation of 22,500 founder share subscription warrants (hereinafter entitled BSPCE2014) to the benefit of Erytech directors (12,000 warrants) and to a category of "employees with management status" not yet identified by name (10,500 warrants).
The plan's characteristics are as follows:
| Founder's share warrants (BSPCE)2014 | ||
|---|---|---|
| 22,500 | ||
| 12,000 | ||
| 0 | ||
| Jan. 22, 2014 | ||
| € 12.250 | ||
| Jan. 22, 2024 | ||
| 1 warrant for 10 shares | ||
| In the event of the beneficiary's death, it is stipulated that, pursuant to the provisions of article 163 bis G of the general tax code, the decedent's heirs may exercise the warrants within six months starting from the death. The founder's share warrants (BSPCE)2014 can be exercised: on one single occasion, or except in the event of an M&A operation, at most four (4) times per year, and for the exercise of a minimum of fifty (50) founder's share warrants (BSPCE)2014. In the event of a so-called M&A operation, holders of BSPCE20124 shall have five (5) business days starting from notice by the Company of the occurrence of such an event to exercise all of their BSPCE20124. However, the exercise of the BSPCE2014 may be canceled in the event of the ultimate non-performance of the takeover or the merger operation, for any reason whatsoever. |
||
| 120,000 | ||
In the event of a beneficiary's departure from the Group for any reason whatsoever, this beneficiary shall retain the BSPCE2014 to which he subscribed prior to his departure. However, in the event of a beneficiary's departure from the Group, for any reason whatsoever, prior to subscription of the BSPCE2014 to which the beneficiary has a right, the BSPCE2014 shall be considered invalid vis-a-vis this beneficiary. Within this hypothesis, the BSPCE2014 not subscribed may be re-allocated to other beneficiaries within the same category and/or replacing the person who left the company.
In any case, the BSPCE2014 not exercised at January 22, 2024 shall become duly and fully expired.
Concerning the directors and in accordance with IFRS 2, it was considered that the entirety of the 12,000 warrants were assigned on January 22, 2014. The fact that the directors can only subscribe to one third of these warrants each year constitutes a condition of service. In other words, these warrants form the object of a gradual 3-year acquisition period.
In the absence of a nominal allocation to "employees with management status", the Group estimated that definition of the allocation date in accordance with IFRS 2 could not be January 22, 2014 for the latter warrants, and that the allocation of each tranche of warrants would take place subsequently, during the 2nd quarter of each year over the period of 2015 to 2017, upon designation of the beneficiaries (with immediate acquisition of the rights associated with each tranche of warrants). Consequently, as no designation had yet been made at December 31, 2014, the Group did not record any expense for the period in relation to these BSPCE2014.
In conformity with IFRS 2, Erytech performed a valuation of the BSPCE2014 allocated to directors, and used the Black & Scholes measurement model to perform this valuation.
The primary assumptions used to determine the fair value of the BSPCE2014 allocated to directors are:
Risk-free rate: between 1.12% and 1.70% in function of the tranches (in function of the zero coupon government bond rates curve);
Anticipated dividends: zero;
The fair value of the plan was valued at €372,059. This expense will be distributed gradually over the duration of the 3-year plan in conformity with IFRS 2 ("graded vesting method"). An expense of €157,798 was recorded to this end under personnel expenses, "Structural and general costs", at December 31, 2014.
Moreover, the board of directors' meeting of December 4, 2014 transformed 3,000 BSPCE2014 into 3,000 BSA2014 for a Medical Director at the subsidiary ERYECH PHARMA INC., in accordance with Annex IV-BSA2014 Regulations, as recorded in the minutes. This allocation is conditional upon the recruitment of a person to this position. As this suspensive clause has not yet been lifted, these BSA2014 had no accounting effect on the 2014 financial year.
| in euros | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Research and development costs | 32,435 | 81,187 |
| Clinical studies | 189,738 | 141,293 |
| Intellectual property costs | - | - |
| Structural and general costs | 28,065 | 38,681 |
| Net allocation to amortizations and provisions | 250,238 | 261,161 |
| (in euros) | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Interest on leasing | (6,801) | (4,656) |
| Interest on bonds | - | (1,059,272) |
| Financial charges | (43,205) | (55,860) |
| Net cost of debt | (50,006) | (1,119,788) |
| Earnings (losses) from disposal of VMP | 140,935 | 19,689 |
| Other Financial Income | 619 | 3,210 |
| Other Financial Charges | (23,375) | (2,700) |
| Other income & financial charges | 118,179 | 20,199 |
| Total Income (Loss) | 68,173 | (1,099,589) |
The financial expenses were impacted in 2013 by the fair-value conversion of the A, B, and Recordati bonds, an amount of €240,000 paid to bondholders within the scope of the conversion and for expenses related to the restatement performed on the repayable advances. These bonds were converted in 2013.
| in euros | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Deferred tax assets | - | - |
| Deferred tax liabilities | - | - |
| Net deferred taxes | - | - |
| in euros | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Before-tax results | (8,880,194) | (8,285,346) |
| Nominal tax proceeds | 3,057,451 | 2,852,645 |
| Non-activated deficit from fiscal year | (3,144,880) | (2,626,328) |
| CICE ( jobs & competitiveness tax credit) non | 14,748 | 9,877 |
| taxation Tax credits |
524,606 | 470,540 |
| Cancellation of the non-conversion premium. | (476,742) | |
| Impact of the IFRS 2 restatement | (425,515) | (201,374) |
| Other differences | (6,252) | 11,400 |
| Effective tax (loss)/income | 20,158 | 40,018 |
As a prudential measure, the losses that can be carried forward were activated only in the amount of the deferred tax liabilities; the amounts activated are not significant.
| in euros | 12.31.2013 | Acquisitions/Provisio n for depreciation |
Disposals | 12.31.2014 |
|---|---|---|---|---|
| Other intangible assets | ||||
| Gross | 109,177 | 25,798 | - | 134,975 |
| Amortization and depreciation | (94,900) | (9,124) | - | (104,024) |
| Net book value | 14,277 | 16,674 | 30,951 |
| in euros | 12.31.2012 | Acquisitions/Provisi on for depreciation |
Disposals | 12.31.2013 |
|---|---|---|---|---|
| Other intangible assets | ||||
| Gross | 100,168 | 9,009 | - | 109,177 |
| Amortization and depreciation | (70,575) | (24,325) | - | (94,900) |
| Net book value | 29,593 | (15,316) | 14,277 |
| in euros | 12.31.2013 | Acquisitions/Provision | Disposals/Transfe | 12.31.2014 |
|---|---|---|---|---|
| for depreciation | rs | |||
| Assets financed through lease with option | ||||
| to buy | ||||
| Laboratory equipment | ||||
| Gross | 973,877 | 973,877 | ||
| Amortization and depreciation | (654,154) | (98,593) | (752,747) | |
| Net book value | 319,723 | 221,130 | ||
| Assets under construction | 20,000 | (20,000) | - | |
| Assets not financed through lease with option to buy |
||||
| Plant, equipment, and tooling | ||||
| Gross | 337,673 | 279,784 | 617,457 | |
| Amortization and depreciation | (308,027) | (38,371) | (346,398) | |
| Net book value | 29,646 | 271,059 | ||
| General equipment, fixtures and fittings | ||||
| Gross | 953,455 | 5,390 | 958,845 | |
| Amortization and depreciation | (540,239) | (95,616) | (635,855) | |
| Net book value | 413,216 | 322,990 | ||
| Office equipment and computers | ||||
| Gross | 57,668 | 17,988 | 75,656 | |
| Amortization and depreciation | (27,306) | (8,535) | (35,841) | |
| Net book value | 30,362 | 39,815 | ||
| Assets under construction | 218,109 | (105,629) | 112,480 | |
| GRAND TOTAL | ||||
| Gross | 2,342,673 | 521,270 | (125,629) | 2,738,314 |
| Amortization and depreciation | (1,529,726) | (241,114) | - | (1,770,840) |
| Net book value | 812,947 | 280,156 | (125,629) | 967,474 |
| in euros | 12.31.2012 | Acquisitions/Provision for depreciation |
Disposals/Transfers | 12.31.2013 |
|---|---|---|---|---|
| Assets financed through lease with option to | ||||
| buy | ||||
| Laboratory equipment | ||||
| Gross | 733,464 | 240,413 | 973,877 | |
| Amortization and depreciation | (547,573) | (106,581) | (654,154) | |
| Net book value | 185,891 | 319,723 | ||
| Assets under construction | 40,000 | 122,340 | (142,340) | 20 000 |
| Assets not financed through lease with option to buy |
||||
| Plant, equipment, and tooling | ||||
| Gross | 318,096 | 19,577 | 337,673 | |
| Amortization and depreciation | (281,622) | (26,405) | (308,027) | |
| Net book value | 36,474 | 29,646 | ||
| General equipment, fixtures and fittings | ||||
| Gross | 949,721 | 3,734 | 953,455 | |
| Amortization and depreciation | (444,513) | (95,726) | (540,239) | |
| Net book value | 505,208 | 413,216 | ||
| Office equipment and computers | ||||
| Gross | 25,041 | 32,627 | 57,668 | |
| Amortization and depreciation | (21,184) | (6,122) | (27,306) | |
| Net book value | 3,857 | 30,362 | ||
| Assets under construction | ||||
| GRAND TOTAL | ||||
| Gross | 2,066,322 | 418,691 | (142,340) | 2,342,673 |
| Amortization and depreciation | (1,294,892) | (234,834) | - | (1,529,726) |
| Net book value | 771,430 | 183,857 | (142,340) | 812,947 |
| in euros | 12.31.2013 | 12.31.2014 |
|---|---|---|
| Security deposits and bonds | 82,908 | 81,814 |
| Total other non-current financial assets | 82,908 | 81,814 |
| in euros | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Production inventory | 122,936 | 55,848 |
| Laboratory inventory | 75,420 | 82,391 |
| Total Inventory | 198,356 | 138,238 |
| in euros | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Research Tax Credit | 1,523,688 | 1,366,656 |
| Tax receivables (VAT, etc.) and other | 494,271 | 233,151 |
| receivables Prepayments |
216,779 | 101,067 |
| Other subsidies to be received | - | - |
| Other current assets | 2,234,738 | 1,700,874 |
| in euros | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Cash and cash equivalents | 36,988,436 | 15,112,523 |
| Bank overdrafts | - | - |
| Net cash on hand and at bank | 36,988,436 | 15,112,523 |
The cash position is composed of the following items:
On April 30, 2013, the Group signed a liquidity agreement with the company Bryan Garnier for an amount of 600,000 euros. The agreement was since reduced, in April 2014, to €200,000. At December 31, 2014, the Group held under mandate, within the scope of the liquidity agreement, €251,102 in cash included in the net cash position (€0 at December 31, 2013).
At December 31, 2013, the capital of the parent company was broken down into 5,558,952 shares, fully paid up, with a nominal value of 0.1 euro.
Following a new raising of funds on the Euronext market in October 2014, as well as the exercise of subscription warrants, the capital was increased to 6,882,761 shares with a nominal value of 0.1 euro.
| Number of shares as of December 31, 2013 | 5,558,952 |
|---|---|
| Exercise of share warrants | 99,320 |
| Issuance of new shares on Euronext | 1,224,489 |
| Number of shares as of December 31, 2014 | 6,882,761 |
The costs for listing on the regulated market were allocated to the issue premium.
At December 31, 2014, the Group held, under mandate within the scope of the liquidity agreement signed with Bryan Garnier, 4,500 company shares at a weighted price of €28.00, i.e., €126,006 (52,935 shares at a weighted price of €11.34, i.e., €599,573 at December 31, 2013).
| in euros | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Net income | (8,860,036) | (8,144,721) |
| Weighted number of shares for the period | 5,874,794 | 4,686,150 |
| Basic earnings per share | (1.51) | (1.74) |
| Diluted earnings per share | (1.51) | (1.74) |
At December 31, 2014, the 452,180 potential shares that could be issued within the scope of exercising subscription warrants issued were not taken into consideration in calculation of the diluted earnings, as their effects would be anti-dilutive.
The provisions can be broken down in the following manner:
| in euros | 12.31.2014 | 12.31.2013 |
|---|---|---|
| IDR provisions | 88,594 | 117,144 |
| Provisions for disputes. | - | - |
| Provisions | 88,594 | 117,144 |
The regime applicable at Erytech Pharma SA is defined by the collective agreement for the pharmaceutical industry.
The Group recognizes actuarial differences under other items of comprehensive income. The pension commitments are not covered by plan assets. The portion of the provision for which the maturity is less than one year is not significant.
The calculation assumptions for measuring the provision concerning employees are as follows:
| 12.31.2014 | 12.31.2013 | |
|---|---|---|
| Discount rate | 1.49% | 3.17% |
| Wage increase | 2% | 3% |
| Social welfare contribution rate | Non-executive 44% |
Non-executive 47% |
| Age of retirement: | Executive 65-67 years |
Executive 55% 65-67 years |
| Mortality table | 54% INSEE 2014 |
INSEE 2013 |
| in euros | BEGINNING | Other* | Provisions | Unused reversals |
ENDING | |
|---|---|---|---|---|---|---|
| Period from 01.01 to 12.31.2014 |
||||||
| IDR provision Provision for disputes. |
117,144 - |
(28,550) | 88,594 - |
|||
| Net closing balance | 117,144 | (28,550) | 88,594 | |||
| Period from 01.01 to 12.31.2013 |
||||||
| IDR provision | 97,098 | 20,046 | 117,144 | |||
| Provision for disputes. | 106,665 | 106,665 | - | |||
| Net closing balance | 203,763 | 20,046 | 106,665 | 117,144 |
* The "Other movements" correspond to actuarial differences recognized.
| in euros | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Debt associated with leases | 220,376 | 303,217 |
| Bank overdrafts | - | - |
| Conditional advances | 549,161 | 693,669 |
| Convertible bonds | - | - |
| Loans | - | 15,000 |
| Debt | 769,537 | 1,011,886 |
| in euros | 2014 | ||||||
|---|---|---|---|---|---|---|---|
| Amounts due | TOTAL | ||||||
| Less than one year More than one | |||||||
| Loans | year | - | |||||
| Conditional advances | 257,500 | 291,661 | 549,161 | ||||
| Debt associated with leases | |||||||
| Convertible bonds | 76,002 | 144,374 | 220,376 | ||||
| Bank overdrafts | - | ||||||
| Total loans | 333,502 | 436,035 | 769,537 |
| in euros | 2013 | |||||
|---|---|---|---|---|---|---|
| Amounts due | TOTAL | |||||
| Less than one year More than one | ||||||
| Loans | year 15,000 |
15,000 | ||||
| Conditional advances | 144,502 | 549,167 | 693,669 | |||
| Debt associated with leases | ||||||
| Convertible bonds | 82,841 | 220,376 | 303,217 | |||
| Bank overdrafts | - | - | - | |||
| Total loans | 242,343 | 769,543 | 1,011,886 |
The conditional advances from public authorities form the object of agreements with BPI FRANCE. The Group benefits from three agreements on repayable advances with BPI FRANCE Innovation. These advances are not interest-bearing and are 100% repayable (nominal value) in the event of technical and/or commercial success.
Within the IFRS framework, the fact that a repayable advance does not require an annual interest payment amounts to the consideration that the Group has benefited from a zero-interest loan, i.e., more favorable than market conditions. The difference between the amount of the advance at its historical cost and that of the advance discounted at the risk-free rate (10 year OAT) increased by an estimated credit spread is considered as a grant received from the State. These grants are distributed over the estimated duration of the projects financed by these advances.
The portion of the conditional advances at more than one year is recorded under financial debts - non-current portion, while the portion at less than one year is recorded under financial debts - current portion.
Since its creation, the Group has received 3 advances from BPI FRANCE, repayable under certain conditions, the main terms of which are presented below:
The first assistance, granted by BPI FRANCE, for a total amount of €735,000, concerns the program for the "development of a new treatment against pancreatic cancer through the administration of allogenic red blood cells incorporating L-asparaginase".
This assistance was distributed in 3 phases:
The repayment of this conditional advance will be made according to a fixed payment schedule that will end at the latest on 06/30/2016.
The Group has undertaken to repay the entirety of the loaned amount according to the following payment schedule:
The second assistance, granted by BPI FRANCE FEDER, which provided for a total amount of €135,000, concerns a program for the "preclinical validation of the encapsulation of interfering RNA for therapeutic use in red blood cells, notably to limit inflammation of the cirrhotic liver and/or prevent the development of hepatocellular carcinomas".
This assistance provided for distribution in 4 phases:
The Group will have received €81,000 from BPI FRANCE/FEDER under this program. As the work corresponding to the FEDER assistance is currently terminated, the Group will not receive the last two payments of €27,000.
The repayment of this conditional advance will be made according to a fixed payment schedule that will end at the latest on June 30, 2016.
The Group has undertaken to repay the entirety of the loaned amount according to the following payment schedule:
The third assistance, granted by BPI FRANCE within the scope of the TEDAC project, is for a total amount of €4,895,052. This assistance is distributed upon completion of the following key milestones:
The Group undertakes to repay BPI FRANCE initially:
In a second phase, where the cumulative sales revenue reaches €60,000,000, the Group undertakes to pay BPI FRANCE a sum of 2.5% of the sales revenue generated by development of the products resulting from the project, within the limit of a total repayment of €15M over 15 years.
| in euros | 12.31.2014 | 12.31.2013 |
|---|---|---|
| Other current liabilities | ||
| Taxation and social security | 970,629 | 815 |
| Deferred income | 368,436 | 617 648 |
| Other payables | 500,593 | 854 347 |
| Other current liabilities | 1,839,658 | 1,811, 388859 |
Gil Beyen, Pierre Olivier Goineau, and Yann Godfrin are the Group directors; Jérome Bailly is its head pharmacist. The other related parties are members of the board of directors.
| For 2014 in euros | Total gross compensation |
Fixed portion | Variable or exceptional portion |
In-kind benefits (excluding GSC) |
Net attendance fees |
Fees, net of outlays |
Optional unemployment scheme GSC |
|---|---|---|---|---|---|---|---|
| Gil Beyen | €338,168 | €244,000 | €91,500 | €2,668 | |||
| Pierre-Olivier Goineau | €252,922 | €175,783 | €67,500 | €4,020 | €5,619 | ||
| Yann Godfrin | €252,768 | €175,550 | €67,500 | €4,099 | €5,619 | ||
| Jérôme Bailly | €69,258 | €60,755 | €5,172 | €3,331 | |||
| Galenos sprl * | €1,000 | €1,000 | |||||
| Sven Andreasson | €19,476 | €19,476 | |||||
| Philippe ARCHINARD | €20,476 | €20,476 | |||||
| Hilde WINDELS | €9,024 | €9,024 | |||||
| Martine GEORGE | €10,024 | €10,024 |
| For 2014 in euros | Total warrants allocated end 2013 |
warrants allocated in 2014 |
warrants exercised in 2014 |
Balance end 2014 |
Fair Market Value of warrants allocated in 2014 |
|---|---|---|---|---|---|
| by value | |||||
| Gil Beyen | 5,632 | 7,631 | 3,400 | 9,863 | €513,960 |
| Pierre-Olivier Goineau | 4,993 | 3,515 | - | 8,508 | €220,482 |
| Yann Godfrin | 4,993 | 3,515 | - | 8,508 | €234,127 |
| Jérôme Bailly | 943 | 515 | 500 | 958 | €39,166 |
| Galenos sprl * | - | - | |||
| Sven Andreasson | 1,288 | 500 | 1,788 | - | €38,025 |
| Philippe ARCHINARD | 837 | 500 | 1,337 | - | €38,025 |
| Hilde WINDELS | - | - | |||
| Martine GEORGE | - | - |
* Company controlled by Mr. Sven Andreasson
| For 2013, in euros | Total gross compensation |
Fixed portion | Variable or exceptional portion |
In-kind benefits (excluding |
Net attendance fees |
Fees, net of outlays |
Optional unemployment scheme GSC |
|---|---|---|---|---|---|---|---|
| Gil Beyen | €164,736 | €164,736 | GSC) | ||||
| Gil Beyen BVBA | €87,500 | €87,500 | |||||
| Pierre-Olivier Goineau | €251,007 | €165,771 | €75,000 | €4,351 | €5,885 | ||
| Yann Godfrin | €251,110 | €164,996 | €75,000 | €5,229 | €5,885 | ||
| Jérôme Bailly | €62,644 | €55,293 | €5,000 | €2,351 | |||
| Galenos sprl * | €5,250 | €5,250 | |||||
| Sven Andreasson | €12,958 | €12,958 | |||||
| Philippe ARCHINARD | €13,083 | €13,083 | |||||
| Marc BEER | €8,333 | €8,333 | |||||
| Alain MAIORE | |||||||
| Auriga Partners | €120,000 | €120,000 | |||||
| IDInvest Partners | €120,000 | €120,000 |
| For 2013, in euros | Total warrants allocated end 2012 |
warrants allocated in 2014 |
warrants exercised in 2013 |
Balance end 2013 |
Fair Market Value of warrants allocated in |
|---|---|---|---|---|---|
| by value 2013 | |||||
| Gil Beyen | 5 632 | 5,632 | €239.811 | ||
| Gil Beyen BVBA | |||||
| Pierre-Olivier Goineau | 2,478 | 2,515 | 4,993 | €107,089 | |
| Yann Godfrin | 2,478 | 2,515 | 4,993 | €107,089 | |
| Jérôme Bailly | 428 | 515 | 943 | €21,929 | |
| Galenos sprl * | |||||
| Sven Andreasson | 1,033 | 255 | 1,288 | €10,858 | |
| Philippe ARCHINARD | 684 | 153 | 837 | €6,515 | |
| Marc BEER | 1,033 | 51 | 1 084 | €2,172 | |
| Alain MAIORE | 816 | 816 |
* Company controlled by Mr. Sven Andreasson
The Group has no further related parties.
| 12/31/2014 in euros | Balance sheet value |
Fair market value by earnings |
Loans and receivables |
Debt at amortized cost |
Fair market value |
|
|---|---|---|---|---|---|---|
| Non-current financial assets | (1) | 81,814 | 81,814 | 81,814 | ||
| Other current assets | (1) | 2,234,738 | 2,234,738 | 2,234,738 | ||
| Cash and cash equivalents | (2) | 36,988,436 | 36,988,436 | 36,988,436 - |
||
| Total financial assets | 39,304,988 | 36,988,436 | 2,316,552 | - | 39,304,988 | |
| Financial liabilities - Non-current portion | (1) | 436,035 | 436,035 | 436,035 | ||
| Financial liabilities - Current portion | (1) | 333,502 | 333,502 | 333,502 | ||
| Trade payables & related accounts | (1) | 2,084,546 | 2,084,546 | 2,084,546 | ||
| Total | 2,854,083 | - | - | 2,854,083 | - 2,854,083 |
|
| 12/31/2013 in euros | Balance sheet value |
Fair market value by earnings |
Loans and receivables |
Debt at amortized cost |
Fair market value |
|
| Non-current financial assets | (1) | 82,908 | 82,908 | 82,908 | ||
| Other current assets | (1) | 1,700,874 | 1,700,874 | 1,700,874 | ||
| Cash and cash equivalents | (2) | 15,112,523 | 15,112,523 | 15,112,523 | ||
| Total financial assets | 16,896,305 | 15,112,523 | 1,783,782 | - | - 16,896,305 |
|
| Financial liabilities - Non-current portion | (1) | 730,545 | 730,545 | 730,545 | ||
| Financial liabilities - Current portion | (1) | 281,341 | 281,341 | 281,341 | ||
| Trade payables & related accounts | (1) | 1,421,436 | 1,421,436 | 1,421,436 | ||
| Total | 2,433,323 | - | - | 2,433,323 | - 2,433,323 |
(1) The book value of these assets and liabilities is a reasonable approximation of their fair value.
