Oxurion NV — Management Reports 2013

Nov 20, 2013

ThromboGenics Business Update

• JETREA® slowly continues to gain acceptance with the US retina community.
• Company increasing US medical education efforts: increasing number of USbased Medical Science Liaison managers to 12.
• US Organizational update: Dr Keith Steward appointed Head of US Business Operations.
• Benefits of JETREA®, particularly in early stage patients, confirmed by positive reimbursement guidance from both the GB-A in Germany and NICE in the UK.
• Alcon delivers important milestones with JETREA® in Rest of the World: Product approved in Canada, important clinical bridging study initiated in Japan, other multiple submissions are ongoing and planned.
• Continued focus on diabetic eye diseases: Prevention of Proliferative Diabetic Retinopathy (PDR) is next JETREA® target indication.
• On September 30, 2013, the Company's cash position is Euro 183 Million, from Euro 193.6 Million on June 30, 2013.

Leuven, Belgium – 7 November, 2013 - ThromboGenics NV (Euronext Brussels: THR), an integrated biopharmaceutical company focused on developing and commercializing innovative ophthalmic medicines, today issued a business update for the period ending 30 September, 2013.

ThromboGenics has developed JETREA®, the first and only pharmacological treatment indicated for an important sight-threatening condition, symptomatic vitreomacular adhesion (VMA)/ vitreomacular traction (VMT) in the US and Europe respectively. VMT/ symptomatic VMA is a progressive, sight-threatening condition that may lead to visual distortion, decreased visual acuity and central blindness.

In mid-January 2013, the Company launched JETREA® in the US through its own commercial organization.

In April 2013, its partner Alcon launched JETREA® in Europe after it was approved by the European Commission in March. In Europe the drug is now available in the UK, Germany, Finland, Norway, Denmark and Sweden. First patients were also treated in Belgium, France and the Netherlands. ThromboGenics received €90 million in milestone payments from Alcon for the EU approval and first European sale of JETREA®.

In October, G-BA, the highest German decision-making body responsible for determining the health care services which will be reimbursed for over 70 million

publicly insured persons in Germany, confirmed the exceptional benefit appraisal JETREA® received from IQWiG. G-BA concluded in its value assessment of JETREA® that JETREA® demonstrates significant therapeutic benefits for patients suffering from mild and moderate symptoms of VMT when compared with watchful waiting.

In October, UK's National Institute for Health and Care Excellence (NICE) final guidance has recommended that JETREA® (ocriplasmin) should be reimbursed within the National Health Service (NHS) in England and Wales as an option for treating VMT patients.

The NICE final guidance highlighted metamorphopsia as a 'severe and distressing' symptom, with its impact on the patient being comparable to a loss of two lines in visual acuity. In its final ruling, NICE has recommended reimbursing JETREA® when used to treat patients suffering from metamorphopsia, one of the early signs of VMT.

In RoW, JETREA® was approved in Canada in August, for the treatment of symptomatic vitreomacular adhesion. This was the first approval of this innovative drug in a market outside the US and Europe.

In Japan, Alcon has started its first clinical study with JETREA®. This clinical bridging study is recruiting patients with symptomatic VMA/VMT including those associated with macular hole. The study is an important step in potentially gaining regulatory approval for ocriplasmin in Japan, the world's second largest pharmaceutical market.

Dr Patrik De Haes, CEO of ThromboGenics comments: "We are continuing to work to drive the adoption of this novel treatment option in patients with symptomatic VMA/VMT. Our medical education efforts are focused on changing a treatment paradigm for early stage patients who usually undergo a period of watchful waiting prior to surgery. We are increasing the number of MSLs in the US so we are better placed to highlight to retina physicians the multiple benefits of treating mild to moderate patients early.

"It is clear that these expanded educational efforts along with the provision of reimbursement and medical information support will require more time before they lead to a significant uptick in JETREA®'s prescribing. However, given the positive outcomes we have seen in a number of JETREA® excellence centers across the US, we remain confident of generating a higher level of sales with this innovative new drug.

