Guilford Pharmaceuticals Inc. announced that it has regained from Pfizer all rights to develop and commercialize NAALADase inhibitors. In May 2003, Guilford and Pfizer entered into an exclusive license agreement, which provided Pfizer with research, development and commercialization rights to Guilford's NAALADase inhibitor technology.

The agreement included a $5 million payment to Guilford at signing and an additional $10 million milestone payment due on or before March 31, 2004. Pfizer has informed Guilford that the milestone payment will not be made and they are terminating the agreement.

"We enjoyed a good scientific and business relationship with Pfizer," remarked Craig R. Smith, M.D., president and chief executive officer of Guilford. "However, Pfizer was not successful in identifying a lead clinical candidate during the ten months our agreement was in effect and unfortunately we were unable to reach agreement on terms for an extension."

Dr. Smith continued, "In pre-clinical studies we and Pfizer have consistently demonstrated robust efficacy in pre-clinical models of neuropathic pain. During 2003, Guilford initiated a collaboration with Dr. Howard Scher of Memorial Sloan-Kettering Cancer Center to study the use of NAALADase inhibitors as a potential treatment for prostate cancer. In preclinical studies NAALADase inhibitors were found to significantly retard the growth of prostate cancer cells. We also established collaboration with the National Institute for Drug Addiction (NIDA) to evaluate the use of NAALADase inhibitors as a potential treatment for cocaine addiction. NIDA is presently conducting pre-clinical studies and plans to conduct clinical trials."

NAALADase, or N-Acetylated-Alpha-Linked-Acidic-Dipeptidase, is a membrane- bound enzyme found principally in the central and peripheral nervous systems. Guilford has created several unique classes of NAALADase inhibitors and evaluated their potential therapeutic application in pre-clinical models of various acute and chronic neurodegenerative disorders, including diabetic peripheral neuropathy, neuropathic pain, Lou Gehrig's Disease (ALS), head and spinal cord trauma, and stroke. Guilford has also shown that NAALADase inhibitors may have utility for diagnostic or therapeutic purposes in prostate cancer and drug addiction.

NAALADase is believed to play a role in modulating the release of glutamate, one of the most common chemical messengers between nerves. During conditions of acute injury or chronic neurodegenerative disorders, there may be a large increase in glutamate release that incites a cascade of biochemical events, ultimately leading to cell injury and death. NAALADase is the same protein as prostate specific membrane antigen (PSMA), a protein found on the surface of prostate cancer cells. Guilford has also shown that its compounds may have utility for diagnostic or therapeutic purposes in prostate cancer.

Guilford has 37 issued US patents and 10 pending patent applications, and corresponding foreign counterparts protecting its NAALADase inhibitor technology.