PRESS RELEASE: EPIX Pharmaceuticals Reports Compelling Clinical Results for PRX-03140 in Alzheimer's Disease

EPIX Pharmaceuticals Reports Compelling Clinical Results for PRX-03140 in Alzheimer's Disease; Statistically Significant Improvement in Cognitive Function Achieved Within Two Weeks

EPIX to Host Investor Conference Call Today at 10:30 a.m. EST to Discuss Results

LEXINGTON, Mass.--(BUSINESS WIRE)--Dec. 18, 2007--EPIX Pharmaceuticals (NASDAQ: EPIX), today announced compelling top-line results from a Phase 2a two-week clinical trial of its novel 5-HT4 agonist, PRX-03140, in patients with Alzheimer's disease. The results show that patients receiving 150 mg of PRX-03140 orally once daily as monotherapy achieved a mean 5.7 point improvement on the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) versus a 0.2 point worsening in patients on placebo (p= 0.005). Patients on a 50 mg dose of PRX-03140 showed a 1.1 point improvement on the ADAS-cog. The ADAS-cog endpoint is the current standard for evaluating drug efficacy for cognition in Alzheimer's disease and is an established and accepted registration endpoint.

"The responses observed in this clinical trial over a short duration are promising, and clearly indicate that PRX-03140 is worthy of further study over a longer period and in a larger patient population," stated Paul Solomon, Ph.D., Professor, Department of Psychology and Program in the Neurosciences, Williams College, and the Clinical Director of the Memory Clinic in Bennington, Vermont. "Our patients are always in need of safe and effective treatments for Alzheimer's disease, and I am very encouraged by these data."

After reviewing these data, Serge Gauthier, M.D., Director of the Alzheimer's Disease Research Unit at McGill University, stated, "There is such an urgent and undeniable need for additional safe and effective treatments for Alzheimer's patients. Findings like these data are not only encouraging and compelling - they appear to represent a step forward in our ability to understand and combat the effects of Alzheimer's. I look forward to the next clinical trial of PRX-03140 as the development of this drug could be an important advance toward effective Alzheimer's treatment."

This Phase 2a clinical trial was a randomized, double-blind, placebo-controlled study to assess the effects of PRX-03140 following two weeks of treatment as monotherapy and separately in combination with donepezil (Aricept(R)) in patients with mild Alzheimer's disease. PRX-03140 appeared to be well tolerated alone and in combination with donepezil (Aricept(R)) with no serious drug-related adverse events. The results show that patients on PRX-03140 alone achieved a statistically significant improvement in ADAS-cog; ADAS-cog changes in the combination arms of the trial were not statistically significant. According to the literature supporting currently approved Alzheimer's therapies, significant improvements in ADAS-cog measures are not typically observed in less than 12 weeks of therapy.

"We had several responses of note in this trial," stated Marvin Kalafer, M.D., Principal Investigator at The Clinical Trial Center in Jenkintown, Pennsylvania. "The compelling efficacy and tolerability data observed in this two-week trial are indicative of a profile that would be highly differentiated in the category."

In pre-clinical models, PRX-03140 has been shown to have a novel mechanism of action that differentiates it from current Alzheimer's therapies. This oral drug candidate selectively activates the 5-HT4 receptor in the brain. Activation of 5-HT4 not only stimulates the production/release of acetylcholine, which may improve cognitive symptoms of Alzheimer's, but also stimulates the alpha secretase pathway, potentially slowing disease progression. PRX-03140 has the potential to be the first-in-class 5-HT4 agonist for the treatment of Alzheimer's disease.

Michael G. Kauffman, M.D., Ph.D., chief executive officer of EPIX Pharmaceuticals stated, "We are very excited by the measurable impact on memory and cognition, achieved in such a short period of time, in a trial that was designed primarily to assess safety and tolerability. While we recognize that this is a two-week study on a relatively small population of patients, these statistically significant results, as well as the anecdotal reports we have received from study investigators and patients' families since the trial concluded, support our belief that PRX-03140 has the potential to improve memory and cognition. We look forward to initiating a larger Phase 2b clinical trial early next year to further explore the potential of PRX-03140."

Trial Design and Results

This Phase 2a clinical trial was conducted across 17 U.S. sites and included 80 patients who were treated for two weeks. Patients were studied on PRX-03140 alone (across three dose arms of 10 patients each: 50 mg once-daily, 150 mg once-daily and placebo) or in a placebo-controlled combination with 10 mg donepezil (Aricept(R)) (across five dose arms of 10 patients each: PRX-03140 at 5, 25, 50, 100 and 200 mg with donepezil (Aricept(R))10 mg once-daily). Primary endpoints were safety, tolerability and assessment of quantitative electroencephalograms (qEEG). A battery of cognitive measures, including ADAS-cog assessment, and pharmacokinetic evaluations were measured as secondary endpoints.

