Regulatory Filings • Nov 23, 2012
Regulatory Filings
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Innate Pharma launched itsshareholders' club 'Innate en
Innate Pharma will be present for the second time at Actionaria, a forum dedicated to p , individual shareholders.
Since its IPO on Euronext Paris(2006), Innate Pharma has endeavored to provide its shareholders with accurate, detailed information in compliance with the best practices of financial communications.
Innate Pharma's IR team will be on the East Coast of the United States in the first week ofDecember and on the West Coast in the second week of January. The Company will also be present at the Oddo Midcap Forum in Lyon on January 11.
Supported by its individual shareholders, Innate Pharma intends to pursue consolidating relations with its shareholders, which was the idea behind thecreation of 'Innate en Actions'.Open to private individuals only, the club proved to be a great success with more than ahundred applicants registered in the first few weeks, some of them were warmly welcomed by Innate Pharma at a meeting held on site in September. A visit of the offices and laboratories wasorganized, together with a meeting with the CEO, Hervé Brailly, with the manager in charge of the IPH21 and IPH41 programmes and the Investor Relations team.
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You can join the 'Innate en Actions'club here:
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www.innatepharma.com/fr/finances/clubactionnaires
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(in French only)
OGBBA Van Herk BV, a company incorporated under Dutch laws, reported to the French Authority (AMF) that it crossed over the 5% threshold of the share capital and voting rights of the Company. The crossing of this threshold results from the purchase of IPH shares on the market. OGBBA Van Herk BV announced that it held 2 335 380 shares representing 6.16 % of the capital and voting rights of Innate Pharma
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I am happy to be back again during We celebrated the 2011 Nobel Prize this very busy month of November. As you will discover herein, a number of important events for Innate have already taken place this year. First and foremost, a little more than a year after signing our first partnership with Bristol-Myers Squibb, the anti-KIR programme has successfully compleyeloid p g yp ted several key stages, with a Phase II trial soon to begin in Acute Myeloid Leukemia, together with a Phase I trial in combination in a variety of solid y tumors.
in Medicine awarded to researchers for their work on innate immunity by organizing a dedicated roundtable with Bristol-Myers Squibb in Paris in May. This event proved to be extremely productive in terms of the discussions and opinions on how immunotherapy can contribute to py treating cancer over the next decade.
On a completely different level, we have been particularly active on i t l ti th t 12investor relations over the pastmonths, whether with institutional investors whom we have met severaltimes in France, Europe and the US, ithor withindividualinvestors for whomwe set up a shareholders' club last spring.
shareholders' clublaunched in April 2012
The immuno-oncology sector continues to draw attention. It was inth li li ht t th A i S it i di id l i t f h ''Innate en the limelightatthe American Society of Clinical Oncology (ASCO) international meeting in June. It also very recently garnered recognition by h i i P i G li USA overperformance on the shareholdersthe prestigious Prix Galien USA, honoring the best biotech product, which was awarded to the anti-CTLA-4monoclonal antibody, YERVOY® (ipilimumab), of Bristol-Myers Squibb. Thank you for your confidence!
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Innate'sInnate sstock market over the past two years can only encourage us to keep going!
Paris,
HERVÉ BRAILLYBRAILLY, Chairman of the Executive BoardChief Executive Officer
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Infl tion am ma , aut oim nity mu |
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| foll n-S l be tric ted the ing adv ed lign ies: No ll to res ow anc ma anc ma Ce ll L Can and hist olo hist olo Ren al C ell Car ma Car cino cino , M a Me elan lano Co lore l C and cta nu cer - sq o s squ am am ous non -sq o s squ am am ous ma om ma anc er g gy, , Ser Ov aria n C ino ous arc ma |
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fIPH2101* (hybridoma anti KIR anti-KIRantibody) in elderly patients with Acute Myeloid Leukemia in first l b ll d d id Ph II i l complete remission published online in the journal Blood See press release (October 18, 2012)
See press release (September 4, 2012)
Innate Pharma received regulatory authorization to start a d bl bli ddouble-blindplacebo-controlledrandomizedPhase trial of IPH2102/BMS-986015 as maintenance treatment inelderly patients with Acute Myeloid Leukemia in first complete remission (study IPH2102-201, the "EffiKIR" trial).