"In Europe, with our partner Alcon, we are encouraged by the very positive final guidance from the G-BA in Germany and NICE in the UK. Particularly important is that both of these rulings highlight the significant value of using JETREA® for the treatment of patients with early symptoms. We are looking forward to further launches of JETREA® across the EU during the next twelve months.

Outside Europe, Alcon is continuing to make good progress with JETREA®, having recently received approval for the drug in Canada and having started an important clinical bridging study in Japan. This study is a key step in potentially gaining approval for JETREA® in the world's second largest pharmaceutical market."

JETREA® – The Benefits of Treating Symptomatic VMA Early

During the last three months a number of developments have occurred that provide further support for ThromboGenics' long-held view that the major opportunity for JETREA® is for the early treatment of patients with mild to moderate symptoms.

At a presentation made at EURETINA in September, Prof. Dr. Peter Stalmans, Department of Ophthalmology, University Hospitals Leuven, Belgium, reported that VMA/VMT clearly is a progressive condition. He also reported that spontaneous resolution of VMT is a low occurrence; in this study spontaneous resolution occurred in 20% of patients with VMT. These data were collected over four years in one of the largest retrospective studies of over 500 VMA/ VMT patients monitored using high resolution OCT technology.

As part of his presentation Prof Stalmans confirmed that early treatment of these early stage patients may be important to help them resolve debilitating symptoms such as metamorphopsia, and further sight threatening complications such as macular hole.

The importance of treating early stage patients was also reinforced by the final guidance of the German Federal Joint Committee (G-BA) concluding that JETREA® demonstrates considerable added benefit for VMT patients with mild and moderate symptoms when compared with existing comparative treatment (watchful waiting).

This view was reinforced by UK's National Institute for Health and Care Excellence (NICE) final guidance that recommended that JETREA® should be reimbursed within the National Health Service (NHS) in England and Wales as an option for treating VMT patients.

Moreover, in its final ruling, NICE has recommended reimbursing JETREA® when used to treat patients suffering from metamorphopsia. NICE said that metamorphopsia is a severe and distressing symptom and that this important symptom is a suitable trigger for treatment, and reimbursement by NHS.

Given these developments ThromboGenics is convinced that there is a major commercial opportunity for JETREA® in the treatment of earlier patients with mild to moderate symptoms.

JETREA® in the US

ThromboGenics launched JETREA® in the US on 14 January, 2013, via its own commercial organization.

JETREA® is indicated for all patients who suffer from the symptoms of vitreomacular adhesion, and offers an immediate active treatment option for retina physicians. If left untreated, symptomatic VMA/VMT frequently leads to retinal distortion, continued deterioration in vision and has the potential to cause irreversible damage and complications which may necessitate surgery.

ThromboGenics' introduction of JETREA® in the US has meant that for the first time physicians have a treatment option that can be used for both moderate to severe

patients, as well as for earlier stage (mild and moderate) symptomatic VMA patients who up until now have remained largely untreated.

Previously, earlier stage patients underwent a period of watchful waiting prior to being treated surgically after further progression of the disease and deterioration of their visional function. In many cases, surgery would only take place when it was clearly needed to restore a patient's deteriorated vision and their ability to undertake everyday tasks.

Establishing JETREA® in clinical practice

Most of JETREA®'s initial sales uptake has been generated with later stage patients, suffering severe symptoms. In a pre-JETREA® environment, those patients would typically be treated via a vitrectomy. With JETREA®, treating physicians now have a novel innovative pharmacological option.

Today, it is clear that it will take time and continued significant investment in medical education for ThromboGenics to establish JETREA® as a treatment for patients suffering from the earlier symptoms of symptomatic vitreomacular adhesion so that they are treated with this novel drug.

To achieve this goal, the ThromboGenics team will develop programs with retina physicians on the importance of recognizing metamorphopsia (distorted vision), a point where early treatment with JETREA® could yield positive benefits for patients.

