OSI Pharmaceuticals Announces Initiation of Phase IIa Trial for Its Glycogen Phosphorylase Inhibitor, PSN357.

MELVILLE, N.Y. -- OSI Pharmaceuticals, Inc. (Nasdaq: OSIP) announced today that it has initiated a Phase IIa clinical trial for its glycogen phosphorylase inhibitor, PSN357, which the company is developing for type 2 diabetes. In the Phase IIa study, PSN357 will be administered to up to thirty type 2 diabetic patients as daily doses over an initial period of 14 days providing safety, pharmacokinetic and pharmacodynamic endpoints in a placebo controlled dose escalation design. The study is expected to last approximately six months.

"PSN357 is the first clinical candidate to emerge from the Company's internal discovery research efforts in diabetes and is designed to prevent glucose levels rising in diabetic patients by preventing glycogen breakdown to glucose in the liver," stated Anker Lundemose, M.D., Ph.D., Executive Vice-president and President of (OSI) Prosidion, the company's UK-based diabetes research & development arm. "We believe that PSN357, together with our DPIV inhibitor, PSN9301, which is scheduled to begin Phase IIb studies this year and PSN010, our glucokinase activator, which entered Phase I trials last week, together comprise an innovative clinical pipeline of novel, molecularly targeted therapies for the treatment of type 2 diabetes."

The initiation of the Phase IIa trial follows the completion of a Phase I safety and tolerability study for PSN357. In the single-center, placebo controlled, dose escalation study, PSN357 was administered in single and multiple doses (daily dose for 7 days) to 80 healthy volunteers. Results showed no unexpected safety or pharmacokinetic outcomes. Data will be presented at a diabetes meeting in the future.

Background

The inappropriate over-production of glucose by the liver as a result of glycogen breakdown is a contributor to the hyperglycemia in type 2 diabetes. As the rate of glycogenolysis is regulated by glycogen phosphorylase (GP), inhibition of this key enzyme may constitute a therapeutic option for the treatment of type 2 diabetes. Pre-clinical data presented at the 2005 American Diabetes Association's Annual Scientific Session showed that PSN357 inhibits GP and reduces blood glucose levels in animal models with diabetes following acute and chronic dosing. An increase in liver glycogen was also seen in the study, however heart and skeletal muscle glycogen showed no changes from controls. In addition, a 9-day study in mice showed once daily oral administration of PSN357 maintained anti-hyperglycemic efficacy throughout this period. Other endpoints observed in this study were a 57 percent increase in liver glycogen and no changes in other glycogen deposits or in levels of plasma insulin or alanine aminotransferase.

About OSI Pharmaceuticals

OSI Pharmaceuticals is committed to "shaping medicines and changing lives" by discovering, developing and commercializing high-quality and novel pharmaceutical products that extend life or improve the quality of life for patients with cancer, eye diseases and diabetes. The Company operates through three business teams, (OSI) Oncology, (OSI) Eyetech and (OSI) Prosidion. (OSI) Oncology is focused on developing molecular targeted therapies designed to change the paradigm of cancer care. (OSI) Eyetech specializes in the development and commercialization of novel therapeutics to treat diseases of the eye. (OSI) Prosidion is committed to the generation of novel, targeted therapies for the treatment of type 2 diabetes and obesity. OSI's flagship product, Tarceva(R) (erlotinib), is the first drug discovered and developed by OSI to obtain FDA approval and the only EGFR inhibitor to have demonstrated the ability to improve survival in both non-small cell lung cancer and pancreatic cancer patients. OSI markets Tarceva through partnerships with Genentech, Inc. in the United States and with Roche throughout the rest of the world. Macugen(R) (pegaptanib sodium injection