IL4I1, an enzyme that is expressed by tumor cells and antigen presenting cells, metabolizes phenylalanine, tyrosine and tryptophan to produce hydrogen peroxide, an inhibitor of T-cell function. In particular, IL4I1 can metabolize tryptophan to kynurenic acid and other metabolites that lead to immunosuppression in the tumor microenvironment. IL4I1 expression has been correlated with poor outcomes in several tumor types, has a potential role in immune invasion and may decrease the ability of checkpoint therapy to stimulate an anti-tumor immune response. IL4I1 expression is elevated in multiple tumor types with particularly high expression in ovarian and B-cell tumors. We have developed an investigational first-in-class, potent, orally available IL4I1 inhibitor. Preclinical data demonstrated that our novel small-molecule inhibitor of IL4I1 has single-agent antitumor activity in syngeneic mouse tumor models and augments the activity of checkpoint inhibitors.

Calithera continues to leverage its discovery engine to build a robust preclinical pipeline of undisclosed synthetic lethality targets with a focus on paralog genes. These will be announced as the company advances preclinical development