Calithera aims to develop caspase activators that trigger apoptosis in cancer cells.

Cancer therapeutics company Calithera Biosciences raised $40 million in a Series A financing round led by Morgenthaler Ventures. The firm said it will use the funds to progress the development of caspase activator technology developed by the firm’s co-founder James Wells, Ph.D., chair of the department of pharmaceutical chemistry at the University of California, San Francisco. The initial goal is to take one or more caspase activator candidates through preclinical development and into Phase I trials. In parallel, Calithera aims to expand its technology to the activation of other enzymes with therapeutic potential in cancer.

“Most drug discovery efforts are focused on identifying drugs that inhibit enzyme function,” Dr. Wells points out. “But interestingly, many cellular enzymes remain dormant until activated. In the case of caspases they can be activated on demand by mimicking the natural process with small molecules.”

Calithera was founded earlier this year to commercialize caspase activation IP. The technology is based on the use of small molecules that bind to allosteric sites on the caspase proenzyme and effectively trigger the proteolytic cleavage that generates the mature, active form. The firm believes that this approach to inducing apoptosis in tumor cells has potential utility across a broad range of cancer types. Moreover, Calithera believes, the direct activation of enzymes such as caspase-9 and executioner caspases occurs downstream of chemoresistance pathways such as p53 deletion or bcl-2 protein expression, which should make the approach effective even in chemoresistant tumors.

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