Synta Pharmaceuticals presents preclinical results of STA-9090 at AACR-IASLC Joint Conference

Jan 13 2010

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 preclinical results presented at the AACR-IASLC (American Academy of Cancer Research – International Association for the Study of Lung Cancer) Joint Conference based on work done at Synta and at the Dana-Farber Cancer Institute in Boston showed that STA-9090, a potent, synthetic inhibitor of heat shock protein 90 (Hsp90), demonstrated potent activity against 100% of all non-small cell lung cancer cell lines tested, including those with EGFR, HER2 or KRAS mutations including the EGFR T790 mutation that is present in roughly 50% of cases of erlotinib or gefitinib resistance.

“Taken together, the in vitro and in vivo results presented at this conference demonstrate the potency, broad activity, and safety profile of STA-9090, both as a single agent and in combination with taxanes in NSCLC”

Synta is currently enrolling patients in a Phase 2 single-arm, open-label, single-agent study of STA-9090 in patients with stage IIIB or IV non-small cell lung cancer, with patient cohorts defined by the genetic profile of their tumors.

STA-9090 potently inhibited cell proliferation in 24 out of 24 human NSCLC lines tested irrespective of EGFR, HER2 or KRAS mutational status. In vivo, STA-9090 stopped tumor growth in both Tarceva^® (erlotinib)-sensitive and Tarceva-resistant NSCLC xenograft models. In addition, in a HER2 positive adenosquamous lung cancer study, 3 out of 4 animals treated with STA-9090 experienced partial responses as measured by MRI.

Analysis of protein expression showed that STA-9090 causes substantial down-regulation of client proteins relevant to lung cancer growth and proliferation including AKT, EGFR, MET, HER2, CDK4, and RAF1.

Results in the animal models also showed that STA-9090 preferentially accumulates in tumors, with the half-life in tumors 10-19 times longer than the half-life in normal tissues and plasma. Six days after dosing, the tumor concentration of STA-9090 remained 215-fold higher than the median in vitro concentration needed for killing 50% of cells (IC-50) against the panel of 24 human NSCLC lines.

In in vitro studies of combination activity, STA-9090 demonstrated synergy with paclitaxel and docetaxel. These anti-cancer agents are widely used in the treatment of advanced-stage NSCLC. In vivo, the combination of STA-9090 with paclitaxel displayed greater efficacy than either agent used alone without additional toxicity.

“Taken together, the in vitro and in vivo results presented at this conference demonstrate the potency, broad activity, and safety profile of STA-9090, both as a single agent and in combination with taxanes in NSCLC,” said Vojo Vukovic, M.D., Ph.D., Chief Medical Officer, Synta Pharmaceuticals. “Based on the strong scientific results we and others have seen with STA-9090, the improved safety and activity profile compared to first-generation Hsp90 inhibitors, and the encouraging early clinical results seen to date with STA-9090, we believe STA-9090 can be the first Hsp90 inhibitor to realize the true clinical potential of this drug class.”