– Results Suggest Targeting Hsp90 May Inhibit Angiogenesis without
Tumor Rebound Effects Associated with VEGF-Targeted Anti-angiogenic
Therapies –
– Support Rationale for Combining Ganetespib with Standard
Anti-angiogenic Agents –
LEXINGTON, Mass.--(BUSINESS WIRE)--Jul. 17, 2013--
Synta Pharmaceuticals Corp. (NASDAQ: SNTA) announced today publication
of results from in vitro, in vivo, and translational clinical studies
demonstrating the effect of ganetespib on the ability of tumors to grow
new blood vessels (angiogenesis). The paper appeared in the July 10,
2013, online issue of Angiogenesis.
Ganetespib, a selective inhibitor of the Hsp90 chaperone protein in
development by Synta, is being evaluated in over 20 clinical trials for
different types of cancer, including a pivotal Phase 3 trial in
non-small cell lung cancer.
“To date two therapeutic strategies have been established for inhibiting
new tumor blood vessel formation: agents that bind directly to
vasculature growth factors (e.g., VEGF), or agents that bind to their
cellular receptors (e.g., VEGFR),” said Dr. Bassel El-Rayes, Director of
the GI Oncology Translational Research Program, Winship Cancer
Institute, Emory University and senior author of the paper. “The results
published this week show that ganetespib may offer a third way to
suppress angiogenesis: inhibiting the transcription factors that turn on
production of VEGF and other pro-angiogenic factors. This is like
turning off the faucet at the source, rather than trying to empty the
sink once it is full.”
The publication describes results from preclinical studies and a rectal
cancer clinical trial conducted at Emory University showing that
ganetespib simultaneously downregulates the expression of many cellular
proteins involved in new blood vessel formation, including VEGF, PDGFA,
FGF2, Ang-1, Ang-2, TGFb1, HIF-1a, and STAT-3.
“Targeting angiogenesis with anti-VEGF therapies has demonstrated
meaningful clinical benefit, but has also been associated with greater
disease aggressiveness and metastasis from increased expression of
VEGF-A and activation of HIF-1a in the hypoxic tumor,” said Dr.
El-Rayes. “These studies show that the unique mechanism of action of
ganetespib may provide a means to downregulate angiogenesis without
upregulating HIF-1a activation and VEGF expression. These effects
strongly support the rationale to combine ganetespib with standard
anti-angiogenic agents.”
Previously presented results showed synergistic activity of ganetespib
and the anti-angiogenic agent bevacizumab, an antibody targeting VEGF,
in preclinical models of cancer.
About Ganetespib
Ganetespib, an investigational drug candidate, is a selective inhibitor
of heat shock protein 90 (Hsp90), a molecular chaperone which controls
the folding and activation of a number of client proteins that drive
tumor development and progression. Many solid and hematologic tumors are
dependent on Hsp90 client proteins including proteins involved in
“oncogene addiction” (ALK, HER2, mutant BRAF and EGFR, androgen
receptor, estrogen receptor, JAK2); proteins involved in resistance to
chemotherapy and radiation therapy (ATR, BCL2, BRCA1/2, CDK1/4, CHK1,
survivin, and WEE1); proteins involved in angiogenesis (HIF-1alpha,
VEGFR, PDFGR, and VEGF); and proteins involved in metastasis (MET, RAF,
AKT, MMPs, HIF-1alpha, and IGF-1R). In preclinical models, inhibition of
Hsp90 by ganetespib results in the inactivation, destabilization, and
eventual degradation of these cancer-promoting proteins. Ganetespib is
being evaluated in over 20 clinical trials including trials in lung,
breast, colorectal, and hematologic malignancies. Information on these
trials can be found at www.clinicaltrials.gov.
About Synta Pharmaceuticals
Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on
discovering, developing, and commercializing small molecule drugs to
extend and enhance the lives of patients with severe medical conditions,
including cancer and chronic inflammatory diseases. Synta has a unique
chemical compound library, an integrated discovery engine, and a diverse
pipeline of clinical- and preclinical-stage drug candidates with
distinct mechanisms of action and novel chemical structures. All Synta
drug candidates were invented by Synta scientists using our compound
library and discovery capabilities. For more information, please visit www.syntapharma.com.
Safe Harbor Statement
This media release may contain forward-looking statements about Synta
Pharmaceuticals Corp. Such forward-looking statements can be identified
by the use of forward-looking terminology such as "will", "would",
"should", "expects", "anticipates", "intends", "plans", "believes",
"may", "estimates", "predicts", "projects", or similar expressions
intended to identify forward-looking statements. Such statements,
including statements relating to the developments and progress of our
clinical and preclinical programs, reflect our current views with
respect to future events and are based on assumptions and subject to
risks and uncertainties that could cause actual results to differ
materially from those expressed or implied by such forward-looking
statements, including those described in "Risk Factors" of our Form 10-K
for the year ended December 31, 2012 as filed with the Securities and
Exchange Commission. Synta undertakes no obligation to publicly update
forward-looking statements, whether because of new information, future
events or otherwise, except as required by law.
Source: Synta Pharmaceuticals Corp.
Investor Relations Contacts:
Synta Pharmaceuticals Corp.
George
Farmer, 781-541-7213
gfarmer@syntapharma.com
or
Argot
Partners
Andrea Rabney, 212-600-1494
andrea@argotpartners.com