Pro-active treatment with JETREA® is designed to stop patients' experiencing the deterioration in their visual acuity which often occurs during a period of watchful waiting. Early treatment could stop the further progression of the disease, and therefore offer important benefit in a patient's quality of life.

Appropriate patient selection has been shown to be critical to achieving the best results with JETREA® and this for all patients (mild – moderate – severe). Experience has shown that physicians' success rates with this innovative new product improve as they treat more patients.

In order to help retina physicians best define the most suitable patients for treatment with JETREA® we are encouraging more peer-to-peer communications about their experience with this innovative new treatment.

To help increase the medical education capabilities in the US, ThromboGenics has decided to increase its number of Medical Science Liaison Managers to a total of 12 during Q4.

In addition, Thrombogenics is building a patient registry of all patients treated with JETREA® in the US. The registry will provide data on the status of the patient's condition at the time they received JETREA® and the outcome of their treatment. Through this registry we expect to gain a thorough understanding of the types of symptomatic VMA patients who are best treated with JETREA®

From mid 2014 onwards, we expect the patient registry to become an important tool in educating physicians about the future use of JETREA®.

US Organisation update: Appointment Head of US Business Operations

During the past month, ThromboGenics has evaluated, pressure-tested and optimized the US business operations, including Sales, Marketing, Medical Affairs and Market Access.

Amongst other, ThromboGenics has decided to initiate a search for a Head of US Business Operations. This person will be in charge of providing strategic alignment and leadership for the Marketing, Sales, Medical Affairs and Market Access teams in the US.

Until that person comes on board, Dr Keith Steward, Head of Medical Affairs, has been appointed as interim Head of US Business Operations with immediate effect, reporting to ThromboGenics' CEO.

Reimbursement J- Code expected from 1 January 2014

ThromboGenics market research conducted in July 2013 highlighted that the lack of a permanent J-code was having an impact on the uptake of JETREA®.

The absence of a J-code requires physicians to submit paper-based claims to the payers, leading to delays in reimbursement, and certain inefficiencies in use of financial working capital on a retina practice management level.

The Company expects to have a J-code in place and becoming effective from January 1, 2014.

A permanent J-code will be an important facilitator for JETREA® acceptance, as it will lead to the reimbursement process being automated and is expected to result in physicians being reimbursed in a more timely manner.

A Significant Opportunity Remains

ThromboGenics has started to establish JETREA® as an attractive treatment option at a significant number of clinics in the US, and we have identified a number which we consider centers of excellence.

Also, we have received considerable positive feedback from patients who have been treated successfully, and the impact it had on their professional and personal lives strengthens our belief that JETREA® is a truly life-changing treatment.

We continue to believe that neither vitrectomy nor watchful waiting is the optimal treatment option for many patients suffering from symptomatic VMA/ VMT, especially for those patients suffering mild and moderate symptoms.

Against this background we remain confident that further medical education and clinical experience will allow US retina physicians to build confidence in using JETREA® and progressively integrate the drug into their clinical practice, leading to growth in the product's sales.

JETREA® in Europe

JETREA®– Alcon Roll-Out Making Good Progress

Our partner Alcon is continuing to make good progress in building a strong platform for the further development of JETREA®'s revenues in Europe. Since the product's approval in March, Alcon has introduced JETREA® in the UK, Germany, the Benelux countries and the Nordic region.

In the last six weeks there has also been further positive news with regard to market access and reimbursement for JETREA® in two of the key European pharmaceutical markets, which will result in this innovative product being reimbursed for a broad range of patients with VMT, importantly including those with mild and moderate symptoms.

Positive Reimbursement Guidance in Germany and the UK

Germany

In Germany, the German Federal Joint Committee (G-BA) in its final guidance concluded that JETREA® (ocriplasmin) demonstrates considerable added benefit for VMT patients with mild and moderate symptoms when compared with existing comparative treatment (watchful waiting). The mild to moderate VMT population, as referred to by G-BA in its final assessment, represents the vast majority (94%) of the total patient population covered by the approved label.

