�Synta Pharmaceuticals Corp., (NASDAQ: SNTA) announced the publication of new findings in the American Association for Cancer Research journal, Molecular Cancer Therapeutics that describe the novel mechanism of action of elesclomol: drive programmed cubicle death (apoptosis) in malignant neoplastic disease cells through the selective induction of oxidative tenseness. Elesclomol is currently in a spherical, pivotal Phase 3 clinical trial (SYMMETRYSM) in combination with paclitaxel for the treatment of metastatic malignant melanoma.
"These results confirm that elesclomol potently and selectively induces apoptosis in cancer cells by increasing the level of reactive atomic number 8 species (ROS) beyond sustainable levels," said James Barsoum, Ph.D., Senior Vice President, Research, Synta Pharmaceuticals. "Elevated ROS levels and susceptibleness to further 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 to selectively targeting and killing cancer cells. The findings too suggest that elesclomol canful substantially enhance the efficacy of certain other anticancer therapies when given in combination. These results together with indicate the potential of oxidative strain induction as a new therapeutic alternative for treating multiple types of cancers, either as a single agent or in combination. We ar excited by the potential of this new mechanism category, particularly for difficult-to-treat cancers such as malignant melanoma that get not been responsive to chemotherapy or other prior approaches."
Oxidative stress occurs when there is an elevated degree of responsive oxygen species (ROS) in cells. Superoxide, hydrogen peroxide and hydroxyl radicals ar examples of reactive o species. ROS levels canful increase in a variety of situations including exposure to bacterium or viruses, a get up in cell proliferation, or an increase in cellular telephone metabolism. Prolonged exposure to elevated levels of ROS can initiate a sequence of protective events culminating in the ultimate self-protection mechanism, programmed cell demise (apoptosis). Normal, non-cancerous cells have a strong antioxidant capacity which guards against excessive levels of ROS. In contrast, cancer cells operate at a much higher level of oxidative stress and have a greatly weakened antioxidant capacity. The elevated level of ROS and diminished antioxidant capacity leave 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 increase in ROS was observed by measurement the levels of responsive oxygen species such as hydrogen peroxide directly and by mensuration 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 malignant neoplastic disease cell types, including malignant melanoma, leukemias and lymphomas as well as breast, prostate gland, ovarian, costa Rican colon, and lung. Specifically:
- Elesclomol rapidly induced the accumulation of intracellular ROS as detected by fluorescent microscopy;
- Elesclomol robustly induced the expression of many genes regulated by ROS such as warmth shock proteins and metallothionein genes, which is a signature transcription profile of cells under oxidative focus; and
- Pretreatment of cells with antioxidants blocked elesclomol-induced ROS production and caspase-mediated cell death.
"These new findings high spot the potency of oxidative stress initiation," said Dr. Barsoum. "Cancer types that may be especially sensitive to this mechanism are those known to have particularly heights levels of oxidative accent, including, malignant melanoma, prostate, titty, ovarian, and hematologic cancers."
The ongoing 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 planned 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 focused on discovering, developing, and commercializing little molecule drugs to cover and enhance the lives of patients with severe medical conditions, including crab and inveterate inflammatory diseases. Synta has a unique chemical combine 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 heighten library and discovery capabilities. Synta has a partnership with GlaxoSmithKline for the joint development and commercialisation of its lead investigational drug prospect, elesclomol, which is in a planetary, pivotal Phase 3 clinical trial for the handling of metastatic melanoma. For more information, please call in http://www.syntapharma.com.
About Elesclomol
Elesclomol is a novel, injectable, investigational drug campaigner that triggers apoptosis (programmed cell decease) in cancer cells. Cancer cells work at high levels of reactive oxygen species, or oxidative stress. Elesclomol is believed to act by increasing the level of oxidative stress in cancer the Crab cells even further, beyond sustainable levels, inducing programmed cell death. This mechanism of action mechanism, called oxidative stress inductance, represents a novel way of selectively targeting and killing crab cells.
In a double blind, randomized, controlled Phase 2b clinical trial in 81 patients with stage IV metastatic malignant melanoma, elesclomol in combination with paclitaxel met the primary endpoint, doubling the median time patients survived without their disease progressing, compared to paclitaxel alone (p = 0.035). The most usual adverse events in the elesclomol summation paclitaxel mathematical group included weariness, alopecia, constipation, 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 malignant 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 denomination from the FDA for metastatic malignant melanoma, and the Phase 3 SYMMETRY trial has completed a Special Protocol Assessment process with the FDA. Information around the SYMMETRY trial can be establish at hypertext transfer protocol://www.symmetrymelanomastudy.com, or http://www.clinicaltrials.gov.
About Metastatic Melanoma
Melanoma, the most deadly form of peel cancer, arises from melanocytes, the pigment-producing cells of the skin. According to the American Cancer Society, melanoma accounts for around five percentage 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 kick the bucket from melanoma this year in the U.S. alone. If diagnosed and surgically removed patch localized in the outmost skin stratum, melanoma is potentially curable; however, for patients with metastatic disease the medical prognosis is poor, with limited available treatments and an expected survival of only six to nine months. The incidence of melanoma has increased more rapidly than whatever other cancer during the past x years. The FDA has not sanctioned a novel, small molecule drug for the discourse of metastatic melanoma in over 30 years.
Safe Harbor Statement
This media release may contain modern statements about Synta Pharmaceuticals Corp. Such forward-looking statements can be identified by the use of modern terminology such as "will", "would", "should", "", "anticipates", "intends", "plans", "believes", "may", "estimates", "predicts", "projects", or similar expressions intended to place forward-looking statements. Such statements, including statements relating to the timing and onward motion of our clinical and preclinical programs and fiscal guidance for 2008, reverberate our current views with respect to future events and ar based on assumptions and subject to risks and uncertainties that could case actual results to disagree 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 over December 31, 2007 as filed with the Securities and Exchange Commission. Synta undertakes no obligation to publicly update forward-looking statements, whether because of newfangled information, future events or otherwise, take out as mandatory by law.
Synta Pharmaceuticals
More info
