OSI Pharmaceuticals Summarizes Research Data Presented at the 93rd Annual Meeting of the American Association for Cancer Research
MELVILLE, N.Y.--(BUSINESS WIRE)--April 10, 2002--OSI Pharmaceuticals, Inc. (Nasdaq: OSIP - news) today provided an informational update for investors on the presentations made by the Company's scientists at the 93rd Annual Meeting of the American Association for Cancer Research (AACR) in San Francisco, CA. Presentations included studies on the Company's lead anti-cancer drug, Tarceva(TM) (erlotinib HCl, OSI-774), a small molecule inhibitor of the epidermal growth factor receptor (EGFR), and two of its next-generation cytotoxics, OSI-7904L (formerly GS7904L) and OSI-7836 (formerly GS7836). OSI-7904L is a novel liposomal thymidylate synthase inhibitor and OSI-7836 is a nucleoside analog being developed as a next-generation gemcitabine.
Targeted Therapy: Tarceva(TM) (erlotinib HCl, OSI-774)
Data were presented outlining a series of studies on the dimerization of EGFRvIII, a mutant form of the EGF receptor detected in a high percentage of glial tumors, breast carcinomas and ovarian tumors. Dimerization is an important part of the biology for all members of the erbB family of receptors, including both EGFR and EGFRvIII. The studies indicated that EGFRvIII can form dimers and that this dimerization is induced for both EGFR and mutant EGFR by Tarceva(TM). Furthermore, these studies show Tarceva(TM) is effective in inhibiting the tyrosine kinase activity of EGFRvIII, thus blocking cell signaling through EGFRvIII. The data also indicated that long-term exposure to Tarceva(TM) resulted in a decrease in the number of mutant receptors at the cell surface. Investigations are planned to assess the impact of this on anti-tumor activity.
Tarceva(TM), currently in Phase III registration trials, is being developed by OSI in collaboration with Genentech, Inc. and Roche in a comprehensive, global development program.
Next Generation Cytotoxic Agents: OSI-7904L & OSI-7836
OSI scientists also presented data on two of its next-generation cytotoxic drugs currently in clinical development. OSI presented pre-clinical data on two of these products, OSI-7904L and OSI-7836 both in Phase I clinical trials for the treatment of certain cancers.
OSI-7904L is a thymidylate synthase inhibitor (TSI), a well established class of agents often used to treat patients with metastatic colorectal and breast cancers. 5-Fluoro-uracil (5-FU), one of the leading TS inhibitors currently marketed, is the most frequently prescribed agent for colorectal cancer today. Many cancer researchers believe that next generation TSIs which extend the exposure of the drug at the tumor site will enhance the value of this class of agents.
Two abstracts were presented on OSI-7904L, a liposomal formulation of a potent TSI (GW1843) which is designed to improve activity by maintaining active concentrations of drug in the tumor for extended periods of time. The pre-clinical studies demonstrated that OSI-7904L resulted in increased plasma exposure (a 700-fold increase in AUC, a measure of total exposure to drug) as compared to the non-liposomal drug (free drug). Additional research in tumor xenograft models showed a greater than two hundred 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.
OSI-7836 is a member of the nucleoside class of cytotoxic drugs of which gemcitabine is the market leader. OSI is developing OSI-7836 as a next-generation gemcitabine. Study results presented on OSI-7836 at AACR demonstrated that OSI-7836 was more active than gemcitabine in six of nine xenografts tested and was equally active in the remaining three. The anti-tumor activity of OSI-7836 also appeared to be less schedule dependent than gemcitabine. OSI-7836 was also more active than ara-C (another clinically used nucleoside analog) in all nine models and more active than either paclitaxel or cisplatin in the two lung xenograft models tested. OSI-7836 showed no unexpected toxicities; those observed appeared to be similar to other nucleoside agents. Additional studies showed that OSI-7836 appears to have a different mechanism of tumor growth inhibition blocking the cell division cycle at a different point (the G2 phase) than gemcitabine.
Posters Presented by OSI Scientists at AACR
* ``Effects of OSI-774 on EGFR and EGFRvIII Receptor Dimerization,'' presented by Kenneth K. Iwata, Ph.D., Director, Translational Research, OSI Pharmaceuticals.
* ``In Vivo Anti-tumor Activity and Biodistribution of OSI-7904L, a Low Clearance Liposomal Formulation of a Novel Thymidylate Synthase Inhibitor,'' presented by David L. Emerson, Ph.D., Sr. Director, In-Vivo Pharmacology & Translational Research, OSI Pharmaceuticals.
* ``Pharmacokinetics of the Liposome Encapsulated Thymidylate Synthase Inhibitor OSI-7904L in Mice and Dogs,'' presented by Laurel M. Adams, Ph.D., Director, Clinical Research, OSI Pharmaceuticals.
* ``Non-clinical Toxicologic and Pharmacokinetic Evaluation of the Nucleoside Analogue OSI-7836,'' presented by Frank C. Richardson, D.V.M., Ph.D., Director, Toxicology, OSI Pharmaceuticals.
* ``The Anti-tumor Activity of OSI-7836 (4'-thio-araC), a Nucleoside Analog, in Mouse Xenografts: Comparison to Standard Cytotoxic Agents and Schedule Dependence,'' presented by Blake F. Tomkinson, Ph.D., Director, Project Management, OSI Pharmaceuticals.
* ``OSI-7836 (4'-thio-(beta)-D-arabinofuranosylcytosine): A Novel Anti-Cancer Nucleoside Analog that Inhibits DNA Polymerases and Induces G2 Arrest,'' presented by April L. Blajeski, Ph.D., Research Scientist, OSI Pharmaceuticals.... |
