HAYWARD, Calif., April 18 /PRNewswire-FirstCall/ -- Kosan Biosciences
Incorporated (Nasdaq: KOSN) 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.
About Kosan
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.
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 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.
SOURCE Kosan Biosciences Incorporated
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Related links:
http://www.kosan.com/
CONTACT:
Jane Green, VP, Corporate Communications of
Kosan Biosciences, +1-510-731-5335, or mobile, +1-415-652-4819,
or green@kosan.com
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