Pharmacopeia
(Nasdaq: PCOP), an innovator in the discovery and development of novel
small molecule therapeutics, announced the initiation of a Phase 2a
clinical study of PS433540, the company's lead internal product candidate.
PS433540 is a dual-acting angiotensin and endothelin receptor antagonist
(DARA) that is being developed as a potential treatment for hypertension
and diabetic nephropathy. PS433540, the first and only DARA compound in
development, possesses two clinically proven mechanisms of action in a
single compound. The compound works by selectively blocking the action of
two potent vasoconstrictor and mitogenic agents, angiotensin II (AII) and
endothelin 1 (ET1), at their respective receptors. Preclinical studies have
shown that PS433540 is highly selective 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. There are considerable preclinical and initial
clinical data suggesting that compared to either agent alone,
simultaneously blocking the actions of both AII and ET1 may provide
significantly improved treatment options for several cardiovascular
diseases.
The objective of the Phase 2a randomized, double-blind, placebo-
controlled, parallel-group study is to evaluate the compound's safety and
efficacy in subjects with Stage I and Stage II hypertension. This multi-
center trial is expected to enroll 170 subjects. After a lead-in period,
patients will be randomized into three study arms (placebo and two active
arms of 200 mg and 500 mg) receiving PS433540 or placebo once daily for 28
days. Following the four week treatment period, investigators will evaluate
the patients' change from baseline in mean 24-hour ambulatory systolic
blood pressure; mean 24-hour ambulatory diastolic blood pressure; and mean
seated systolic and diastolic blood pressure.
"We are very pleased to have initiated this important Phase 2a concept
validation study of PS433540 approximately six months ahead of our original
clinical development timeline," said Les Browne, Ph.D., President and Chief
Executive Officer of Pharmacopeia. "The goal of this study is to prove that
PS433540 lowers blood pressure in hypertensive patients."
Results from the initial Phase 1 trial of PS433540, a single ascending
dose (SAD) study, indicated that the compound was well tolerated at all six
doses administered ranging from 20 mg to 1,000 mg and that the compound has
a half-life that is consistent with once daily administration. In the Phase
1 multiple ascending dose (MAD) study, 4 dose levels ranging from 50 mg to
500 mg did not produce safety or tolerability issues. Consistent with prior
guidance, Pharmacopeia expects to report results of an on-going Phase 1
angiotensin II challenge study in September or early in the fourth quarter;
and initiate a Phase 1 endothelin challenge study later this year. These
studies are designed to evaluate the dual pharmacology of PS433540 in
healthy individuals.
"We are approaching this Phase 2a study with great anticipation as it
is designed to provide us with important initial indications regarding
PS433540's therapeutic potential in patients with cardiovascular disease,"
stated Rene Belder, M.D., Pharmacopeia's Vice President of Clinical and
Regulatory Affairs.
ABOUT PHARMACOPEIA
Pharmacopeia is committed to discovering and developing novel
therapeutics to address significant medical needs. The company has a broad
portfolio advancing toward clinical validation, both independently and with
partners. Pharmacopeia's most advanced internal program is a dual-acting
angiotensin and endothelin receptor antagonist (DARA) for hypertension and
diabetic kidney disease for which a Phase 2 clinical trial is underway.
Other internal proprietary programs address primarily immunoregulation.
Pharmacopeia's collaborative efforts have resulted in a portfolio that
includes one partnered program currently in Phase 2 clinical trials
targeting chronic obstructive pulmonary disease (COPD) and three partnered
programs in Phase 1 clinical trials targeting rheumatoid arthritis,
oncology, and inflammatory disease. Four additional partnered compounds are
in preclinical development. Pharmacopeia's current strategic alliances are
with Cephalon, GlaxoSmithKline, Organon and Wyeth.
This press release, and oral statements made with respect to
information contained in this press release, constitute forward-looking
statements within the meaning of the Private Securities Litigation Reform
Act of 1995. Such forward-looking statements include those which express
plan, anticipation, intent, goal, contingency or future development and/or
otherwise are not statements of historical fact. These statements are based
upon management's current expectations and are subject to risks and
uncertainties, known and unknown, which could cause actual results and
developments to differ materially from those expressed or implied in such
statements. These forward- looking statements include, but are not limited
to, statements about the successful implementation of Pharmacopeia's
strategic plans, Pharmacopeia's plans to develop PS433540, a product
candidate from its DARA program, Pharmacopeia's Phase 2 and Phase 1
clinical studies with respect to PS433540, including timing and expected
outcomes of such studies, Pharmacopeia's estimates of the market
opportunities for its product candidates, including PS433540,
Pharmacopeia's ability to successfully perform under its collaborations
with Cephalon, GlaxoSmithKline, Organon and Wyeth, Pharmacopeia's ability
to build its pipeline of novel drug candidates through its own
internally-funded drug discovery programs, third party collaborations and
in-licensing, Pharmacopeia's ability to raise additional capital,
Pharmacopeia's expectations concerning the development priorities of its
collaborators, their ability to successfully develop compounds and its
receipt of milestones and royalties from the collaborations, Pharmacopeia's
anticipated operating results, financial condition, liquidity and capital
resources, Pharmacopeia's expectations concerning the legal protections
afforded by U.S. and international patent law, Pharmacopeia's ability to
pursue the development of new compounds and other business matters without
infringing the patent rights of others, additional competition, and changes
in economic conditions.
Further information about these and other relevant risks and
uncertainties may be found in Pharmacopeia's Reports on Form 8-K, 10-Q and
10-K filed with the U.S. Securities and Exchange Commission. Pharmacopeia
urges you to carefully review and consider the disclosures found in its
filings which are available in the SEC EDGAR database at sec
and from Pharmacopeia at pharmacopeia. All forward-looking
statements in this press release and oral statements made with respect to
information contained in this press release are qualified entirely by the
cautionary statements included in this press release and such filings.
These risks and uncertainties could cause actual results to differ
materially from results expressed or implied by such forward-looking
statements. These forward-looking statements speak only as of the date of
this press release. Pharmacopeia undertakes no obligation to (and expressly
disclaims any such obligation to) publicly update or revise the statements
made herein or the risk factors that may relate thereto whether as a result
of new information, future events, or otherwise.
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