(2) Fair value at level 2
The Group uses the Euro as its reference currency within the scope of its disclosures and financial communications. However, a significant portion, in the amount of 10% of its operating expenses, is denominated in US dollars (agency office in Philadelphia, collaborations relating to the production of clinical batches with the American Red Cross, business development consultants, consultants for the development of clinical trials in the United States, and various collaborations around tests and clinical projects in the United States).
To date, the Group has not opted to use active hedging techniques, and has not made recourse to derivative instruments to this end. Unfavorable exchange rate fluctuations between the euro and the dollar that are difficult to predict could affect the financial position of the Company.
This dependency will increase, as the Group will perform clinical trials in the USA and, in the longer term, sell on this market. The Group will opt to use exchange rate hedging techniques.
Expenses in US Dollars totaled \$949,232 during the 2014 financial year. The counter-values recorded in the accounts totaled €714,807 in relation to the receipt of invoices and price fluctuations. This represents an average annual rate of \$1.328 per €1 (\$1.324/€ on average in 2013).
However, the EUR/USD rate fell considerably at the period end, reaching \$1.2141 per €1 at December 31, 2014.
The Group purchased 1 million dollars at the rate of \$1.2197 per €1 during December 2014.
The exchange rate differences are not significant for the periods presented.
The Group has been structurally loss-generating since its creation. The net cash flows associated with the Group's operating activities were respectively -7.2 million Euros at December 31, 2014 and -6.5 million Euros at December 31, 2013.
Historically, the Group has financed its growth by strengthening its shareholders' equity in the form of capital increases and the issue of convertible bonds. The capital increase associated with its introduction on the stock market in May 2013, as well as the operation renewed in 2014, enables the Group to ensure its business continuity over several years.
The remaining contractual maturities of financial liabilities are broken down as follows (including interest payments):
| in euros | 2014 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Contractual cash flows | |||||||||
| Book value | Total | Less than 1 | 1 to 5 years | ||||||
| Loans | |||||||||
| Conditional advances | 549,161 | (580,107) | (257,500) | (322,607) | |||||
| Debt associated with leases | |||||||||
| Convertible bonds | 220,376 | (230,183) | (80,702) | (149,481) | |||||
| Bank overdrafts | |||||||||
| Trade payables and related | |||||||||
| accounts | |||||||||
| 2,084,546 | (2,084,546) | (2,084,546) | |||||||
| Total | 2,854,083 | (2,894,836) | (2,422,748) | (472,088) |
| in euros | 2013 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Contractual cash flows | |||||||||
| Book value | Total | Less than 1 | 1 to 5 years | ||||||
| Loans | 15,000 | (15,499) | (15,499) | - | |||||
| Conditional advances | 693,669 | (763,607) | (183,500) | (580,107) | |||||
| Debt associated with leases | |||||||||
| Convertible bonds | 303,217 | (319,826) | (89,643) | (230,183) | |||||
| Bank overdrafts | - | - | - | - | |||||
| Trade payables and related | - | - | - | - | |||||
| accounts | |||||||||
| 1,421,436 | (1,421,436) | (1,421,436) | |||||||
| Total | 2,433,322 | (2,520,368) | (1,710,078) | (810,290) |
The costs associated with clinical trials are recognized as expenses as and when they are sustained.
Each patient included results in an obligation for Erytech to sustain certain costs whether or not the study continues, and to do so in addition to the expenses already incurred. When a patient is recruited, the Group establishes a provision to cover all the costs sustained to continue the clinical trial.
The remainder of the costs sustained leading up to the end of the clinical trial (patients not yet recruited) are monitored off-balance sheet.
| 12/31/2014 in Keuros | ERYTECH contractual commitment | |||
|---|---|---|---|---|
| Clinical trial name |
Accrued payables, tax incl. |
Definite accrued payables |
Uncertain (Off balance sheet, net of taxes) |
Comment |
| 2007/04 | - | - | - | Trial ended |
| 2008/02 | - | - | - | Trial ended |
| 2009/06 | 200 | - | - | Trial ended |
| 2012/09 | 41 | - | 1 014 | Recruitment begun |
| 2012/10 | 4 | - | - | Recruitment begun |
| 2013/03 | 256 | - | 4 526 | Recruitment begun |
| Accrued payables | off-balance sheet | |||
| 501 | 5 539 |
| 12/31/2013 in Keuros | ERYTECH contractual commitment | |||
|---|---|---|---|---|
| Clinical trial name |
Accrued payables, tax incl. |
Definite accrued payables |
Uncertain (Off balance sheet, net of taxes) |
Comment |
| 2007/04 | - | - | - | Trial ended |
| 2008/02 | - | - | - | Trial ended |
| 2009/06 | 347 | - | - | Recruitment ended |
| 2012/09 | - | - | - | Recruitment not begun |
| 2012/10 | - | - | - | Recruitment not begun |
| 2013/03 | - | - | - | Recruitment not begun |
| Accrued payables | off-balance sheet | |||
| 347 | - |
The off-balance sheet commitments relating to simple leases total €687,000 and essentially correspond to the lease of buildings. The maturities on these expenses are as follows:
Less than 1 year: €397,000 Between 1 year and 5 years: €290,000 More than 5 years: €0
For the 2014 financial year, the auditor fees paid on the financial year totaled:
ERYTECH PHARMA
Period from 01/01/14 to 12/31/14
| HEADINGS | GROSS | Amortization | Net (N) 12/31/2014 |
Net (N-1) 12/31/2013 |
|---|---|---|---|---|
| SUBSCRIBED CAPITAL NOT CALLED UP | ||||
| INTANGIBLE ASSETS Start-up costs Development costs Licenses, Patents, and similar rights Business goodwill Other intangible assets |
134,975 | 104,025 | 30,951 | 14,277 |
| Advances and payments on intangible assets | ||||
| TOTAL intangible assets TANGIBLE FIXED ASSETS Land Buildings |
134,975 | 104,025 | 30,951 | 14,277 |
| Technical systems, industrial equipment and infrastructure Other tangible assets Assets under construction Advances and deposits |
617,457 1,034,501 112,480 |
346,398 671,695 |
271,059 362,806 112,480 |
29,646 443,579 20,000 |
| TOTAL tangible assets INVESTMENTS Investments in companies counted using the equity method Other participating interests Receivables relating to participating interests Other investments |
1,764,439 1 |
1,018,093 | 746,345 1 |
493,225 |
| Loans Other financial assets |
458,923 | 458,923 | 581,873 | |
| TOTAL Investments | 458,524 | 458,924 | 581,873 | |
| NONCURRENT ASSETS | 2,358,337 | 1,122,117 | 1,236,220 | 1,089,375 |
| INVENTORY AND WORKS IN PROGRESS Raw materials and supplies Inventory of in-process goods Inventory of in-process services Inventories of intermediate and finished products |
198,356 | 198,356 | 138,238 | |
| Inventory of goods for resale TOTAL Inventory |
198,356 | 198,356 | 136,238 | |
| RECEIVABLES Advances and payments on account Trade receivables Other receivables Called up share capital, not paid |
104,870 2,128,952 |
104,870 2,128,962 |
429 87,192 1,716,965 |
|
| TOTAL receivables: | 2,233,832 | 2,233,832 | 1,804,586 | |
| MISCELLANEOUS CASH AT BANK AND IN HAND Marketable securities Cash at bank and in hand Prepayments |
3,000,583 33,654,518 216,779 |
3,000,583 33,654,518 216,779 |
15,112,523 101,067 |
|
| TOTAL Miscellaneous cash at bank in hand: | 36,871,880 | 36,871,880 | 15,213,590 | |
| CURRENT ASSETS | 39,304,069 | 39,304,069 | 17,156,414 | |
| Debt issuance costs to be spread out Bond redemption premiums Asset translation adjustments |
TOTAL ASSETS 41,662,406 1,122,117 40,540,288 18,245,790
Translated from French for convenience purposes only
Period from 01/01/14 to 12/31/14
TOTAL ASSETS 40,540,288 18,245,790
| HEADINGS | Net (N) 12/31/2014 |
Net (N-1) 12/31/2013 |
|---|---|---|
| NET FINANCIAL POSITION | ||
| Individual or share capital of which paid 688,276 |
688,276 | 555,895 |
| Issuance, merger, contribution premiums, etc. | 71,375,715 | 42,335,338 |
| Revaluation adjustments of which includes the equity method evaluation |
||
| Legal reserve difference |
||
| Reserves required by articles of association or contract | ||
| Regulated reserves Other reserves |
||
| Carry forward | (28,774,932) | (22,295,938) |
| Financial year's results | (7,283,237) | (6,478,994) |
| TOTAL Net financial position: | 36,005,821 | 14,116,301 |
| INVESTMENT GRANTS | ||
| REGULATED PROVISIONS | ||
| SHAREHOLDERS' EQUITY | 36,005,821 | 14,116,301 |
| Proceeds from the issuance of equity securities | ||
| Conditional advances | 580,107 | 763,607 |
| OTHER SHAREHOLDERS' EQUITY | 580,107 | 763,607 |
| Provisions for liabilities Provisions for charges |
||
| PROVISIONS FOR RISKS AND LIABILITIES | ||
| FINANCIAL DEBTS | ||
| Convertible bonds | ||
| Other bonds | ||
| Bank loans and overdrafts Miscellaneous other loans and advances |
15,000 | |
| TOTAL debt: | 15,000 | |
| ADVANCES AND DEPOSITS RECEIVED ON CONTRACTS | ||
| OTHER LIABILITIES | ||
| Trade payables and related accounts | 2,096,901 | 1,524,652 |
| Taxation and social security | 988,430 | 829,988 |
| Liabilities on fixed assets and related Other payables |
500,593 | 347,388 |
| TOTAL miscellaneous debt: | 3,585,925 | 2,702,028 |
| DEFERRED INCOME | 368,436 | 648,854 |
| DEBTS | 3,954,360 | 3,365,881 |
| Translation differences -liabilities | ||
Period from 01/01/14 to
12/31/14
ERYTECH PHARMA
| HEADINGS | France | Export | Net (N) 12/31/2014 |
Net (N-1) 12/31/2013 |
|---|---|---|---|---|
| Sale of goods purchased for resale | ||||
| Production of goods sold | ||||
| Services sold | 791,853 | 791,853 | 483,964 | |
| Net sales revenue | 791,853 | 791,853 | 483,964 | |
| Production transferred to inventory | ||||
| Production capitalized | ||||
| Operating subsidies | 271,231 | 294,150 | ||
| Reversals of provisions and amortization, transfers of charges | 39,754 | 133,225 | ||
| Other earnings | 10,294 | 464 | ||
| OPERATING INCOME | 1,113,132 | 911,804 | ||
| EXTERNAL CHARGES | ||||
| Purchases of goods for resale (including customs duties) | ||||
| Change in inventory of goods for resale | ||||
| Purchases of raw materials and other consumables | 613,929 | 578,915 | ||
| Change in inventory [raw materials and consumables] | (60,118) | (22,255) | ||
| Other purchases and external charges | 5,866,460 | 4,308,504 | ||
| TOTAL external charges: | 6,420,271 | 4,865,164 | ||
| TAXES DUTIES AND SIMILAR PAYMENTS | 66,537 | 38,114 | ||
| EMPLOYEE CHARGES | ||||
| Wages and salaries | 2,359,456 | 2,475,736 | ||
| Social security charges | 1,211,628 | 1,192,720 | ||
| TOTAL employee charges: | 3,571,084 | 3,668,456 | ||
| PROVISIONS FOR OPERATIONS | ||||
| Charges to impairment of non-current assets | 151,645 | 152,578 | ||
| Charges to provisions of non-current assets | ||||
| Charges to provisions on current assets | ||||
| Provisions for liabilities and charges | ||||
| TOTAL operating provisions: | 151,645 | 152,578 | ||
| OTHER OPERATING CHARGES | 88,250 | 43,325 | ||
| OPERATING CHARGES | 10,297,787 | 8,767,638 | ||
| OPERATING RESULTS | (9,184,655) | (7,855,834) | ||
ERYTECH PHARMA
| HEADINGS | Net (N) 12/31/2014 |
Net (N-1) 12/31/2013 |
|---|---|---|
| OPERATING RESULTS | (9,184,655) | (7,855,834) |
| Allocated profit or transferred loss Loss borne or profit transferred |
||
| FINANCIAL INCOME | ||
| Financial income from participating interests Income from other securities and fixed asset receivables Other interest and similar income Reversals of provisions, transfers of charges |
317,545 100,607 605 |
534,771 3,195 |
| Foreign exchange gains Net proceeds from the disposal of marketable securities |
513 | |
| FINANCIAL EXPENSES Financial allocations for amortization and provisions Interest payable and similar expenses Foreign exchange losses Net expenses on the disposal of term investments |
419,270 429 24,867 |
537,966 100,607 436,881 2,700 |
| 25,367 | 542,188 | |
| NET FINANCIAL INCOME(LOSS) | 393,903 | (4,222) |
| EARNINGS BEFORE INCOME TAX | (8,790,751) | (7,860,056) |
| NON-RECURRING INCOME Non-recurring income on revenue transactions Exceptional income on capital operations |
201 | 27,829 |
| Reversals on provisions and transfers of expenses | 201 | 27,929 |
| NON-RECURRING CHARGES Non-recurring charges on revenue transactions Non-recurring charges on capital transactions Non-recurring allocations for amortization and provisions |
15,605 770 |
13,423 |
| 16,375 | 13,423 | |
| NONRECURRING PROFIT (LOSS) | (16,174) | 14,406 |
| Employee profit sharing Income taxes |
(1,523,688) | (1,366,656) |
| TOTAL INCOME TOTAL CHARGES |
1,532,603 8,815,841 |
1,477,599 7,956,593 |
Appendix to the balance sheet prior to annual distribution, characterized by:
| - total from statement of financial position in €: |
€40,540,288.21 |
|---|---|
| - sales revenue in €: |
€791,852.77 |
| - net book results in €: |
(€7,283,237.28) |
The financial year had a duration of 12 months, covering the period from 01/01/2014 to 12/31/2014.
The notes and tables presented below form an integral part of the annual financial statement.
In October 2014, the company successfully raised €30 M, pertaining to a total of 1,224,489 new shares issued within the scope of a capital increase, with suppression of the preferential subscription right, reserved for investors regularly investing in securities specific to the fields of health care, representing approximately 17.8% of the number of shares in circulation (post-issue).
The issue price was set at 24.50 Euros per share, in compliance with resolution no. 10 of the mixed general shareholders' meeting of June 17, 2014. This price reflects a 3.5% reduction as compared to the weighted average of the Company's share price in the last five trading sessions prior to establishing the price, i.e., 25.39 Euros. In total, 80% of the issue was performed internationally, with 68% in the United States.
Prior to this, the company had announced the positive Phase III results on its clinical study with GRASPA® in the treatment of AML. Analysis of the data from the GRASPIVOTALL clinical trial (GRASPALL2009- 06), after one year of monitoring, demonstrates that the study convincingly achieved its primary objectives, and its secondary objectives confirm a favorable profile for the clinical efficacy of GRASPA®. The study also shows favorable results in patients with histories of allergies to L-asparaginase.
During the financial year, the company also recruited the first patient for its Phase II study on pancreatic cancer in Europe, as well as its first patient for its Phase I/II study in the United States.
The company announced the positive opinion by its second committee of independent experts (DSMB) for its Phase IIb study on AML. The independent experts analyzed the tolerance data for the first 60 patients treated, and as with the first DSMB committee review on 30 patients, continuation of the study was unanimously confirmed, without requesting any modifications to the study or formulating any particular observations.
The company likewise obtained Orphan Drug Designation from the FDA for its product ERY-ASP in the treatment of AML in the United States.
The company created its subsidiary "ERYTECH PHARMA Inc." in the USA in April 2014. The Company then proceeded to appoint the firm RSM-CCI Conseils as co-Statutory Auditors in the AGM of June 17, 2014. At June 30, 2014, the Group's financial statements were supplemented, for the first time, by consolidation of the 100% held American subsidiary.
Pierre-Olivier Goineau, co-founder of the company ERYTECH Pharma SA, Delegated Managing Director, member of the Board of Directors, and Deputy Chairman, submitted his resignation from all his positions within the company ERYTECH PHARMA SA at the end of the parent company's Board of Directors' meeting of January 11, 2015. Mr. Goineau remains treasurer and secretary of the American subsidiary ERYTECH PHARMA Inc.
The Company's loss-making situation is explained by the innovative nature of the products developed, therefore involving a multi-year research and development phase. The general accounting conventions were applied in compliance with the principle of prudence, in accordance with the underlying assumptions of:
and in accordance with the general rules for the preparation and presentation of annual financial statements.
The annual financial statement was prepared and presented in accordance with the accounting rules in effect in France, in compliance with the principle of prudence and the independence of fiscal years, and within the assumption of business continuity.
The basic method adopted for measuring the items recorded in the accounts is the historical cost method.
The accounting conventions were applied in conformity with the provisions of the Code of Commerce, the accounting decree of November 29, 1983, as well as CRC Regulations no. 2000-06, no. 2004-06, and no. 2002- 10, and of ANC Regulation no. 2014-03 of June 5, 2014 relative to the general chart of accounts.
No changes in accounting regulations or accounting methods took place during the financial year ended December 31, 2014.
The primary other methods used are as follows:
The intangible assets are measured at their capitalized cost or at their production cost.
R&D costs are recognized based on the following method in the research phase:
The balance of the research and development costs item is zero on the balance sheet. In effect, not all of the criteria for recognition under intangible fixed assets have been met, and the corresponding expenses have therefore been kept under operating expenses.
The tangible fixed assets are measured at their purchase cost (purchase price and accessory costs, excluding costs for the purchase of assets) or at their production cost.
The amortizations for impairment are calculated according to the straight-line or decreasing charge method in function of anticipated lifetime:
| - Licenses, software, patents |
1 to 10 years |
|---|---|
| - Technical systems |
3 to 10 years |
| - Industrial equipment and infrastructure |
1 to 5 years |
| - Office equipment and furniture |
3 to 5 years |
The gross value is composed of the purchase cost excluding accessory expenses. Where the current value is lower than the gross value, a provision for impairment is established in the amount of the difference.
Inventories are measured according to the FIFO method.
The gross value of merchandise and supplies includes the purchase price and the accessory expenses.
Manufactured products are valued at their production cost, including consumption and direct and indirect production expenses, the amortization of assets involved in production. The cost of the sub-activity is excluded from the value of inventories.
A provision for the impairment of inventories, equal to the difference between the gross value determined based on the above-indicated methods and the spot price or the realizable value less the proportional sales costs, is made where this gross value is greater than the other value given.
Receivables are valued at their nominal value. A provision for impairment is made where the current value is lower than the book value.
The accounting method for convertible bonds is that entitled "two separate transactions," i.e., the bond, nonconversion premium included, is recorded under the liabilities in the balance sheet, and the non-conversion premium is recorded under the assets.
The non-conversion premium is then amortized proportionately to the accrued interest.
The grant income is recognized, where it is granted, upon its collection.
According to the matching principle, the corresponding pace of spending is taken into account and, where applicable, a portion of the grant is recorded under "deferred revenue" where the grant agreement explicitly stipulates the expenses that must be incurred. Vice-versa, an accrual is recorded where the expenses incurred allow for recognition of a portion of the grant receivable.
The company therefore records a deferred income corresponding to the portion of the grant received corresponding to expenses not incurred.
The advances received from the State generally contain a portion in grants for which repayment is not required, and a portion repayable in the event of technical or commercial success, classified as conditional advances.
Conditional advances are presented in the balance sheet under the item "Other shareholders' equity" where a doubt exists regarding the technical or commercial success.
A public grant to be received either in compensation for the expenses or losses already incurred, or in the form of immediate financial support to the Company with no related future costs, is recognized under income for the financial year during which the expenses relating to the program in question are incurred.
The costs associated with clinical trials are recognized as expenses as and when they are sustained.
Each patient included results in an obligation for ERYTECH to sustain certain costs whether or not the study continues, and to do so in addition to the expenses already incurred. When a patient is recruited, the company establishes a provision to cover all the costs sustained to continue the clinical trial over a one-year horizon.
