AHR Antagonist Program
AHR is an emerging target in cancer, autoimmunity and inflammation, and Ikena’s IK-175 is poised to become an industry leading AHR antagonist program for the treatment of cancer.
AHR Antagonist Program
IK-175 is poised to become an industry leading AHR antagonist program for the treatment of cancer.
Aryl Hydrocarbon Receptor (AHR) is a transcription factor which mediates expression of multiple immune related and tumor cell signal transduction and proliferation genes. AHR can be activated in tumor and immune cells by multiple ligands, including kynurenine. Activated AHR prevents immune recognition of a range of cancers by modulating both innate and adaptive immunity. This attribute makes AHR a compelling drug target, especially in patients who do not fully benefit from standard-of-care, including checkpoint inhibitors. In addition to mediating immunosuppression, Ikena has identified a tumor cell intrinsic dependence of AHR in certain cancers.
Ikena is advancing internally developed IK-175, a selective AHR antagonist, which prevents AHR-modulated tumor promotion. Although kynurenine is the best characterized endogenous ligand that activates AHR, other ligands induce AHR-mediated immunosuppression. Therefore, direct inhibition of AHR with antagonistic small molecules represents a distinct and broader approach from upstream targets within this pathway.
In January 2019, Ikena entered into an exclusive global strategic collaboration with Bristol Myers Squibb Corporation for the development of IK-175 and IK-412. Ikena is responsible for research and development activities for IK-175 through Phase 1b. Bristol Myers Squibb is then eligible to globally license IK-175 and would be responsible for further development and commercialization. For more information, please see the press release announcing the Ikena-Bristol Myers Squibb partnership.
AHR antagonism has potential applications in several high unmet need indications:
- Potential for single-agent activity in cancers with activated AHR
- AHR plays a role in the modulation of the adaptive and innate immune systems
- AHR is downregulated in autoimmune diseases
In pre-clinical studies, AHR antagonism:
- Demonstrates tumor cell intrinsic AHR dependence in certain cancers
- Increases T-cell expansion as well as IL2 and IFN-γ
- Reduces functional regulatory T-cells stimulated by kynurenine, and decreases suppressive cytokines and function of myeloid-derived suppressor cells