GIST Support Wiki9 Nov 2007 Subject: Synta Pharmaceuticals Initiates Phase 1 Clinical Trial of STA-9090, a Novel Hsp90 Inhibitor
A press release from the company... Synta Pharmaceuticals Initiates Phase 1 Clinical Trial of STA-9090, a Novel Hsp90 Inhibitor
LEXINGTON, Mass., Nov 08, 2007 (BUSINESS WIRE) -- Synta Pharmaceuticals Corp., (NASDAQ: SNTA) a biopharmaceutical company focused on discovering, developing, and commercializing small molecule drugs to treat severe medical conditions, today announced that the first patient has been treated in a Phase 1 clinical study of its novel heat shock protein 90 (Hsp90) inhibitor, STA-9090. STA-9090 is a synthetic, small molecule Hsp90 inhibitor with a novel chemical structure that is unrelated to the Hsp90 inhibitor geldanamycin or its family of related compounds, such as 17-AAG.
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 (Gleevec(R)), erlotinib (Tarceva(R)), and sunitinib (Sutent(R)). In addition, STA-9090 has shown potency 10 to 100 times greater than the geldanamycin family of Hsp90 inhibitors, 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, Tarceva, and Sutent.
"Initiating our Phase 1 trial for STA-9090 represents a key clinical milestone for Synta and an important step in delivering on our strategy to build a pipeline of oncology compounds with first- or best-in-class mechanisms, strong scientific rationale, and broad therapeutic utility," said Safi Bahcall, Ph.D., President and Chief Executive Officer, Synta. "We are particularly excited about STA-9090 because of the strength of the preclinical data package, including activity against highly resistant cancers and superior potency to first-generation Hsp90 inhibitors."
The open-label Phase 1 study in patients with solid tumors is designed to identify the maximum tolerated dose of STA-9090 based on a twice-a-week intravenous dosing schedule. In addition to an evaluation of safety and tolerability, patients will be assessed for response rate based on the RECIST criteria. A second Phase 1 study with an alternative, once-a-week dosing schedule is planned.
"Hsp90 inhibition has the potential to provide a new strategy for treating cancer," said Geoffrey Shapiro, M.D., Ph.D., Dana-Farber Cancer Institute and lead investigator of the Phase 1 trial. "Based on the strength of the preclinical data we have seen to date, we believe STA-9090 is differentiated in important ways from other Hsp90 inhibitors, and this Phase 1 trial can advance our knowledge of this new therapeutic category."
About Hsp90 Hsp90 is an emerging therapeutic target of interest for the treatment of cancer. It is responsible for modulating cellular response to stress by maintaining the 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.