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Predix Pharmaceuticals Obtains Special Protocol Assessment for PRX-00023

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midastouch017   Wednesday, 11/30/05 09:42:35 AM
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Predix Pharmaceuticals Obtains Special Protocol Assessment for PRX-00023 Pivotal Study in Anxiety; Predix Also Initiates Phase Ib Clinical Trial for PRX-08066 in Pulmonary Arterial Hypertension

LEXINGTON, Mass. & RAMAT GAN, Israel--(BUSINESS WIRE)--Nov. 30, 2005--

Predix Pharmaceuticals, a drug discovery and development
company, announced today that under the Special Protocol Assessment
process, it has reached final agreement with the United States Food
and Drug Administration (FDA) on the design and statistical analysis
plan of its first pivotal study for PRX-00023, its 5-HT1A agonist and
lead product candidate, to treat generalized anxiety disorder (GAD).
In addition, Predix announced continued progress on its pipeline of
internally discovered product candidates with the initiation of a
Phase Ib clinical trial of PRX-08066, the company's novel
small-molecule 5-HT2B antagonist, in conditioned athletic adults with
transient pulmonary artery hypertension induced by a low oxygen
environment.



"We are very pleased to have reached final agreement with the FDA
on the Special Protocol Assessment for our Phase III clinical trial of
PRX-00023 in generalized anxiety disorder. With three of our
internally discovered product candidates currently in clinical trials
and an extensive pipeline of novel compounds in preclinical
development, we believe that our targeted drug discovery technology
and approach will enable us to continue to bring at least one new
product candidate into the clinic annually," said Michael Kauffman,
M.D., Ph.D., president and CEO of Predix.



Dr. Kauffman further commented, "The proof-of-concept trial of
PRX-08066 is an exciting event for Predix, as we believe there is a
significant need for improved treatment of pulmonary arterial
hypertension (PAH), a serious and often fatal cardiovascular disease.
Because of its selectivity - in preclinical models PRX-08066 reduces
only pulmonary and not systemic blood pressure - we believe that this
product candidate may lack the systemic blood pressure effects of
currently approved therapies for the disease."



PRX-00023 Phase III Study Design for GAD



Predix and the FDA had previously agreed upon the design and
primary and secondary endpoints for this Phase III trial, which was
initiated in August. The trial is an eight-week, double-blind,
placebo-controlled, multi-center study. The trial includes
approximately 20 sites in the United States and is expected to enroll
up to 310 patients with moderate-to-severe GAD who will be randomized
into one of two arms, consisting of approximately 155 patients each: a
placebo arm, or a PRX-00023 treatment arm, in which patients receive a
dose of 40 mg administered over a three-day period followed by a dose
of 80 mg once daily for the remainder of the study. The primary
objectives in this trial are to evaluate the efficacy of PRX-00023 in
GAD as measured by the change from baseline in the HAM-A scale, and to
assess the safety and tolerability of PRX-00023 during treatment of
patients with GAD. The HAM-A scale is the only FDA accepted standard
for the evaluation of anti-anxiety activity, and has been used in all
pivotal trials of drug candidates for the treatment of GAD. This trial
will be the first of at least two pivotal trials with PRX-00023 for
the treatment of GAD.



About PRX-00023



PRX-00023 is Predix's lead product candidate and represents a
novel, highly selective , non-azapirone class of 5-HT1A agonists
discovered using PREDICT(TM), the company's proprietary G-Protein
Coupled Receptors (GPCR) modeling, screening and lead optimization
technology. Buspirone is currently the only 5-HT1A agonist approved in
the United States for GAD but is generally taken three times a day,
requires approximately three weeks of dose adjustment to reach
therapeutic levels, and may cause lightheadedness and nausea. Several
other 5-HT1A agonists have shown efficacy in Phase II and III clinical
trials in depression. However, most of these drugs belong to a
chemical class of drugs called azapirones and their development has
been hindered by poor tolerability at therapeutic doses, rapid
metabolism, resulting in a short half-life and, therefore, requiring
multiple daily dosing, and the requirement of slow dose escalation to
effective doses because of nausea and lightheadedness, which are
thought to be caused by their binding to off-target G-Protein Coupled
Receptors (GPCRs).



In contrast, PRX-00023 is designed to have minimal affinity for
the GPCRs associated with the side effects of 5-HT1A agonists that are
in the azapirone chemical class, and to have a more convenient dosing
profile than azapirones.



