Kosan Presents Preclinical Data on Nuclear Export Inhibitors, Novel Anticancer Agents, at AACR
HAYWARD, Calif., April 16, 2008 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated presented preclinical data on its proprietary nuclear export inhibitors (NEI) showing potent in vitro and in vivo activity as well as tolerability in leukemia xenograft models, and further elucidating the NEI anticancer mechanism of action correlating inhibition of the target CRM1 with induction of apoptosis selectively in cancer cells compared to normal cells. Data on Kosan's NEIs were presented at the 2008 Annual Meeting of the American Association for Cancer Research (AACR), being held in San Diego, CA.
Kosan's NEIs are potent, specific inhibitors of CRM1, a highly conserved, essential protein that exports key regulatory proteins ("cargo" proteins) from the nucleus to the cytoplasm. Many cargo proteins that depend on CRM1 for nuclear export, such as p53, Bcr-Abl and FOXO-3a, function as tumor suppressors or transcription factors that protect normal cells by regulating cell growth and apoptosis (cell death). Accumulation of these CRM1 cargo proteins in the nucleus, by blocking nuclear export, leads to the inhibition of cell growth and apoptosis selectively in cancer cells. Kosan's polyketide-based NEI compounds have optimized pharmaceutical properties, including potency, durability of action and a wide therapeutic index.
"Kosan's NEI preclinical compounds continue to demonstrate attractive biological and pharmacological properties and potent anticancer activity and tolerability in both solid and liquid tumors," said Helen S. Kim, Kosan's President and Chief Executive Officer. "We are currently seeking a development partner for our NEI program, as we believe that the optimal strategy for continuing to explore the therapeutic utility of these unique compounds is with an oncology collaborator committed to initiating an NEI clinical program in the near-term."
Abstract 1591: "Mechanistic Analyses of the Therapeutic Activity of Nuclear Export Inhibitors (NEIs) in Cancer" presented data demonstrating a direct correlation between target (CRM1) occupancy and the downstream consequences of CRM1 inhibition, including nuclear export inhibition and cytotoxicity. Exposure of NEIs to cancer cell lines with normal (wild-type) p53 results in upregulation of p53, while only a transient upregulation of p53 is observed in normal cells exposed to NEIs. In cancer cell lines harboring PTEN mutations, NEI-induced nuclear entrapment of FOXO, which is regulated by the PTEN/PI3K/Akt pathway, is directly linked to the induction of apoptosis. NEIs induce apoptosis in tumor derived cell lines but not in normal cells, further confirming the hypothesis of the novel, potent and selective anticancer activity of NEIs.
Abstract 5688: "Anti-Tumor Activity of Novel Nuclear Export Inhibitors (NEIs) in Multiple Murine Leukemia Models" presented data from NEI compounds tested in murine models of leukemia, including acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) models. KOS-2464, Kosan's lead preclinical NEI compound induced marked and durable antitumor responses, including a doubling of survival in an orthotopic ALL model. KOS-2464 was well-tolerated at efficacious doses in all of the leukemia models tested.
Kosan Biosciences is a biotechnology company advancing two new classes of anticancer agents through clinical development -- a Hsp90 (heat shock protein 90) inhibitor and an epothilone. Hsp90 inhibitors have a novel mechanism of action targeting multiple pathways involved in cancer cell growth and survival. Tanespimycin (KOS-953) is being tested in combination with Velcade(R) (bortezomib) in patients with multiple myeloma in a clinical program called TIME. Tanespimycin is also being studied in HER2-positive metastatic breast cancer in combination with Herceptin(R) (trastuzumab). Epothilones inhibit cell division with a mechanism of action similar to taxanes, one of the most successful classes of anti-tumor agents. KOS-1584 is in Phase 1 clinical trials in patients with solid tumors. Kosan's motilin agonist compound, KOS-2187, licensed to Pfizer for development in gastroesophagel reflux disease, is in a Phase 1 trial.
This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995 (the "Act"). Such forward-looking statements include but are not limited to statements regarding the further development and potential safety, efficacy, regulatory status, commercial potential and other characteristics of Kosan's product candidates; the continuation of current clinical trials; the initiation of additional clinical trials and the timing thereof and the use of Kosan's financial resources. Words such as "will," "expect," "believe," "may," "intend," "plan," "potential" and similar expressions are intended to identify forward-looking statements. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements are based upon Kosan's current expectations. Forward-looking statements involve risks and uncertainties. Kosan's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to the uncertain progress and results of Kosan's preclinical and clinical testing, including the risks that studies and trials may not demonstrate safety and efficacy sufficient to initiate clinical trials on the timing currently anticipated, or at all, continue clinical development, obtain the requisite regulatory approvals or result in a marketable product; the conduct of clinical trials; manufacturing; regulatory approval requirements and process; the effort and expense necessary for further development of Kosan's product candidates, including the costs of bortezomib; intellectual property matters, including Kosan's ability to obtain valid and enforceable patents covering its product candidates; Kosan's dependence on its collaboration with Pfizer for development of its motilin agonist product candidate; Kosan's need for additional financing and Kosan's strategy to enter into partnering or licensing arrangements. These and other risk factors are discussed under "Risk Factors" in Kosan's Annual Report on Form 10-K for the year ended December 31, 2007 and other periodic filings with the SEC. Kosan expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein.
Velcade(R) (bortezomib) is a registered trademark of Millennium Pharmaceuticals, Inc.
Herceptin(R) (trastuzumab) is a registered trademark of Genentech, Inc.
Posted: April 2008