The remainder of the costs sustained leading up to the end of the clinical trial (patients not yet recruited) are monitored off-balance sheet.
A provision for risks and liabilities is recorded where an equity item has a negative economic value for the entity, which translates into an obligation in relation to a third party for which it is probable or certain that it will result in an outflow of resources to the benefit of this third party, without an at least equivalent compensation anticipated by this third party.
No transactions of this nature were performed during the fiscal year.
The company has signed no special agreements relating to retirement commitments.
These commitments are therefore limited to the contractual retirement indemnity. No provision for liabilities was recognized in relation to this fiscal year.
The method adopted is the projected unit credit method (or the accrual of rights method).
The technical assumptions used are the following: Age of retirement: 65-67 years Average turnover (non-management), high turnover (management) Evolution of wages: management and non-management at 2% INSEE 2014 mortality table Discount rate: IBOXX Corporates AA rate of 1.49% at December 2014 Employer contribution rate adopted: 50% (non-management) and 54% (management and directors).
The tax credit for competition and jobs (CICE) is a tax benefit for companies with employees and is equivalent to a decrease in their social security contributions.
The CICE must be allocated to the corporate tax due for the year in which the remuneration taken into account for calculation of the CICE was paid.
According to the ANC [French accounting standards authority] guidelines, the Company recognizes the CICE as a credit in the sub-account dedicated to account 64 "Personnel expenses."
The amount of research costs recognized as expenses for the financial year and not activated total €4,886,273.
The Company has stipulated a liquidity agreement with the company Bryan Garnier with a view to encouraging the liquidity of transactions and the regularity of share prices, as well as avoiding discrepancies in share price that are not warranted by market trends.
To this end, the Company carried a credit on the liquidity account initially in the amount of €600,000, which was reduced in March 2014 by €400,000 to €200,000.
The company Bryan Garnier reported on its portfolio of Erytech Pharma securities at 12/31/2014, which totaled 4,500 securities valued at an average price of €28.00, i.e., €126,000 (recorded under financial assets).
The available cash balance at 12/31/2014 totaled €251,1023.
The other financial assets are composed of deposits & sureties in the amount of €81,814.
The company holds, in equity securities, 100% of the capital of the subsidiary ERYTECH PHARMA Inc., i.e., 1 USD valued at €0.73.
The company's investment stakes can be summarized as follows:
| Capital | Reserves and retained earnings before allocation of earnings |
Portion of capital held (in %) |
Book value of shares held Gross |
Net | Loans and advance s granted by the company and not yet repaid |
Amount of bonds and deposits made by the company |
Pretax revenue from the last fiscal year |
Earnings (profit or loss of the last fiscal year ended) |
Dividends received by the company during the fiscal year |
Remarks | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| A- DETAILED INFORMATION CONCERNING SUBSIDIARIES AND PARTICIPATING INTERESTS |
|||||||||||
| 1. Subsidiary (+50% of the capital owned by the company) - ERYTECH PHARMA Inc. |
0.73 | 0,00 | 100.00 | 0.73 | 0.73 | 80,847.28 | 0.00 | 0.00 | -108.72 | 0,00 | |
| 2. Participating interest (10 to 50% of the capital held by the company) |
|||||||||||
| B - GENERAL INFORMATION ABOUT THE | |||||||||||
| OTHER SUBSIDIARIES AND PARTICIPATING INTERESTS |
|||||||||||
| 1. Subsidiaries not shown in A 1. French |
|||||||||||
| 2. Foreign | |||||||||||
| 2. Participating interests not shown in A 1. French |
Period from 01/01/14 to 12/31/14
| HEADINGS | Gross value start of year |
Increases through revaluations |
Purchases, contributions, creation of transfers |
|---|---|---|---|
| INTANGIBLE ASSETS | |||
| Startup and development costs | |||
| Other intangible assets | 109,177 | 25,798 | |
| TOTAL intangible assets: | 109,177 | 25,798 | |
| TANGIBLE FIXED ASSETS | |||
| Land | |||
| Structures on own ground | 337,674 | ||
| Structures on someone else's ground | 953,455 | 279,784 | |
| General facilities construction | 5,390 | ||
| Mechanical systems and industrial tooling | 57,668 | 17,988 | |
| General facilities, plant and tooling | |||
| Shipping equipment | |||
| Office equipment, computers And furniture | |||
| Recoverable packaging and other | 20,000 | 218,109 | |
| Assets under construction | |||
| Advances and deposits | |||
| TOTAL tangible assets | 1,368,797 | 521,270 | |
| INVESTMENTS | |||
| Investments in companies counted using the equity methodmises | |||
| Other participating interests | 1 | ||
| Other investments | |||
| Other long-term financial investments | 682,481 | 377,212 | |
| TOTAL Investments: | 682,481 | 377,213 | |
| TOTAL ASSETS | 2,160,455 | 924,281 |
| HEADINGS | Decreases through transfers |
Decreases by disposals and retirements |
Gross value year end |
Legal revaluations |
|---|---|---|---|---|
| INTANGIBLE ASSETS | ||||
| Start-up and development costs | ||||
| Other intangible assets | 134,975 | |||
| TOTAL intangible assets | 134,975 | |||
| TANGIBLE FIXED ASSETS | ||||
| Land | ||||
| Structures on own ground | ||||
| Structures on someone else's ground General facilities construction |
||||
| Technical systems, industrial equipment and | 617,457 | |||
| infrastructure | 958,845 | |||
| General facilities, tools and other | 75,656 | |||
| Shipping equipment Office equipment, computers and furniture |
||||
| Recoverable packaging and other Tangible | 125,629 | 112,480 | ||
| fixed assets under development | ||||
| Advances and deposits TOTAL tangible assets |
125,629 | 1,764,438 | ||
| INVESTMENTS | ||||
| Interests measured using the equity method | ||||
| Other participating interests | 1 | |||
| Other investments | ||||
| Loans and other long-term financial | 600,770 | 458,923 | ||
| investments TOTAL Investments |
600,770 | 458,924 | ||
| TOTAL ASSETS | 125,629 | 600,770 | 2,358,337 |
Page | 224 of 302
| POSITIONS AND TRANSACTIONS IN THE FISCAL YEAR | ||||
|---|---|---|---|---|
| AMORTIZABLE ASSETS | Start of FY amount | Increased allocations |
Decreases reversals | Amount end of fiscal year |
| INTANGIBLE ASSETS Startup and development costs Other intangible assets TOTAL intangible assets: |
94,900 94,900 |
9,124 9,124 |
104,025 104,025 |
|
| TANGIBLE FIXED ASSETS Land Structures on own ground Structures on someone else's ground General facilities construction |
||||
| Technical systems and industrial infrastructure General systems, layouts, and other Shipping equipment |
308,028 540,238 |
36,371 95,616 |
346,398 635,854 |
|
| Office and IT equipment and furniture Recoverable packaging and other |
27,306 | 8,535 | 35,841 | |
| TOTAL tangible assets | 875,572 | 142,521 | 1,018,093 |
| TOTAL ASSETS | 970,473 | 151,645 | 1,122,117 | |
|---|---|---|---|---|
| -------------- | --------- | --------- | -- | ----------- |
| BREAKDOWN OF PROVISIONS FOR DEPRECIATION FOR THE FISCAL YEAR | ||||
|---|---|---|---|---|
| FIXED ASSETS SUBJECT TO AMORTIZATION |
Straight-line depreciation |
Declining balance depreciation |
Exceptional amortizations |
|
| INTANGIBLE ASSETS Startup and development costs Other intangible assets TOTAL intangible assets: |
104,025 104,025 |
|||
| TANGIBLE FIXED ASSETS | ||||
| Land Structures on own ground Structures on someone else's ground General facilities construction Mechanical systems and industrial tooling General facilities, plant and tooling Shipping equipment Office equipment, computers And furniture Recoverable packaging and other |
346,398 635,854 35,841 |
|||
| TOTAL tangible fixed assets: | 1,018,093 | |||
| Acquisition costs for participating interests |
| GENERAL TOTAL | 1,122,118 | ||||
|---|---|---|---|---|---|
| -- | -- | --------------- | ----------- | -- | -- |
Debt issuance costs to be spread out
Bond redemption premiums
| Period from 01/01/14 to 12/31/14 | ||||
|---|---|---|---|---|
| -- | -- | -- | -- | ---------------------------------- |
| TRANSACTIONS AFFECTING PROVISIONS FOR DEPRECIATION TO BENEFIT FROM TAX LAW | ||||
|---|---|---|---|---|
| FIXED ASSETS SUBJECT TO AMORTIZATION |
Provisions | Reversals | ||
| INTANGIBLE ASSETS Start-up and development costs Other intangible assets |
||||
| TOTAL intangible assets | ||||
| TANGIBLE FIXED ASSETS Land Buildings on own land Buildings on others' land Buildings general systems Technical systems and industrial infrastructure General facilities, plant and tooling Shipping equipment Office equipment, computers And furniture Recoverable packaging and other |
||||
| TOTAL tangible assets | ||||
| Acquisition costs for participating interests | ||||
| TOTAL ASSETS | ||||
| MOVEMENTS DURING THE FINANCIAL YEAR AFFECTING EXPENSES DISTRIBUTED OVER MULTIPLE FINANCIAL | YEARS | |||
| HEADINGS | Net amount at year start |
Increases | Allocations to amortizations during the financial year |
Net amount year end |
ERYTECH PHARMA
| HEADINGS | At end of | At start of financial | Change in inventory | |
|---|---|---|---|---|
| financial year | year | Increases | Decreases | |
| Goods for resale | ||||
| Inventory resold as is | ||||
| Goods for resale | ||||
| Provisions | ||||
| Provisions inventory | ||||
| Raw materials | 122,936 | 55,848 | 67,088 | |
| Other provisions | 75,420 | 82,391 | 6,970 | |
| TOTAL I | 198,356 | 138,238 | 60,118 |
| Production Intermediate goods Finished goods By-products |
||
|---|---|---|
| TOTAL II |
| Work in progress – production | ||
|---|---|---|
| Income | ||
| Works | ||
| Studies | ||
| Delivery of services | ||
| TOTAL III |
The line "Raw materials" concerns the inventory of products dedicated to the production of batches for clinical usage. The increase in activities in 2014 led to a large increase in the related inventory.
The line "Other supplies" concerns the inventory of products dedicated to pre-clinical research.
ERYTECH PHARMA
| STATEMENT OF RECEIVABLES | Gross amount |
At 1 year or less |
At greater than 1 year |
|---|---|---|---|
| NONCURRENT ASSETS | |||
| Receivables relating to participating interests | |||
| Loans | |||
| Other long-term financial investments | 458,923 | 377,109 | 81,814 |
| TOTAL of capital assets: | 458,923 | 377,109 | 81,814 |
| CURRENT ASSETS | |||
| Doubtful clients or disputes | |||
| Other client receivables | |||
| Receivables representing shares loaned or delivered as collateral | 104,870 | 104,870 | |
| Personnel and associated accounts | |||
| Social security and other social welfare entities | 167 | 167 | |
| Statement – Income taxes | |||
| Statement – value-added tax | 1,523,688 | 1,523,688 | |
| Statement - Other taxes, duties, and similar payments | 457,513 45,369 |
457,513 45,369 |
|
| Statement- Miscellaneous | |||
| Group and partners | 80,847 | 80,847 | |
| Sundry debtors | 21,378 | 21,378 | |
| TOTAL current assets: | 2,233,832 | 2,233,832 | |
| Prepayments | 216,779 | 216,779 | |
| TOTAL ASSETS | 2,909,534 | 2,827,720 | 81,814 |
| STATEMENT OF DEBT | Amount gross |
At 1 year or less |
At greater than 1 year and less than 5 years |
At greater than 5 years |
|---|---|---|---|---|
| Convertible bonds | ||||
| Other bonds | ||||
| With lending institutions: | ||||
| - at 1 year maximum from origin | ||||
| - at more than 1 year from origin | ||||
| Miscellaneous other loans and advances | ||||
| Trade payables and related accounts | 2,096,901 | 2,096,901 | ||
| Personnel and associated accounts | 453,484 | 453,484 | ||
| Social security and other bodies | 466,594 | 466,594 | ||
| Income taxes | ||||
| Value-added tax | 17,634 | 17,634 | ||
| Guaranteed bonds | ||||
| Taxes (other than corporate taxes) | 50,719 | 50,719 | ||
| Liabilities on fixed assets and related accounts | ||||
| Group and partners | ||||
| Other payables | 500,593 | 500,593 | ||
| Debts representing borrowed securities | ||||
| Deferred income | 368,436 | 368,436 | ||
| TOTAL ASSETS | 3,954,360 | 3,954,360 |
The Company has benefited, since its creation in 2004, from the research tax credit (Crédit d'Impôt Recherche - CIR) as defined in Article 244, quater B I of the French General Tax Code.
It is recognized in the results, less the income tax, with a tax receivable contra-entry.
The amount of the company's CIR for the last three fiscal years totaled:
The company benefits from a tax credit for competition and jobs (CICE) created under article 66, law no. 2012- 1510 of December 29, 2012, the amending finance law for 2012.
The amount for 2014 totaled €42,835.62 and was recorded minus salary expenses, with a tax receivable contraentry in the statement of financial position.
Sundry debtors concern credit notes with suppliers having provided services within the context of the ADR program, and for which the Company will be reimbursed a portion of expenses.
The Company's cash position totaled €36,655,100.94, of which €32,000,000 was placed in term deposits, stipulated:
The cash position was therefore divided based on the following categories:
| Total | €36,655,100.94 |
|---|---|
| Money market funds | €3,000,583.15 |
| Accrued interest | €112,962.38 |
| Term deposits | €32,000,000.00 |
| Current accounts | €1,541,555.41 |
ERYTECH PHARMA
| HEADINGS | Charges | Income |
|---|---|---|
| Operating charges or income | 216,779 | 368,436 |
| Financial charges or income | ||
| Non-recurring charges or income | ||
| TOTAL | 216,779 | 368,436 |
The prepaid expenses primarily concern maintenance contracts, as well as lease agreements on movable and immovable property.
The deferred income is the portion of the grant from the TEDAC project for which associated costs have not yet been sustained.
ERYTECH PHARMA
Period from 01/01/14 to 12/31/14
| AMOUNT OF INCOME TO RECEIVE INCLUDED IN THE FOLLOWING BALANCE SHEET ENTRIES |
Amount |
|---|---|
| - Investments Receivables relating to participating interests Other long-term financial investments |
|
| Receivables Trade receivables Staff |
2,465 |
| Social security and similar Statement Miscellaneous, income to receive Other receivables |
45,369 12,355 |
| Marketable securities Cash at bank and in hand |
| TOTAL | 60,188 |
|---|---|
ERYTECH PHARMA
Period from 01/01/14 to 12/31/14
| SHARE CLASSES | Number | Nominal value |
|---|---|---|
| 1 - Shares or stock comprising the share capital at the start of the fiscal year | 5558952 | 0,1 |
| 2 - Shares or stock issued during the fiscal year | 1323809 | 0,1 |
| 3 - Shares or stock redeemed during the financial year | ||
| 4 - Shares or stock constituting the share capital at financial year end | 6882761 | 0,1 |
The Company proceeded with the admission, on the EURONEXT market, of 1,224,489 new shares in October 2014.
The exercise of BSA2012 and BSPCE2012 created 99,320 new shares during the financial year.
| Number of shares | Share capital | Issue premium | Reserves & carried forward |
FY profit(loss) | Regulatory provisions |
Total Shareholders' Equity |
|
|---|---|---|---|---|---|---|---|
| Balance as of Dec. 31, 2013 | 5,558,952 | €555,895.20 | €42,335,338.33 | (€22,295,938.09) | (€6,478,994.29 ) | - € |
€14,116,301.15 |
| Allocation of earnings 2013 | (€6,478,994.29 ) | €6,478,994.29 € | |||||
| Capitalization of convertible bond | |||||||
| interest Bond conversions | |||||||
| Admission of new shares | 1,224,489 | €122,448.90 | €29,877,531.60 | ||||
| Charging of costs associated with | (€1,558,417.27) | ||||||
| shares Share Warrants & Founder's |
99,320 | €9,932.00 | €721,261.84 | ||||
| Warrants Conversion Fiscal year profit (loss) 2014 |
(€7,283.237.28) | ||||||
| Balance as of Dec. 31, 2014 | 6 882 761 | €688,276.10 | €71,375,714.50 | (28,774,932.38 ) | (€7,283.237.28) | - € |
€36,005,820.94 |
The conditional advances, totaling €580,107, were divided as follows at 12/31/2014:
BPI FRANCE ISI (advance 3): €62,607
Assistance granted by BPI FRANCE INNOVATION (€735,000): program for the "development of a new treatment against pancreatic cancer through the administration of allogenic red blood cells incorporating L-asparaginase".
This assistance was distributed in 3 phases:
The repayment of this conditional advance will be made according to a fixed payment schedule that will end at the latest on 06/30/2016. To this end, the company repaid its first maturity of €100,000 in 2013, and its second of €150,000 in 2014.
This assistance was distributed in 4 phases:
The repayment of this conditional advance will be made according to a fixed payment schedule that will end at the latest on 06/30/2016.
As the program was interrupted early, only the first two calls for funds were paid, for a total of €81,000. To date, the company has repaid €48,500.
This assistance is distributed upon completion of the following key milestones:
The company undertakes to repay BPI FRANCE a sum of €5,281,000 upon achieving a cumulative amount of before-tax sales revenue equal to or greater than 10 million Euros and, where applicable, an annuity equal to 50% of the income generated by the sale of intellectual property rights resulting from the project. In a second phase, where the cumulative sales revenue reaches €60,000,000, the company undertakes to pay BPI FRANCE a sum of 2.5% of the sales revenue generated by development of the products resulting from the project, within the limit of a total repayment of €15M over 15 years.
ERYTECH PHARMA
| HEADINGS | Start of FY amount |
Increased allocations |
Decreases reversals |
Amount year end |
|---|---|---|---|---|
| Provision for restoring deposits Provisions for investment Provisions for price increases Depreciation benefiting from tax law Including exceptional increases of 30% Tax provisions for establishment abroad, established prior to 01/01/1992 Tax provisions for establishment abroad, established subsequent to 01/01/1992 Provisions for facilities loans Other regulated provisions |
||||
| REGULATED PROVISIONS |
| Provisions for disputes. | ||
|---|---|---|
| Provisions for guarantees given to clients | ||
| Provisions for losses on futures markets | ||
| Provisions for fines and penalties | ||
| Provisions for exchange losses | ||
| Provisions for pensions and similar obligations | ||
| Provisions for taxes | ||
| Provisions for building renovation | ||
| Provisions for large-scale maintenance and major | ||
| overhauls | ||
| Provisions for social security and tax expenses on | ||
| holidays owing | ||
| Other provisions for liabilities and charges | ||
| PROV. FOR LIABILITIES AND CHARGES |
| Prov. for intangible assets Prov. for tangible assets Provisions for blocked securities counted by the equity method Provision for blocked participating interests Provision for other non-current financial assets Provisions for inventory and works in progress Provisions for client accounts Other provisions for depreciation |
100 607 | 100 607 | |
|---|---|---|---|
| PROVISIONS FOR DEPRECIATION | 100 607 | 100 607 |
| TOTAL ASSETS 100 607 100 607 |
|
|---|---|
| ------------------------------------ | -- |
At the end of 2013, the company recorded a provision for impairment associated with company securities purchased under mandate, within the scope of liquidity. The company's share price having significantly increased during the period, the establishment of this provision was no longer considered necessary and formed the object of a reversal.
By way of reminder, in 2012, the Company stipulated an exclusive distribution agreement for its product in the indication of acute lymphoblastic leukemia with Orphan Europe.
The Company likewise entered into a contract with the Recordati Group to financially support clinical trial of GRASPA AML 2012 01 in AML, in the amount of €5 M.
To this end, the Company continues to re-invoice, with no margin and on a monthly basis, the costs relative to the trial, which totaled €791,853 in 2014.
Amounts re-invoiced are recorded in the books under sundry income.
The Company recorded the portion of the TEDAC grant associated with the program's annual expenses, totaling €271,230.72.
The total compensation paid to executive corporate officers was €715,943.83.
The securities held giving the right to a future portion of the capital are presented in the detailed table "Subscription warrants."
Period from 01/01/14 to 12/31/14
| NON-RECURRING INCOME | Amount | Reported in account |
|---|---|---|
| for insurance adjustment | (2,749) | 77200000 |
| gifts received | 2,950 | 77180000 |
| и | ||
|---|---|---|
| NON-RECURRING CHARGES | Amount | Reported in account |
|---|---|---|
| adjustment differences | (4) | 67180000 |
| loss of security | 770 | 67500000 |
| for insurance adjustment | 6,165 | 67200000 |
| adjustment of contributions | 9,420 | 67200000 |
| adjustment differences | 24 | 67200000 |
| TOTAL | 16,375 | |
|---|---|---|
| ------- | -------- | -- |
| Amount | |
|---|---|
| FY profit(loss) | (€7,283,237) |
| Income tax | ( €1,523,688) |
| Before-tax results | (€8,806,925) |
| Profit (loss) excluding exceptional that tax assessments pre-tax | (€8,806,925) |
| Taxable income (loss) for the fiscal year | (€8,831,602) |
| Deficits remaining to be carried forward the previous fiscal year | €34,298,815 |
| Total deficits remaining to be carried forward | €43,130,417 |
| Amount | Current profit (loss) | Exceptio nal results |
|
|---|---|---|---|
| FY profit(loss) | (€7,283,237) | (€7,267,063) | (€16,174) |
| Income tax | ( €1,523,688) | ( €1,523,688) | |
| Before-tax results | (€8,806,925) | (€8,790,751) | (€16,174) |
The income tax amount corresponds to the research tax credit. Its basis corresponds to research costs excluded from the exceptional results.
The costs associated with clinical trials are recognized as expenses as and when they are sustained.
