Plexxikon and Servier Signed Cardiovascular Collaboration.

NEUILLY, France & BERKELEY, Calif. -- Plexxikon Inc., a private biotechnology company, and Servier, the leading French independent pharmaceutical company, today announced a collaboration to discover novel, non-peptidic inhibitors of renin, an enzyme known to play a direct role in hypertension, renal failure and vascular disease.

Under the terms of the agreement, Plexxikon will receive an upfront payment, research funding, and potential milestone payments, totaling over $100 million. In addition, Plexxikon may receive royalties on potential product sales. Servier will be responsible for clinical development and commercialization of the products and will receive an exclusive worldwide license for any renin inhibitors discovered through the collaboration in the field of cardiovascular disease, including hypertension.

"We are confident that Plexxikon's Scaffold-Based Drug Discovery[TM] platform provides a unique competitive advantage to quickly identify novel, non-peptidic renin inhibitors with attractive pharmaceutical properties," said K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. "For over half of all people suffering from high blood pressure, hypertension medications do not adequately control their blood pressure. We believe Servier is an ideal partner to develop novel therapeutics for the significant unmet need in hypertension."

Dr. Hirth added, "With this new effort in renin, we capture the technology upside of our platform, validate our approach for the family of aspartyl protease drug targets, and complement our portfolio in metabolic disease, inflammation and oncology."

"Cardiovascular disease is the leading cause of mortality worldwide and Servier has acquired unrivalled experience and international renown in this therapeutic area. As demonstrated with the discovery and development of ivabradine, the first selective and specific inhibitor of the sinus node I(f) current, Servier is committed to offer novel treatments to patients with cardiovascular diseases. We are confident that the collaboration with Plexxikon will efficiently complement our research portfolio in that therapeutic area," said Laurent Perret, M.D., Ph.D., president of Servier research and development.

"Servier is entering into this collaboration with Plexxikon as a key step in our strategy to expand our efforts in the development of new drugs for cardiovascular diseases. This partnership will expedite the development of novel renin inhibitors with potential use in therapeutic indications with high unmet medical need," added Emmanuel Canet, M.D., Ph.D., vice president Servier research and development.

The Role of Renin in Hypertension

Hypertension is a disease in which blood pressure is abnormally high, placing stress on the heart, blood vessels, kidney and brain. Hypertension affects more than 65 million adults in the U.S., or one in three people over the age of 35, and is a major cause of death in North America and Europe. While global antihypertensive drug sales are forecasted by Datamonitor to grow to $50 billion by 2009, nearly 35% of patients on treatment do not achieve blood pressure goals. Renin inhibitors represent a new class of compounds for the development of hypertension. Renin is an enzyme that initiates the signaling cascade that upregulates the vasoconstricting peptide, angiotensin II. Current agents target the renin-angiotensin system by inhibiting angiotensin II signaling (ARBs) or angiotensin II formation (ACE inhibitors). Data suggest that renin inhibition may have additive benefits in blood pressure control to ARBs and ACE inhibitors, potentially resulting in superior end-organ protection. Renin inhibitors may also be effective in the treatment of congestive heart failure and chronic renal disease.

About Aspartyl Proteases

Renin is a member of the aspartyl protease protein family. Aspartyl proteases play integral roles in several aspects of our overall physiology and health including blood pressure (renin), digestion (chymosin and pepsin), the maturation of the Human Immunodeficiency Virus (HIV I Protease), and the development of Alzheimer's disease (Bace). Plexxikon scientists, using the company's unique Scaffold-Based Drug Discovery(TM) platform, are developing novel drug candidates to address a number of these important drug targets.

About Servier

Servier is an independent pharmaceutical company, established in 1954 by its founder and current chairman, Jacques Servier, M.D., Pharm.D. Servier allocates approximately 25% of its turnover to research and development. The Servier Group has 17,500 employees worldwide including 2,500 in research and development. The Servier Group is established in 140 countries with its main therapeutic products used to treat cardiovascular disease, diabetes, neuropsychiatric disorders, cancer and osteoarticular diseases. Currently, there are 27 molecules in the Servier research and development pipeline, 14 of which at the preclinical, and 13 at the clinical stage of development.

Plexxikon Profile

Plexxikon is a leader in the discovery and development of novel small molecule pharmaceuticals to treat human disease. Plexxikon's proprietary Scaffold-Based Drug Discovery[TM]platform is being applied to build therapeutic franchises in metabolic and cardiovascular disease, inflammation and oncology. This discovery process integrates a number of state-of-the-art technologies, including structural screening as one key component that provides a significant competitive advantage over other drug discovery approaches. To date, the company has discovered a portfolio of clinical and preclinical stage compounds in each of these franchises.

Currently, the company's most advanced program is a PPAR pan-agonist for the treatment of diabetes and related cardiovascular complications, with the lead candidate now in Phase 2 clinical testing in collaboration with Wyeth Pharmaceuticals. Other programs include a dual kinase inhibitor for the treatment of rheumatoid arthritis and a B-Raf inhibitor for the treatment of cancer. Plexxikon is seeking pharmaceutical and biotechnology partners for select collaboration opportunities. For more information, please visit www.plexxikon.com.