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Phase II Study of OSI-7904L in Gastric Cancer Initiated

MELVILLE, N.Y.--(BUSINESS WIRE)--Oct. 24, 2003--OSI Pharmaceuticals, Inc. (NASDAQ:OSIP) today announced that it has initiated a Phase II clinical study of OSI-7904L, an investigational anti-cancer drug, in patients with previously untreated advanced gastric cancer. OSI-7904L is a novel member of a well-established class of drugs known as thymidylate synthase (TS) inhibitors.

OSI-7904L is a liposomal formulation of a potent TS inhibitor which is designed to improve activity by changing the drug exposure (pharmacokinetic) profile when compared to its non-liposomal formulation, thereby maintaining active concentrations of drug in the tumor for extended periods of time. OSI-7904L is being developed as a potential next-generation cytotoxic drug and competitor to 5-fluorouracil (5-FU) and capecitabine, two of the leading TS inhibitors currently marketed. Evidence suggests that prolonged infusions of 5-FU are associated with improved activity compared with the normal 5-FU protocol. OSI-7904L is designed to mimic the effects of a long-term infusion with a single dose of the liposomal product.

"The initiation of this Phase II study is based on the successful demonstration of a favorably altered drug exposure profile and the predictable and manageable safety profile seen in the Phase I single-agent study conducted with this agent," stated Nicole Onetto, M.D., Executive Vice President and Chief Medical Officer of the Company. "We also saw encouraging preliminary indications of anti-tumor activity in the form of several prolonged disease stabilizations amongst heavily pretreated patients in this Phase I trial."

This multi-center, open-label, non-randomized study is scheduled to enroll approximately 50 patients in Europe and the United States, and is designed to evaluate the efficacy and safety of OSI-7904L in chemotherapy-naive gastric cancer patients. OSI-7904L will be administered to patients at the Phase I recommended dose of 12 mg/m2 every 21 days. The primary endpoint of this trial is response rate.

Background
OSI acquired OSI-7904L as part of its acquisition of the oncology business of Gilead Sciences in December 2001. The agent is a key product in OSI's differentiated cytotoxic drug development program.

OSI-7904L Development Program
In addition to the initiation of this Phase II study in gastric cancer OSI is also broadening the OSI-7904L development program with two studies evaluating the use of OSI-7904L in combination with the chemotherapy agents cisplatin and oxaliplatin.

OSI-7904L Phase I Study
At this year's Annual Meeting of the American Society of Clinical Oncology (ASCO) in May results were presented from a Phase I dose escalation study to determine the recommended Phase II dose of OSI-7904L when administered on an every 21 days schedule. The study identified 12 mg/m2 as the recommended dose of OSI-7904L, demonstrating it was clinically manageable, with predictable toxicities, characteristic of other TS inhibitors (i.e. rash, fatigue, stomatitis, neutropenia, and thrombocytopenia). Prolonged disease stabilization was also observed in several heavily pretreated patients including those with extensive prior exposure to other TS inhibitors. Among the 31 evaluable patients who were treated with OSI-7904L, 7 patients (22.5%) achieved disease stabilization lasting for 3 to 14 cycles.

OSI-7904L Pre-clinical Data
Earlier pre-clinical studies demonstrated that the liposomal formulation of OSI-7904L resulted in a 700-fold increase in plasma exposure as compared to the non-liposomal drug (free drug). Additional research in tumor xenograft models showed a greater than 200-fold increase in tumor tissue exposure of the liposomal formulation and demonstrated superior anti-tumor activity as compared to either the free drug or 5-FU, one of the leading TS inhibitors currently marketed.

Source: OSI Pharmaceuticals, Inc.

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