G-BA is the highest decision-making body of the joint self-government of physicians, dentists, hospitals and health insurance funds in Germany. Since the introduction of the early benefit assessment procedure in Germany in January 2011, G-BA has assessed more than sixty innovative new drugs. JETREA® is to-date one of only six innovative medicines appraised by G-BA to provide considerable additional therapeutic benefits for patients.

''Considerable' is defined as a sustained and large improvement in the therapyrelevant benefit. In its assessment, G-BA particularly considered the potential improvement in visual acuity and the avoidance of surgery in the back of the eye by JETREA® as beneficial for patients.

UK

In the UK, National Institute for Health and Care Excellence (NICE) final guidance, which was also issued in October, recommended that JETREA® should be reimbursed within the National Health Service (NHS) in England and Wales.

In its guidance, NICE recommends reimbursement of JETREA® for treatment of a broad range of VMT patients, from early-stage to late-stage. Patients with epiretinal membranes (ERMs) are excluded. It also recommended reimbursement of JETREA® for patients suffering from VMT with FTMH < 400 microns. A further important element of the guidance was its view that JETREA® should be reimbursed for the treatment of patients with metamorphopsia (blurred vision). This recommendation

was based on the finding that the impact of metamorphopsia on a patient is considered to be equal to the loss of 2 lines in visual acuity.

JETREA® is now reimbursed in the UK, following the final guidance from NICE. However the Department of Health allows NHS organizations up to three months to put in place the systems needed to reimburse NICE recommended treatments from the date the final guidance is issued.

New Disease VMT Progression Data Presented at Euretina

At the recent EURETINA annual meeting of European Society of Retina Specialists held in late September in Hamburg Prof. Dr. Peter Stalmans, Department of Ophthalmology, University Hospitals Leuven, Belgium, delivered a presentation entitled "Adoption of JETREA® in My Everyday Practice."

In his presentation, Prof. Stalmans provided details of the largest retrospective, observational study to-date that looked at his "real world" experience with patients with VMA, VMT and MH. Key findings from the study were that VMA is a progressive disease. The exact time and/or impact of progression are patient dependent. In addition, the study found that the spontaneous resolution of VMA occurred in only 20% of patients with VMT and as a result early treatment may be required to stop further disease progression and improve the visual function outcome for patients.

During his presentation, Prof Stalmans also provided insights into his own successful clinical experience with JETREA® when treating patients with early VMT and MH.

Prof. Stalmans works at a large, tertiary care ophthalmology center in Leuven, Belgium. The Leuven center sees 50,000 ambulatory eyecare patients every year and conducts around 2500 intravitreal injections and 7000 surgical procedures per annum. This retrospective study is based on data collected from electronic medical records gathered at the center between July 2009 and May 2013.

JETREA®– Progressing in the Rest of the World

Japan

In Japan, Alcon has started its first clinical study with JETREA® and the first study with this novel drug outside the US and Europe. This clinical bridging study is recruiting a total of 168 with patients symptomatic VMA including those associated with macular hole. It is a randomized, double blind, multicenter study with patients receiving either ocriplasmin or a sham injection. The study is due to complete in 2014. The results from the study are expected to form part of the regulatory submission that will be made to the Japanese Ministry of Health, Labour and Welfare to gain approval to market ocriplasmin in Japan.

Other RoW Markets

Alcon will launch JETREA® in Canada in Q4 2013. This follows the product's approval for the treatment of symptomatic VMA by Health Canada in August 2013.

In South Africa, Alcon's regulatory filing for JETREA® is undergoing priority review.

Update on Pipeline

JETREA® next indications

ThromboGenics has investigated clinical opportunities to expand the established value of JETREA® in VMA/VMT while at the same time identifying additional ophthalmic diseases with high functional unmet medical need.

Prevention of Proliferative Diabetic Retinopathy (PDR) is expected to be the next JETREA® target indication.

