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Phase II Trial for Post-Prostatectomy Erectile Dysfunction Therapy Set To Begin

BALTIMORE, Nov. 18 /PRNewswire-FirstCall/ -- Guilford Pharmaceuticals Inc. (Nasdaq: GLFD - News) announced today that it has begun a Phase II clinical trial of its novel neuroimmunophilin ligand, GPI 1485, for the treatment of post- prostatectomy erectile dysfunction (PPED). Neuroimmunophilin ligands are orally administered drugs that have shown an ability to promote the regeneration and protection of both central and peripheral nerves in preclinical studies. A separate Phase II clinical trial of GPI 1485 for the treatment of Parkinson's disease is currently underway in 21 centers across the United States.

In PPED, sexual dysfunction occurs as a result of compression or stretch injury to nerve fibers that surround the prostate and which are responsible for stimulating blood flow to sustain an erection. Unfortunately, a high proportion of men undergoing radical prostate surgery may experience side effects from their surgery including urinary incontinence and sexual dysfunction, which is frequently unresponsive to currently available drug therapies, including Viagra®. If successful, Guilford's GPI 1485 represents a novel approach to the treatment of PPED by potentially promoting the protection and regeneration of peripheral nerves that may sustain injury during radical prostate surgery.

"We're very excited to begin our second Phase II clinical development program for GPI 1485," commented William Vincek, Ph.D., Senior Vice President, Development. "Our preclinical results in models of PPED suggest that oral treatment with GPI 1485 either concurrent with or up to 7 days following peripheral nerve injury can produce significant neuroprotection, preventing cavernous nerve degeneration and preserving erectile function at greater than 90% of normal levels for up to 28 days after injury. We are eager to evaluate the treatment effect of GPI 1485 in prostate cancer patients undergoing radical surgery, and look forward to reporting the results from both of our ongoing clinical studies of GPI 1485 over the next two years."

Patrick C. Walsh, M.D., David Hall McConnell Professor, Chairman and Urologist-in-Chief of The James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, commented, "The advent of the first nerve- sparing radical prostatectomy two decades ago has meant safer surgeries and, I believe, has contributed to a decrease in mortality in patients with prostate cancer. Essential to this continued progress is the ability to offer procedures that effectively treat the cancer while reducing the overall impact of the surgery on the patient. With the promise of significant neuroprotection in preclinical studies, we look forward to the results of the first human tests of GPI 1485 in conjunction with aggressive surgical treatment."

About the Phase II Clinical Trial
The Phase II clinical trial is a multi-center, randomized, double-blind, placebo-controlled, 3-arm, 12-month study designed to evaluate the safety, pharmacokinetics and efficacy of GPI 1485 in patients undergoing bilateral nerve-sparing radical retropubic prostatectomy for the treatment of prostate cancer. A total of 150 patients aged 40 to 55, and 90 patients aged 60 to 69 will be enrolled and randomly assigned to receive either placebo, low dose GPI 1485, or high dose GPI 1485 orally four times a day.

The objective of the study is to evaluate the efficacy of high dose and low dose GPI 1485 compared to placebo in promoting the recovery of erectile function in patients who have undergone prostatectomy. The primary endpoint in the study will compare the effect of a post-surgical, six-month course of treatment with GPI 1485 to placebo on erectile function as reported by patients aged 40-59 in the International Index of Erectile Function questionnaire. Secondary endpoints in the study include: a similar comparison of erectile function in patients aged 60-69; an evaluation of the safety and pharmacokinetics of GPI 1485; a comparison of the time to first recovery of erectile function in each of the treatment groups compared to the placebo group, and a comparison of Viagra® use in each of the treatment groups and placebo group over an eleven-month follow-up period.

Preclinical Evidence
In September 2002, Guilford Pharmaceuticals announced that oral dosing in animals with GPI 1485 stimulates significant neuroprotective and neuroregenerative activity in preclinical models of post-prostatectomy erectile dysfunction. Treatment with GPI 1485 at the time of injury maintained intracavernosal pressure at near normal levels for up to 28 days after injury. In addition, delayed treatment with GPI 1485 up to seven days after the peripheral nerve injury procedure promoted significant restoration of function, restoring intracavernosal pressure to between 90%-100% of normal levels when measured at one month after injury.

About GPI 1485 and Neuroimmunophilin Ligands
GPI 1485 is an investigational new drug that belongs to a class of compounds called neuroimmunophilin ligands. Neuroimmunophilin ligands are small molecules that in preclinical experiments have been shown to be orally bioavailable and repair and regenerate damaged nerve terminals without affecting normal nerves. Neuroimmunophilin ligands may have application in the treatment of a broad range of indications, including: spinal cord injury, brain trauma, and peripheral nerve injury. A second Phase II study investigating GPI 1485 for the treatment of Parkinson's disease is currently underway in the United States.

About PPED
The American Cancer Society estimates that approximately 190,000 American men will be diagnosed with prostate cancer this year. Of these, the cancer will be localized in 70% of patients, and a significant proportion will undergo prostatectomy for treatment. Potential complications of surgery include urinary incontinence and sexual dysfunction. In a retrospective study of patient outcomes, published in the Journal of the American Medical Association, the incidence of sexual dysfunction reported at eighteen months following prostatectomy ranged from 60 percent to 85 percent (JAMA. 2000; 283:354-360).

Source: Guilford Pharmaceuticals Inc.

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