Synta Pharmaceuticals initiates STA-9090 Phase 2 clinical trial for GIST

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 it is initiating a Phase 2 clinical study of STA-9090 in patients with advanced gastrointestinal stromal tumors (GIST). This is the sixth clinical study of STA-9090, a potent, synthetic, small molecule Hsp90 inhibitor with a novel chemical structure.

“Both imatinib (Gleevec®) and sunitinib (Sutent®) have proven very effective in helping patients with GIST to live longer; however, the majority of patients will eventually experience disease progression despite treatment with both of those molecularly targeted therapies”

"Both imatinib (Gleevec^®) and sunitinib (Sutent^®) have proven very effective in helping patients with GIST to live longer; however, the majority of patients will eventually experience disease progression despite treatment with both of those molecularly targeted therapies," said George Demetri, M.D., Dana-Farber Cancer Institute. "Once those two standard drugs fail, patients have a poor prognosis and very limited treatment options. Hsp90 inhibition is a promising therapeutic approach for these patients because the mutated kinase proteins that are the cause of resistance to both Gleevec^® and Sutent^® depend upon being chaperoned and protected by the function of Hsp90. STA-9090 can potently inhibit the Hsp90 function and disrupt the mutant signaling in multidrug-resistant GIST. Based on the preclinical and early clinical results seen to date, STA-9090 has the potential to unlock the true potential of Hsp90 as a therapeutic target in GIST."

Preclinical results related to STA-9090 in GIST were presented by Jonathan Fletcher, M.D., Brigham and Women’s Hospital, at the AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics in November 2009.

“We have shown that as many as eight different secondary KIT Gleevec-resistance mutations can occur in different metastases from a single GIST patient whose disease has progressed after treatment with Gleevec^®, which poses a significant challenge for treating drug-resistant GIST,” said Dr. Fletcher. “Importantly, all of these different resistance mutations were still sensitive to STA-9090. In these studies, STA-9090 was also 5-15 fold more potent than 17-AAG, a first-generation, ansamycin-family Hsp90 inhibitor. Additionally, STA-9090 was active against GIST cells that were resistant to 17-AAG.”

“We and our collaborators have been encouraged by the strong preclinical results for STA-9090 in GIST as well as early clinical results from our solid tumor Phase 1 trials, where STA-9090 has generated objective tumor responses and has been well-tolerated, with the most common adverse events, fatigue and gastrointestinal toxicities, being manageable and reversible,” said Vojo Vukovic, M.D., Ph.D., Senior Vice President and Chief Medical Officer, Synta Pharmaceuticals. “A particularly encouraging observation was that a GIST patient on our once- weekly dosing Phase 1 solid tumor study, who experienced disease progression while on multiple prior therapies, including Gleevec^® and Sutent^®, experienced substantial tumor shrinkage and stabilization of disease following treatment with STA-9090. We are looking forward to working closely with leading GIST investigators to evaluate the potential of STA-9090 to benefit patients with this disease.”

Synta expects to report data from the ongoing Phase 1 and Phase 1/2 trials and initiate studies in multiple other cancer indications in the first half of 2010.