Each patient included results in an obligation for ERYTECH to sustain certain costs whether or not the study continues, and to do so in addition to the expenses already incurred. When a patient is recruited, the company establishes a provision to cover all the costs sustained to continue the clinical trial over a one-year horizon.
The remainder of the costs sustained leading up to the end of the clinical trial (patients not yet recruited) are monitored off-balance sheet.
| 12/31/2014 in Keuros | ERYTECH contractual commitment | |||
|---|---|---|---|---|
| Clinical trial name |
Accrued payables, tax incl. |
Definite accrued payables |
Uncertain (Off balance sheet, net of taxes) |
Comment |
| 2007/04 | - | - | - | Trial ended |
| 2008/02 | - | - | - | Trial ended |
| 2009/06 | 200 | - | - | Trial ended |
| 2012/09 | 41 | - | 1,014 | Recruitment begun |
| 2012/10 | 4 | - | - | Recruitment begun |
| 2013/03 | 256 | - | 4,526 | Recruitment begun |
| Accrued payables | off-balance sheet | |||
| 501 | 5,539 |
| 12/31/2013 in Keuros | ERYTECH contractual commitment | |||
|---|---|---|---|---|
| Clinical trial name |
Accrued payables, tax incl. |
Definite accrued payables |
Uncertain (Off balance sheet, net of taxes) |
Comment |
| 2007/04 | - | - | - | Trial ended |
| 2008/02 | - | - | - | Trial ended |
| 2009/06 | 347 | - | - | Recruitment ended |
| 2012/09 | - | - | - | Recruitment not begun |
| 2012/10 | - | - | - | Recruitment not begun |
| 2013/03 | - | - | - | Recruitment not begun |
| Acc | off-balance sheet | |||
| rue | - - |
In consideration of the company data, for actuarial assumptions adopted, i.e., primarily a gross discount rate of 1.49%, the total commitment relating to retirement indemnities measured at 12/31/2014 totals 88,594 Euros.
No provision for liabilities was recognized in relation to this fiscal year.
By way of reminder, on May 24, 2013, the board of directors authorized severance indemnities to the benefit of:
Mr. BEYEN may claim an indemnity equal to:
Mr. Goineau may claim an indemnity equal to twelve times his average monthly remuneration (bonuses included) effectively received during the twelve months prior to the revocation decision or expiry of his term of office.
Mr. Godfrin may claim an indemnity equal to twelve times his average monthly remuneration (bonuses included) effectively received during the twelve months prior to the revocation decision or expiry of his term of office.
Within the context of his resignation, we specify that Pierre-Olivier GOINEAU did not receive any indemnities.
For the 2014 financial year, the external auditor fees paid on the financial year totaled:
within the scope of its legal term of office: €95,000, excluding out-of-pocket expenses,
in relation to the capital increase: €12,000
Share options have been allocated to the directors, to certain employees, as well as to members of the Board of Directors in the form of share subscription warrants ("BSA") or founder subscription warrants ("BSPCE").
"2012 Plan"
| Types of securities | Share warrants (BSA)2012 Founder's share warrants2012 |
|||||
|---|---|---|---|---|---|---|
| Number of warrants authorized for issue | 33,788 | 30,034 | ||||
| Number of warrants that the shares authorized to issue, for all types of shares |
45,050 | |||||
| Total number of warrants issued |
33,788 | 11,262 | ||||
| 2012/2013/2014 Total number of warrants Allocated |
33,788 5,025 |
|||||
| 2012/2013/2014 Number of warrants exercised |
6,807 | 5,025 | ||||
| Date of General Meeting | May 21, 2012 | |||||
| Exercise price per new share subscribed | € 7,362 | |||||
| Final date for exercising warrants | May 20, 2020 | |||||
| Parity | 1 warrant for 10 shares | |||||
| General conditions of exercise | Warrant holders can only exercise their subscribed warrants: (i) )only upon the occurrence of a firm, definitive operation involving the initial listing of Company shares for trading on a regulated or unregulated stock market, in France or the European Union, or a foreign securities exchange; (ii) on one single occasion, or (iii) on multiple occasions, within a limit of twice a year and at least 100 warrants. Warrant holders shall only be able to exercise the entirety of their warrants, already subscribed or Allocated but not yet subscribed, in the event that one of the following operations occurs: (i) acceptance, by shareholders representing at least sixty-six point six seven percent (66.67%) of the shares constituting the Company's capital, of a firm, definitive buyback offer pertaining to control of the Company (as pursuant to Article L. 233-3 of the Commercial Code). (ii) the formation of a merger agreement providing for absorption of the Company. The securities to which the warrants give rights are common shares. Each warrant shall give the right to ten (10) shares in the Company's share |
|||||
| Maximum number of new shares that can be issued |
capital. 332 180 The new shares resulting from the exercise of founder's share warrants (BSPCEs) |
Within the scope of the BSA2012 and BSPCE2012plans, the board of directors' meeting of July 17, 2014 defined the additional list of beneficiaries, as well as the number of warrants to which each employee may subscribe within the scope of the BSA2012 and BSPCE2012, in relation to the period of June 1st, 2013 to May 31, 2014. As such, 1,000 additional BSA2012 and 13,176 additional BSPCE2012 were allocated to Erytech employees.
At the end of 2014, the subscription warrants for the 2012 plan were broken down as follows:
| BSA / BSPCE (Share warrants/founder's warrants) reference |
GAB reference | Parity | Period of exercise |
Number of warrants issued |
Number of warrants allocated |
fiscal year | Number of warrants remaining to be exercised |
Number of warrants remaining to be allocated |
|---|---|---|---|---|---|---|---|---|
| Founder's share warrants (BSPCE) 2012 | 21/05/2012 | 1 warrant = 10 | 20/05/2020 | 33,788 | 33,788 | 6,807 | 26,981 | - |
| Share warrants (BSA) 2012 | 21/05/2012 | shares 1 warrant = 10 |
20/05/2020 | 11,262 | 5,025 | 5,025 | - | 6,237 |
| shares | Total | 45,050 | 38,813 | 11,832 | 26,981 | 6,237 |
On January 22, 2014, the board of directors used the delegation granted by the mixed general shareholders' meeting of April 2, 2013, in its twenty-fifth resolution, to decide on a plan for the free allocation of 22,500 founder share subscription warrants (hereinafter entitled BSPCE2014) to the benefit of Erytech directors (12,000 warrants) and to a category of "employees with management status" not yet identified by name (10,500 warrants).
The plan's characteristics are as follows:
| Types of securities | Founder's share warrants (BSPCE)2014 | ||
|---|---|---|---|
| Number of warrants issued | 22,500 | ||
| Number of warrants awarded | 12,000 | ||
| Number of warrants exercised | 0 | ||
| Board of Directors Date | Jan. 22, 2014 | ||
| Exercise price per new share subscribed | €12,250 | ||
| Final date for exercising warrants | Jan. 22, 2024 | ||
| Parity | 1 warrant for 10 shares | ||
| General conditions of exercise | In the event of the beneficiary's death, it is stipulated that, pursuant to the provisions of article 163 bis G of the general tax code, the decedent's heirs may exercise the warrants within six months starting from the death. The founder's share warrants (BSPCE)2014 can be exercised: - on one single occasion, or - except in the event of an M&A operation, at most four (4) times per year, and for the exercise of a minimum of fifty (50) founder's share warrants (BSPCE)2014. In the event of a so-called M&A operation, holders of BSPCE20124 shall have five (5) business days starting from notice by the Company of the occurrence of such an event to exercise all of their BSPCE20124. However, the exercise of the BSPCE2014 may be canceled in the event of the ultimate non-performance of the takeover or the merger operation, for any reason whatsoever. |
||
| Maximum number of new shares that can be issued |
120,000 |
In the event of a beneficiary's departure from the Company for any reason whatsoever, this beneficiary shall retain the BSPCE2014 to which he subscribed prior to his departure. However, in the event of a beneficiary's departure from the Company, for any reason whatsoever, prior to subscription of the BSPCE2014 to which the beneficiary has a right, the BSPCE2014 shall be considered invalid vis-a-vis this beneficiary. Within this hypothesis, the BSPCE2014 not subscribed may be re-allocated to other beneficiaries within the same category and/or replacing the person who left the company.
In any case, the BSPCE2014 not exercised at January 22, 2024 shall become duly and fully expired.
Moreover, the board of directors' meeting of December 4, 2014 transformed 3,000 BSPCE2014 into 3,000 BSA2014 for a Medical Director at the subsidiary ERYECH PHARMA INC., in accordance with Annex IV-BSA2014 Regulations, as recorded in the minutes.
Within the scope of the individual right to training established by Law 2004-391 of May 4, 2004 relative to life-long professional training, at 12/31/2014, the volume of cumulative training hours relative to rights acquired and not exercised was 2,431.58 hours.
It should be noted that, in accordance with:
the DIF (individual right to training) system has been replaced by that of the personnel training account (CPF) as of January 1st, 2015. The transferable DIF will likewise disappear as of January 1st, 2015.
Period from 01/01/14 to 12/31/14
| HEADINGS | Land | Buildings | Systems equipment infrastructure |
Other | Total |
|---|---|---|---|---|---|
| Original value | 973,877 | 973,877 | |||
| Amortization: - totals from prior fiscal years - allocations from the fiscal year |
654,154 98,593 |
654,154 98,593 |
|||
| TOTAL | 221,129 | 221,130 | |||
| ROYALTIES PAID: - totals from prior fiscal years - allocations from the fiscal year |
753,675 89,587 |
753,675 89,587 |
|||
| TOTAL | 843,262 | 843,262 | |||
| ROYALTIES REMAINING TO PAY: - up to one year - from one year up to five years - over five years |
80,702 149,481 |
80,702 149,481 |
|||
| TOTAL | 230,183 | 230,183 | |||
| RESIDUAL VALUE - up to one year - from one year up to five years - over five years |
143,279 3,009 |
143,279 3,009 |
| TOTAL | 146,288 | 146,288 | |
|---|---|---|---|
| Amount reported for the financial year |
| Note: Lease concessions | 89,587 |
|---|---|
| ------------------------- | -------- |
This table includes the leases financing equipment for R&D and Production. The furthest maturity is December 2018.
ERYTECH PHARMA
Period from 01/01/14 to 12/31/14
| STAFF | Staff salaried |
Personnel made available to the company |
|---|---|---|
| Management | 21 | |
| Chargehands and technicians | ||
| Employees | 17 | |
| Laborers | ||
| TOTAL | 38 |
During the financial year, the company hired 12 employees and had 6 employees leave.
ERYTECH PHARMA
Period from 01/01/14 to 12/31/14
| COMMITMENTS MADE | Amount |
|---|---|
| Discounted notes not yet matured Deposits and guarantees |
|
| Pension, retirement, and compensation commitments | 88,595 |
| Other commitments made: | |
| TOTAL | 88,595 |
|---|---|
| COMMITMENTS RECEIVED | Amount |
|---|---|
| Deposits and guarantees and securities | |
| Other commitments received: | 3,724,182 |
|--|
The Recordati commitment on the GRASPA-AML study contractually totals €5,000,000 and was valued at €3,724,182.23 at the end of 2014, the difference corresponding to 2013 and 2014 re-invoicing.
The Company uses the euro as a reference currency for its financial information and communication activities. However, a significant portion, in the amount of 10% of its operating expenses, is denominated in US dollars (agency office in Philadelphia, collaborations relating to the production of clinical batches with the American Red Cross, business development consultants, consultants for the development of clinical trials in the United States, and various collaborations around tests and clinical projects in the United States).
To date, the company has not opted to use active hedging techniques, and has not made recourse to derivative instruments to this end. Unfavorable exchange rate fluctuations between the euro and the dollar that are difficult to predict could affect the financial position of the Company.
This dependency will increase, as the company will perform clinical trials in the USA and, in the longer term, sell on this market. The Company will opt for exchange rate hedging techniques.
Expenses in US Dollars (USD) totaled \$949,232 during the 2014 financial year. The counter-values recorded in the accounts totaled €714,807 in relation to the receipt of invoices and price fluctuations. This represents an average annual rate of \$1.328 per €1 (\$1.324/€ on average in 2013).
However, the EUR/USD rate fell considerably at the period end, reaching \$1.2141 per €1 at December 31, 2014.
The Company purchased 1 million dollars at a rate of \$1.2197 per €1 during December 2014.
The exchange rate differences are not significant for the periods presented.
(The corporate financial staetments prepared in accordance with IFRS standards for the 2012 financial year are addressed in the external auditor's report under Section 20 of the Reference Document registered on April 17, 2013 by the AMF under visa no. 13-166.)
(The corporate financial staetments prepared in accordance with IFRS standards for the 2013 financial year are addressed in the external auditor's report under Section 20 of the Reference Document registered on June 4, 2014 by the AMF under visa no. R14-038.)
Headquarters: 60 avenue Rockefeller – Bâtiment Adénine – 69008 Lyon Share capital: € 688,276
Financial year ended December 31, 2014
Dear shareholders,
In fulfillment of the assignment that was entrusted to us by your general meeting, we hereby present you our report pertaining to the financial year ending December 31, 2014 concerning:
The financial statements were issued by the Board of Directors. Our task, on the basis of our audit, is to express an opinion on these financial statements.
We conducted our audit in accordance with professional standards applicable in France; these standards require that certain diligence reviews be performed so as to obtain a reasonable assurance that the consolidated financial statements do not contain significant errors. An audit consists of verifying, by sampling or other selection methods, elements that will support the amounts and statements found in the consolidated financial statements. It also consists of evaluating the accounting principles followed, any significant estimates used, and the presentation of the financial statements as a whole. We believe that the information that we collected is sufficient and appropriate on which to base our opinion.
We certify that the consolidated financial statements are, with regard to IFRS standards as adopted by the European Union, complete and truthful and provide a faithful reflection of the assets, the financial position, and the results of the group, composed of the persons and entities included in the consolidation.
In application of the provisions of Article L.823-9 of the Commercial Code pertaining to the basis for our appraisals, we direct your attention to the following elements.
Note 5.15 "Income from regular operations" in the annex to the consolidated financial statements outlines the accounting rules and methods relative to the recognition of subsidy-related revenue and income.
As part of our assessment of the accounting rules and principles that your group followed, we verified the appropriate nature of the above-referenced accounting methods and the information provided in the annex to the consolidated financial statements and we assured ourselves of their correct application.
Note 9 "Off-balance sheet commitments" in the annex to the consolidated financial statements outlines the accounting rules and methods relative to the recording of clinical trial figures.
As part of our assessment of the accounting rules and principles that your group followed, we verified the appropriate nature of the above-referenced accounting methods and the information provided in the annex to the financial statements and we assured ourselves of their correct application.
The assessments thus performed took place within the context of our audit of the consolidated financial statements, considered as a whole, and thus contributed to the establishment of our opinion as expressed in the first part of this report.
In accordance with the applicable standards for professional conduct in France, we also conducted those specific verifications required by law on the information provided in the group's management report and on the information relative to the group as provided in the annual report.
We have no observations to formulate regarding their accuracy and consistency with the consolidated financial statements.
| The auditors | |
|---|---|
| Lyon, March 30, 2015 | Lyon, March 30, 2015 |
| KPMG Audit Rhône Alpes Auvergne | RSM CCI Conseils |
Sara Righenzi de Villers Gaël Dhalluin Auditor Deputy auditor
(The corporate financial statements prepared for the 2012 financial year were discussed in a statutory auditors' report on the annual financial statements in Section 20 of the Reference Document registered with the AMF on April 17, 2013 under No. 13-166.
The corporate financial statements prepared for the 2013 financial year were discussed in a statutory auditors' report on the annual financial statements in Section 20 of the Reference Document registered with the AMF on June 4, 2014 under No. R.14-038.)
Headquarters: Share capital: €
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In performance of the mission that was entrusted to us by your general meeting, we hereby present you our report pertaining to the fiscal year ending December 31, 2014 concerning:
the audit of the annual financial statements for Erytech Pharma S.A., as attached to this report;
the basis for our appraisals;
the inspections and specific statements provided by law.
The financial statements were issued by the Board of Directors. Our task, on the basis of our audit, is to express an opinion about these financial statements.
We conducted our audit following the professional standards applicable in France; the standards require that certain verifications be made so as to obtain a reasonable assurance that the restated financial statements do not contain significant errors. An audit consists in verifying, whether through spot-checks or other selection methods, elements that will support the amounts and statements found in the financial statements. It also consists in evaluating the accounting principles followed, any significant estimates used, and the presentation of the financial statements as a whole. We believe that the information that we collected is sufficient and appropriate on which to base our opinion.
We certify that the annual financial statements are complete and truthful and a faithful reflection of the result of operations during the past fiscal year, as well as the Company's financial condition and that of its assets as of the end of the fiscal year.
In application of the provisions of article L.823-9 of the Commercial Code pertaining to the basis for our appraisals, we direct your attention to the following elements.
The notes "Recognition of proceeds and subsidies" and "Clinical trials" present the accounting methods and rules pertaining to the treatment on the profit and loss statement of any subsidies and the cost of clinical trials.
As part of our assessment of the accounting rules and principles that your company followed, we verified the appropriate nature of the above-referenced accounting methods and the statements provided in the appendix to the financial statements and we assured ourselves of their correct application.
The assessments thereby made are part of our approach to auditing annual financial statements, taken as a whole, and thus contributed to the formation of our opinion expressed in the first part of this report.
In accordance with the applicable standards for professional conduct in France, we also conducted those specific verifications provided by law.
We have no comments to make about the accuracy and consistency of the information provided in the Board of Director's management report and in the documents sent to the shareholders about the financial circumstances and the annual financial statements.
Concerning the information provided in application of the provisions of article L.225-102-1 of the Commercial Code concerning remuneration and benefits paid to corporate officers as well as commitments made it to them, we have verified that they are consistent with the financial statements or with the data which were used to produce these financial statements and, as applicable, with the information collected by your company from companies controlling your company or controlled by it. On the basis of such work, we certify the accuracy and veracity of this information.
As required by law, we have assured ourselves that the various information pertaining to the identity of the shareholders has been provided to you in the annual report.
Lyon, March 30, 2015 Lyon, March 30, 2015
KPMG Audit Rhône Alpes Auvergne RSM CCI Conseils
Sara Righenzi de Villers Gaël Dhalluin Auditor Deputy auditor 20.4. Date of last financial information
December 31, 2014
20.5. Table of results for the last five financial years (Erytech Pharma SA, annual financial statements prepared in accordance with French accounting standards)
| 12/31/2010 | 12/31/2011 | 12/31/2012 | 12/31/2013 | 12/31/2014 | |
|---|---|---|---|---|---|
| CAPITAL AT END OF YEAR | |||||
| Number of common shares outstanding | 315,355 | 315,355 | 315,355 | 5,558,952*** | 6,882,761 |
| Number of existing priority dividend shares Maximum number of future shares to be created |
315,355 | 315,355 | 315,355 | 5,558,952*** | 6,882,761 |
| - by conversion of bonds | 67,916* | 135,833* | - | - | |
| - by subscription right exercise | 147,027 | 172,876** | 244 855 | 22,736 | 452,180 |
| OPERATIONS AND RESULTS | |||||
| Revenue excluding taxes Income before tax, employee sharing and depreciation of amortization and provisions |
(5,373,958) | (6,605,757) | (2,149,309) | 483,964 (7,592,464) |
791,853 ( 8,755,887) |
| Income taxes Employee sharing for fiscal year |
(721,327) | (798,967) | (812,570) | (1,366,656) | (1,523,688) |
| Income before tax, employee sharing and depreciation of amortization and provisions Retained earnings |
(4,822,357) | (5,983,691) | (2,011,394) | (6,478,994) | (7,283,237) |
| EARNINGS PER SHARE | |||||
| Results after taxes, employee profit-sharing, but before | |||||
| allocations to amortizations and provisions | (14.75) | (18.41) | (4.23) | (1.12) | (1.05) |
| Income before tax, employee sharing and depreciation | |||||
| of amortization and provisions | (15.29) | (18.97) | (6.38) | (1.17) | (1.06) |
| Dividend per share | |||||
| Staff | |||||
| Average number of employees during the year | 41 | 41 | 38 | 36 | 38 |
| Amount of payroll for the fiscal year | 1,715,167 | 1,847,841 | 1,718,300 | 2,504,423 | 2,402,291 |
| Amount of sums paid in relation to company benefits during the financial year |
463,122 | 833,826 | 827,736 | 1,164,033 | 1,168,792 |
*the assumption of a raising of funds of 18 million euros with a valuation of 73.62 euros per share
**not including share subscription warrant lapsed at 12/31
*** division of the nominal share value by 10 in 2013
None.
No plan exists to initiate a dividend policy in the short term, given the Company's stage of development.
At the registration date of this Reference Document, no government, legal, or arbitration proceedings existed, including any proceedings of which the Company has knowledge, that are suspended or with which it is threatened, such as will have or had during the last 12 months a significant effect on the financial position, activity, or results of the Company and/or of its subsidiary.
To the knowledge of the Company, no significant changes have taken place in the Company's financial or commercial situation since December 31, 2014.
The before-tax sales revenue totaled 791,852 Euros following the re-invoicing, with no margin, of the GRASPA-AML clinical trial to Orphan Europe/Recordati Group, as compared to 483,964 Euros in 2013.
The total operating income was equal to 1,113,132 Euros, as compared to 911,804 Euros in the previous financial year. This increase is associated with the progress of the AML clinical trial re-invoiced to Orphan Europe.
The year's operating expenses totaled 10,297,787 Euros, as compared to 8,767,638 Euros in the previous financial year, therefore a +17.4% variation. This variation in operating expenses is explained in the very significant increase in purchases and external expenses associated with the clinical and pre-clinical developments of ERY-ASP/GRASPA®, as well as personnel expenses.
The operating results totaled a loss of 9,184,655 Euros, as compared to a loss of 7,855,834 Euros in the previous financial year, therefore a variation of +17%.
The average employee numbers remained stable at 38, as compared to 36 in the previous financial year, therefore an insignificant variation.
