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Kosan Presents Preclinical Data on Nuclear Export Inhibitors, Novel Anticancer Agents, at AACR
Date:4/16/2008

ility 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.

About Kosan

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. Tane
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SOURCE Kosan Biosciences Incorporated
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