Arginase Inhibitor INCB001158 (CB-1158)

The INCB001158 program in oncometabolism 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 believed to play an immunosuppressive role. INCB001158 may also have the ability to combine with chemotherapy and immuno-oncology therapies.