Arginase Inhibitor INCB001158 (CB‑1158)

Calithera’s program in onco-metabolism is directed at developing inhibitors of the enzyme arginase and may provide a first-in-class therapeutic agent for this novel target. Arginase exerts its immunosuppressive effect by depleting the amino acid arginine in the tumor microenvironment and preventing the immune system’s cytotoxic T-cells and natural killer (NK) cells from proliferating and killing the tumor. Inhibition of arginase activity reverses this immunosuppressive block and restores T-cell function.

Calithera has discovered novel, orally active arginase inhibitors that have shown inhibition of tumor growth in mice. This inhibition of tumor growth is accompanied by a rapid increase in the local concentration of arginine, resulting in a rise in the number of CD3+ T-cells within the tumor. INCB001158 has the potential for anti-tumor activity in renal cell cancer, breast cancer, non-small cell lung cancer, acute myeloid leukemia, and other tumor types where arginase-secreting MDSCs are known to play an immunosuppressive role. INCB001158 may also have the ability to combine with other immuno-oncology therapies that target T-cell activation, such as CTLA-4 and PD-1 antibodies.

In December 2014, Calithera entered into an exclusive license agreement with Mars Corporation’s Symbioscience Division, under which the company has been granted the exclusive, worldwide license rights to develop and commercialize Symbioscience’s portfolio of arginase inhibitors for use in human healthcare.

In July 2016, Calithera’s Investigational New Drug (IND) application was accepted by the FDA for the oral arginase inhibitor INCB00158. The Phase I clinical trial is enrolling patients with advanced solid tumors. Patients will be treated with INCB001158 as a monotherapy, as well as in combination with an anti-PD1 antibody. Clinical trials are also planned to treat patients with INCB001158 in combination with chemotherapy and with an IDO inhibitor.