Incyte Corporation / Calithera Biosciences, Inc.

Advanced Solid Tumors and Hematologic Malignancies (Immuno-Oncology)

Disease Overview

CB-1158 (INCB001158) targeted arginase, an enzyme released by myeloid-derived suppressor cells and tumor cells that depletes arginine in the tumor microenvironment, blunting T-cell and NK-cell activation. The thesis: a substantial fraction of patients fail to respond to PD-1/PD-L1 checkpoint inhibitors because of metabolic immunosuppression — restoring arginine availability could re-sensitize tumors to immunotherapy. The asset was being explored across multiple solid-tumor and hematologic indications as a combination partner to pembrolizumab and chemotherapy.

Competitive Landscape

At deal time (January 2017) the immuno-oncology landscape was exploding with combination strategies aimed at overcoming primary and acquired resistance to PD-1/PD-L1 blockade. Direct mechanistic competitors targeting tumor-microenvironment immunosuppression included Incyte/NewLink's IDO1 inhibitor epacadostat (which catastrophically failed the ECHO-301 trial in 2018, derailing the IDO class), Merck's own IDO programs, A2A receptor antagonists from Corvus and AstraZeneca, and adenosine pathway plays from Arcus. CB-1158 was the most clinically advanced arginase inhibitor and was structured around combination with pembrolizumab and Incyte's own pipeline. Phase 1/2 readouts showed modest single-agent activity but reasonable signals in combination — a 24% ORR with chemotherapy in biliary tract cancer. The collaboration unraveled in 2020 when Calithera, citing a milestone-payment dispute and a need to refocus on internal programs, terminated the agreement effective September 30, 2020 — leaving Incyte with full global rights but limited continued development of INCB001158. The deal stands as a case study in I-O combination partnerships that did not deliver against an aggressive milestone schedule.