�Synta Pharmaceuticals Corp., (NASDAQ: SNTA) proclaimed the publishing of raw findings in the American Association for Cancer Research journal, Molecular Cancer Therapeutics that describe the novel mechanism of action of elesclomol: driving programmed cell death (programmed cell death) in malignant neoplastic disease cells through the selective induction of oxidative strain. Elesclomol is currently in a world, pivotal Phase 3 clinical trial (SYMMETRYSM) in combination with paclitaxel for the treatment of metastatic melanoma.
"These results confirm that elesclomol powerfully and selectively induces programmed cell death in cancer cells by increasing the level of reactive o species (ROS) beyond sustainable levels," aforementioned James Barsoum, Ph.D., Senior Vice President, Research, Synta Pharmaceuticals. "Elevated ROS levels and susceptibility to farther increases in ROS are fundamental characteristics of cancer cells that differentiate them from normal non-cancerous cells. Exploiting this special vulnerability represents a novel approach path to selectively targeting and killing cancer the Crab cells. The findings likewise suggest that elesclomol stool substantially enhance the efficaciousness of certain other antitumour therapies when given in combination. These results collectively indicate the potential of oxidative tension induction as a new therapeutic choice for treating multiple types of cancers, either as a single agent or in combination. We are excited by the potentiality of this new mechanism category, peculiarly for difficult-to-treat cancers such as malignant melanoma that receive not been responsive to chemotherapy or other prior approaches."
Oxidative stress occurs when there is an elevated spirit level of responsive oxygen species (ROS) in cells. Superoxide, hydrogen peroxide and hydroxyl group radicals ar examples of reactive oxygen species. ROS levels commode increase in a sort of situations including exposure to bacteria or viruses, a go up in prison cell proliferation, or an addition in cubicle metabolism. Prolonged exposure to elevated levels of ROS can lead up a episode of protective events culminating in the ultimate self-protection mechanism, programmed cell decease (apoptosis). Normal, non-cancerous cells have a strong antioxidant capacity which guards against excessive levels of ROS. In dividing line, cancer cells operate at a a great deal higher storey of oxidative stress and have a greatly diminished antioxidant electrical capacity. The raised level of ROS and diminished antioxidant capacity exit cancer cells particularly vulnerable to further increases in oxidative accent.
The results of the new in vitro studies demonstrated that elesclomol causes apoptosis in cancer cells through the induction of oxidative strain. The step-up in ROS was ascertained by measurement the levels of responsive oxygen species such as hydrogen peroxide directly and by measurement the increased expression of genes that are induced by the presence of high levels of ROS. Elesclomol demonstrated potent and cancer-specific initiation of oxidative stress and apoptosis in multiple cancer cell types, including malignant melanoma, leukemias and lymphomas as well as breast, prostate, ovarian, colon, and lung. Specifically:
- Elesclomol rapidly induced the aggregation of intracellular ROS as detected by fluorescent microscopy;
- Elesclomol robustly induced the expression of many genes regulated by ROS such as high temperature shock proteins and metallothionein genes, which is a signature written text profile of cells under oxidative stress; and
- Pretreatment of cells with antioxidants blocked elesclomol-induced ROS production and programmed cell death.
"These new findings highlight the potential of oxidative stress generalisation," said Dr. Barsoum. "Cancer types that may be especially sensitive to this mechanism ar those known to have particularly high levels of oxidative tension, including, malignant melanoma, prostate, breast, ovarian, and hematologic cancers."
The on-going Phase 3 SYMMETRY test of elesclomol in metastatic melanoma is expected to have initial results in early 2009. Phase 2 studies of elesclomol in other indications are aforethought for the fourth quarter of 2008 and in 2009. Synta has a partnership with GlaxoSmithKline for the joint development and commercialization of elesclomol.
About Synta Pharmaceuticals
Synta Pharmaceuticals Corp. is a biopharmaceutical company focussed on discovering, developing, and commercializing small molecule drugs to stretch out and enhance the lives of patients with severe medical conditions, including cancer and inveterate inflammatory diseases. Synta has a unique chemical compound library, an integrated discovery engine, and a various 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 victimisation our compound library and discovery capabilities. Synta has a partnership with GlaxoSmithKline for the joint development and commercialization of its lead investigational drug nominee, elesclomol, which is in a globose, pivotal Phase 3 clinical trial for the treatment of metastatic melanoma. For more information, please visit http://www.syntapharma.com.
About Elesclomol
Elesclomol is a novel, injectable, investigational drug nominee that triggers apoptosis (programmed cell last) in cancer cells. Cancer cells operate at high levels of reactive o species, or oxidative tension. Elesclomol is believed to act by increasing the level of oxidative strain in crab cells even further, beyond sustainable levels, inducing caspase-mediated cell death. This mechanics of action, called oxidative stress inductance, represents a novel way of selectively targeting and killing genus Cancer cells.
In a double blind, randomized, controlled Phase 2b clinical test in 81 patients with stage IV metastatic melanoma, elesclomol in combination with paclitaxel met the primary endpoint, doubling the average time patients survived without their disease progressing, compared to paclitaxel alone (p = 0.035). The most common adverse events in the elesclomol asset paclitaxel grouping included fatigue, alopecia, stultification, nausea, hypoaesthesia, arthralgia, insomnia, diarrhea, and anemia.
A pivotal Phase 3 clinical trial of elesclomol in combination with paclitaxel in patients with stage IV metastatic melanoma (the SYMMETRY(SM) trial) is ongoing; Phase 2 trials in other indications, and in combination with other agents, are planned. Elesclomol has received Fast Track and Orphan Drug designation from the FDA for metastatic melanoma, and the Phase 3 SYMMETRY trial has completed a Special Protocol Assessment process with the FDA. Information around the SYMMETRY trial privy be set up at hypertext transfer protocol://www.symmetrymelanomastudy.com, or http://www.clinicaltrials.gov.
About Metastatic Melanoma
Melanoma, the most deadly form of skin cancer, arises from melanocytes, the pigment-producing cells of the peel. According to the American Cancer Society, melanoma accounts for about five pct of all skin cancers but causes about 75% of all skin cancer-related deaths. An estimated 60,000 people will be diagnosed and nearly 8,200 people will die from melanoma this year in the U.S. unequaled. If diagnosed and surgically removed patch localized in the outermost skin layer, melanoma is potentially curable; however, for patients with metastatic disease the prospect is poor, with limited available treatments and an expected survival of only six to nine months. The relative incidence of malignant melanoma has increased more rapidly than whatever other cancer during the past ten years. The FDA has not approved a novel, small speck drug for the treatment of metastatic melanoma in over 30 years.
Safe Harbor Statement
This media release whitethorn contain forward-looking statements nearly Synta Pharmaceuticals Corp. Such forward-looking statements can be identified by the enjoyment of advanced terminology such as "will", "would", "should", "", "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 and advancement of our clinical and preclinical programs and fiscal guidance for 2008, reflect our electric 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 terminated December 31, 2007 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, demur as requisite by practice of law.
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