PRESS RELEASE: EPIX Pharmaceuticals Says Blood Pressure Drug Promising, Shares Rise

PRX-08066 resulted in statistically significant reductions in systolic pulmonary artery pressure (SPAP); responder (greater than or equal to 4mmHg drop in SPAP) rates were 45% on 400 mg once-daily vs. 14% on placebo (p=0.043) Well-tolerated, with potential for co-administration with other therapies First-in-class 5-HT2B antagonist in PH associated with COPD The Phase 2a trial was a randomized, double-blind, placebo-controlled trial of 71 patients with PH associated with COPD. Patients were randomized to one of three arms: 200 mg of PRX-08066 once-daily; 400 mg of PRX-08066 once-daily; or placebo. The two-week double-blind phase of the study was followed by an open-label extension in which 10 patients received 200 mg daily for six weeks. The primary endpoints of the trial were safety and tolerability of PRX-08066. Efficacy was measured by the effect of PRX-08066 compared to placebo on systolic pulmonary artery pressure (SPAP) and included 62 evaluable patients who completed the double-blind portion of the study.

In a population where decreases of 3mmHg to 4mmHg in a post-exercise SPAP are considered clinically significant, the results show a statistically significant (p=0.036) dose-response for the patients that demonstrated a decrease of 4mmHg or more (responders). In the 400 mg dose group, 45% of the patients had a reduction in post-exercise SPAP of 4mmHg or more versus 14% on placebo (p=0.043). An analysis of SPAP changes in all subjects revealed a dose response with median reductions of 1.1mmHg and 3.37mmHg in the 200 mg and 400 mg dose groups, respectively, compared with no change on placebo (p=0.08 for high dose versus placebo). As observed in prior trials, PRX-08066 had no effect on systemic blood pressure, further demonstrating its selective pulmonary vasodilatory action.

"This is the first 5-HT2B antagonist to be developed to treat this patient population and the first clinical trial in patients," said Michael G. Kauffman, M.D., Ph.D., chief executive officer of EPIX. "We believe these results are very exciting for the COPD community and look forward to continuing to advance the clinical development of PRX-08066 for the treatment of PH associated with COPD."

PRX-08066 was generally well-tolerated. There were no serious adverse events considered related to PRX-08066, and the majority of adverse events were mild or moderate in nature. Patients enrolled in the trial had advanced COPD and were on numerous concomitant medications. One subject in the 400 mg dose group who continued into the six-week open-label extension experienced a modest increase in liver enzyme levels at the end of the extension that was believed to be drug-related. These values returned to normal within two weeks and the subject remained asymptomatic.

"We are very pleased with the results of this Phase 2a trial, particularly in light of this very ill and heterogeneous population, and are excited about the potential for PRX-08066 in this population of patients with a high unmet medical need," stated Andrew Uprichard, M.D., president and head of R&D for EPIX. "Based on the significant responses observed in nearly half the patients, we intend to conduct a right-heart catheterization study to better define the clinical parameters for responders - data we will use to refine the patient inclusion criteria in our subsequent clinical trials. From there, we anticipate assessing the effect of PRX-08066 in the COPD/PH population in a 12-week clinical trial utilizing the standard six-minute walk distance as the primary endpoint."

COPD is a progressive lung disease that affects nearly 30 million people worldwide and is characterized by airflow obstruction that interferes with normal breathing and impairs the ability to exercise and perform daily activities. According to a December 2005 Datamonitor report, PH is estimated to be present in approximately 20 percent of patients who have COPD. Patients with COPD and concomitant PH are generally known to have a very poor prognosis and currently there are no agents approved for this indication.

About PRX-08066

Discovered and designed using EPIX's proprietary G-protein coupled receptor (GPCR) modeling and optimization technology, EPIX is developing PRX-08066 to provide both symptomatic improvement, through selective dilation of diseased pulmonary blood vessels, and to also slow disease progression by inhibiting the thickening of the pulmonary artery vessels. EPIX is currently developing what it believes to be the only selective 5-HT2B antagonist for pulmonary hypertension. The company has completed two Phase 1 clinical trials with PRX-08066 in healthy volunteers, as well as a Phase 1b trial. The Phase 1b trial assessed the effects of PRX-08066 on pulmonary artery pressure in athletes whose pulmonary pressures were increased by exposure to a reduced oxygen level (hypoxia). The results of this Phase 1b trial indicated that 200 mg of PRX-08066 given orally twice daily significantly reduced the increase in pulmonary artery blood pressure during hypoxic exercise (by 3.6mmHg compared with placebo), without affecting systemic blood pressure. PRX-08066 was well-tolerated in the single dose study up to 500 mg and up to 400 mg twice-daily in the multiple dose study. The half life of PRX-08066 is approximately 20 hours.

PRX-08066 represents a novel mechanism for selectively dilating pulmonary arteries without affecting the systemic circulation. Blocking 5HT2B in patients with PH associated with COPD could reduce or prevent the acute rise in pulmonary pressures which occur when patients increase their activity. This means that the heart would do less work for a given level of activity, allowing for improvements in exercise tolerance. Moreover, by blocking the serotonin-dependent growth of pulmonary vascular smooth muscle cells, which further increases pulmonary pressures and increases workload demand on the heart, PRX-08066 could slow the progression of disease. Over time, this could translate into improved exercise tolerance and slowing of the vascular remodeling that leads to right sided heart failure. These kinds of effects have been seen with PRX-08066 in animal models of hypoxia-induced pulmonary arterial hypertension (PAH).

About EPIX

EPIX Pharmaceuticals is a biopharmaceutical company focused on discovering and developing novel therapeutics through the use of its proprietary and highly efficient in silico drug discovery platform. The company has a pipeline of internally-discovered drug candidates currently in clinical development to treat diseases of the central nervous system and lung conditions. EPIX also has collaborations with leading organizations, including GlaxoSmithKline, Amgen, Cystic Fibrosis Foundation Therapeutics, and Bayer Schering Pharma AG, Germany. For more information, please visit the company's website at www.epixpharma.com.

This news release contains express or implied forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, that are based on current expectations of management. These statements relate to, among other things, our expectations regarding the progress, timing and results of our clinical development program for PRX-08066 and management's plans, expectations and strategies. These statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, among other things: risks that product candidates, including PRX-08066, may fail in the clinic or may not be successfully marketed or manufactured; risks relating to our ability to advance the development of product candidates currently in the pipeline or in clinical trials, any failure to comply with regulations relating to our products and product candidates, including FDA requirements; failure to obtain the financial resources to complete development of product candidates; the risk that the FDA may interpret the results of our studies differently than we have; competing products may be more successful; our inability to interest potential partners in our technologies and products; our inability to achieve commercial success for our products and technologies; the possibility of delays in the research and development necessary to select drug development candidates; the risk that we may be unable to successfully secure regulatory approval of and market our drug candidates; and risks of new, changing and competitive technologies and regulations in the U.S. and internationally. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. We undertake no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. For additional information regarding these and other risks that we face, see the disclosure contained in our filings with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q.