The financial results totaled 393,903 Euros, as compared to -4,222 Euros in the previous financial year, primarily resulting from reversal of the provision for impairment of securities, totaling 100,607 Euros, as well as the performance of investments in term deposits and the decrease in interest following conversion of the convertible bonds in 2013.
The current results before tax for the year totaled a loss of 8,790,751 Euros, against a loss of 7,860,056 Euros for the previous financial year, therefore a variation of +11.8%.
In consideration of the preceding information,
The financial year's results total a loss of 7,283,237 Euros, as compared to a loss of 6,478,994 Euros in the previous financial year, therefore a variation of 12.24%.
At December 31, 2014, the Company's balance sheet total was 40,540,288 Euros, as compared to 18,245,790 Euros in the previous financial year, i.e., a variation of +22.3%.
The ERYTECH PHARMA Group is composed:
The Group's financial statements include consolidation of the American subsidiary. The financial statements for the ERYTECH PHARMA Group are prepared in conformity with the International Financial Reporting Standards (IFRS) published by the International Accounting Standards Board (IASB), as adopted by the European Union at the date of issue of the financial statements by the board of directors, as applicable at December 31, 2014.
The Group has recorded no sales revenue either in relation to the 2014 financial year or in relation to the 2013 financial year. The other income was primarily generated by the research tax credit, the grants associated with the pre-clinical research programs in partnership with BPI France. The Research Tax Credit totaled 1,523,688 Euros in 2014, as compared to 1,366,656 Euros, i.e., an increase of 11.50%. For 2014, the other income also includes the re-invoicing, to Orphan Europe, of 230,769 Euros in internal costs sustained by the Group within the context of the AML study.
Operating expenses increased by 23%, totaling 10,974,054 Euros in 2014, as compared to 8,915,188 Euros in 2013.
Excluding personnel costs, research and development costs decreased by 24% to 892,651 Euros in 2014, as compared to 1,171,016 Euros in 2013, the sub-contracting expenses having decreased by 273,746 euros. Clinical study expenses increased from 2013 to 2014 by 1,211,723 Euros, i.e., an increase of 74%, in line with the increase in the Group's activities. Intellectual property costs totaled 418,645 Euros in 2014, as compared to 265,371 Euros in 2013, the increase being primarily associated with intellectual property adviser fees. Lastly, general costs increased by 245,776 Euros between 2013 and 2014, primarily associated again with services, sub-contracting, and fees, this increase being 14% greater than the 2013 figure.
Personnel costs increased by 2% between 2013 and 2014, from 3,503,601 Euros in 2013 to 3,574,796 Euros in 2014, excluding the fair value impact of share-based compensation plans (IFRS 2).
The fair value of share-based compensation plans (IFRS 2) increased by 113%, from 580,621 Euros in 2013 for allocation of the 2and tranche of the BSPCE2012 and BSA2012 plan, as compared to 1,235,883 Euros for allocation of the 3rdtranche of the BSPCE2012 and BSA2012 plan, as well as for allocation of the BSPCE2014 to Group directors.
The Group's financial results showed a profit of 68,173 Euros in 2014, as compared to a loss of 1,099,589 Euros in 2013, primarily caused by the financial cost of the convertible bonds issued by the Group.
Income tax highlights income associated with revaluation of the liability relating to defined benefit plans (IAS 19), presented under Other items of the Group's comprehensive income.
The Group's consolidated statement of financial position shows total assets and liabilities of 40,606,639 Euros in 2014, as compared to 17,948,960 Euros in 2013, i.e., an increase of 22,657,679 Euros.
In October 2014, the Group performed a capital increase, making recourse to the market to obtain 29,172,757 Euros. Disinvestments within the scope of the liquidity agreement led to a variation of 650,675 Euros in shareholders' equity, the net results for the period showing a loss of 8,860,036 Euros, actuarial differences of 38,389 Euros, as well as the impact of the fair value valuation of 1,235,883 Euros for the compensation plans, which changed the Group's shareholders' equity by 22,237,669 Euros.
Financial liabilities decreased by 242,349 Euros between 2013 and 2014, the Group continuing to reduce its debt both in the conditional advances and in the financial debts associated with leases.
The variation in working capital requirements increased, in line with the growth in the Group's activities, totaling 1,874,169 Euros in 2014, as compared to 1,491,607 Euros in 2013.
It will be proposed to the General Assembly of Shareholders that it approve the annual financial statements (statement of financial position, statement of comprehensive income, and annex) as presented, and that the loss of 7,283,237 Euros be allocated to the "carry forward" account.
In consideration of this allocation, the Company's shareholders' equity would be 36,005,821 Euros.
The financial statements for 2014 include expenses of 18,855 Euros corresponding to expenditures not tax deductible.
Consequently, the tax sustained by reason of these expenditures and expenses totals 6,285 Euros.
The breakdown, at the end of the last two financial years, of the balance of debts to suppliers, by maturity date:
| MATURED | TOTAL |
|---|---|
| Less than 1 month | 345,332 |
| Between 1 and 3 months | 187,552 |
| Between 3 and 6 months | 107,799 |
| More than 6 months | 28,088 |
| TOTAL = | 668,771 euros |
| MATURING | TOTAL |
| Less than 1 month | 1,224,565 |
| Between 1 and 3 months | 33,266 |
| Between 3 and 6 months | - |
| More than 6 months | - |
2014 financial year:
I.e., a total of 1,926,602 Euros for the item supplier debts.
| MATURED | TOTAL |
|---|---|
| Less than 1 month | 351,861 |
| Between 1 and 3 months | 379,550 |
| Between 3 and 6 months | 97,639 |
| More than 6 months | 4,114 |
| TOTAL = | 833,163 euros |
| MATURING | TOTAL |
| Less than 1 month | 407,904 |
| Between 1 and 3 months | 4,933 |
| Between 3 and 6 months | - |
| More than 6 months | - |
I.e., a total of 1,246,000 Euros for the item supplier debts.
The agreements reached, where applicable, directly or through a third party, between, on one part, one of the members of the board of directors, the managing director, one of the delegated managing directors, or one of the shareholders holding a portion of the voting rights greater than 10% in the company ERYTECH Pharma and, on the other hand, another company in which the latter directly or indirectly holds more than half the capital are outlined in detail in the special auditors' report on the agreements outlined under Article L. 225-38 of the French Code of Commerce.
The agreements outlined under Article L. 225-38 of the Code of Commerce and stipulated during the financial year elapsed shall be submitted for the approval of the shareholders, it being specified that the auditor has been duly notified of these agreements, which it has described in its special report. (See also Chapter 19 of this Reference document).
At the date of the present Reference Document, the share capital, fully paid up, totaled 688,276.10 Euros, divided into 6,882,761 common shares with a nominal value of 0.10 Euro each, all in the same category.
None
The Company's mixed general shareholders' meeting of June 17, 2014, modified as follows the authorization given to the Board of Directors by the mixed general shareholders' meeting of April 2, 2013 to implement a buyback program on the Company shares, in conformity with the provisions of Article L. 225-209 of the Code of Commerce and the General Regulations of the Autorité des Marchés Financiers:
Maximum number of shares that can be repurchased: 5% of the number of shares constituting the Company's share capital at the performance date of these buybacks, as calculated in conformity with applicable legislative and regulatory provisions, it being nevertheless specified that the maximum number of shares held after these buybacks cannot exceed 10% of the capital.
Objectives of the share repurchase:
Maximum purchase price: twenty (20) Euros (excluding purchase costs),, it being specified that, in the event of a capital operation, notably by incorporation of reserves and allocation of free shares, or division or regrouping of shares, or even modification of the nominal value of shares, this price will be consequently adjusted.
During the financial year ended December 31, 2014, this buyback program was used exclusively within the scope of a liquidity agreement responding to the objective of market making or liquidation of the Company shares, stipulated with the company Bryan Garnier as investment service provider.
| Securities purchased | 167 345 |
|---|---|
| Nominal share value | €0.10 |
| Average share price | 19.487 Euros |
| Total amount paid for acquisition of securities | 3,261,099.75 euros |
| Shares sold | 215 780 |
| Nominal share value | €0.10 |
| Average share price | 18.129 Euros |
| Total amount received for the sale of shares | 3,911,775.10 Euros |
Trading costs totaled 7,223.09 Euros for the 2014 financial year.
At December 31, 2014, the Company held 4,500 ERYTECH shares, valued at 125,100 Euros (0.07% of the share capital), reduced to 1,500 shares at March 20, 2015 (0.02% of the share capital).
All the securities giving access to the Company's capital and in circulation at April 20, 2015 are described in the table below.
| Founder's share warrants2012 |
Share warrants (BSA)2012 |
Founder's share warrants (BSPCE)2014 |
||||
|---|---|---|---|---|---|---|
| Date of meeting | May 21, 2012 | April 2, 2013 | ||||
| Number of shares that the Company is authorized to issue |
45,050 | 22,500 | ||||
| Total number of subscription warrants issued | 38,812 | 0 | ||||
| Number of warrants exercised 12,400 |
0 | |||||
| Number of warrants not yet exercised | 26,412 | 22,500 | ||||
| Maximum number of shares remaining to be issued | 264,120 | 225,000 | ||||
| Of which the maximum | Y. GODFRIN | 75,080 | 30,000 | |||
| number of shares that can be subscribed by: |
P.O. GOINEAU | 75,080 | 10,000 |
| G. BEYEN | 78,630 | 60,000 | |
|---|---|---|---|
| Number of shares issued | 124,000 | 0 | |
| Starting point for exercise of subscription warrants | May 21, 2012 | April 1, 2015 | |
| Expiry date of subscription warrants | May 20, 2020 | Jan. 22, 2024 | |
| Warrant subscription price | €0.00 | €0.00 |
| 45,050 22,500 Number of shares that the company is authorized to issue Maximum 26,412 22,500 number of warrants not yet exercised Number of 33,787 5,025 0 warrants awarded Date of General May 21, 2012 April 2, 2013 Meeting Exercise price per €7.362 €12.25 new share subscribed Final date for May 20, 2020 January 22, 2024 exercising warrants 1 warrant for 10 shares Parity |
Types of securities | Founder's share warrants2012 | Share warrants (BSA)2012 |
Founder's share warrants (BSPCE)2014 |
|
|---|---|---|---|---|---|
| Warrant holders can only exercise their subscribed General warrants upon the occurrence of a firm, definitive conditions of operation involving the initial listing of Company (BSPCE)2014 exercise shares for trading on a regulated or unregulated stock - market, in France or the European Union, or a foreign or securities exchange: - (i) on one single occasion, or (ii) on multiple occasions, within a limit of twice a year and at least 100 warrants. year, and for Upon the occurrence of one of the following |
The founder's share warrants can be exercised: on one single occasion, except in the event of an M&A operation, at most four (4) times per the exercise of a minimum |
| operations: | of fifty (50) founder's | |
|---|---|---|
| (i) acceptance, by shareholders representing |
share warrants (BSPCE)2014. |
|
| at least sixty-six point six seven percent (66.67%) of the shares constituting the Company's capital, of a firm, definitive buyback offer pertaining to control of the Company (as pursuant to Article L. 233- 3 of the Code of Commerce); |
By way of exception, the possibility of early exercise was been established in the event of (i) a change of control as pursuant to article L. 233-3, par. 1 of the Commercial Code, or |
|
| (ii) the stipulation of a merger agreement providing for absorption of the Company; Warrant holders can exercise the entirety of their warrants |
(ii) a merger of the Company, and this without conditions on minimum threshold or frequency. |
|
| The securities to which the warrants give rights are common shares. |
The securities to which the warrants give rights are common shares. |
|
| Each warrant shall give the right to ten (10) shares in the Company's share capital. The new shares resulting from the exercise of |
Each warrant shall give the right to ten (10) shares in the Company's share capital. |
|
| founder's share warrants (BSPCEs) shall form the object of periodic requests for admission for trading on the regulated market NYSE Euronext. |
The new shares resulting from the exercise of founder's share warrants (BSPCEs) shall form the object of periodic requests for admission for trading on the regulated market NYSE Euronext. |
|
| Number of shares issued as of the date of the prospectus |
124,000 | 0 |
| Maximum number of new shares that can be issued* |
264,120 | 225,000 |
| Maximum dilution of shares and % resulting from the exercise of warrants |
489,120 shares, i.e., a maximum dilution of approximately 7.10%** |
* Post division of the nominal value of Company shares
** Based on the exercise of all diluting instruments (i.e., the BSA and BSPCE) and a share capital of €688,844.10
At the date of the Reference Document, no "guarantee of value" (ratchet) share subscription warrants exist any longer. These 233,855 warrants previously in circulation were canceled by the general shareholders' meeting of April 2, 2013.
The general shareholders' meeting of May 21, 2012 decided on a maximum issue of:
and delegated the Executive board, for a duration of 36 months, the necessary powers to allocate these BSAs2012 and BSPCEs2012.
The Board of Directors used this delegation:
The Company's mixed general shareholders' meeting of April 2, 2013, in its twenty-fifth resolution, delegated its powers to the Board of Directors for the purpose of issuing shares and securities giving access, immediately or in future, to common shares existing or to be issued by the Company, with suppression of the preferential subscription right outlined, through offerings as established under no. II, Article L. 411-2 of the Monetary and Financial Code.
The Board of Directors used this delegation:
At March 20, 2015, 28,738 warrants remained to be allocated, and 26,612 warrants allocated but not exercised, i.e., a total of 55,350 warrants to be exercised.
The general shareholders' meetings of April 2, 2013 and June 17, 2014 delegated to the Company's Board of Directors the power to issue securities in the proportions and for the amounts summarized in the table below.
| Date of General Meeting |
Maximum nominal amount of capital increase or Nature of authorization issue of securities representing debt securities resulting from the issue |
Cumulative ceiling |
Preferential subscription right |
Duration | Use | Maximum nominal amount remaining |
|
|---|---|---|---|---|---|---|---|
| 04/02/2013 | Increase in share capital to the issuance of common stock and/or securities giving access to the share capital immediately or over time while maintaining the preferential subscription right (22nd resolution) |
€500,000 | yes | 26 months 06/02/2015 |
N/A | ||
| 06/17/2014 | Capital increase through the issue of shares and/or securities giving immediate or future access to common shares, with suppression of the preferential subscription right to the benefit of categories of investors (10th resolution) |
€500,000 | No | 18 months 12/17/2015 |
10/22/2014 in the amount of 122,448.90 Euros |
€377,551.10 | |
| 06/17/2014 | Capital increase through the issue of shares and/or securities giving immediate or future access to common shares, with suppression of the preferential subscription right to the benefit of categories of investors* (11th resolution) |
€500,000 €500,000 |
No | 18 months 12/17/2015 |
N/A | ||
| 04/02/2013 | Capital increase through the issue of shares and/or securities giving immediate or future access to common shares in the company, with suppression of the preferential subscription right, by way of a public offering (24th resolution) |
€500,000 (Ceiling 13th resolution of the Combined General Meeting of 06/17/2014) |
No | 26 months 06/02/2015 |
04/30/2013 in the amount of €148,711.40 |
€500,000 | |
| 04/02/2013 | Capital increase through the issue of shares and/or securities giving immediate or future access to common shares in the company, with suppression of the shareholders' preferential subscription right, by way of an offering as established under Article L. 411-2, II of the Monetary and Financial Code (25th resolution) |
20% of the share capital (per 12-month period), within a limit of €500,000 (Ceiling 13th resolution of the Combined General Meeting of 06/17/2014) |
€500,000 | No | 26 months 06/02/2015 |
01/22/2014 in the amount of €22,500 |
€137,728.82 |
| Date of General Meeting |
Nature of authorization | Maximum nominal amount of capital increase or issue of securities representing debt securities resulting from the issue |
Cumulative ceiling |
Preferential subscription right |
Duration | Use | Maximum nominal amount remaining |
|---|---|---|---|---|---|---|---|
| 04/02/2013 | Increase in the number of shares to be issued in the event of a capital increase with or without suppression of the preferential subscription right |
Limited to 15% of the initial issue in application of the 10th and 11th resolutions of the general meeting of June 17, 2014 (12th resolution Combined General Meeting of 06/17/2014) |
Yes/No | 18 months 12/17/2015 |
N/A | €75,000 Euros (15% of 500,000 Euros) |
|
| 06/17/2014 | Limited to 15% of the initial issuance in application of the 22nd, 24th, and 25th resolutions of the general meeting of April 2, 2013(26th resolution of the General Meeting of 04/02/2013) |
Yes/No | 26 months 06/02/2015 |
03/30/2013 in the amount of €3.722 |
€71,278 (15% of €500,000 – €3,722) |
||
| 04/02/2013 | Share capital increase through the incorporation of premiums, reserves, profits or bonuses (29th resolution) |
€1 million | N/A | 26 months 06/02/2015 |
N/A | €1 million |
* Legal entities or individuals traditionally investing in securities in the healthcare domain **on the basis of a share capital of €688,644.10.
The ceilings outlined in the 22nd, 24th , and 25th resolutions of the General Meeting of April 2, 2013, initially set at 1,000,000 Euros, were decreased to €500,000 by the General Meeting of June 17, 2014, it being specified that this ceiling was set without taking into consideration the capital realized up to June 17, 2014.
Lastly, the General Meeting of June 17, 2014 terminated:
In its meetings on April 12, 2013 and April 30, 2013, the Executive Board made use of the delegation granted to it under the twenty-fourth resolution by the Mixed General Shareholders' Meeting of April 2, 2013 pertaining to a capital increase through the issue of shares and/or securities giving access to the Company's capital, with suppression of the preferential subscription right, through a public offering, and thus proceeded to issue 1,487,114 shares at a unit price of 11.60 euros.
On April 30, 2013, the Executive Board made use of the delegation granted to it under the twenty-sixth resolution by the Mixed General Shareholders' Meeting of April 2, 2013 pertaining to an increase in the number of securities to be issued in the event of a capital increase with or without suppression of the preferential subscription right, and thus proceeded to issue 37,220 shares at a unit price of 11.60 euros.
On January 22, 2014, the Board of Directors made usage of the delegation granted to it under the twenty-fifth resolution by the mixed general shareholders' meeting of April 2, 2013 relative to a capital increase through the issue of shares and/or securities giving access to the Company's capital with suppression of the preferential subscription right, through offerings as established under ii, Article L. 411-2 of the Monetary and Financial Code, and thus proceeded with the issue of 22,500 BSPCE2014, to the benefit of the Company's top directors and managers with employment contracts.
The mixed general shareholders' meeting of June 17, 2014, in its 10th resolution, delegated its powers to the Board of Directors for a duration of 18 months, for the purpose of proceeding, on one or more occasions, with the issue of shares, the subscription of which could be undertaken either in cash or through the offsetting of claims, for a maximum nominal amount of 500,000 Euros.
The Board of Directors made usage of this delegation of powers during its meeting of September 22, 2014, deciding in principle on a capital increase in accordance with certain conditions, and gave full powers to the Managing Director, who, holding the right to sub-delegate his powers to a Delegated Managing Director, used this delegation on October 8, 2014, giving Pierre-Olivier GOINEAU, in his capacity as Delegated Managing Director of the Company, the power to perform the above-described capital increase.
The Delegated Managing Director used this delegation on October 22, 2014 and decided to proceed with a capital increase in cash, with suppression of the preferential subscription right, for a nominal amount of 122,448.90 Euros through the issue of 1,224,489 new common shares with a nominal value of 0.10 Euros at a price set at 24.50 Euros per share (i.e., a nominal value of 0.10 Euro and an issue premium of 24.40 Euros), with a resulting capital increase in the amount, issue premium included, of 29,999,980.50 Euros and an issue premium in the amount of 29,877,531.60 Euros. The Delegated Managing Director acknowledged final completion of this increase on October 27, 2014.
The Board of Directors acknowledged the use of these delegations by the Chief Executive Officer and the Delegated Managing Director, and consequently modified the Company's articles of incorporation.
To the Company's knowledge, no call or put options or other commitments exist to the benefit of the Company shareholders or granted by the latter and pertaining to the Company shares.
The table below outlines the evolution of the Company's share capital during the last three financial years, it being specified (i) that no modification of the capital took place between 12/31/2010 and 12/31/2012, and (ii) that the Company proceeded, on October 27, 2014, with a cash-based capital increase with suppression of the preferential subscription right for a nominal amount 122,448.90 Euros through the issue of 1,224,489 new common shares with a nominal value of 0.10 Euros:
| 12/31/2013 | 12/31/2014 | 20/04/2015 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| SHAREHOLDERS | SHARES | % of capital |
% of the total voting rights1 |
SHARES | % of capital |
% of the total voting rights1 |
SHARES | % of capital |
% of the total voting rights1 |
| MANAGEMENT | 558,350 | 10.04% | 13.16% | 599,230 | 8.71% | 13.94% | 152,390 | 2.21% | 3.65% |
| Gil Beyen | 34,000 | 0.49% | 0.41% | 0 | 0.00% | 0.00% | |||
| Pierre-Olivier Goineau | 263,490 | 4.74% | 6.20% | 263,490 | 3.83% | 6.36% | No longer part of management2 | ||
| Yann Godfrin | 292,990 | 5.27% | 6.90% | 292,990 | 4.26% | 7.07% | 142,990 | 2.08% | 3.53% |
| Jérôme Bailly | 3,500 | 0.05% | 0.04% | 2,500 | 0.04% | 0.03% | |||
| Other management | 1870 | 0.03% | 0.06% | 5,250 | 0.08% | 0.06% | 6,900 | 0.10% | 0.09% |
| FINANCIAL INVESTORS/PE FUNDS |
2,827,284 | 10.04% | 60.51% | 1,069,742 | 15.54% | 22.70% | 1,069,742 | 15.53% | 23.25% |
| AMORCAGE RHONE ALPES | 109,200 | 1.96% | 2.59% | 0 | 0.00% | 0.00% | 0 | 0.00% | 0.00% |
| IDINVEST Partners | 1,221,392 | 21.97% | 25.72% | 51,530 | 0.75% | 1.24% | 51,530 | 0.75% | 1.27% |
| AURIGA Partners | 1,018,212 | 18.32% | 20.94% | 1,018,212 | 14.79% | 21.46% | 1,018,212 | 14.78% | 21.97% |
| AXA | 478,480 | 8.61% | 11.26% | 0 | 0.00% | 0.00% | 0 | 0.00% | 0.00% |
| RECORDATI ORPHAN DRUGS | 431,034 | 7.75% | 5.07% | 431,034 | 6.26% | 5.20% | 431,034 | 6.26% | 5.32% |
| MEMBERS OF THE BOARD OF DIRECTORS |
0 | 0.00% | 0.00% | 10,500 | 0.15% | 0.13% | 8,500 | 0.12% | 0.10% |
| OTHER SHAREHOLDERS | 67,502 | 1.21% | 1.54% | 61,263 | 0.89% | 1.21% | 274,083 | 3.98% | 6.50% |
| SUB-TOTAL REGISTERED SHAREHOLDERS |
3,884,170 | 69.87% | 80.29% | 2,171,769 | 31.55% | 43.17% | 1,935,749 | 28.10% | 38.83% |
| SUB-TOTAL BEARER SHAREHOLDERS |
1,674,782 | 29.18% | 19.71% | 4,710,992 | 68.45% | 56.83% | 4,952,692 | 71.90% | 61.17% |
| TOTAL | 5,558,952 | 100.00% | 100.00% | 6,882,7613 | 100.00% | 100.00% | 6,888,4413 | 100.00% | 100.00% |
1See also Section 18.3 of the Reference Document
2Pierre-Olivier GOINEAU resigned from his positions of Deputy Chairman, Delegated Managing Director, and Director at the end of the Board of Directors' meeting of January 11, 2015. Consequently, the number of shares held by Mr. GOINEAU (see Chap. 18.1) have been placed in the "Other shareholders" account.
