Evotec Announces the Successful Completion of the First Phase I Study with EVT 401, an Oral P2X7 Receptor Antagonist - Very Good Safety Profile and Confirmed "On Target Activity"


Hamburg, Germany - Evotec AG (Frankfurt Stock Exchange: EVT; NASDAQ: EVTC) today announced the successful completion of the first Phase I study with its P2X7 receptor antagonist EVT 401. EVT 401 is a small molecule drug candidate and a potentially novel approach to orally treat inflammatory conditions such as Rheumatoid Arthritis.

The study was a double-blind, placebo controlled study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of EVT 401. A total of 96 healthy male volunteers received single oral ascending doses of the compound as a suspension or capsule.

The compound was very safe and well tolerated and there were no serious adverse events or withdrawals. In addition, the pharmacodynamic assay used in this study demonstrated the ability of EVT 401 to block ATP-stimulated IL-1ß release in whole blood samples taken from subjects, thereby proving "on target" activity at well tolerated oral doses.

In Rheumatoid Arthritis, the first potential indication for EVT 401, there is a significant need for new oral therapies. Oral drugs can be used both as alternatives to and in combination with existing agents to increase the responder rates and potentially reduce or delay the need for expensive biological therapies.

Dr Werner Lanthaler, Chief Executive Officer of Evotec, commented: "We are encouraged that EVT 401 showed positive results in its first human trial. It was well tolerated and demonstrated the desired pharmacodynamic activity in healthy volunteers. We are now focussing our efforts on optimizing the oral dose formulation, completing the Phase I studies, and preparing Phase II studies in Rheumatoid Arthritis." 


About P2X7 antagonists

The P2X7 receptor is an ATP-gated ion channel primarily expressed on cells of the immune system and is thought to play an important role in inflammatory processes through the regulation of a number of proinflammatory cytokines such as IL-1ß. P2X7 receptor antagonism may therefore provide a novel approach to the treatment of rheumatoid arthritis and other inflammatory conditions.
Release of IL-1ß is stimulated by ATP activation of P2X7 receptors expressed on monocytes in the blood. The pharmacodynamic assay used in this study demonstrated the ability of EVT 401 to block ATP-stimulated IL-1ß release in whole blood samples taken from subjects, thereby confirming "on target" activity following oral dosing.

About Rheumatoid Arthritis (RA)

RA is a chronic autoimmune disease that causes pain, stiffness, swelling and limitations in the motion and function of multiple joints. Current treatment guidelines for RA focus on preventing or slowing joint damage with the use of disease modifying anti-rheumatic drugs (DMARDs). Typical first line treatment is with older oral DMARDs such as methotrexate. Biological therapies, predominantly anti-TNF agents such as etanercept, are used in patients with significant disease who fail to respond adequately to first line treatment. While more effective than older oral DMARDs these biological treatments are expensive, cannot be administered orally and have certain drawbacks, including an increased risk of serious infections. In addition, around 30% of patients fail to respond adequately to a first-line TNF-alpha inhibitor.

About the RA market

It is estimated that over 5 million patients in the 7 major markets suffer from RA (US 2.2 million, EUR 2.3 million, Japan 0.6 million). The TNF-alpha inhibitors dominate this market by value, with their use in RA generating over $6 billion in sales 2008 across these markets. However, only around 17% of RA patients are prescribed TNF-alpha inhibitors, in part due to their high cost resulting in reimbursement restrictions. (source: DecisionResources).

Forward-Looking Statements

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