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Pharmacopeia Announces Positive Results from Initial DARA Clinical,Trial

PS433540 Shown to Be Well Tolerated and Potentially Suited for Once Daily Administration

PRINCETON, N.J., April 10, 2007 /PRNewswire-FirstCall/ -- Pharmacopeia , an innovator in the discovery and development of novel small molecule therapeutics, today announced positive results from the initial Phase 1 clinical trial of PS433540, the company's lead internal product candidate for the treatment of hypertension and diabetic nephropathy. Data from the single ascending dose (SAD) study indicated that PS433540 was well tolerated at all six doses administered. In addition, study findings suggested that the compound possesses linear pharmacokinetics and a half-life that is consistent with once daily administration.

PS433540 is the first and only dual-acting angiotensin and endothelin receptor antagonist (DARA) in development. The compound, which possesses two clinically validated mechanisms of action in a single molecule, works by selectively blocking the action of two potent vasoconstrictor and mitogenic agents, angiotensin II (AII) and endothelin 1 (ET1), at their respective receptors. PS433540 is highly selective (10,000-fold) for the AII receptor sub-type 1 and the ET receptor sub-type A. As such, PS433540 combines the properties of an angiotensin receptor blocker (ARB) and an endothelin receptor antagonist (ERA) in the same molecule. Preclinical data suggests that, compared to either mechanism alone, simultaneously blocking the actions of both AII and ET1 may provide improved treatment options for several cardiovascular diseases.

"By showing that PS433540 is well tolerated over a broad range of doses while also possessing characteristics consistent with once-a-day dosing, we have taken an important initial step in the development of this first-in-class compound," said Rene Belder, M.D., Pharmacopeia's Vice President of Clinical and Regulatory Affairs. "Based on these findings, we are moving forward w
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