3 Increase in the number of shares resulting from exercise of the BSPCE2012 and BSA2012. The capital increase will be recognized in a future Board of Directors' meeting, in conformity with Article L. 225-149 of the Code of Commerce.
To its knowledge, the company has no pledges on its capital.
It should be noted that, on May 6, 2013, the Company adopted a double voting right to the benefit of shareholders holding registered shares for more than two years (see Chap. 21.4.4); as such, the number of voting rights may increase on May 6, 2015 and result in a dilution.
The table below summarizes the operations occurring on the share capital during the last three fiscal years:
| Date | Operation | Securities issued/exercised |
Amount of capital increase (excluding issue premium) |
Number of shares/securities issued |
Nominal value |
Issue premium per share |
Number of shares after operation |
Price per share (issue premium included) |
Capital post operation |
|---|---|---|---|---|---|---|---|---|---|
| 04/30/13 | Capital increase |
Compensation for bond interest |
€8,375 | 83 750 | €0.10 | €11.50 | 3,237,300 | €11.60 | €323,730 |
| 04/30/13 | Capital increase |
New Shares |
€144,058.40 | 1,440,584 | €0.10 | €11.50 | 4,677,884 | €11.60 | €467,788.40 |
| 04/30/13 | Capital increase |
Convertible bonds |
86,206.80€ | 862 068 | €0.10 | €11.50 | 5,539,952 | €11.60 | €553,995.20 |
| 18/07/13 | Capital increase |
Share warrants (BSA)2012 |
€60,073.92 | 8 160 | €0.10 | €7,262 | 5,548,112 | €7,362 | €554,811.20 |
| 03/12/13 | Capital increase |
Share warrants (BSA)2012 |
€79,804.08 | 10 840 | €0.10 | €7,262 | 5,558,952 | €7,362 | €555,895.20 |
| 05/05/2014 | Capital increase |
BSA2012 BSPCE2012 |
€762.00 | 7 620 | €0.10 | €7,262 | 5,566,572 | €7,362 | €556,657.20 |
| 04/12/2014 | Capital increase |
BSA2012 BSPCE2012 |
€9,170 | 91 700 | €0.10 | €7,262 | 5,658,272 | €7,362 | €565,827.20 |
| 04/12/2014 | Capital increase |
Issue of new shares |
€122,448.90 | 1,224,489 | €0.10 | 24,40 | 6 882 761 | €24.50 | €688,276.10 |
The evolution of Company shares since the initial listing of its shares on the regulated market NYSE Euronext in Paris can be summarized in the table below:
| Since listing | |||||||
|---|---|---|---|---|---|---|---|
| highest price | Wednesday, October 1, 2014 | €34.97 | i.e., for | 5 584 272 | shares | a value of | €195.3 M |
| price at | Monday, April 20, 2015 | €29.80 | i.e., for | 6 886 941 | shares | a value of | €205.2 M |
| lowest price | Monday, December 16, 2013 | €8.58 | i.e., for | 5 548 112 | shares | a value of | €47.6 M |
| number of shares traded: | 14 895 302 | ||||||
| 2013 | |||||||
| highest price | Tuesday, May 7, 2013 | €12.07 | i.e., for | 5 539 952 | shares | a value of | €66.9 M |
| lowest price | Monday, December 16, 2013 | €8.58 | i.e., for | 5 548 112 | shares | a value of | €47.6 M |
| number of shares traded: | 864 643 | ||||||
| 2014 | |||||||
| highest price | Wednesday, October 1, 2014 | €34.97 | i.e., for | 5 584 272 | shares | a value of | €195.3 M |
| lowest price | Thursday, January 2, 2014 | €10.16 | i.e., for | 5 558 952 | shares | a value of | €56.5 M |
| number of shares traded: | 10 136 876 | ||||||
| 2015 | |||||||
| highest price | Tuesday, January 13, 2015 | €32.99 | i.e., for | 6 882 761 | shares | a value of | €227.1 M |
| lowest price | Tuesday, February 3, 2015 | €25.20 | i.e., for | 6 882 761 | shares | a value of | €173.4 M |
| number of shares traded: | 3 374 537 |
The Company has the purpose, in France and in any country, of:
and generally, all financial, commercial, industrial, civil, property, or security-related transactions, such as may directly or indirectly relate to one of the purposes specified or such as may facilitate their fulfillment.
The company may act directly or indirectly and perform all these operations in any country, on its own behalf and on behalf of third parties, either alone or with third parties in a joint venture, association, grouping, or company, through the creation of new companies, contributions, partnerships, subscription, purchase of company securities or rights, merger, alliance, joint venture companies, or the obtaining or provision, under lease or management, of any assets and rights or other items.
The Company is governed by a Board of Directors composed of at least three members and at most eighteen members, without prejudice to the derogation established by law in the event of merger.
The Board of Directors is composed by seeking a balanced representation of women and men.
During the life of the company, directors are appointed, renewed, or removed in Ordinary General Meetings. They can always be re-elected.
The duration of a director position is three (3) years; this position ends at the end of the Ordinary General Meeting called to rule on the annual financial statements for the year just ended and held during the year in which their term of office expires.
A person cannot be appointed as director where, having surpassed sixty-five years of age, this person's appointment has the effect of bringing the number of Board members having surpassed this age to more than one-third of the number of directors. Where this limit has been surpassed, the oldest director shall be deemed as having duly resigned.
Directors can be shareholders or non-shareholders of the Company.
A Company employee cannot be appointed director where his/her employment contract corresponds to an effective job. The number of directors tied to the Company by way of an employment contract cannot exceed one third of the directors in position.
Directors can be natural persons or legal persons. In the latter case, upon its appointment, the legal person is required to designate a permanent representative, who is subject to the same conditions and obligations and who incurs the same civil and criminal liability as if this person was a director in his/her own name, without prejudice to the several liability of the legal person that he/she represents. The permanent representative of a director as a legal entity is subject to the age conditions pertaining to directors as natural persons.
The term of office of the permanent representative designated by the legal person appointed as director is given to him/her for the duration of the latter's term of office.
Where the legal person revokes the term of office of its permanent representative, he/she is required to provide the Company, without delay and by registered letter, this revocation as well as the identify of its new permanent representative. The same is applicable in the event of the death or resignation of the permanent representative.
Designation of the permanent representative and discontinuation of his/her term of office are subject to the same publication formalities applicable as if he/she had been a director in his/her own name.
In the event of a vacancy, due to death or resignation, of one or more director positions, the Board of Directors may, between two general meetings, proceed with temporary appointments.
Where the number of directors has become lower than the legal minimum, the remaining directors shall immediately call an Ordinary General Meeting with a view to supplementing the Board's numbers.
Temporary appointments made by the Board are subject to ratification at the next Ordinary General Meeting. In default of such ratification, the resolutions made and acts performed by the Board prior to this meeting shall no longer be considered valid.
In the event of absence of a director at more than four consecutive Board of Directors' meetings, this director shall be considered as having duly resigned.
The Board of Directors shall elect a Chairman from among its members, the Chairman being a natural person, on penalty of invalidity of this appointment. It shall determine the Chairman's remuneration.
Any person older than sixty-five years of age may not be appointed Chairman. Where the Chairman in office comes to surpass this age, he/she shall be deemed as having duly resigned.
The Chairman is appointed for a duration that cannot exceed that of his/her director term of office. He/she can be re-elected. The Board of Directors may remove the Chairman at any time.
The Board may likewise appoint a Vice President from among its members who are natural persons, and he/she shall preside over Board meetings in the Chairman's absence.
The Board may designate, within a maximum limit of two, one or more observers who are natural persons, directors or otherwise, and who are 65 years of age at most at the day of their appointment.
These observers are appointed for a duration of two years.
These observer positions shall be fulfilled free of charge. The observers shall be summoned to all meetings of the Board of Directors and shall take part in deliberations for consultation purposes only. With the Board of Directors, the observers shall perform a general mission of consultation and supervision.
The Board of Directors shall meet as often as the Company's interests so require, upon summons by its Chairman or the Chief Executive Officer. Where the Board has not met for more than two months, at least one third of the directors may request that the Chairman, who is bound by this request, summon a Board of Directors meeting on a specific agenda.
Summonses shall be given by any means, including verbally.
Meetings shall take place either at the headquarters or at any other location indicated in the summons.
The Board may only validly deliberate where half of its directors are present.
Decisions shall be made by the majority of members present or represented.
In the event of a tie, the meeting Chairman's vote shall carry the decision.
Pursuant to the provisions of internal rules established by the Board of Directors, for calculation of the quorum and the majority, the directors participating in a Board meeting by videoconference or other means of telecommunications allowing for identification of the participants and guaranteeing their effective participation shall be deemed present, in compliance with current regulations.
This provision is not applicable for decisions on the annual financial statements, the consolidated financial statements, and preparation of the annual report and the group's annual report.
The Board of Directors determines the orientation of the Company's activities and oversees their implementation. Without prejudice to the powers expressly assigned by law to the shareholders and within the limit of the corporate purpose, the Board of Directors is responsible for all matters relating to the successful operation of the Company and governs matters concerning the Company, through its resolutions.
In relations with third parties, the Company is committed by the actions of the Board of Directors including where not pertaining to the corporate object, except where it can prove that the third party knew that such action fell outside this purpose or that it could not be ignorant of such fact, given the circumstances, mere publication of the articles of incorporation not being sufficient to constitute such proof.
The Board of Directors shall perform the controls and verifications that it deems appropriate. Each director may arrange for the communication to him/her of all documents and information necessary to the fulfillment of his/her mission.
The Board of Directors may decide on the creation of a study committee responsible for studying matters that the Board of Directors or its Chairman submits to it.
Senior Management is provided under its responsibility, by a natural person appointed by the Board of Directors and holding the title of Chief Executive Officer. This natural person can be the Chairman of the Board of Directors.
The Board of Directors chooses between two operating methods for the Senior Management.
The Board resolution pertaining to the choice of operating method for the Senior Management shall be carried by the majority of directors present or represented. Shareholders and third parties shall be informed of this choice in accordance with the conditions established by current regulations.
The Chief Executive Officer shall be a natural person selected from among the directors or elsewhere.
The duration of the Chief Executive Officer's duties is determined by the board at the time of his/her appointment. However, where the Chief Executive Officer is a director, the duration of his/her duties cannot exceed that of the director term of office.
Any person older than seventy years of age cannot be appointed as Chief Executive Officer. When the Chief Executive Officer reaches this age limit, he/she shall be deemed as having duly resigned.
The Chief Executive Officer can be removed by the Board of Directors at any time. Where the removal is decided without just cause, it may result in the payment of damages, except where the Chief Executive Officer holds the position of Chairman of the Board of Directors.
The Chief Executive Officer is vested with the broadest of powers to act in all circumstances in the name of the Company. He shall exercise his powers within the limits of the corporate purpose and without prejudice to those that the law expressly assigns to the shareholders and to the Board of Directors.
He shall represent the Company in its relations with third parties. The Company is committed by the actions of the Chief Executive Officer including where not pertaining to the corporate object, except where it can prove that the third party knew that such action fell outside this purpose or that it could not be ignorant of such fact, given the circumstances, mere publication of the articles of incorporation not being sufficient to constitute such proof.
The Board of Directors may limit the powers of the Chief Executive Officer, but these limitations are not binding against third parties.
Upon the proposal of the Chief Executive Officer that this position be assumed by the Chairman of the Board of Directors or by another person, the Board of Directors may appoint one or more natural persons assigned to assist the Chief Executive Officer, with the title of Chief Operating Officer.
The Board of Directors may choose the Chief Operating Officers from among the directors or elsewhere, and cannot appoint more than five (5) persons.
The age limit is set at seventy (70) years. When a Chief Operating Officer reaches this age limit, he/she shall be deemed as having duly resigned.
The Chief Operating Officer can be removed at any time by the Board of Directors, upon such proposal by the Chief Executive Officer. Where such removal is decided on without just cause, it may result in the payment of damages.
Where the Chief Executive Officer ceases or is unable to perform his/her duties, the Chief Operating Officers shall retain, except where decided otherwise by the Board, their duties and powers until the appointment of a new Chief Executive Officer.
In accordance with the Chief Executive Officer, the Board of Directors shall determine the extent and duration of powers granted to the Chief Operating Officers. The Chief Operating Officers shall have, in relation to third parties, the same powers as the Chief Executive Officer.
1 - The General Meeting may allocate to the directors, in remuneration for their activity and in the form of attendance fees, a fixed annual sum, the amount of which is reported under operating expenses and shall be maintained until a decision is made to the contrary. Its distribution among the directors shall be determined by the Board of Directors.
2 - The Board of Directors shall determine the remuneration for the Chairman of the Board of Directors, the Chief Executive Officer, and the Chief Operating Officer. This remuneration can be fixed and/or proportional.
The limitation on the plurality of terms of office as director and Chief Executive Officer applies in accordance with the conditions and subject to the derogations established by law.
REGULATED AGREEMENTS (as this provision has been proposed to the General Meeting of June 23, 2015 for approval)
All regulated agreements taking place, directly or through a third party, between the Company and one of its directors, its managing director, one of its delegated managing directors, one of its shareholders holding a portion of the voting rights greater than 10% or, where relating to a shareholder company, the company controlling it as defined under Article L. 233-3 of the Code of Commerce, must be submitted for the prior authorization of the Board of Directors.
The same is likewise applicable for agreements in which one of the persons outlined in the previous paragraph has an indirect interest, and for agreements taking place between the Company and another company, where the managing director, one of the delegated managing directors, or one of the Company's directors is the owner, shareholder with unlimited liability, manager, director, member of the supervisory board, or generally any director of this company.
The prior authorization of the Board of Directors shall be supported by reasons justifying the Company's interests in stipulating the agreement, and shall notably specify the financial conditions associated with this agreement.
Agreements stipulated and authorized during previous financial years, the fulfillment of which was continued into the last financial year, shall be examined each year by the Board of Directors and disclosed to the external auditors as established under the law.
The provisions of the preceding paragraphs shall not be applicable either to agreements relating to day-to-day operations stipulated under normal conditions or to agreements stipulated between two companies where one of these companies directly or indirectly holds the entirety of the other's capital, where applicable after deducting the minimum number of shares required to satisfy the requirements of Article 1832 of the Civil Code and Articles L. 225-1 and L. 226-1 of the Code of Commerce.
The report outlined under Article L. 225-102 of the Code of Commerce mentions, save where these are agreements relating to day-to-day operations stipulated under normal conditions, agreements reached directly or through a third party and between, on one part and as applicable, the managing director, one of the delegated managing directors, one of the directors, or one of the shareholders holding a portion of the voting rights greater than 10% of the Company's capital and, on the other part, another company in which the Company directly or indirectly holds more than half the capital.
All shareholders who come to hold or cease to hold, directly or indirectly, alone or jointly with another person, a number of shares or similar securities representing a portion of the capital or voting rights established by law must inform the Company of this, in accordance with the conditions established by the law and regulations.
Shareholders who have not respected these provisions shall be deprived of the voting rights attached to the shares exceeding the portion that should have been declared. The loss of voting rights shall apply to all shareholders' meetings held up to the expiry of a two-year period following the date on which the declaration was normalized.
The share capital shall be increased by any means and according to any methods established by law.
An Extraordinary General Meeting, acting on a report by the Board of Directors, is the sole entity with competency to decide on a capital increase. It may delegate such competency or powers to the Board of Directors.
The shareholders have, proportionately to the amount of their shares, a preferential right to the subscription of shares issued by way of a cash contribution to perform a capital increase, a right that they can waive individually. An Extraordinary General Meeting may decide to withdraw this preferential subscription right under legally established conditions.
The right to the assignment of new shares to shareholders, following an incorporation of reserves, income, or issue premiums into the capital, belongs to the bare owner, without prejudice to the rights of the usufructuary.
All the original shares constituting the initial capital and representing cash contributions must be paid up in the amount of at least half their nominal value at the time of their subscription.
Shares subscribed during a cash-based capital increase must be paid up in the amount of at least one quarter of their nominal value at the time of their subscription and, where applicable, the entirety of the issue premium. Payment of the remainder must take place on one or more occasions on the decision of the Board of Directors within a period of five years, i.e., this period starting on the day of registration in the Trade and Companies Register or, for a capital increase, on the day on which the capital increase became final.
Calls for funds shall be brought to the knowledge of subscribers by registered letter with acknowledgment of receipt sent at least fifteen days prior to the date established for each payment. Payments shall be paid either at the headquarters or at any other location indicated to this end.
Any delays in the payment of sums owing on the share amount not paid up shall result, duly and without the need to proceed with any formalities whatsoever, in the payment of interest at the legal rate, starting on the due date, without prejudice to any personal action that the Company may exercise against the defaulting shareholder and the enforcement measures established by law.
A reduction of the capital may be authorized or decided on in an Extraordinary General Meeting which may delegate to the board of directors all powers to perform such reduction. In no case shall this harm the equal treatment of the shareholders.
A reduction in share capital for an amount below the legal minimum can only be decided pursuant to the suspensive condition of a capital increase intended to return the share capital to an amount at least equal to this minimum amount, except where the Company is transformed into another form of company.
In the event of non-compliance with these provisions, any interested parties may seek dissolution of the Company through the courts.
Nevertheless, the court cannot order its dissolution where, on the date on which it rules based on grounds, the situation has been normalized.
The capital may be amortized in accordance with legal provisions. Amortization of the capital may be decided in an Extraordinary General Meeting and must be performed, through sums distributable in accordance with article L. 232-11 of the Commercial Code, by way of an equal reimbursement on each share of the same class. It shall not result in a reduction of the capital. Shares fully or partially amortized shall lose the right to reimbursement at their nominal value, up to the amount of this amortization. They shall retain all their other rights.
The shares are nominal, up to their full payment. Where they are fully paid up, they can be nominal or bearer, as decided by the shareholders.
They shall give rise to the registration of an account opened pursuant to the conditions and methods established under current legal and regulatory provisions, by the issuing company or by a financial broker authorized by the French Minister of the Economy and Finance.
The shares are indivisible in the eyes of the Company. Indivisible co-owners of shares shall be represented in General Meetings by one of the co-owners or by a joint representative of their choice. In default of an agreement between them on the choice of a representative, this representative shall be designated by order of the President of the Commercial Court, ruling in an interim order on the application of the co-owner first making such request.
The voting right attached to a share belongs to the usufructuary for Ordinary General Meetings and to the bare owner for Extraordinary General Meetings. However, the shareholders may agree amongst themselves on any other distribution for the exercise of a voting right in General Meetings. In this case, they must bring their agreement to the knowledge of the Company by registered letter sent to the headquarters, the Company being required to respect this agreement for any General Meetings held after the expiry of a one-month period following mailing of the registered letter, the postmark being considered proof of the mailing date.
The shareholder's right to obtain the communication of company documents or to consult these documents may likewise be exercised by each co-owner of an undivided share, by the usufructuary, and the bare owner of shares.
Shares can be freely traded, without prejudice to legal and regulatory provisions.
The ownership of shares issued in nominal form shall result from their registration in the name of the owners on the registers held to this end. Shares that are registered as necessarily being nominal may only be traded on the market where they have first been placed in a management account with an authorized broker.
Shares that are not registered as necessarily being nominal may only be traded on the market where they are converted to bearer shares.
Ownership of bearer shares shall result from their registration in a bearer account with an authorized financial broker.
The assignment of nominal or bearer shares shall take place, with regard to third parties and the company, by an account-to-account transfer into the accounts of the issuing company or those of the authorized financial broker.
The transfer of shares, free or charge or following a death, shall likewise take place by an account-to-account transfer upon the provision of evidence supporting the change in legal conditions.
Each share gives right to the profits, the company assets in a share proportional to the proportion of capital that it represents.
All shareholders shall have the right to be informed of the Company's performance and to obtain the communication of certain company documents at the times and in accordance with the conditions established by the law and regulations.
Shareholders shall only sustain losses up to the amount of their contributions.
The possession of a share requires due adherence to the decisions of the shareholders in General Meetings and to these articles of incorporation. Assignments shall include all dividends matured and not paid or maturing in future, as well as any share in the reserve funds, except where provisions to the contrary are reported to the Company.
