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Kosan Presents Preclinical Data on Novel Third-Generation Hsp90 Inhibitors at AACR
Date:4/16/2008

HAYWARD, Calif., April 16 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN) presented data on its novel, proprietary third-generation Hsp90 inhibitors demonstrating a high degree of target specificity, strong binding affinity and potency, a long lifetime in tumor tissue and significant antitumor activity and safety in murine xenograft and orthotopic models.

Hsp90 is a protein chaperone that acts to stabilize and/or activate a number of proteins required for cellular signaling pathways, including several known determinants of carcinogenesis such as HER2 (Erb2), B-Raf, c-Kit, Flt-3 and Raf-1. Hsp90 is effectively inhibited by benzoquinone ansamycins, such as geldanacmycin and its derivatives, which bind to the ATP binding site in the N-terminal domain. Kosan's lead Hsp90 inhibitor, tanespimycin (17-AAG), is a geldanamycin derivative. Kosan's third-generation Hsp90 inhibitors are non-benzoquinone ansamycins that have been genetically engineered to retain a high degree of specificity of tanespimycin for the ATP binding pocket of Hsp90 yet do not rely upon activation of the quinone moiety for maximal inhibitor activity. These third-generation Hsp90 inhibitors are highly potent molecules in tumor models with properties that significantly distinguish them from other Hsp90 inhibitors.

"Kosan's third-generation Hsp90 inhibitors expand our Hsp90 portfolio, and represent opportunities for product diversification and life-cycle extension," said Helen S. Kim, Kosan's President and Chief Executive Officer. "Developing tanespimycin, our first generation Hsp90 inhibitor, in multiple myeloma and in breast cancer, is Kosan's highest priority. We believe that our next-generation molecules add value to our Hsp90 program and enhance its attractiveness to potential oncology partners."

Data on Kosan's third-generation Hsp90 inhibitors were presented in two posters at the 2008 Annual Meeting of the American Association for Cancer Research (AACR), being held in San Diego, CA.

Abstract 5636, "Correlation between In Vitro and In Vivo Activities of Hsp90 Inhibitors," presented data showing the KOS-2484, Kosan's lead non-benzoquinone ansamycin, has demonstrated the tightest binding affinity for Hsp90 reported to date, accumulates in tumor cells and has superior retention properties leading to a long lifetime in tumor tissue. These properties of KOS-2484 result in this molecule showing pronounced efficacy in multiple preclinical tumor models.

Abstract 5630, "Anti-Tumor Activity of Non-Benzoquinone Ansamycin Hsp90 Inhibitors in Murine Xenograft Models," presented data showing that KOS-2484 induces tumor regression at well-tolerated doses in xenograft models of both liquid and solid tumors, including acute myelogenous leukemia (AML), multiple myeloma and colon cancer models. Most notably, KOS-2484 demonstrated almost complete regression of very large (1000 mm3) AML xenografts when dosed on an infrequent (twice a week) schedule. KOS-2484 also prolongs survival in a mouse orthotopic model of AML. These findings underscore that KOS-2484, Kosan's lead non-benzoquinone ansamycin Hsp90 inhibitor, has significant potential as a novel anticancer agent.

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. 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. For additional information on Kosan Biosciences, please visit the company's website at http://www.kosan.com.

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.


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SOURCE Kosan Biosciences Incorporated
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