HYBRIGENICS : Update on the clinical study of inecalcitol in chronic lymphocytic leukemia

Press Release

Paris, 08 April 2013 - Hybrigenics SA (ALHYG), a bio-pharmaceutical company listed on Alternext (NYSE-Euronext) in Paris, with a focus on research and development of new treatments against proliferative diseases, today gives an update on the clinical study of inecalcitol in chronic lymphocytic leukemia (CLL) and announces the allowance of the patent on the therapeutic use of inecalcitol at high doses in the United States.

The Phase II clinical study is an open-label trial assessing the safety and potential efficacy of inecalcitol given to CLL patients not yet requiring immuno-chemotherapy but at high risk of disease progression. It is coordinated by Prof. Hermine, Head of Clinical Haematology at Necker Hospital in Paris, with the endorsement and active participation of the French Cooperative Group on CLL. The study currently involves thirteen centres in France.

Inecalcitol is given orally at 2 milligrams per day during at least 6 months or until progression occurs. The objectives are to decrease or stabilize the number of blood-circulating CLL cells and to delay the onset of other signs of progression, such as swelling of lymph nodes or anemia and, thereby, the need for immuno-chemotherapy.

As of today, a total of twenty CLL patients have been enrolled in the study. Nine of them have completed at least 3 months of treatment. So far, no patient had to stop treatment to undergo immuno-chemotherapy, nor experienced any side effects, such as hypercalcemia.

Hybrigenics has received the notice of allowance from the US Patent and Trademark Office for the patent which will protect the therapeutic use of doses of inecalcitol higher than one milligram per day in the US until 2029. Originally filed simultaneously in 2009 in Europe and in the US, this patent has already been granted in Europe under an accelerated examination (see Hybrigenics' press release of January 24, 2011). The examination of the same patent application extended worldwide according to the Patent Cooperation Treaty (PCT) is well under way in the most important countries of the rest of the world.

"The enrolment is on schedule and no patient has dropped out, meaning that the treatment is well tolerated," said Dr. Jean-François Dufour-Lamartinie, Hybrigenics' Head of Clinical R&D. "The high dose regimen of inecalcitol, currently being tested in the ongoing CLL trial, is now definitively patent-protected until 2029 in Europe as well as in the United States," said Remi Delansorne, Hybrigenics' CEO.

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Press Release

CLL is the most frequent form of leukemia (cancerous proliferative disease of circulating blood cells) and accounts for about 35% of all leukemic patients. Annual estimates of newly diagnosed CLL cases amount to
close to 15,000 in the United States (American Leukemia Lymphoma Society, Facts 2012), 14,000 in
Europe and 130,000 world-wide (Globocan 2008). CLL is designated as an orphan disease in the United
States, Europe and Japan.
People with CLL produce too many lymphocytes (mononuclear white blood cells) of one single abnormal "family" (monoclonal) which are not fully developed (immature). Over time, these circulating CLL cells (monoclonal immature lymphocytes) in excess build up in the lymphatic system and cause large, swollen lymph nodes. They may also fill the bone marrow, reducing the number of normal white cells, red cells and platelets that can be made, thereby lowering their blood counts. There is no definitive cure for CLL.

Hybrigenics (www.hybrigenics.com) is a bio-pharmaceutical company listed (ALHYG) on Alternext (NYSE- Euronext) in Paris, focusing its internal R&D programs on innovative targets and therapies for the treatment of proliferative cancerous or non-cancerous diseases.

Hybrigenics' current development program is based on inecalcitol, a vitamin D receptor agonist active by oral administration. Oral inecalcitol has shown excellent tolerance and strong presumption of efficacy for the first-line treatment of metastastic castrate-resistant prostate cancer in combination with Taxotere®,

which is the current gold-standard chemotherapeutic treatment for this indication. Oral inecalcitol has recently been studied in a clinical trial for the treatment of moderate-to-severe psoriasis, and is currently being tested in chronic lymphocytic leukemia patients.

Hybrigenics has a research collaboration with Servier on deubiquitinating enzymes and their inhibitors in
oncology, neurology, psychiatry, rheumatology, ophthalmology, diabetes and cardiovascular diseases. Hybrigenics continues to build on its pioneer research position in the field of ubiquitin-specific proteases by exploring their role in other areas of particular relevance, such as inflammation and virology.
Hybrigenics Services (www.hybrigenics-services.com), a fully-owned subsidiary, is the market leader in Yeast Two-Hybrid (Y2H) and related services to identify, validate and inhibit protein interactions for researchers in all areas of life sciences, using its ISO 9001-certified high-throughput Y2H screening platform, its sophisticated bioinformatics tools and extensive database, along with its chemical library and chemical screening platform.

Tel.: +33 (0)1 58 10 38 00 investors@hybrigenics.com

Financial communication

Axelle Vuillermet / Pierre Laurent Tel.: +33 (0)1 44 71 94 94 hybrigenics@newcap.fr

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