Sunesis Pharmaceuticals Presents Nonclinical Data on SNS-595 at the Annual Meeting of the American Association for Cancer Resear
15 April 2008 - 7:05AM
PR Newswire (US)
Nonclinical Studies Demonstrate that SNS-595 Acts through a Dual
Mechanism and May Evade Common Drug Resistance Mechanisms SOUTH SAN
FRANCISCO, Calif., April 14 /PRNewswire-FirstCall/ -- Sunesis
Pharmaceuticals, Inc. (NASDAQ:SNSS) today presented nonclinical
data on SNS-595's unique mechanism of action and its anticancer
activity at the Annual Meeting of the American Association for
Cancer Research (AACR) in San Diego, CA. A Phase 2 single agent
clinical trial of SNS-595 in ovarian cancer and a Phase 1b clinical
trial of SNS-595 in combination with cytarabine in
relapsed/refractory acute myeloid leukemia (AML) are both ongoing.
"Data presented today provide important new insights into SNS-595's
mechanism as a site-selective DNA intercalator and topoisomerase
poison with selectivity for proliferating cells. Through its unique
chemical structure and molecular mechanism, SNS-595 avoids common
drug resistance pathways and may have advantages over other
topoisomerase poisons," said Daniel C. Adelman, M.D., Senior Vice
President, Development and Chief Medical Officer. "Taken together,
these data support our ongoing clinical trials of SNS-595 in
platinum-resistant ovarian cancer and acute myeloid leukemia, and
provide compelling evidence for future studies of SNS-595 in
indications such as breast cancer where topoisomerase II poisons
are active." Sunesis researchers conducted in vitro and cell-based
studies elucidating SNS-595's mechanism of action. SNS-595
selectively intercalates DNA and poisons topoisomerase II,
resulting in replication-dependent DNA damage, irreversible G2
arrest and rapid apoptosis. SNS-595's targeted DNA-topoisomerase II
interactions may contribute to the broad therapeutic window
observed in patients treated with SNS-595. In a translational
research study designed to evaluate SNS-595's activity in primary
patient samples of breast and ovarian cancers and acute myeloid
leukemia against other agents, SNS-595 demonstrated potent activity
and compared favorably with doxorubicin, etoposide and platinum
therapy at clinically relevant concentrations. SNS-595 is not a
P-glycoprotein substrate and its activity is independent of the p53
family. This finding is noteworthy, as high or increased expression
of P-glycoprotein is a common form of drug resistance. In addition,
the activity of many cancer agents requires functional p53 family
members, and p53 mutations or deletions are also a frequent cause
of drug resistance. Based on these findings, evidence from prior
nonclinical studies in drug-resistant tumor models and the
objective clinical responses observed to date among patients who
have failed prior anthracycline-based therapies, SNS-595 may be
active in settings where other topoisomerase poisons are no longer
effective. These findings support the ongoing clinical trials in
AML and ovarian cancer, and indicate that SNS-595 may also be
well-suited to the treatment of breast cancer. In a third set of
studies reported today, Sunesis researchers profiled the potential
relationship between SNS-595 activity and DNA repair pathways.
Since SNS-595 causes double-strand breaks, the integrity of DNA
repair pathways could impact cell sensitivity to SNS-595.
Identification of the role of various DNA repair pathways may
contribute to the identification of biomarkers for patient
stratification. Researchers found that the DNA damage induced by
SNS-595 is repaired by homologous recombination repair (HRR), and
that cells deficient in HRR have greater sensitivity to SNS-595.
Breast and ovarian cancers with BRCA mutations have compromised HRR
and may be particularly sensitive to SNS-595. Data from these
nonclinical studies of SNS-595 were presented today at the AACR
Annual Meeting in three posters: -- SNS-595 is a potent anti-tumor
agent that has a dual mechanism of action: DNA intercalation and
site-selective topoisomerase II poisoning [Abstract #1860] -- Ex
vivo activity of SNS-595 against biopsies of acute myeloid
leukemia, triple negative breast and ovarian cancers supports
ongoing and potential clinical [Abstract #2830] -- Sensitivity to
SNS-595 is related to activation of double strand DNA break repair
pathways including homologous recombination [Abstract #1859]
SNS-595 is a novel naphthyridine analog, structurally related to
quinolones, a class of compounds which has not been used previously
in the treatment of cancer. About Sunesis Pharmaceuticals Sunesis
is a clinical-stage biopharmaceutical company focused on the
discovery, development and commercialization of novel small
molecule therapeutics for oncology and other serious diseases.
Sunesis has built a broad product candidate portfolio through
internal discovery and in-licensing of novel cancer therapeutics.
Sunesis is advancing its product candidates through in-house
research and development efforts and strategic collaborations with
leading pharmaceutical and biopharmaceutical companies. For
additional information on Sunesis Pharmaceuticals, please visit
http://www.sunesis.com/. SUNESIS and the logo are trademarks of
Sunesis Pharmaceuticals, Inc. Safe Harbor Statement This press
release contains forward-looking statements including without
limitation statements related to the potential efficacy, mechanism
of action and benefits of SNS-595, and the potential for SNS-595 to
be tested in other indications. Words such as "may," "potential,"
"could" and similar expressions are intended to identify
forward-looking statements. These forward-looking statements are
based upon Sunesis' current expectations. Forward-looking
statements involve risks and uncertainties. Sunesis' 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, the
risk that Sunesis' drug discovery and development activities,
including enrollment and reporting of results, could be halted
significantly or delayed for various reasons, the risk that
Sunesis' clinical trials for SNS-595 may not demonstrate safety or
efficacy or lead to regulatory approval, the risk that preliminary
data and trends may not be predictive of future data or results,
the risk that Sunesis' preclinical studies and clinical trials may
not satisfy the requirements of the FDA or other regulatory
agencies, risks related to the conduct of Sunesis' clinical trials
and manufacturing of SNS-595 and risks related to Sunesis' need for
additional funding. These and other risk factors are discussed
under "Risk Factors" and elsewhere in Sunesis' annual report on
Form 10-K for the year ended December 31, 2007 and other filings
with the Securities and Exchange Commission. Sunesis expressly
disclaims any obligation or undertaking to release publicly any
updates or revisions to any forward-looking statements contained
herein to reflect any change in the company's expectations with
regard thereto or any change in events, conditions or circumstances
on which any such statements are based. DATASOURCE: Sunesis
Pharmaceuticals, Inc. CONTACT: Investors, Eric Bjerkholt, SVP,
Corp. Development & Finance of Sunesis Pharmaceuticals, Inc.,
+1-650-266-3717; or Media, Karen L. Bergman, +1-650-575-1509, or
Michelle Corral, +1-415-794-8662, both of BCC Partners, for Sunesis
Pharmaceuticals, Inc. Web site: http://www.sunesis.com/
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