The protocol calls for inclusion of 150 patients, randomized into three arms. Two arms will test single agent IPH2102/BMS-986015 at different doses and one arm will receive placebo. The primary efficacy endpoint is leukemia-free survival. Secondary endpoints include safety and overall survival.
This trial is sponsored by Innate Pharma and will be performed in France, with the participation of the two p y ,French clinical cooperative groups, ALF A and p g p GOELAMS*, harnessing the research effort of the French centers qualified to treat patients with AML. The principal investigator is Dr. Norbert Vey.
First patient inclusion is expected before the end of the year.
* ALFA : Acute Leukemia French Association. GOELAMS : Groupe Ouest- trial, Est des Leucémies Aiguës et Maladies du Sang (Acute Leukemia and Blood Diseases West-Est Group)
In January, the Company announced the discovery of a novel immune regulation mechanism involving the chemotherapy g gNKp46 receptor on Natural Killer cells. It was described and published in Science magazine by team from the CIML, a key academic partner of Innate Pharma. Innate Pharma co-owns intellectual property rights relating to C lid i pp yg gthis discovery with INSERM, the French National Institute of Health and Medical Research.
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Over the past 12 months, the Company's expertise in innate immunity has been in the spotlight thanks to the 2011 Nobel Prize in Medicine which was awarded to three researchers having contributed to its discovery.
In January, one of Innate Pharma's co-founders and Director of the Marseille-Luminy Immunology Centre (CIML), Eric Vivier, also published an article in the journal Science on a new mechanism that controls NKcells and involving NKp46 (see above).
These progresses in the field of innate immunity improve the Company's visibility, as well as strengthen its position as a leading industry player in that field.
On October 17, Yervoy®, a monoclonal antibody developed by Bristol-Myers Squibb, received the prestigious prix Galien USA award for the best biotechproduct of 2012 Yervoy® was the first drug to gain approval for metastatic melanoma in the last 10 years.
Innate Pharma co-organized a special roundtable with 2012.Bristol-Myers Squib France this May at the Paris Oceanographic Institute: "Innate immunity – From Revolutionary Discovery to Therapeutic Revolution". With Bruce Beutler and Jules Hoffman – the 2011 Nobel Prize winners in Medicine – as its guests of honor, this event clearly stressed the importance of immunology and innate immunity in treating cancer patients.
The roundtable was a roaring success thanks to its 150 international participants from the scientific and medical communities.
This prize was awarded by a first-class scientific committee including several Nobel Prize winners. It recognizes the g technical, scientific and medical capacities required to develop innovative drugs. The Prix Galien is considered to be the most prestigious prize in biopharmaceutical research and development.
Source: news.bms.com
You can watch a video of the event and download the summary of the roundtable at:http://www.immunite-innee.com/fr/
This year again, immunotherapy was a headliner at the ASCO annual meeting and especially "antigen-independent immunotherapy". This concerns a series of new approaches using antibodies that activate immune cells so they work against the cancer. The principle: the immune system has inhibitory mechanisms that prevent its over-activation which are exploited by the tumor to help it grow. These negative checkpoints of the immune response therefore need to be blocked. This is the main idea behind the development of anti-KIR by Innate Pharma, and which has demonstrated its efficacy with Yervoy® (BMS) and presented some very interesting early results at the last ASCO annual meeting with the anti-PD-1 of Bristol-Myers Squibb.
For our 10th shareholder newsletter, we have chosen to describe the technical approach behind the programmes developed by Innate Pharma: fully human or humanized monoclonal antibodies (mAb).
Manipulating the immune system's checkpoints by means of antibodies is a very innovative approach since it was only recently validated in 2010 by the clinical results of the first authorized drug using this mechanism of action: ipilimumab (Yervoy®, Bristol-Myers Squibb). This product targets the CTLA-4 receptor found in T-cells – killers of the adaptive immune system. In 2011, it became the first drug to be approved for metastatic melanoma (skin cancer) in the last decade.
Manipulation of the immune system's control pathways is a cutting-edge field that is attracting the attention of numerous industry players. Nonetheless, most of the targeted receptors currently belong to adaptive immunity , as is the case for ipilimumab.
Innate Pharma was founded in 1999 with the primary goal of targeting innate immune cells. It very quickly carved out a strong intellectual property portfolio on receptors in this category of the immune system. Over time, the Company has progressively become specialized in a type of drug - a tool for targ g etin innate immune cells: monoclonal antibodies (mAbs).
