 |
 |
 |
 |
 |
 |
|
 Apoptosis Program The Cell Pathways acquisition gave us access to a broad technology platform in apoptosis. We acquired an extensive intellectual property estate including rights to two development candidates, Aptosyn® and OSI-461. These products are mixed c-GMP phosphodiesterase inhibitors. In March 2003, Cell Pathways completed enrollment of a 600-patient Phase III study for Aptosyn® in second-line NSCLC prior to the closing of the deal. Based upon the absence of clinical data in NSCLC and the lack of potency exhibited in pre-clinical models, we consider Aptosyn® to be a high-risk drug candidate and the focus of our attention has been on OSI-461 and other follow-on molecules that represent more potent and effective second-generation candidates to Aptosyn®. We are currently optimizing the dose for OSI-461 in extended Phase I trials, although exploratory Phase II studies in chronic lymphocytic leukemia, hormone refractory prostate cancer and renal cell carcinoma are ongoing. |
 |
|
|
Next-Generation Cytotoxics Our lead product candidate in this area is OSI-7904L, a liposomal formulation of the thymidylate synthase inhibitor, GW1843. Thymidylate synthase inhibitors, or TSIs, are a well-proven class of cytotoxic chemotherapy agents that include 5-fluorouracil (5-FU) and Xeloda™. 5-FU remains the most prescribed anti-cancer agent used in the treatment of cancer, especially gastrointestinal and breast cancers. Data have demonstrated that a long-term infusion schedule of 5-FU, although inconvenient to administer, improves its activity. OSI-7094L was formulated in liposomes with a goal of extending its pharmacokinetic half-life, thereby mimicking long infusion 5-FU and improving its therapeutic index as a direct competitor to bolus 5-FU. Data from a Phase I study, demonstrated that OSI-7904L extended the exposure of the drug in patients’ blood. We have therefore initiated a Phase II program for OSI-7904L which includes testing the drug in patients with previously untreated advanced gastric or gastro-esophageal junction cancer. Targeting Cancer Cell Growth In addition to Tarceva™, we also have three molecules currently in clinical trials resulting from our historical relationship with Pfizer in cancer drug discovery. CP-547,632, a potent and selective inhibitor of the vascular endothelial growth factor receptor (VEGFR), has been advanced to a Phase II study in ovarian cancer patients with minimal disease and continues in a Phase I/II study in NSCLC. Phase I trials have been initiated for CP-868,596, a platelet-derived growth factor receptor of PDGF receptor inhibitor. Phase I studies also continue for CP-724,714, an oral HER2 receptor inhibitor. Research We have focused our pre-clinical research activities on the discovery of small molecule drugs targeting two core biological processes, namely signal transduction pathways that either drive cancer cell proliferation or prevent apoptosis. Building upon our historical strengths in automated screening, combinatorial chemistry and lead profiling, we have been partnering extensively with academic institutions and biotech companies to create a comprehensive technology and knowledge base for our research organization. The group also chalked up its first success this year moving our dual c-kit/KDR co-inhibitor program to the IND-track stage of development. c-kit and KDR are both receptor tyrosine kinases which function as key regulators in the control of small cell lung cancer growth and angiogenesis respectively. In Conclusion Performance has been the key to another busy and successful year at OSI. The Company is now well positioned as a world-class oncology franchise with the ability to meet the challenges inherent in a competitive marketplace. We are entering 2004 with a high degree of optimism in our prospects of success with Tarceva™, a robust cash position, two marketed products and a solid pipeline. As we move forward, our commitment to you, our shareholders, is that we will continue to build an enduring company with the capacity to discover, develop and commercialize high-quality oncology products that will both extend life and improve the quality-of-life for cancer patients around the world. |