    Key trial findings include:

    --  Robust and statistically significant improvement in cognitive
        function as measured by ADAS-cog with PRX-03140 at 150 mg
        once-daily monotherapy vs. placebo (p=0.005); the rigorous
        analysis of covariance with the ADAS-cog baseline was used

    --  This 5.7-point mean improvement in ADAS-cog for the 150 mg
        dose group compared to a 0.2-point mean worsening on placebo
        is better than ADAS-cog responses seen in previously published
        information with approved and experimental agents

    --  PRX-03140 also showed a statistically significant
        dose-response for 150 mg vs. 50 mg (monotherapy) vs. placebo

    --  The onset of benefit of PRX-03140 in Alzheimer's patients was
        observed within two weeks

    --  PRX-03140 produced strong trends in the alteration in brain
        wave activity (alpha:theta ratio) in the 150 mg dose group
        versus placebo as measured by qEEG, similar to changes
        observed with cholinesterase inhibitors

    --  As monotherapy and in combination with donepezil (Aricept(R)),
        PRX-03140 appeared to be well-tolerated with no serious
        drug-related adverse events
PRX-03140 is part of EPIX's worldwide, multi-target strategic collaboration with GlaxoSmithKline to discover, develop and market novel medicines targeting four G-protein coupled receptors (GPCR) for the treatment of a variety of diseases, including Alzheimer's disease. EPIX is responsible for discovery and development of products in the collaboration, including PRX-03140, through to clinical proof of concept, at which point GSK has an exclusive option to license each product for further development and commercialization on a worldwide basis. As part of the collaboration, EPIX received total initial payments of $35 million, including $17.5 million through the purchase of its common stock, and may be eligible to earn up to $1.2 billion in milestones across the four GPCR programs. If GSK exercises the option to license EPIX's PRX-03140 program, EPIX will retain the right to co-promote any products from that program in the United States. Under the collaboration, EPIX is also entitled to receive tiered double-digit royalties of sales by GSK on all collaboration-developed product sales. The alliance is conducted through GSK's Center of Excellence for External Drug Discovery (CEEDD).

About PRX-03140

PRX-03140 is a novel, oral investigational drug candidate for Alzheimer's disease. It is selective for the 5-HT4 receptor in the brain and is believed to stimulate both acetylcholine production/release - which enables symptomatic improvement in Alzheimer's patients - and the alpha-secretase pathway - which slows Alzheimer's disease progression. In three Phase 1 trials and this Phase 2a trial, with more than 180 patients and healthy subjects, PRX-03140 has been well-tolerated. In a 14-day Phase 1b clinical trial, treatment with PRX-03140 resulted in changes in brain wave activity in Alzheimer's patients that are consistent with those seen in clinical trials with currently approved drugs for Alzheimer's disease. In preclinical studies, PRX-03140 has shown to improve cognitive function through increasing levels of acetylcholine, soluble amyloid precursor protein (sAPP) and brain-derived neurotrophic factor (BDNF) in regions of the brain known to be important for memory.

PRX-03140 is one of EPIX's four drug candidates currently in clinical trials discovered through the use of its proprietary computer-based G-Protein Coupled Receptors (GPCR) platform and optimized with integrated computational-medicinal chemistry.

About Alzheimer's Disease

Alzheimer's disease is a debilitating neurodegenerative disorder characterized by progressive loss of memory and cognitive function, affecting more than 5 million Americans according to the Alzheimer's Association, and more than 9 million worldwide according to the Alzheimer's Disease International Association. The U.S. National Institute of Aging estimates that about 5 percent of the population aged 65-74 and as many as 50 percent of those over age 85 have the disease. Although treatment options are limited, the global market for Alzheimer's disease drugs is growing, from $4 billion in 2006 to over $5 billion expected in 2010, as estimated by Thomson-Pharma.

Today's Conference Call

EPIX has scheduled an investor conference call for today, December 18, 2007, at 10:30 a.m. EST to further discuss these data. Dr. Paul Solomon, Ph.D., Professor, Department of Psychology and Program in the Neurosciences, Williams College, and the Clinical Director of the Memory Clinic in Bennington, Vermont, will join EPIX on the call.

The live webcast - which will include accompanying presentation slides - can be accessed by visiting the Investor Relations section of EPIX's website at The call can be accessed by dialing (866) 761-0749 (domestic) or (617) 614-2707 (international) five minutes prior to the start time and providing the pass code 86773081. A replay of the call will be available on the EPIX website approximately two hours after completion of the call and will be archived, along with the slide presentation, for 30 days.

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

    Aricept(R) is a registered trademark of Eisai Co., Ltd.

    Forward Looking Statements
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 timing and results of future clinical development of PRX-03140 and its potential efficacy, safety and tolerability. 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 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; failure to obtain the financial resources to complete development of product candidates; our inability to further identify, develop and achieve commercial success for new products and technologies; our inability to achieve commercial success for our products and technologies; our failure to comply with regulations relating to our products and product candidates, including FDA requirements; the risk that the FDA may interpret the results of our studies differently than we have; 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.