Kosan Presents Preclinical Data on Novel Third-Generation Hsp90 Inhibitors at AACR
16 Abril 2008 - 6:09PM
PR Newswire (US)
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. DATASOURCE: Kosan Biosciences Incorporated CONTACT: Jane
Green, VP, Corporate Communications of Kosan Biosciences
Incorporated, +1-510-731-5335, mobile, +1-415-652-4819, Web site:
http://www.kosan.com/
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