Synta Pharmaceuticals Corp. (NASDAQ: SNTA) today announced that results
pre-published in the online edition of the journal Blood show
that STA-9090 causes degradation of the Wilms' tumor 1 (WT1) protein and
its downstream target proteins, c-Myc and Bcl-2, key factors in acute
myeloid leukemia (AML) and certain other leukemias; and that treatment
with STA-9090 showed strong activity in both in vitro and in
vivo models of AML both as single agent and in combination with
chemotherapy. STA-9090, a potent, second-generation, small-molecule
Hsp90 inhibitor, is currently being evaluated in two clinical trials in
AML and other hematologic cancers.
?AML is a disease with very limited treatment options, which have not
changed in decades, and an urgent medical need,? said Vojo Vukovic,
M.D., Ph.D., Senior Vice President and Chief Medical Officer, Synta
Pharmaceuticals. ?The results presented in Blood provide insight
into both the underlying biology of what drives AML and the potential
role that STA-9090 may play in treating this disease. We look forward to
fully evaluating the role STA-9090 may play in AML and other hematologic
indications.?
?WT1 gene expression is known to be a prognostic factor that correlates
with survival in myeloid leukemia patients,? said hematologist
Swaminathan Padmanabhan, M.D., the Principal Investigator of this
preclinical work. Dr. Padmanabhan is an assistant professor with the
Cancer Therapy & Research Center (CTRC) at The University of Texas
Health Science Center at San Antonio and serves as director of
hematological malignancies for the CTRC Institute for Drug Development.
?Our work shows for the first time that this important oncoprotein
directly interacts with and is regulated by the Hsp90 chaperone complex.
In these studies, inhibition of Hsp90 by STA-9090 potently
down-regulated WT1 expression and also enhanced the activity of
etoposide, a topoisomerase II inhibitor that is used in the treatment of
hematologic and solid tumor cancers. These results suggest a possible
role for STA-9090 in the treatment of leukemias both as a single agent
and in combination with other anticancer agents.?
In in vitro experiments, STA-9090 reduced the expression of WT1
in a dose-dependent manner and induced apoptosis in myeloid leukemia
cells, and the combination of STA-9090 and etoposide displayed enhanced
cytotoxicity relative to either agent alone. In vivo results
demonstrated inhibition of Hsp90 by STA-9090 blocked tumor growth in
multiple xenograft tumor models using leukemia cells expressing WT1.
Importantly, WT1 down-regulation by STA-9090 was also observed in
primary myeloid leukemic blast cells isolated from AML patients.
The article can be found at http://bloodjournal.hematologylibrary.org/cgi/content/abstract/blood-2009-10-247239v1.
About STA-9090
STA-9090 is a potent, second-generation, small-molecule Hsp90 inhibitor,
with a chemical structure unrelated to the first-generation, ansamycin
family of Hsp90 inhibitors (e.g., 17-AAG or IPI-504). In preclinical
studies, STA-9090 has shown potency up to 100 times greater than the
first-generation Hsp90 inhibitors as well as activity against a wider
range of kinases. In in vitro and in vivo models, STA-9090
has shown potent activity against a wide range of cancer types,
including lung, prostate, colon, breast, gastric, pancreatic,
gastrointestinal stromal tumors (GIST), melanoma, AML, chronic myeloid
leukemia, Burkitt's lymphoma, diffuse large B-cell lymphoma, and
multiple myeloma – as well as potent activity against cancers resistant
to imatinib (Gleevec®), sunitinib (Sutent®),
erlotinib (Tarceva®), and dasatinib (Sprycel®).
STA-9090 is currently being evaluated in eight clinical trials: four
Phase 2 trials in solid tumor cancers – non-small cell lung cancer,
gastrointestinal stromal tumors, colon cancer, gastric cancer; two
trials in hematologic cancers; and two Phase 1 solid tumor trials.
Trials in colon cancer and gastric cancer are investigator-sponsored.
Information on clinical trials with STA-9090 can be found at www.clinicaltrials.gov.
About Hsp90
Hsp90 is a chaperone protein required for the proper folding and
activation of other cellular proteins, particularly kinases. Many of
these ?client proteins? of Hsp90 – such as AKT, BCR-ABL, BRAF, KIT, MET,
EGFR, FLT3, HER2, PDGFRA, VEGFR – have been shown to be critical to
cancer cell growth, proliferation, and survival and are the targets of
clinically validated cancer drugs. In preclinical studies, inhibiting
Hsp90 causes the degradation of multiple client proteins and leads to
cancer cell death. Because mutated kinases which no longer respond to
treatment with kinase inhibitors remain dependent on Hsp90 for their
activity, inhibiting Hsp90 offers the potential for treating cancers
that have become resistant to targeted therapies such as kinase
inhibitors.
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 timing, developments and progress
of our STA-9090 clinical program, 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, 2009 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.

Synta Pharmaceuticals Corp.
Rob Kloppenburg, 781-541-7125