Despite recent therapeutic advances, current approaches to treating cancer remain incomplete. Cellular systems critical to the growth and survival of many tumors remain unaddressed by currently available treatments. Heat shock protein 90 (Hsp90) is a central component of the cellular chaperone system – a system that supports and stabilizes cancer-causing proteins such as c-Kit, EGFR, and HER2. Inhibition of Hsp90 knocks out a critical source of support for cancer cells, leading to tumor growth inhibition and cancer cell death. Thus, targeted anti-chaperone therapy via inhibition of Hsp90 may represent a significant yet currently unaddressed strategy for treating patients with cancer.

Hsp90 Structure and Function Hsp90 Inhibition

IPI-504 (retaspimycin hydrochloride) is a novel, targeted anti-chaperone agent that has shown potent and selective inhibition of Hsp90 in preclinical studies. IPI-504 is currently being evaluated in multiple disease-focused clinical trials, as well as in combination with chemotherapy. Infinity anticipates launching a Phase 3 registration trial of IPI-504 in patients with refractory gastrointestinal stromal tumors in the third quarter of 2008.

Infinity is also developing an oral inhibitor of Hsp90, IPI-493, and anticipates commencing a Phase 1 clinical trial with IPI-493 in mid-2008.

IPI-504 and IPI-493 are being jointly developed by AstraZeneca/MedImmune.