Kosan Presents Preclinical Data on Nuclear Export Inhibitors, Novel Anticancer Agents, at AACR
HAYWARD, Calif., April 18, 2007 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated today presented preclinical data on its proprietary nuclear export inhibitors (NEI) showing induction of potent, fast-acting and long-lasting anticancer activity with a high degree of tolerability in multiple human tumor xenograft cancer models.
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 anticipates becoming the first company to advance a nuclear export inhibitor into clinical development.
"We believe that Kosan has established an industry-leading position in NEI technology and has the only NEI inhibitor in late-stage preclinical development," said Pieter B.M.W.M. Timmermans, Ph.D., Kosan's Senior Vice President, Drug Discovery and Preclinical Development. "Our NEIs have demonstrated potent anticancer activity in human tumor xenograft models of breast, cervical, colon and non-small cell lung cancers, melanoma and leukemia, and have been shown to have robust efficacy in vivo at doses that are well-tolerated. We believe that NEIs represent a novel mechanism of action and have the potential to work additively and synergistically with a broad spectrum of cancer chemotherapies such as DNA-damaging agents that have limited durability of effect. We anticipate selecting a lead candidate from our family of NEIs to advance into investigational new drug (IND) enabling studies in the near term."
Data on Kosan's NEIs were presented in two posters at the 2007 Annual Meeting of the American Association for Cancer Research (AACR), being held in Los Angeles, CA.
-- Abstract 5609: "Nuclear Export Inhibitors (NEIs) as Novel Cancer Therapeutics" presents results from analyses of the in vitro activity of NEIs showing that upon the addition of low nanomolar concentrations of polyketide-based nuclear export inhibitors to cancer cells, the accumulation of CRM1-dependent cargo proteins sequestered in the nucleus is detected rapidly. Results also show that exposure to NEIs causes an increase in multiple markers of apoptosis including plasma membrane alterations (Annexin V binding) and caspase activation in cancer cells. NEI treatment induces cell cycle arrest, but not apoptosis, in normal cells. NEIs show potent activity as single agents in in vivo tumor models and may also have application in combination therapies as NEIs are synergistic when combined with a broad spectrum of cancer therapeutics in in vitro experiments. -- Abstract 5597: "Anti-Tumor Activity of Novel Nuclear Export Inhibitors (NEIs) in Multiple Xenograft Models" presents data on two members of Kosan's lead NEI series which are shown to have a wide therapeutic window in several in vivo xenograft models, including human tumor xenograft models of cervical cancer, colon cancer, breast cancer, non-small cell lung cancer, melanoma and leukemia. Kosan's lead NEI analogs have a high level of tolerability and demonstrated efficacy, and represent potentially novel anticancer agents.
Kosan Biosciences is a biotechnology company advancing two new classes of anticancer agents through clinical development -- Hsp90 (heat shock protein 90) inhibitors and epothilones. Kosan is leveraging its proprietary discovery platform to generate a pipeline of potentially significant product candidates, primarily in the area of oncology.
Hsp90 inhibitors have a novel mechanism of action targeting multiple pathways involved in cancer cell growth and survival. Kosan's proprietary formulation of tanespimycin (KOS-953) is currently in Phase 1 and 2 clinical trials, primarily for multiple myeloma in combination with Velcade(R) (bortezomib) and HER2-positive metastatic breast cancer in combination with Herceptin(R) (trastuzumab). In addition, intravenous and oral formulations of Kosan's second-generation Hsp90 inhibitor, alvespimycin (KOS-1022), are being evaluated in Phase 1 clinical trials.
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 epothilone program is partnered with Roche through a global development and commercialization agreement.
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 relating to the further development and potential safety, efficacy and commercialization of Kosan's product candidates; and initiations of pre-clinical and clinical studies and the timing thereof. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. There are a number of important factors that could cause the results of Kosan to differ materially from those indicated by these forward-looking statements, including, among others, risks related to the development of Kosan's product candidates, including the risk that studies may not demonstrate safety and efficacy sufficient to initiate clinical trials, continue clinical development, obtain the requisite regulatory approvals or to result in a marketable product; and other risks detailed from time to time in the Company's SEC reports, including its Annual Report on Form 10-K for the year ended December 31, 2006 and other periodic filings with the SEC. Kosan does not undertake any obligation to update forward-looking statements.
NOTE: Velcade(R) (bortezomib) is a registered trademark of Millennium Pharmaceuticals, Inc.
Herceptin(R) (trastuzumab) is a registered trademark of Genentech, Inc.
Posted: April 2007