Results Presented at AACR Differentiate STA-9090 in Hsp90 Inhibitor Class and Show Activity in Erlotinib (Tarceva(R))-resistant Lung Cancer Models
STA-9090 shows activity in models resistant to 17-AAG
“The results presented today from the preclinical experiments performed
at Dr.
“In addition to our three on-going clinical trials of STA-9090, we are excited to advance this program in the clinic. We are pleased by the enthusiasm from the scientific and medical community for this program and plan to initiate trials in a range of new cancer types later this year,” continued Dr. Barsoum.
STA-9090 is an example of the ability of Synta to continue to generate novel, best-in-class drug candidates using its discovery platform and unique compound library of diverse, proprietary chemical structures. Synta has five drug candidate programs in preclinical or clinical development each representing distinct mechanisms of action, chemical structures, and market opportunities. All programs have been discovered and developed internally.
The Hsp90 data, presented in a poster by
Additional findings demonstrated that:
- STA-9090 inhibited proliferation and induced apoptosis in a large panel of NSCLC cell lines with a more than four–fold greater potency than 17-AAG.
- STA-9090 displayed activity against cell lines expressing seventeen different epidermal growth factor receptor (EGFR) mutations commonly found in NSCLC patients, including ten mutations that conferred resistance to the EGFR inhibitor erlotinib (Tarceva).
- STA-9090 induced depletion of Hsp90 clients such as AKT, EGFR, ERBB4, IGF-1R, c-MET, PDGFRα, and c-RET a 3 to 9-fold lower drug concentrations than for 17-AAG.
- STA-9090 retained activity against lung cancer cell lines that were resistant to treatment with 17-AAG.
- STA-9090 showed greater efficacy and an increased therapeutic index relative to 17-AAG in mouse models of Tarceva-resistant NSCLC.
It is estimated that 215,020 men and women (114,690 men and 100,330
women) in
STA-9090 is currently being studied in two Phase 1 solid tumor clinical trials and one Phase 1/2 trial in hematologic cancers. Synta has announced that a second Phase 2 hematologic cancer trial will be started in 2009.
Additional Abstracts Presented at AACR
Also presented at AACR was a poster by
About STA-9090
In preclinical studies, STA-9090 has shown the ability to inhibit multiple kinases with comparable potency to, and a broader activity profile than specific kinase inhibitors such as imatinib, erlotinib, and sunitinib. In addition, STA-9090 has shown potency 10 to 100 times greater than the ansamycin family of Hsp90 inhibitors such as 17-AAG, as well as activity against a wider range of kinases. In in vivo models, STA-9090 has shown strong efficacy in a wide range of cancer types, including cancers resistant to Gleevec and Tarceva.
About Hsp90
Hsp90 is an emerging therapeutic target of interest for the treatment of cancer. It is responsible for the maturation and function of numerous signaling proteins – known as ‘client proteins’ – that are associated with cancer cell survival and proliferation. Many cancers result from specific mutations in, or aberrant expression of, these client proteins. Examples of cancer-associated client proteins of Hsp90 include c-KIT in gastrointestinal stromal tumors, epidermal growth factor receptor (EGFR) in lung cancer, and BCR-ABL in chronic myelogenous leukemia. In preclinical studies, inhibiting Hsp90 causes the degradation of these proteins and cancer cell death. Inhibiting Hsp90 has also proven effective in killing cancer cells that have developed resistance to targeted therapies such as kinase inhibitors.
About Elesclomol
Elesclomol is a novel, injectable, investigational drug candidate that triggers apoptosis (programmed cell death) in cancer cells. Cancer cells operate at high levels of reactive oxygen species, or oxidative stress. Elesclomol is believed to act by increasing the level of oxidative stress in cancer cells even further, beyond sustainable levels, inducing apoptosis. This mechanism of action, called oxidative stress induction, represents a novel way of selectively targeting and killing cancer cells. Clinical trials of elesclomol are on hold pending further analysis of the full results of the Phase 3 (SYMMETRY) trial.
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Safe Harbor Statement
This media release may contain forward-looking statements about
1. NCI SEER database, 2009 http://seer.cancer.gov/statfacts/html/lungb.html
Source:
Synta Pharmaceuticals Corp.
Rob Kloppenburg, 781-541-7125