Kosan Presents Preclinical Data on Nuclear Export Inhibitors, Novel Anticancer Agents, at AACR
Wednesday April 18, 11:00 am ET
HAYWARD, Calif., April 18 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN - News) 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. |