PRX-08066 in PAH



PRX-08066 is a novel, highly selective, oral 5-HT2B antagonist
being developed for PAH. Over the past decade, the 5-HT2B receptor has
been shown to be linked to the development and progression of PAH,
including cases associated with the use of certain diet drugs in
humans. PRX-08066 is the first 5-HT2B antagonist being developed for
PAH and has completed two Phase I clinical trials in healthy
volunteers. The first Phase I clinical trial was a randomized,
placebo-controlled, double-blind, single-dose escalation study with 24
subjects. Over a dose range from 25 mg to 800 mg, PRX-08066 was
well-tolerated and there were no serious adverse events or liver
toxicity issues associated with treatment. A separate 14-day,
multiple-dose Phase I clinical trial in healthy volunteers showed that
PRX-08066 was well-tolerated. Preliminary pharmacokinetic data from
these two Phase I studies is consistent with once or twice daily oral
dosing.



Phase Ib Study Design in PAH



The Phase Ib clinical trial will study the pharmacodynamics and
tolerability of PRX-08066 in approximately 12 adults conditioned to
exercise at high altitudes, with elevated pulmonary artery pressures
induced by low oxygen levels (hypoxia). The trial will explore the
effects of PRX-08066 on pulmonary blood pressure and exercise
capacity.



This Phase Ib study features a randomized, double-blind,
three-period crossover design, where each subject receives drug or
placebo twice daily for 3 days in three separate periods, with an
interval of 1-2 weeks between visits. Pharmacodynamics of PRX-08066
will be characterized by the noninvasive measurement of pulmonary
artery blood pressure, right atrial pressure, cardiac index (i.e.,
cardiac output indexed to body size) and exercise capacity.



The trial is expected to be completed in mid- to late-2006, and if
the results are favorable, the initiation of a Phase II clinical trial
is anticipated in the second half of 2006.



About PRX-08066



PRX-08066 is Predix's third of three product candidates currently
in the clinic, all of which were internally discovered utilizing
computer-based G-Protein Coupled Receptor (GPCR) models and optimized
with integrated computational-medicinal chemistry. PRX-08066 is a
highly selective, small-molecule 5-HT2B antagonist being developed for
the treatment of PAH and other pulmonary disorders. PRX-08066 was
designed to provide both symptomatic improvement, through selective
dilation of diseased pulmonary blood vessels, and to slow disease
progression, by inhibiting the thickening of the pulmonary arteries
that occurs as PAH worsens.



PRX-08066 has demonstrated selective dilation of pulmonary blood
vessels in both acute and chronic pre-clinical models of PAH, as well
as disease-modifying effects in vivo and in in vitro signal
transduction pathway studies.



About Pulmonary Arterial Hypertension



Pulmonary Arterial Hypertension (PAH) is a serious and often fatal
cardiovascular disease affecting nearly 50,000 Americans and 50,000
Europeans. The disease is characterized by the elevation of pulmonary
artery blood pressure and progressive thickening and narrowing of the
blood vessels to the lungs, which can lead to heart failure. Symptoms
of PAH include fatigue after minimal exertion, dizzy spells, chest
pain, shortness of breath and fainting. The global market for PAH
drugs is growing rapidly, from approximately $600 million in 2004 to
an estimated $1 billion in 2010, as more patients with PAH are
diagnosed and initiated on drug therapy.



PAH results from the accelerated proliferation of
blood-vessel-associated smooth muscle cells that lead to the
constriction of pulmonary arteries. Blood supply to the lungs is
mediated by contraction of the right ventricle in the heart, which can
accommodate normal pulmonary blood pressures but is poorly suited to
tolerate the increased pulmonary pressures associated with the
arterial constriction that occurs in PAH. Over time, as the right
ventricle loses the ability to pump blood into the hypertensive
pulmonary system, the right ventricle heart muscle weakens and becomes
enlarged and dilated, eventually leading to heart failure in many
cases.



About Predix



Predix Pharmaceuticals Holdings, Inc. is a pharmaceutical company
focused on the discovery and development of novel, highly selective,
small-molecule drugs that target G-Protein Coupled Receptors (GPCRs)
and ion channels. Using its proprietary drug discovery technology and
approach, Predix has advanced three product candidates into clinical
trials and has six additional programs in preclinical development and
discovery. Predix initiated the first of at least two pivotal Phase
III clinical trials for generalized anxiety disorder for its lead drug
candidate, PRX-00023, in August 2005, and is conducting this Phase III
study under a Special Protocol Assessment agreed to with the FDA in
November 2005. Predix has two other clinical-stage drug candidates:
PRX-03140 for the treatment of Alzheimer's disease, entering Phase II,
and PRX-08066 for the treatment of pulmonary arterial hypertension,
now in Phase Ib.



Source: Predix Pharmaceuticals

Dubi




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