Creating total PVD is accepted to be an important step in preventing further neovascularization in Proliferative Diabetic Retinopathy (PDR). This rationale represents an important potential therapeutic target for JETREA® in PDR, as there is currently no approved drug treating patients with this debilitating and highly prevalent eye disease.

50% of patients with severe non-proliferative diabetic retinopathy (NPDR) and 75% of patients with very severe NPDR will develop diabetic retinopathy within one year.

ThromboGenics is currently validating JETREA® as a new treatment paradigm for the management of diabetic eye disease through an international expert panel.

The goal is to achieve a consensus as soon as possible, before starting a Phase IIa proof of concept study in patients with severe non-proliferative diabetic retinopathy.

The currently approved label does not exclude the use of JETREA® for the treatment of symptomatic VMA/VMT with Wet Age-Related Macular Degeneration (wAMD) patients.

Although no statistical significance was reached, the recent Phase II results in wAMD did confirm that anatomic VMA release can be obtained in the same order of magnitude as shown in the pivotal 006 and 007 studies.

The same Phase II study also confirmed the safety profile in wAMD.

ThromboGenics does not see the need to pursue further clinical studies into specific subgroups of patients with AMD.

Dr Patrik De Haes, CEO ThromboGenics comments: "At ThromboGenics, we focus on developing drugs that address real unmet medical needs, allowing us to deliver grass-root innovation and significant patient benefits. With that will come value to all ThromboGenics' stakeholders.

"We have decided that diabetic eye diseases for which there are currently no approved drugs available, and little under development, represent a bigger opportunity for us to deliver important patient benefits."

Diabetic eye diseases

The above mentioned commitment to diabetic eye diseases is also highlighted by ThromboGenics entering into a collaboration and license agreement with Bicycle Therapeutics to develop and commercialize novel drugs inhibiting a specific target for the treatment of ophthalmic diseases, such as diabetic macular edema (DME). DME is a leading cause of adult vision loss, with a significant proportion of patients failing to respond adequately to existing therapies for this condition.

ThromboGenics intends to develop therapeutics based on Bicycle's bicyclic peptides, which inhibit a target involved in vascular permeability. Selective inhibition of this target represents a new approach that offers the potential to improve the treatment of DME. ThromboGenics and Bicycle will collaborate on the preclinical development of these bicyclic peptide inhibitors. ThromboGenics has also gained an exclusive license from Bicycle to undertake clinical development and commercialization of identified drug candidates.

ThromboGenics will pay Bicycle an undisclosed upfront fee, development and regulatory milestone payments and royalties on sales of products resulting from the collaboration.

DME is a common consequence of diabetic retinopathy and a leading cause of significantly impaired vision among patients with diabetes. Globally, 350 million people are estimated to suffer from diabetes (WHO). An estimated 30% of all patients suffering from diabetes for over 20 years are at risk of developing DME.

American Depositary Receipt Program Established in the US

In late September, ThromboGenics announced that it had established a sponsored Level 1 American Depositary Receipt (ADR) program. Trading of the ADRs commenced on 30 September on the US over the counter (OTC) market under the ticker TBGNY.

ThromboGenics' ADRs are US dollar negotiable certificates with each ADR representing half of one ordinary share of the Company. J.P. Morgan has been appointed as the depositary bank for the ThromboGenics' ADR program.

The ADR program is designed to make it easier for investors in the US to gain exposure to ThromboGenics' shares.

End of Q3 2013 Cash Position

On September 30, 2013, the Company's cash position is Euro 183 Million, from Euro 193.6 Million on June 30, 2013.

With this level of cash, ThromboGenics has the financial resources it needs to fully sustain the US commercialization of JETREA®, research and develop new indications and formulations of JETREA® together with Alcon, and expand its R&D pipeline and broaden its ophthalmology footprint in general.

