OSI Pharmaceuticals Summarizes Research Data Presented at the Annual Meeting of the American Association for Cancer Research.

Business Editors

MELVILLE, N.Y.--(BUSINESS WIRE)--March 31, 2004

OSI Pharmaceuticals, Inc. (Nasdaq: OSIP) today provided an informational update summarizing highlights from presentations made at this year's Annual Meeting of the American Association for Cancer Research (AACR) held from March 27-31 in Orlando, Florida. Presentations included studies on the Company's anti-cancer drug candidates: Tarceva(TM) (erlotinib HCl), a small molecule inhibitor of the epidermal growth factor receptor (HER1/EGFR), OSI-7904L, a novel liposomal thymidylate synthase (TS) inhibitor, and several drug candidates at earlier stages in the Company's proprietary research discovery program.

Tarceva(TM): Pre-clinical Data Highlights

Tarceva(TM), currently in Phase III registration trials in refractory non-small cell lung cancer (NSCLC) and pancreatic cancer, is being developed by OSI in collaboration with Genentech, Inc. and Roche in a comprehensive, global development program.

Data presented in a series of pre-clinical studies revealed that higher EGFR expression levels appear to correlate with increased resistance to radiation in various tumor types, including bladder cancer. Study results showed that Tarceva(TM), when utilized in combination with radiation, contributes to an increase in radiosensitization (sensitivity of tissue to the effects of radiation therapy). Study results also showed that in five of six bladder cancer cell lines, Tarceva(TM) enhanced radio-responsiveness. Additionally, it was concluded that EGFR levels and autophosphorylation might be useful biomarkers to predict the outcome of radiation therapy. The results of these early studies are intriguing and provide a justification for follow up clinical studies.

Tarceva(TM) was also evaluated in a pre-clinical study for responsiveness in pancreatic tumor cell lines as a single agent. Data presented showed that these pancreatic tumor cell lines responded to Tarceva(TM) by demonstrating growth inhibition. These results from the pre-clinical single agent study, in common with previously reported clinical results in other diseases such as NSCLC, suggest that Tarceva(TM) as a single agent in pancreatic cancer may warrant future clinical investigation.

Additionally, pre-clinical studies presented at the meeting support the observation that Tarceva(TM) may demonstrate broad-based anti-tumor activity in a wide variety of solid tumor types including NSCLC, squamous vulvar, bladder, renal, colon, pancreatic and prostate cancers. This observation supports the notion that Tarceva(TM) might provide benefit as a single agent in a broad spectrum of disease settings.

OSI-7904L: Pre-clinical Data

OSI-7904L is a liposomal formulation of a potent TS inhibitor which is designed to improve activity by changing the pharmacokinetic (drug exposure) profile when compared to its non-liposomal formulation. 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.

Data presented at this meeting showed that the combination of OSI-7904L with two platinum analogs commonly used in the treatment of gastrointestinal malignancies, cisplatin and oxaliplatin, was associated with increased efficacy as compared to the single-agent treatment. Experiments were conducted in five tumor models (two colon, three gastric) and the combination regimen was superior to the single agent in four of the five models. In addition, sequence dependency was observed in some models, and activity was greater when OSI-7904L was given after the platinum. These data demonstrate that OSI-7904L can be effectively and safely combined with platinum-based chemotherapy to improve the anti-tumor efficacy in colorectal and gastric xenograft models. In conclusion, these data support the Company's ongoing clinical program for OSI-7904L. The clinical program includes two ongoing Phase I studies evaluating the use of OSI-7904L in combination with cisplatin or oxaliplatin. The clinical program also includes an ongoing Phase II monotherapy study in patients with previously untreated advanced gastric or gastro-esophageal junction cancer.

Highlights from OSI's Research Program

The Company's extensive pre-clinical research program focuses on the discovery of small molecule drugs directed toward core biological processes, by targeting signal transduction pathways that either drive cancer cell proliferation, prevent apoptosis (programmed cell death) and, in selected cases, inhibit angiogenesis. The Company's most advanced research program is focused on the identification of a dual c-kit/KDR inhibitor. C-kit and KDR are both receptor tyrosine kinases, which function as key regulators in the control of tumor growth and angiogenesis (the process of blood vessel growth) respectively. Pre-clinical data presented at the meeting indicate that the lead compounds, in addition to inhibiting KDR, are also equally active against both mutant and wild type c-kit in cellular systems. Prolonged suppression of c-kit phosphorylation in vivo has been shown to correlate with anti-tumor activity in both mutant and wild type c-kit xenograft models. The lead compounds also have activity in tumor models that are thought to be dependent upon angiogenesis, highlighting the importance of the dual c-kit/KDR activity.

The Company's most advanced candidate, OSI-930, is in late-stage pre-clinical development with IND (Investigational New Drug)-track status. The Company anticipates initiating clinical studies by year-end of calendar 2004.

Highlights from OSI's Licensed Programs

CP-724,714, an oral HER2 receptor inhibitor, was discovered as part of OSI's long-standing cancer discovery program with Pfizer Inc. and is currently in Phase I clinical development by Pfizer. Data presented at the meeting demonstrated that CP-724,714, has significant anti-proliferative activity in human breast cancer cell lines with elevated levels of HER2 (9 of 9 cell lines), whereas cell lines without HER2 amplification demonstrated activity in fewer cell lines (3 of 13 cell lines). Additional data reported suggested that the combination of CP-724,714 and Herceptin(R) provided better anti-tumor efficacy than treatment by either agent alone in a human breast carcinoma xenograft model.

About OSI Pharmaceuticals

OSI Pharmaceuticals is a leading biotechnology company focused on the discovery, development and commercialization of high-quality, next-generation oncology products that both extend life and improve the quality-of-life for cancer patients worldwide. OSI has a balanced pipeline of oncology drug candidates that includes both novel mechanism-based, gene-targeted therapies focused in the areas of signal transduction and apoptosis and next-generation cytotoxic chemotherapy agents. OSI's most advanced drug candidate, Tarceva(TM), a small-molecule inhibitor of the HER1 gene, is currently in Phase III clinical trials for lung and pancreatic cancers. OSI has a commercial presence in the U.S. oncology market where it exclusively markets Novantrone(R) (mitoxantrone concentrate for injection) for approved oncology indications and Gelclair(R) for the relief of pain associated with oral mucositis.

This news release contains forward-looking statements. These statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. Factors that might cause such a difference include, among others, the completion of clinical trials, the FDA review process and other governmental regulation, OSI's and its collaborators' abilities to successfully develop and commercialize drug candidates, competition from other pharmaceutical companies, the ability to effectively market products and other factors described in OSI Pharmaceuticals' filings with the Securities and Exchange Commission. Tarceva(TM), OSI-7904L, OSI-930 and CP-724,714 are investigational compounds and have not yet been determined safe or efficacious in humans for their ultimate intended use.