Whenever it is necessary to hold a certain number of shares to exercise a right, in the event of an exchange, regrouping, or assignment of title, or at the time of a capital increase or reduction, a merger, or any other operation, the shareholders holding a number of shares less than that required can only exercise these rights on the condition that they personally arrange to obtain the number of shares required.
The rights of shareholders may be modified in accordance with legal conditions, by way of a modification of the Company's articles of incorporation, an operation that only the extraordinary general meeting is authorized to perform.
Shareholder decisions shall be made in General Meetings.
Ordinary General Meetings are those that are called to make all decisions that do not modify the articles of incorporation.
Extraordinary General Meetings are those called to decide on or authorize direct or indirect modifications to the articles of incorporation.
The resolutions of General Meetings create an obligation on all shareholders, including those who are absent, dissenting, or incompetent.
SUMMONSES AND MEETINGS OF THE GENERAL SHAREHOLDERS (as this provision has been proposed to the General Meeting of June 23, 2015 for approval)
All shareholders have the right to participate in General Meetings or to arrange for their representation in accordance with the conditions established by law.
General Meetings are called either by the Board of Directors or by the statutory auditors, or by a representative designated by the President of the Commercial Court in an interim ruling on the application of one or more shareholders constituting at least one tenth of the capital or, in an emergency, on the application of the participative Management Committee.
Where the Company's shares are admitted for trading on a regulated market or where all its shares are not nominal, it is required, at least thirty-five (35) days prior to any meeting, to publish in the French Bulletin des Annonces Légales Obligatoires (BALO) a meeting notice containing the information outlined in current regulations.
The summons to a General Meeting is made by a notice in a newspaper authorized to publish legal notices in the French département where the headquarters is located, and a notice, furthermore, in the Bulletin des Annonces Légales et Obligatoires [French Bulletin of Compulsory Legal Notices] (BALO).
Nevertheless, the notices outlined in the previous paragraph can be replaced by a summons made, at the Company's expense, by simple or registered letter sent to each shareholder. This summons may likewise be sent by a means of electronic telecommunications implemented in accordance with regulatory conditions.
Meetings shall take place at the headquarters or at any other location indicated in the notice of summons.
General Meetings shall be composed of all the shareholders, whatever the number of shares they hold.
Participation in the General Meetings, in any form whatsoever, is subject to the recording of shares in accordance with the conditions and timeframes established under current regulations. The Board of Directors has the right to accept voting forms and proxies arriving at the Company after the deadline established under current regulations.
A shareholder may arrange for his/her representation at the General Meetings by any natural or legal person of his/her choice, in accordance with legal provisions. Shareholders who are legal persons shall participate in meetings through their legal representatives or through any representative designated to this end.
Shareholders may likewise vote remotely in accordance with the methods established by the law and regulations, sending their remote voting form either in paper format or, on the decision of the Board of Directors, by a means of telecommunications.
The Board of Directors has the right to decide, at the time a meeting is called, whether the shareholders may participate and vote in any meetings by videoconference or any other means of telecommunications or electronic transmission (including via the internet), in accordance with the conditions established by the law and regulations applicable at the time of its utilization. This decision shall be communicated in the meeting notice and the notice of summons published in the Bulletin des Annonces Légales Obligatoires (BALO).
The shareholders who use, to this end and within the required timeframes, the electronic voting form offered on the website established by the coordinator of the shareholders' meeting shall be considered equal to the shareholders present or represented. The submission and signature of the electronic form may be directly performed on this site through any process approved by the Board of Directors and meeting the conditions defined in the first sentence of paragraph two, article 1316-4 of the French Civil Code, i.e., the usage of a reliable identification process guaranteeing the link with the form, notably such as consists of an identifier and a password.
The proxy or the vote thus expressed prior to the meeting by any means of telecommunications or electronic transmission, as well as the acknowledgment of receipt that is given in such case, shall be considered a fully irrevocable and enforceable submission, it being specified that, in the event of an assignment of shares taking place prior to the second (2nd) business day preceding the shareholders' meeting at local Paris time, the Company shall consequently invalidate or modify, as applicable, the proxy or the vote expressed prior to the meeting by any means of telecommunications.
The agenda for Meetings is provided by the person issuing the summons.
One or more shareholders, representing at least the portion of share capital required and acting in accordance with the conditions and timeframes established by law, have the right to request, by registered letter with acknowledgment of receipt or by electronic telecommunications, the inclusion of points or draft resolutions on a Meeting agenda.
The participative management committee may likewise request that draft resolutions be included on a Meeting agenda.
Meetings cannot deliberate on a matter that is not included on the agenda, which cannot be modified in the event of a second summons. It can nevertheless, in all circumstances, remove one or more members of the Board of Directors and proceed with their replacement.
Meetings are presided over by the Chairman of the Board of Directors or, in his absence, by a Vice President or by a director specially delegated to this end by the Board. Failing this, the Meeting shall itself designate its Chairman.
In the event of a summons by a statutory auditor or by an agent appointed by the court, the Meeting shall be presided over by the person issuing the summons.
The two shareholders, present and accepting such duties, representing, both for themselves and as representatives, the largest number of votes shall act as scrutineers and vote counters.
The committee thus established shall designate a secretary, who may be taken from outside the members of the Meeting.
An attendance sheet shall be kept, in accordance with the conditions established by law.
Deliberations and resolutions of the Meetings are recorded in minutes signed by the committee members and kept in a special register, in accordance with the law. Copies and extracts of these minutes shall be validly certified in accordance with the conditions established by law.
QUORUM – VOTE (as this provision has been proposed to the General Meeting of June 23, 2015 for approval
General Meetings, whether they are ordinary, extraordinary, or mixed, shall deliberate in accordance with the conditions for a quorum and majority as established in the provisions governing them, and shall exercise the powers assigned to them by the law.
The voting right attached to capital or dividend shares is proportional to the portion of capital that they represent. Each share gives the right to one vote.
A double voting right is nevertheless assigned, in accordance with legal conditions, to all shares fully paid up for which evidence is provided, at the latest on the second day prior to the date of the shareholders' meeting, of nominal registration for at least two years in the name of the same shareholder, or in the name of a person holding such rights following a succession, a sharing of the community of property between spouses, or an inter vivos gift granted by a shareholder to his/her spouse or to a relative in the direct line of succession, or following a transfer resulting from a merger or a division of a shareholder company.
In the event of a capital increase through the incorporation of reserves, income, or issue premiums, the double voting right is granted, upon their issue, to nominal shares assigned free of charge to replace the previous shares already receiving such benefit.
The double voting right shall be duly withdrawn from any share having been converted to a bearer share or been subject to a transfer of ownership, except where this transfer results from a succession, a sharing of the community of property between spouses, or an inter vivos gift granted by a shareholder to his/her spouse or to a relative in the direct line of succession, or following a transfer resulting from a merger or a division of a shareholder company.
No clauses of the articles of incorporation are such as may have the effect of delaying, deferring, or impeding a change of control in the Company.
The Company's articles of incorporation do not stipulate obligations other than those established by the law and regulations (article 9 of the Company's articles of incorporation).
All modifications to the share capital are subject to legal requirements, the articles of incorporation not stipulating any specific provisions.
The major contracts for the Company during the last two years, other than those stipulated in the normal course of business, are the following:
The parties have stipulated a cooperation agreement within the scope of the TEDAC project: "Therapeutic Enzymes to Deplete Amino acids to treat Cancers resistant to radio/chemotherapy."
This agreement entered into effect retroactively as of January 1st, 2012, for a duration of 8 years.
Within the scope of this project, OSEO will finance the Company in amount of 7 million euros, which shall be paid in multiple tranches, 4.9 million euros of which is in repayable advances and 2.1 million euros in nonrepayable grants.
The OSEO assistance is composed of a grant, as well as repayable assistance, in accordance with the following structure:
| Beneficiary | Project | Cost of eligible activities included (in €) | Maximum assistance provided (in €) | ||||
|---|---|---|---|---|---|---|---|
| amount (in €) |
Industrial research |
Experimental development |
Total | Grants | Repayable advances |
Total assistance |
|
| ERYTECH Pharma |
14,363,850 | 4,573,760 | 9,790,090 | 14,363,850 | 2,058,194 | 4,895,052 | 6,953,246* |
*That being 48% of the project amount
The project is monitored through a series of key milestones defined with a view to enabling OSEO to evaluate the progress of the project and determine the assistance to be paid. The key milestones are as follows (t0 having been established as July 1st, 2012):
| Key Milestone | Stopwatch | Date | ERYTECH Condition |
|---|---|---|---|
| Key Milestone 1 |
t0 + 12 months | Jul-13 | Provision of contract between ERYTECH and the enzyme supplier |
| Key Milestone 2 |
t0 + 24 months | Jul-14 | Enzyme encapsulation capacity |
| Key Milestone 3 |
t0 + 36 months | Jul-15 | Results of toxicology study, selection of therapeutic indication for phase I/II |
| Key Milestone 4 |
t0 + 48 months | Jul-16 | Design of study I/II, approval of regulatory authorities for phase I/II |
| Key Milestone 5 |
t0 + 60 months | Jul-17 | Intermediate results phase I/II |
| Key Milestone 6 |
t0 + 72 months | Jul-18 | Design of study II/III, approval of regulatory authorities II/III, results of I/II |
| Key Milestone 7 |
t0 + 84 months | Jul-19 | Intermediate results phase II/III |
| Key Milestone 8 |
t0 + 96 months | Jul-20 | Final report |
| First | Payments of non-repayable grants by key milestone (in €) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| payment of non repayable grants |
Key Milestone 1 |
Key Milestone 2 |
Key Milestone 3 |
Key Milestone 4 |
Key Milestone 5 |
Key Milestone 6 |
Key Milestone 7 |
Key Milestone 8 |
Total grant payments (in €) |
|
| ERYTEC H Pharma |
992,257 | 463,054 | 294,153 | 0 | 0 | 0 | 0 | 0 | 308,730 | 2,058,194 |
| First | Payments of repayable advances by key milestone (in €) | |||||||||
| payment of repayable advances |
Key Milestone 1 |
Key Milestone 2 |
Key Milestone 3 |
Key Milestone 4 |
Key Milestone 5 |
Key Milestone 6 |
Key Milestone 7 |
Key Milestone 8 |
Total payments of repayable advances (in €) |
|
| ERYTEC H Pharma |
62,607 | 0 | 0 | 217,121 | 901,807 | 1,018,028 | 1,454,167 | 507,064 | 734,258 | 4,895,052 |
The estimated amount of payments is established in the following tables:
The first payment was made after signature of the Framework Agreement with OSEO. In May 2012, the Company therefore received the above-mentioned amounts, i.e., €992,257 in non-repayable grants and €62,607 in repayable advances.
These amounts were therefore received as an advance, and therefore correspond to the amount of expenses estimated for Key Milestone 1 to which the assistance rate is applied.
At the end of key milestone 1, as of June 30, 2013, the Company had incurred an expense volume which came to €438,674, which did not reach the volume for which it had received the advance of €992,257. Consequently, the Company was unable to sollicit payment of the advance for the milestone, namely €463,054. The Company had, furthermore, already recorded deferred revenues amounting to €943,004 as of December 2012.
The following payments are made after each review of a Key Milestone. The amount effectively paid has a ceiling at the amount of the Key Milestone in question, decreased by any overpayments at previous Key Milestones. The total amount of payments made prior to the final Key Milestone shall not exceed 85% of the anticipated amount of the assistance.
The final payment of an estimated amount of 15% of the total amount of assistance shall be made after the Key Milestone and the final review of the project R&D identifying the end of the project and acceptance by OSEO.
Within the context of closing its books on 31 December 2013, the Company did not realize all of the forecast expenses in key milestone 2, as the milestone will be completed in June 2014. Since subsidies are booked on a pro rated basis for costs incurred (corporate financial statements and IFRS), at the end of 2013, the company recorded deferred revenues of €648,854, (refer to note 5.10 in Section 20).
However, the Company is clearly within the planned schedule with regard to the TEDAC project. The expenses incurred are lesser than planned in the initially submitted budget, as, in the end it was not necessary to go beyond that in order to achieve the initial steps of the project.
The Financial Repayments shall be made in specific payment amounts, in function of the anticipated sales revenue generated by the direct or indirect development of products or services resulting from the Project, as listed below:
Therapeutic products, simple or combined, used in the treatment of a solid tumor and composed of enzymes intended to break down a specific amino acid, encapsulated in the red blood cells.
The Financial Repayments include repayment of the Repayable Advance and the Additional Payments explained below. We specify that the amounts of the repayment maturities on the Repayable Advance take into account an annual discount rate of 3.05% (three point zero five percent), calculated according to the methods below.
The amounts M(m) of the advance payments and repayment payments arising in month (m) are thus based on the economic conditions of the month (m0) of signature of the agreement, according to the following calculation:
M (m0) = M (m) (1.0305)(-n/12)
Where n represents the number of months elapsed between (m0) and (m),
And the dates to be taken into consideration are:
The Company undertakes to repay OSEO an amount of €5,281,000 (five million, two hundred and eightyone thousand Euros) upon achieving a cumulative amount of before-tax sales revenue equal to or greater than €10,000,000 (ten million euros), entitled "trigger sales revenue", according to the following estimated lumpsum payment schedule:
| Year 1 at the latest on June 30 | €500,000 (five hundred thousand euros) |
|---|---|
| Year 2 at the latest on June 30 | €750,000 (seven hundred and fifty thousand euros) |
| Year 3 at the latest on June 30 | €1,500,000 (one million, five hundred thousand euros) |
| Year 4 at the latest on June 30 | €2,531,000 (two million, five hundred and thirty-one thousand |
| euros) |
In the event of sales of the intellectual property rights resulting from the project, as well as the assignment of prototypes, test series, and models created within the scope of the project, an annuity equal to 50% (fifty percent) of the income generated shall be lowing to OSEO ISI.
Where repayment of the Repayable Advance has been made in accordance with the above provisions, the Company shall pay OSEO, for a duration of five consecutive years after the termination date of said repayment and insofar as it has achieved a cumulative amount of before-tax sales revenue equal to or greater than €60,000,000 (sixty million euros), 2.5% of the annual sales revenue generated by the development of products resulting from the Project.
In any case:
Early repayment of the Repayable Advance may be required by OSEO, notably in the event of a change of control in the Company.
On March 28, 2011, ERYTECH signed a partnership agreement with Abic Marketing Limited (Groupe Teva), a global player in the pharmaceutical industry based in Israel, to distribute GRASPA® in this country. With a sales revenue of more than \$20 billion in 2013, Groupe Teva is a diversified pharmaceutical group with a strong strategy in innovative and unusual specialty products in therapeutic areas such as the central nervous system, respiratory system, women's health, oncology, and pain.
In accordance with the terms of this agreement, Groupe Teva shall submit an application for approval of the drug in Israel and shall provide for its marketing and long-term distribution in this country. Groupe Teva shall make milestone payments and shall share the income.
Early termination of the agreement may be requested by either party in the event of a change of control in the other party.
On November 23, 2012, ERYTECH signed a marketing agreement with Orphan Europe, a company specialized in the development, production, and marketing of drugs for orphan diseases. Orphan Europe is a subsidiary of Recordati, a major European pharmaceutical group that earned 942 million euros in sales revenue in 2013.
Orphan Europe holds a portfolio of orphan drugs already on the market in different areas, such as neonatology, pediatrics, and metabolic disorders. Orphan Europe is a leading player in the field of orphan diseases and has the medical, clinical, regulatory and commercial expertise to market and effectively sell GRASPA® in Europe. Orphan Europe is a strategic business for Recordati, which acquired the company in 2007 for €135 million and built it up further with the acquisition of a portfolio of rare and orphan disease drugs in the United States for \$100 million.
Orphan Europe will market GRASPA® in 38 European countries, including all the countries in the European Union for the treatment of ALL and AML. The parties have the opportunity to discuss the extension of this agreement to other areas around Europe and other indications.
ERYTECH is keeping the production of GRASPA® at its Lyon site and will supply Orphan Europe in the various European countries where the drug will be sold.
Under this agreement, Orphan Europe contributed €5 million upon signing. Orphan Europe will pay ERYTECH up to €37.5 million on future milestones in function of various clinical, regulatory, and commercial events. Orphan Europe will invest in the development costs for GRASPA® in AML and ERYTECH will receive a payment for product delivered and royalties on the sales made by Orphan Europe with GRASPA®, for a total of up to 45% of the sale price.
The Company considers, in particular, that withdrawal of the objection on the patent, initiated by the Company, allowed for a clause in the agreement to be automatically terminated, this clause stipulating that, where the intellectual property licensed is deemed to be counterfeited or invalid, the Company could be required to reimburse Orphan Europe for certain expenses, or even reduced milestone payments and/or the agreement, terminated in part.
Separately, another company in the Recordati Group has subscribed to bonds that were converted into an investment stake in the capital of ERYTECH for a value of €5M at the time of the IPO (see also Section 18.1 of the Reference Document).
The NIH has granted a license, pertaining to the intellectual property covering a diagnostic method to predict the efficacy of L-asparaginase in patients (see also Chapter 11.2 Intellectual Property). This license covers US territory and development in leukemias and solid cancers. It is exclusive for five years after FDA approval of the drug that will be developed by ERYTECH. This license is granted against the payment of an annual royalty. In the event of commercial use of this license, the Company will be required to pay an additional royalty proportionate to the net sale price.
The parties have entered into multiple agreements for the sale of packed red blood cells for therapeutic use intended for the manufacture of ERY-ASP/GRASPA®, notably on September 1st, 2009, within the context of the GRASPALL 2009-06 clinical study.
The parties have stipulated a forward contract according to which the ARC undertakes to supply ERYTECH within the scope of its requirements for packed red blood cells in the United States.
This contract entered into effect on July 1st, 2009 and will expire on December 4, 2015.
ERYTECH and Medac, a German company, have stipulated two exclusive supply contracts for asparaginase intended for the manufacture of ERY-ASP/GRASPA®.
This second contract contains certain provisions according to which ERYTECH may be required to refrain from any form of promotion of ERY-ASP/GRASPA® where this product is manufactured using a new formulation of asparaginase registered and marketed prior to ERY-ASP/GRASPA® as first-line treatment. It is specified that any restriction against promotion shall only be applicable for the country or countries in which the new formulation is approved first and only for the indication or indications that it obtains, and shall not impede the prescription of ERY-ASP by a physician and its sale by ERYTECH.
It is reiterated that ERY-ASP/GRASPA® is currently manufactured in Europe using native asparaginase and therefore covered by the first supply contract, which contains no promotion-related restrictions. The Company may plan to manufacture ERY-ASP/GRASPA® in Europe using any new Medac formulation, in the event such new formulation is developed, but has no obligation to do so.
In any event, none of the provisions of contracts with medac are such as impede or restrict, in any country, a physician's ability to prescribe ERYTECH drugs.
The Company has stipulated a supply contract for the provision of "Osmocell" devices, as well as the knowhow associated therewith. This contract entered into effect on September 10, 2013 for a duration of one year, with tacit renewal for subsequent one-year periods.
The Company has stipulated a supply contract for the provision of hemodialysis filters that the Company uses in its production system. The contract entered into effect on November 24, 2010 for a duration of 10 years.
The parties have stipulated a subcontracting agreement for the production of batches of ERY-ASP for the Company's clinical trials in the United States.
The contract entered into effect on March 1st, 2009 for an initial duration of 3 years, and is renewable in oneyear periods or, where applicable, until the end of the clinical trial for which ARC produces the batches.
The Company has stipulated a subcontracting agreement for the production of Lysis/resealing solutions that the Company uses within the scope of its activities involving molecule encapsulation in red blood cells. The agreement entered into effect on March 8, 2011 for an initial duration of 2 years, and is renewable for oneyear periods.
None.
Copies of this Reference Document are available at no cost at the Company's headquarters, 60 avenue Rockefeller, 69008 Lyon, France. This Reference Document can likewise be found on the Company's web site (www.erytech.com) and on the AMF web site (www.amf-france.org).
The articles of incorporation, General Meeting minutes, and other Company documents, as well as the historical financial information and all evaluations or declarations made by an expert upon the request of the Company and made available to the shareholders in accordance with applicable legislation can be found, at no cost, at the Company's headquarters.
These documents are likewise available in paper format upon a simple request to the Company.
Further, pursuant to article 221-3 of the French Autorité des Marchés Financiers (AMF) General Rules, the information regulated under article 221-1 of the same Regulations is available on the Company's website (www.erytech.com).
At December 31, 2004, ERYTECH Pharma held 100% of the shares in ERYTECH Pharma Inc., an American company established in April 2014, the objective of which is to develop the Company's activities in the United States of America (see Ch. 20.1 Annexes 2.3 and 5.5 and the table of subsidiaries and investment stakes in the annexes to the corporate financial statements under Ch. 20.5).
IND (Investigational New Drug Application) is an approval request to the FDA to administer an investigational drug or biological product to humans in the United States
Therapeutic Index: Measurement of the relative safety of a drug, expressed as the ratio of toxic dose to therapeutically effective dose.
Headquarters: Share capital: €688,276.10
Dear Shareholders,
In our capacity as statutory auditors of ERYTECH Pharma SA, and in application of the provisions of Article L.225-235 of the Code of Commerce, we hereby present you our report on the report prepared by the Chairman of your company, in conformity with the provisions of Article L.225-37 of the Code of Commerce, for the financial year ending December 31, 2014.
It is the responsibility of the Chairman to prepare and submit, for the approval of the Board of Directors, a report summarizing the internal control and risk management procedures implemented within the company and providing the other information required by Article L.225-37 of the Code of Commerce, notably relative to the system of corporate governance.
Our task is:
We conducted our work in accordance with the professional standards applicable in France.