Innate Pharma's technological choice to focus on monoclonal antibodies corresponds to its intention to build on the experience accumulated with the anti-KIR programme (IPH21). It also reflects the history of this class of products, which has demonstrated – since the first ones on the market in the late 90s – a success rate (approval) greater than that obtained by ch il em ca mol l ecu es (25% compared with ab t ou 11%, C t ar er, 2006) as well as b i e ng an ext l remey successf l u commerci l a venture.
The commercial success of mAbs makes them the most dynamic segment of the pharmaceutical industry in terms of sales – exceeding 40 billion dollars for about thirty marketed products, with an estimated annual growth of about 8% between 2010 and 2016 (Datamonitor, Monoclonal antibodies: 2011 update) – but also in terms of licenses and partnerships.
They represent about 36% of the biological drug market and generally approved for cancer (41% of antibody sales) and inflammation (46% of antibody sales) (Nature Biotechnology, Nov 2011).
Antibodies are large proteins comprising two regions: a variable and a constant region. These two parts have different functions.
The variable part can recognize and specifically bind to some targets, then called antigens (cell receptor, circulating proteins,
The constant region has an effector function: it can block, destroy or activate the target.
Al d d i th l t 19th t i th f f tib d i t lti f d l tib di b Already usedin the late century in the form ofantibody mixtures resulting from serums andplasma, antibodies became key therapeutic drugs in the 21st century thanks to advances made in biotechnologies. These technologies are used to grow cells to make them express certain proteins, something that conventional chemistry cannot achieve since proteins possess extremely complex structures. These cells are hence transformed into veritable mini biological factories. These technologies have made it possible to d l eve op i il ncreasingly complex proteins ( h growt hormones, i li nsu n, i f nter erons, then antib di o es and improved proteins). Improvements to these proteins have been successive: antibodies, for instance, were typically produced in rodents. These antibodies are now being humanized by replacing 'mouse' sequences with human sequences by means of genetic engineering. In this way, the side effects associated with their use can be minimized while optimizing their specific action.
Variable regions of antibodies are capable of recognizing an antigen and of binding with it. Simply by doing this, it can prevent the antigen from binding with its natural ligand.
As for the constant region, various actions and functions are possible when the antigen is carried by a cell: the destruction of the cell (by different means), the activation or inhibition of the cell, or the deposition of another drug (e.g. toxin) inside the cell. Depending on the targeted antigen, the antibody can be designed to perform any of these actions. For instance, Rituxan® kills the cell carrying the cancer marker in the lymphoma. In the case of several solid cancers, Avastin® binds blood vessels growth factor to prevent the blood vessels from growing and irrigating the developing tumor mass. Anti-TNF antibodies, such as Humira® or Remicade® which are used to treat chronic inflammatory pathologies like rheumatoid arthritis, recognize a pro-inflammatory molecule and neutralize it.
The teams at Innate Pharma are working on a new category of therapeutic antibodies: immunomodulating antibodies. These antibodies specifically recognize receptors on the immune cells with the purpose of activating them (in cancer therapy) or inhibiting them (for inflammatory diseases). Yervoy® is the first antibody to use this approach and gain approval. It recognizes a receptor of T-lymphocytes. The anti-KIR programme by Innate Pharma – licensed to Bristol-Myers Squibb – recognizes a receptor of NK cells and activates them against tumor cells. The anti-NKG2A programme – licensed to Novo Nordisk A/S – is designed to activate a sub-category of immune cells capable of regulating over-activated immune cells.
platform not only produces monoclonal antibodies, but also ensures their humanization. Since 2012, it is automatized for a high throughput antibody generation.
In terms of technical innovations, a novel approach enables us the process based on affinity (the variable end), but also the functional
The company is working on a proprietary conjugation known as antibody drug conj gu ates ( ) ADC . This format could
C02 incubator "Kuhner" for the production of a few mg of antibody to be prove to be more efficient for certain antibodies (cytotoxics). purified with a robot.
lymphocytes attack the tumor cells they have activated, previously identified (not shown in this diagram) by binding and then perforating their membrane.
By secreting ch il em ca si l gna s call de cyt ki o nes (in green), activated lymphocytes attract and activate surrounding immune cells so that they in turn contribute to the elimination of the
turn, the tumor cell internalizes the antibody conjugate which Tumor then releases the drug within the latter. The drug is activated and destroys the tumor cell from "inside," sparing the environment.
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