-Results support elesclomol results seen in human clinical trials-
-Elesclomol clinical trials on-going in acute myeloid leukemia and
ovarian cancer-
LEXINGTON, Mass.--(BUSINESS WIRE)--Jan. 12, 2012--
Synta Pharmaceuticals Corp. (NASDAQ: SNTA) – A
report published in the peer-reviewed journal PLoS ONE demonstrate
how a novel yeast screening platform pioneered by researchers at the
University of Toronto was used to elucidate the mechanism of action of
elesclomol, a first-in-class drug that targets cancer cell metabolism
and is currently being clinically developed by Synta Pharmaceuticals
Corp. of Lexington, Massachusetts. Elesclomol is currently in clinical
trials in both solid tumor and hematologic cancers, including a study in
combination with paclitaxel in ovarian cancer and a single agent study
in acute myeloid leukemia (AML) currently being conducted at Princess
Margaret Hospital in Toronto.
“Elesclomol was previously shown to work by increasing the levels of
reactive oxygen species to untenable levels causing cancer cell death,
however details of how this occurs were unclear,” said Corey Nislow,
Ph.D, Assistant Professor, Department of Molecular Genetics, University
of Toronto. “It was critical to understand the mechanism of action of
elesclomol because in clinical trials, a substantial subset of patients
responded to treatment whereas others did not. Using our yeast-based
chemogenomic screening platform and subsequent follow-up work in human
cancer cells, we were able to clearly show that elesclomol works in the
cell’s mitochondrion, where it interacts with the electron transport
chain to cause rapid cell death. Our paper suggests that this
interaction initiates redox reactions within the mitochondrion that
induce a surge of reactive oxygen species resulting in cancer cell
apoptosis. In clinical terms, this improved understanding of how
elesclomol works has allowed Synta, the drug’s developer, to better
select patients who may respond to this novel therapy in their on-going
clinical trials.”
Dr. Nislow added that the collaboration involving the University of
Toronto and Synta is an excellent example of leading academic
institutions working closely with an innovative biotechnology company to
support and accelerate the drug discovery process for the benefit of
patients. The value of this research is being applied directly to the
clinical development of elesclomol today.
“In three previous randomized trials, once-weekly dosing of elesclomol
in combination with paclitaxel demonstrated clear evidence of activity
in patients with low levels of serum lactate dehydrogenase (LDH), a
biomarker associated with tumor hypoxia or low levels of oxygen,” said
Vojo Vukovic, M.D., Ph.D, Chief Medical Officer, Synta. “The improved
understanding of the mechanism of action of elesclomol based on the
research conducted at the University of Toronto, and our ability to
identify patients who are most likely to benefit from treatment suggests
a potentially wide application of elesclomol in a range of human
cancers. The results which were published today allowed us to map a path
forward in the clinical development of elesclomol both as a single agent
and in combination with other anti-cancer agents.”
About the Yeast-based Chemogenomic Screening Platform
The Nislow and Giaever labs at the University of Toronto have developed
an automated drug interrogation platform that relies on the model
organism, baker’s yeast. Each gene in the genome of Saccaromyces
cerevisiae has been systematically deleted and genetically bar coded
with two DNA barcodes that allow rapid chemical screening against these
mutants in parallel. These assays allow, in a single experiment, the
identification of all genes required for survival in any condition (i.e.
during drug treatment), resulting in a prioritized ranking of ALL genes
according to how important they are for responding to the drug
treatment. We have used this assay to understanding how thousands of
compounds affect cell growth, including many FDA-approved drugs. More
recently, the Nislow and Giaever labs have embarked on tackling
promising drugs for which the exact mechanism of their action is not
clear. These efforts are aided by virtue of the fact that thousands of
“chemical genomic” drug signatures are held in the University of Toronto
database against which novel compounds can be compared.
About Elesclomol
Elesclomol is a first-in-class, investigational drug candidate that
triggers programmed cell death (apoptosis) in cancer cells through a
novel mechanism: selectively targeting the electron transport chain in
cancer cell mitochondria, disrupting cancer cell energy metabolism.
Mitochondria generate energy for cells, but also can induce apoptosis
under certain conditions, such as a high level of oxidative stress. By
sensitizing mitochondria and reducing barriers to apoptosis, elesclomol
may provide a means to overcome resistance to traditional chemotherapy
or targeted therapy.
Cancer cell mitochondria can be selectively targeted by elesclomol
because cancer cell mitochondria are structurally and functionally
different from their normal counterparts, making them more susceptible
to changes to mitochondrial metabolism.
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.
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Pharmaceuticals Corp. Such forward-looking statements can be identified
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including statements relating to the timing, developments and progress
of our clinical and preclinical programs, reflect our current views with
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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, 2010 as filed with the Securities and
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Source: Synta Pharmaceuticals Corp.
Synta Pharmaceuticals Corp.
Rob Kloppenburg, 781-541-7125