1. Information about internal control and risk management procedures pertaining to the development and processing of accounting and financial information
Professional standards require the implementation of diligence reviews intended to assess the accuracy of information with respect to internal control and risk management procedures relative to the preparation and treatment of the accounting and financial information contained in the Chairman's report. These verifications consisted specifically in:
On the basis of this work, we have no observations to formulate on the information concerning the Company's internal control and risk management procedures pertaining to the preparation and treatment of the accounting and financial information contained in the Chairman's report to the Board of Directors, prepared in accordance with the provisions of Article L.225-37 of the Code of Commerce.
We hereby certify that the Chairman's report to the Board of Directors contains the other information required under Article L.225-37 of the Code of Commerce.
The statutory auditors Lyon, March 30, 2015
For KPMG Audit Rhône Alpes Auvergne For RSM CCI Conseils
Sara RIGHENZI DE VILLERS Gaël DHALLUIN Statutory Auditor Associate Error! Unknown document property name.
Headquarters: Share capital: €688,276.10
Dear Shareholders,
In our capacity as statutory auditors of ERYTECH Pharma SA, and in application of the provisions of Article L.225-235 of the Code of Commerce, we hereby present you our report on the report prepared by the Chairman of your company, in conformity with the provisions of Article L.225-37 of the Code of Commerce, for the financial year ending December 31, 2014.
It is the responsibility of the Chairman to prepare and submit, for the approval of the Board of Directors, a report summarizing the internal control and risk management procedures implemented within the company and providing the other information required by Article L.225-37 of the Code of Commerce, notably relative to the system of corporate governance.
Our task is:
• to provide you with any observations required of us based on the information contained in the Chairman's report respecting the internal control and risk management procedures relative to the preparation and treatment of accounting and financial information, and
Page | 290 of 302
• to certify that this report contains the other information required under Article L.225-37 of the Code of Commerce, it being specified that we are not responsible for verifying the accuracy of such other information.
We conducted our work in accordance with the professional standards applicable in France.
3. Information about internal control and risk management procedures pertaining to the development and processing of accounting and financial information
Professional standards require the implementation of diligence reviews intended to assess the accuracy of information with respect to internal control and risk management procedures relative to the preparation and treatment of the accounting and financial information contained in the Chairman's report. These verifications consisted specifically in:
• determining whether major deficiencies in internal control, relative to the preparation and treatment of the accounting and financial information, such as we have identified within the context of our mission, were appropriately disclosed in the Chairman's report.
On the basis of this work, we have no observations to formulate on the information concerning the Company's internal control and risk management procedures pertaining to the preparation and treatment of the accounting and financial information contained in the Chairman's report to the Board of Directors, prepared in accordance with the provisions of Article L.225-37 of the Code of Commerce.
We hereby certify that the Chairman's report to the Board of Directors contains the other information required under Article L.225-37 of the Code of Commerce.
The statutory auditors Lyon, March 30, 2015
For KPMG Audit Rhône Alpes Auvergne For RSM CCI Conseils
Sara RIGHENZI DE VILLERS Gaël DHALLUIN Statutory Auditor Associate
ERYTECH Pharma is a biopharmaceutical company which wishes to become an international leader in customized medicine in the field of cancer.
ERYTECH Pharma Company aspires to conduct each of its actions as a Socially Responsible Enterprise.
Placing the patient at the heart of our priorities, demonstrating ethics and respect towards each person are shared values within ERYTECH Pharma and they form the basis for its approach as a socially responsible enterprise.
The employees are the ones who promote these values and develop business on a day-to-day basis. The Company has made a particular commitment to train them and offer them a healthy and safe work setting so that they can continue to form a team that is motivated by the Company's success.
ERYTECH Pharma has made a sustained investment in R&D to meet the challenges of public health and to offer innovative and radical therapeutic responses particularly in the field of cancer.
Its current activities thus are concentrated in research and development and production for clinical trials. They are being developed in close collaboration with health professionals, particularly physicians and pharmacists, whose expectations guide ERYTECH Pharma.
The Company holds regulated status as a Pharmaceutical Company.
This report is intended to present the Company's stakeholders with its contribution in terms of Sustainable Development.
The table below summarizes the numerical indicators used to describe jobs at ERYTECH Pharma over the last three years:
| 2012 | 2013 | 2014 | ||
|---|---|---|---|---|
| Total personnel and the distribution of employees by gender and | ||||
| by age | Personnel at the end of the fiscal year (headings) | 37 | 36 | 42 |
| Staff distribution M/W (%) | 32/68 | 32/68 | 40/60 | |
| Mean age (years) | 35 | 36 | 35 | |
| Employees 45 years of age or greater (employees, %) | 8% | 14% | 12% | |
| Hires and dismissals | ||||
| Net number of jobs created | 1 | -1 | 6 | |
| Remuneration and its evolution | ||||
| Mean gross remuneration | 47,072 | 52,852 | 55,325 | |
| Annual increase ratio (comparable personnel) | nd | 7% | 5% |
ERYTECH Pharma's personnel has remained stable between the 2013 financial year and the 2014 financial year. All personnel is located at a single site in Lyon, in the eighth district. The Men/Women distribution as well as the average age are generally stable. The rate of collaborators more than 45 years of age is nearly stable: 5 in 2014, as compared to 3 in 2013.
Staff are highly qualified: managers represented 48% of the personnel in 2014. At the end of the year, the personnel included 9 employees holding a doctorate in science, medicine, or pharmacy and 16 employees holding a degree in engineering or a master's degree, i.e., respectively 21% and 38% of the total staff.
In 2014, twelve new employees joined the company under different contracts: 6 permanent contracts and 6 fixed-term contracts.
Four employees working under permanent contracts left the company during the year, one as part of a dismissal, one within the context of a mutually agreed departure, and two through resignations. Two employees with fixed-term contracts reached the end of their contracts in 2014.
ERYTECH Pharma receives interns coming from schools or universities. In 2013 and 2014, interns received an indemnity that was above the legal minimum. As with any employee, they receive meal tickets and their transportation costs are reimbursed at a rate of 50%. Periods of internship are considered for purposes of seniority for those interns hired at the end of their internship. One intern was hired at the start of 2014 under a fixed-term contract, at the end of his internship.
ERYTECH Pharma also allows young diploma-holders to benefit from Volontariat International en Entreprise [International Volunteers in Business] (VIE). Additionally, the Company will be entrusting one of its employees with an 18-month professional assignment in Philadelphia (USA).
The Company applies an individual system for evolution in remuneration. There are two components to bonuses: individual and collective based on reaching objectives (quality, personal, department, company). Personnel working under fixed-term contracts receive payment of the bonus for at-risk employment should their contract not be renewed.
ERYTECH Pharma complies with current law and has set the hours of the standard workweek to be 35 hours. These terms apply on prorated basis to part-time employees.
The table below summarizes the indicators used to describe the organization of work at ERYTECH Pharma over the last three years:
| 2012 | 2013 | 2014 | ||
|---|---|---|---|---|
| Organization of time at work | ||||
| Absenteeism | Rate of part-time employees (%) | 9.86% | 6.69% | 8.58% |
| Rate of absenteeism | 2.40% | 2.40% | 1.75% |
The rate of part-time work increased; there were four people working part-time (80%) at the end of 2014, versus three at the end of 2013.
Employees working part-time do so at their request; this is due primarily, but not exclusively, to parental leave. In effect, in order to find a just articulation between professional activity and personal and family life for men and women, the Company examines each request seeking to adapt the organization of work.
The absenteeism rate (excluding maternity, paternity, or parental leave) is stable; in the main, days of absence are days of absence due to illness (97%) and "sick child" days. No absence has been associated with a jobrelated illness.
Given the size of its personnel (fewer than 50 employees), the Company has one employee representative and one deputy. Meetings with the employee representative are held regularly, in accordance with legal procedures and even beyond that, since all questions are considered, even those that do not lie within the purview of powers awarded to the employee representative.
Agreements signed or commitment in the company are as follows:
to or greater than those that were previously established. The memo entered into effect on November 17, 2014.
The life of the company is based on active internal communication and participatory management. The company regularly organizes meetings within the departments about the various projects. Inter-departmental meetings have been implemented. Moreover, some informational meetings with employees, managers, or all categories put together, are organized thematically (for example during the IPO), so as to preserve dialogue and encourage employees to express themselves.
Each quarter, a meeting is organized with HR in which widely ranging themes are discussed such as training programs, end-of-year interviews, company insurance, incentives, etc.
Twice a year, ERYTECH Pharma offers "corporate days" which are essential for building cohesion among the teams.
The company's activities are conducted in a particularly strict setting with regard to authorizations and approvals, and safety of the personnel is a fundamental element for the company's sustainable development.
Additionally, from the beginning, the company has deployed a policy of management through quality with ISO 9001: 2008 certification covering all of its processes. Within this framework, ERYTECH has a general health and safety procedure governing the practices of personnel in relation to the two following risks: biological and chemical.
Finally, problems pertaining to the personnel's hygiene and safety are followed and managed by the implementation of a Single Document, which identifies and evaluates work-related risks. Within this context, ERYTECH Pharma supplemented its team of workplace first-aid rescue workers in 2014 by adding a new member.
The table below summarizes the indicators used to monitor health and safety at ERYTECH Pharma over the last three years:
| Workplace accidents, particularly their frequency and their severity, as well as work-related illnesses |
2012 | 2013 | 2014 |
|---|---|---|---|
| Number of workplace accidents which resulted in work stoppage | 1 | 0 | 2 |
| Frequency rate* of workplace accidents resulting in stoppage | 18/1000000 | 0 | 33/1000000 |
| Severity level** of workplace accidents | 0,02% | 0 | 0,26% |
| Number of workplace accidents without stoppage | 0 | 1 | 0 |
| Frequency rate* of workplace accidents without stoppage | 0 | 17/100000 | 0 |
| Number of incidents | 1 | 0 1 |
0 |
| Frequency rate* of incidents | 18/1000000 | 17/100000 | 0 |
| Number of work-related illnesses | 0 | 0 0 |
0 |
*Frequency rate of workplace/commuting accidents = (Number of accidents involving an absence from work) x 1,000,000/Number of theoretical annual hours worked
**Severity rate = (Number of days of absence associated with workplace/commuting accidents) x 1,000/Number of hours worked
*Frequency rate of incidents = (Number of incidents) x 1,000,000/Number of theoretical annual hours worked
The number of accidents resulting in an absence from work was two for 2014. ERYTECH Pharma files the necessary declarations if there is a workplace accident or an accident during transit, whether or not they result in stoppage of work. They are monitored in the incident log maintained by ERYTECH Pharma.
In terms of Hygiene and Safety, the Company complies with the legal and contractual provisions and, currently, has not signed any additional agreements either with a collective bargaining organization or with the employee representative.
The table below summarizes the indicators used to describe training at ERYTECH Pharma over the last three years:
| 2012 | 2013 | 2014 | |
|---|---|---|---|
| Total number of hours of training Total number of hours of training |
400 | 474 | 600,5 |
| Mean volume of hours of training/employee/year | 11 | 13 | 14 |
| Proportion of personnel 45 years or older who has received training actions (%) (Number of persons concerned) |
100% 3/3 |
40% 2/5 |
40% (2/5) |
| Training expenditure ratio* | 2.13% | 2.22% | 2.31% |
* Training expenditure ratio: Training expenses/wage and salary bill. Considering the size of ERYTECH Pharma, the company is required to comply with a minimum legal training expenditure ratio of 1.6%.
The company continued its training policy within a long-term perspective, on the basis of actions intended to strengthen collective and individual skills and abilities.
ERYTECH Pharma has moreover defined the following areas of focus in relation to professional development, for 2014 and 2015:
These areas of focus have been defined in function of economic outlook and the evolution of jobs, investments, and technologies within the business, and notably, for 2014:
For this reason, the training expenditure rate has been maintained above the legal obligations (1.6% of the wage and salary bill, according to the French Labor Code).
During the Board of Directors' meeting of December 4, 2014, ERYTECH Pharma proposed continuing the measures initiated in 2014 with a view to consolidating equality between men and women possessing equal qualifications and skills, and more particularly to give preference to the hiring of women at the "director" level and to give preference to the hiring of men at other levels.
In conformity with the transitional provisions of Law no. 2011-103 of January 27, 2011 relative to the balanced representation of women and men on boards of directors and supervisory boards and relative to professional quality, the proportion of directors of each gender was greater than 20% at December 31, 2014.
Measures taken to promote employment and integration of handicapped personnel
Recruitment procedures at ERYTECH Pharma provide for the possible inclusion of disabled persons. Despite the publication of 2014 job offers on the site Handi EM (specialized in job insertion and retention for disabled persons in the pharmaceutical industry), no applications have been received from disabled persons.
The external recruitment procedure reviews the regulatory requirements in terms of nondiscrimination when hiring. The procedure illustrates these requirements through a list of "prohibited questions."
f. Promotion and compliance with the stipulations of the fundamental conventions of the International Labor Organization as pertains to the respect for freedom of association and the right to collective bargaining, the elimination of discrimination in terms of jobs and professions, the elimination of forced or mandatory work, and the effect of abolition of child labor
The Company's employees conduct their activities in France.
The activities implemented include contract industrial production. These activities therefore result neither in a massive use of raw materials, nor in significant energy consumption, nor any significant discharge of greenhouse gases into the environment, nor use of soil. Furthermore, the activities inherent to the Company do not generate particular auditory nuisances for its employees or neighbors.
Activities are localized within the Bioparc, a health, safety, and environment-focused business park developed as part of the Rockefeller Health Center in Lyon. The Company possesses quantitative elements which allow it to monitor practically all of its consumption in water and electricity (except for consumption pertaining to the common areas due to the ways the building is managed).
The Company has not identified any significant environmental risks associated with its activity such as could lead to establishing a provision against these risks or specifically training its employees with regard to these issues.
To date, the Company has not identified any opportunities for taking steps to protect biodiversity and adapting to the consequences of climate change.
In this setting, the following environmental indicators were chosen as being relevant:
Despite an environmental impact deemed to be low, the Company and its employees are involved, in terms of sustainable development, in the maintenance of the following actions:
ERYTECH Pharma chose its location in Lyon, at the heart of a center for health, which is well-served by mass transit, rather than outside of the city so as to limit travel by car.
The only energy source used by the Company is electric energy. The following table presents the evolution in annual electricity consumption:
| 2012 | 2013 | 2014 | |
|---|---|---|---|
| Electricity consumption (kWh) | 283,798 | 279,558 | 301,825 |
For information purposes, 301,825 kWh consumed in 2014 represent 23.5 tons of CO2*.
* Application of the emissions factor (indirect energy) from the ADEME (French Environment and Energy Management Agency) (carbon base).
Water consumption corresponds to the pharmaceutical company's activities. Water discharged after use is water that comes from washing cycles (sinks, washing machines). Water that has been contaminated by biological or chemical waste is reprocessed.
| 2012 | 2013 | 2014 | |
|---|---|---|---|
| Consumption of water (m3 ) |
8.37 | 8.21 | 8.21 |
The Company outsources the logistics associated with its activities.
It does not have all the quantitative information enabling it to ensure the exhaustive monitoring of associated CO2 emissions. Further, the information known is presented in the table below:
| 2012 | 2013 | 2014 | |
|---|---|---|---|
| CO2 emissions associated with professional travel |
44.4 | 65.8 | 99.3 |
| (train & airplane) (T) | |||
| CO2 emissions associated with the transportation |
Not | Not | 0.91 |
| of mail and packages (planes & road | Available | Available | |
| transportation) (T) | |||
| CO2 emissions associated with the shipment of |
Not | Not | Not |
| drugs (planes, trains & road transportation) (T) | Available | Available | Available |
Intercontinental business trips are frequently necessary due to the international nature of the Company since 2013.
Despite multiple attempts, information relative to CO2 emissions associated with the shipment of drugs has not been successfully obtained.
Within the context of its SRE activities, ERYTECH focuses the awareness of employees on the rigorous management of their consumables and waste. As such, in 2014, a very large decrease in the volume of expired reagents eliminated (in "Sécuribag") was recorded, reflecting good governance in the management of reagents used.
Further, within the objective of limiting the environmental impact of its waste, the Company arranges for the systematic removal and treatment of its waste resulting from laboratory activities, by a specialized company, with a view to ensuring full traceability through the treatment processes used.
In terms of volumes, quantities picked up and sent to the processing center are as follows:
| 2012 | 2013 | 2014 | |
|---|---|---|---|
| Barrels and cans (in liters) | 17,085 | 29,410 | 34,940 |
| "Securibag" (in Kg) | 78 | 90 | 1 |
The desire to align development of the business with that of our region of origin is a key value for the group:
In 2014, 41.55% of the outlays made when conducting the development of its research projects were external expenditures.
Indeed, the Company has a desire to align development of the business with that of our region, notably by subcontracting certain pre-clinical studies to regional entities, and by creating partnerships with Ecole Vétérinaire de Lyon [the Veterinary School of Lyon] and Université Claude Bernard in Lyon. It also calls on numerous consulting firms in the region (patents, finance, attorneys). Further, in 2014, the Company decided to add a program offered by the Chamber of Commerce and Industry through the Espace Numérique Entreprises [digital business space] for small and medium-sized companies, with a view to changing its information system.
ERYTECH Pharma has chosen to collaborate with ERAI (Entreprise Rhône Alpes International), a structure created by the Rhône Alpes Region, with a view to pursuing its economic development internationally. This choice arose naturally from the Company's volition to foster a strengthening of the attractiveness of Rhône-Alpes, one of the missions of ERAI.
ERYTECH Pharma is also an active member:
ERYTECH PHARMA seeks to create close relationships with training institutions and universities, and allows its employees to teach courses during their work time and within their field of expertise.
ERYTECH Pharma regularly participates in symposia, congresses, and annual conferences, notably including, in 2014:
These meetings allow the Company to meet health care professionals and key opinion leaders with a view to pursuing its areas of development in innovative products and to satisfying unmet medical needs.
All shareholders have access to fall, transparent, and clear information, adapted to the needs of each person and useful for an objective assessment of the Company's growth strategy and results. This financial communications policy is intended to ensure that all shareholders have information in compliance with the practices of the financial marketplace.
A very wide variety of public documents, including those distributed as regulated information, covers the Company's activity, strategy, and financial information and are accessible on the Company's website under the Investors heading, in French and in English. There is also a dedicated email address for investors ([email protected]).
In terms of regulated information, the Company releases the annual information required of a listed company. The financial information is supplemented by periodic information and press releases intended for the financial community and more broadly the public, concerning subjects of significant importance for an understanding of the Company's activities and strategy.
The success of the reserved capital increase in the amount of 30 million Euros on October 23, 2014 attests to the Company's influence not only on the European market, but also on the American market. This operation indirectly enhances the visibility of French biotechnology companies and regional know-how in France and abroad. Lastly, the funds raised during this capital increase will ensure the completion of a portion of the biomedical research for which ERYTECH Pharma is the sponsor, and will launch a new clinical study on a therapeutic indication in oncology or hematological oncology. This biomedical research is performed with the goal of providing a tailored response to unmet medical needs in the indications studied.
In 2014, ERYTECH Pharma participated in two trade fairs, in order to meet small shareholders:
At least once a year, steering committees are organized between the Company and its primary partners, for the purpose of discussing strategy and progress in joint projects.
Through its sponsorship activities, ERYTECH supports associations and projects in the health care field, and notably in the fight against cancer. Their areas of common interest: consistency with our values and our desire for building strong roots in the region.
During 2014, after the sponsorship of Journées Nationales contre la Leucémie [national days against leukemia] on March 29 and 30, employees organized various sales and collections with a view to sponsoring the participation of 2 colleagues in the Course des Héros, in support of the Association Laurette Fugain.
Further, during the company's 10 years of existence, ERYTECH has sought to provide its financial support and show its thanks to the Centre Léon Bérard, its historical partner, which offered it the possibility of producing its first drug candidates upon creation of the company.
ERYTECH Pharma desires to share its values with its suppliers and subcontractors, and encourages regular collaborations, insofar as possible, with a view to building client-supplier and client-subcontractor relationships of trust. This aspect is strengthened by the strategic nature of certain suppliers. As such, the stakes surrounding strategic supplier relationships allow for a closer dialog. These suppliers are specifically monitored internally by dedicated teams, and a single contact person is identified.
The Company also has a supplier selection and monitoring procedure for its business relationships with suppliers for certain critical elements (clinical trials, non-clinical trials, pharmacovigilance, and production unit suppliers). Given the regulatory aspects of the Company's activities, most service providers and suppliers must also comply with the Best Laboratory and/or Clinical and/or Manufacturing Practices.
ERYTECH undertakes to apply SRE principles to its purchasing, selecting goods and services produced and provided in compliance with rigorous environmental, social, and ethical principles. We pursue our involvement in the monitoring of SRE criteria compliance by suppliers, as specified in our internal procedures, giving preference to suppliers who have an SRE policy that complies with the requirements of Grenelle II during the pre-selection stage, all other factors being equal. Indeed, ERYTECH Pharma updated its supplier evaluation questionnaire in 2014, in order to learn about the SRE activities undertaken by its partners. However, no selections have been made since this criterion was added.
The Company's procedures provide for supplier audits based on the type of purchases (pharmaceutical business supplier, new supplier, critical nature, etc.). as well as follow-up audits. However, supplier audits do not incorporate the SRE aspects given the structure of the upstream market.
Various policies have been implemented to reinforce the approach to ethics:
At the current stage of its development, none of the medicinal products being developed by the Company today has been marketed or received marketing approval. The development of medicinal products is highly controlled by strict regulation. The various phases in the development of medicinal products require animal tests at the outset (preclinical development) then tests with humans (clinical development). Each of the development phases requires prior authorization delivered by the oversight authorities following approval by the ethics committees.
As part of the research and development activities, the Company implements preclinical studies within a strict framework. For these phases, the Company may make use of service providers who conduct animal experiments. The latter must follow a national procedure pertaining to the protection of animals used for scientific purposes, in conformity with Decree no. 2013-118 of February 1, 2013, which contains, in particular, an obligation to obtain approval prior to conducting any project involving the performance of one or more experimental procedures using animals.
The Company has not undertaken any additional action to promote human rights.
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