Heat shock protein 90 (Hsp90) is emerging as a major therapeutic target of interest for the treatment of a broad range of cancers. Proteins are the essential building blocks and machines of the human body, and in order for proteins to function properly they must be stable and properly folded. The “chaperone” system of proteins, of which Hsp90 is a member, serves to maintain the structure and activity of specific proteins within the cell. The proteins “chaperoned” by Hsp90 are known as its "client proteins". Many cancers result from specific mutations in, or aberrant expression of, these client proteins. Examples of cancer promoting, or oncogenic, client proteins of Hsp90 include c-Kit in gastrointestinal stromal tumors (GIST), epidermal growth factor receptor, or EGFR, in non-small cell lung cancer (NSCLC), and Her-2 in breast cancer. Hsp90 enables those cancers’ survival by maintaining the function of oncogenic client proteins.

Hsp90 Structure and Function Hsp90 Inhibition

In preclinical studies, inhibition of Hsp90 has been shown to lead to the degradation of these client proteins and to cell death, or apoptosis. Importantly, cancers featuring oncogenic client proteins that have become resistant to approved targeted therapies have also been shown preclinically to remain sensitive to Hsp90 inhibition. As a result, inhibition of Hsp90 has broad therapeutic potential for the treatment of patients with solid tumors and blood-related cancers, including cancers that are resistant to other drugs.

Infinity has developed a novel, proprietary inhibitor of Hsp90, retaspimycin, also known as IPI-504, for the potential treatment of multiple cancers. The drug product, retaspimycin hydrochloride for injection is currently being evaluated in three disease-focused clinical trials. Infinity has also identified two orally available inhibitors of Hsp90: an oral formulation of retaspimycin and a second clinical candidate, IPI-493.