For further information please contact:

ThromboGenics
Wouter Piepers, Global Head of Corporate Communications +32 16 75 13 10 / +32 478 33 56 32
wouter.piepers@thrombogenics.com
Dr. Patrik De Haes, CEO
+32 16 75 13 10
Patrik.dehaes@thrombogenics.com
Chris Buyse, CFO
+32 16 75 13 10
Chris.buyse@thrombogenics.com
Citigate Dewe Rogerson	The Trout Group (US investor relations)
David Dible / Sita Shah	Todd James/ Simon Harnest
Tel: +44 20 7638 9571	Tel: +1 646 378 2926
sita.shah@citigatedr.co.uk	tjames@troutgroup.com

About JETREA® (ocriplasmin)

JETREA® (ocriplasmin) is a truncated form of human plasmin. In the US, JETREA® is indicated for the treatment of symptomatic VMA. In Europe, JETREA® is indicated for the treatment of vitreomacular traction (VMT), including when associated with macular hole of diameter ≤ 400 microns. JETREA® is a selective proteolytic enzyme that cleaves fibronectin, laminin and collagen, three major components of the vitreoretinal interface that play an important role in vitreomacular adhesion.

JETREA® has been evaluated in two multi-center, randomized, double-masked Phase III trials conducted in the U.S. and Europe involving 652 patients with vitreomacular adhesion. Both studies met the primary endpoint of resolution of VMA at day 28.

JETREA®'s Phase III program found that 26.5% of patients treated with ocriplasmin saw resolution of VMA, compared with 10.1% of patients receiving placebo (p<0.01).

The phase III program also showed that JETREA® was generally well tolerated. Any adverse reactions were ocular. The most commonly reported were vitreous floaters, eye pain and photopsia, as well as conjunctival haemorrhage resulting from the injection procedure. Most of the adverse reactions occurred within the first week after the injection. The majority of these reactions was non-serious, mild in intensity and resolved within 2 to 3 weeks. 1

¹ Stalmans P, Benz MS, Gandorfer A et al. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med 2012;367:606–615

About ThromboGenics

ThromboGenics is an integrated biopharmaceutical company focused on developing and commercializing innovative ophthalmic medicines. The Company's lead product, JETREA® (ocriplasmin), has been approved by the US FDA for the treatment of symptomatic VMA and was launched in January 2013.

ThromboGenics signed a strategic partnership with Alcon (Novartis) for the commercialization of JETREA® outside the United States. Under this agreement, ThromboGenics could receive up to a total of €375 million in up-front and milestone payments. It will receive significant royalties from Alcon's net sales of JETREA®. ThromboGenics and Alcon intend to share the costs equally of developing JETREA® for a number of new vitreoretinal indications.

In Europe, JETREA® is approved for the treatment of vitreomacular traction (VMT), including when associated with macular hole of diameter less than or equal to 400 microns. Alcon has launched JETREA® in the UK, Germany and the Nordic Region.

ThromboGenics is also further exploring anti-PIGF (Placental Growth Factor), also referred to as TB-403.

ThromboGenics is headquartered in Leuven, Belgium, and has offices in Iselin, NJ (US) and Dublin, Ireland. The Company is listed on the NYSE Euronext Brussels exchange under the symbol THR. More information is available at www.thrombogenics.com.

Important information about forward-looking statements

Certain statements in this press release may be considered "forward-looking". Such forward-looking statements are based on current expectations, and, accordingly, entail and are influenced by various risks and uncertainties. The Company therefore cannot provide any assurance that such forward-looking statements will materialize and does not assume an obligation to update or revise any forward-looking statement, whether as a result of new information, future events or any other reason. Additional information concerning risks and uncertainties affecting the business and other factors that could cause actual results to differ materially from any forwardlooking statement is contained in the Company's Annual Report.

This press release does not constitute an offer or invitation for the sale or purchase of securities or assets of ThromboGenics in any jurisdiction. No securities of ThromboGenics may be offered or sold within the United States without registration under the U.S. Securities Act of 1933, as amended, or in compliance with an exemption therefrom, and in accordance with any applicable U.S. state securities laws.