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Arginase Inhibitor CB‑1158 (INCB001158)
We are leveraging our core expertise in tumor biology and medicinal chemistry to develop first-in-clinic, oral small molecule arginase inhibitors.
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 believed to play an immunosuppressive role. INCB001158 may also have the ability to combine with chemotherapy and immuno-oncology therapies.
The Phase 1/2 clinical trials with INCB001158 are enrolling patients with advanced solid tumors. Patients are being treated with INCB001158 as a monotherapy, as well as in combination with an anti-PD1 antibody. Clinical trials are also ongoing evaluating INCB001158 in combination with multiple chemotherapy combinations.
Our Pipeline
We are focused on novel treatments for
cancer and other life-threatening diseases.