MONTREAL, Sept. 12 /PRNewswire-FirstCall/ -- Kosan Biosciences
Incorporated (Nasdaq: KOSN) today presented here at the World Congress of
Gastroenterology 2005 preclinical data supporting the selection of KOS-2187, a
novel erythromycin-based motilin agonist, or motilide, as a clinical candidate
for the treatment of gastrointestinal motility disorders such as gastroparesis
and gastroesophageal reflux disease (GERD).
Erythromycin is an effective treatment for gastroparesis; however, some of
its properties, including antibiotic activity, are not appropriate for a drug
designed for chronic use over a patient's lifetime. Earlier efforts to
produce erythromycin analogs with reduced antibiotic activity resulted in
compounds that lost efficacy in repeated dosing regimens (tachyphylaxis).
These compounds also block the hERG channel in the heart, a finding associated
with an increased risk for dangerous arrhythmias, or irregular heart rhythms.
In one presentation ("KOS-2187: An Orally Active Motilin Agonist with an
Improved Safety Profile," Abstract #LB-015), Kosan scientists describe the
properties of KOS-2187 that make it an optimal candidate for further
development. KOS-2187 is a potent motilin agonist that lacks undesirable
antibiotic activity and retains activity in a model of tachyphylaxis. In
vitro studies indicate that KOS-2187 is at least 20-fold more potent as a
motilin agonist than erythromycin and has a 10-fold weaker affinity for the
hERG channel than erythromycin. Testing in a validated dog model showed that
KOS-2187 has high oral bioavailability, is rapidly absorbed, and significantly
accelerates gastric emptying.
"These results demonstrate that KOS-2187 addresses the serious limitations
of first-generation erythromycin analogs," said Pieter Timmermans, Kosan
Senior Vice President, Preclinical Development. "We have initiated studies to
support the entry of this compound into human clinical trials, expected to
begin in the second half of 2006."
A second presentation ("Optimized Motilin Agonist Prokinetics," Abstract
#DR-0158) describes the approach employed by Kosan scientists to design safe
and effective motilin agonists. Early erythromycin derivatives with high
potency, reduced antibiotic activity, and decreased tachyphylaxis were used as
scaffolds for structural optimization to reduce the hERG interaction and
further decrease the potential for tachyphylaxis. Resulting lead candidates
were evaluated in a series of in vitro assays that demonstrated negligible
antibiotic activity, minimal tachyphylaxis, and a five- to 40-fold greater
potency over erythromycin. In addition, the lead candidates had significantly
lower effects of hERG channel inhibition than erythromycin. In vivo studies
confirmed oral availability and the ability to accelerate gastric emptying.
About Kosan
Kosan Biosciences currently has two first-in-class anticancer agents in
Phase II and Phase Ib clinical trials: KOS-862 (Epothilone D) and 17-AAG, an
Hsp90 (heat shock protein 90) inhibitor and geldanamycin analog. Kosan's most
advanced compound, KOS-862, which is in two Phase II clinical trials and
multiple Phase Ib clinical trials, and its follow-on compound, KOS-1584, which
is in Phase I clinical trials, are partnered with Roche through a global
development and commercialization agreement. Kosan is developing 17-AAG and a
second-generation geldanamycin analog, KOS-1022 (DMAG), that is in Phase I
clinical trials, in collaboration with the NCI. Kosan is also conducting Phase
I and Phase Ib clinical trials of its proprietary formulation of 17-AAG, KOS-
953. Kosan has generated a pipeline of additional product candidates for
gastrointestinal motility, infectious diseases and cancer based on its
proprietary technologies for discovering, developing and manufacturing
polyketide analogs. All of Kosan's product candidates, including those in
clinical development, are polyketides. Polyketides are an important class of
natural products that have yielded numerous pharmaceuticals for the treatment
of cancer, infectious diseases, high cholesterol, transplant rejection and
other diseases. For additional information on Kosan Biosciences, please visit
the Company's website at http://www.kosan.com.
This press release contains "forward-looking" statements, including
statements with respect to the further development and potential safety and
efficacy of KOS-2187 or Kosan's other motilin agonists in the treatment of
gastrointestinal disorders and the timing for initiation of clinical trials
for KOS-2187. 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 and uncertainties related to preclinical
testing of KOS-2187 or Kosan's other motilin agonists; the risk that the
advancement of KOS-2187 into clinical trials results may be delayed or
prevented due to the results of further testing of KOS-2187, financial
considerations or other reasons; and other risks detailed from time to time
in the Company's SEC reports, including its Quarterly Report on Form 10-Q for
the quarter ended June 30, 2005 and other periodic filings with the SEC. Kosan
does not undertake any obligation to update forward-looking statements.
SOURCE Kosan Biosciences Incorporated
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Related links:
http://www.kosan.com
CONTACT:
Susan M. Kanaya, Chief Financial Officer of
Kosan Biosciences Incorporated+1-510-732-8400, ext. 5227, or
kanaya@kosan.com
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