Our lead anti-thrombotic drug candidate, APD791, is currently in a Phase 1 clinical trial program. The Phase 1 program is primarily intended to evaluate the safety and tolerability of single and multiple-ascending doses of APD791. In addition, we are also evaluating the pharmacokinetics and pharmacodynamics of APD791. In the Phase 1a clinical trial, dose-dependent inhibition of serotonin-mediated amplification of platelet aggregation was demonstrated, supporting the preclinical data generated around APD791 and establishing initial clinical validation of APD791's novel mechanism of action. Based on the positive Phase 1a results, we initiated a Phase 1b clinical trial in January 2008.
APD791 is a novel, oral and selective inverse agonist of the 5-HT2A serotonin receptor. Serotonin activation of the 5-HT2A receptor on platelets and vascular smooth muscle tissue is thought to play an important role in the events leading to thrombosis, and elevated serotonin levels have been associated with increased cardiovascular risk. Normally, when a platelet is activated by one of a number of factors such as thrombin or collagen, the platelet releases serotonin, which, based on preclinical studies, promotes platelet aggregation, vasoconstriction and intimal hyperplasia. By blocking activation of the 5-HT2A receptor on platelets and in other cardiovascular tissues, APD791 may curb platelet aggregation, vasoconstriction and intimal hyperplasia in the clinical setting, thereby reducing or preventing thrombosis. We believe APD791 represents a new approach to reducing the risk of arterial thromboembolic disease.
The American Heart Association estimates that in the United States over 13.9 million people alive in 2005 had survived either a myocardial infarction or a stroke. To reduce the risk of future events, many patients receive daily anti-thrombotic therapy. Worldwide sales of Plavix®, a leading anti-thrombotic marketed by Bristol-Myers Squibb and sanofi-aventis, totaled $7.3 billion in 2007, making it the second best selling drug in any therapeutic category.
(NOTE: This page was last updated: June 5, 2008.)
