EP4 Antagonist Program
IK-007, an inhibitor of a critical cancer immunosuppressive metabolic pathway and a rapid proof-of-concept opportunity, is now advancing in the clinic as Ikena’s lead program.
EP4 Antagonist Program
IK-007 is an inhibitor of a critical cancer immunosuppressive metabolic pathway with a rapid proof-of-concept opportunity.
A large body of literature demonstrates that activation of the prostaglandin E2 (PGE2) / Prostaglandin E2 Receptor 4 (EP4) metabolic pathway in cancer augments tumor initiation, progression and therapeutic resistance. Increased expression of these pathway components is associated with decreased survival, therapeutic and preventive precedent in a number of cancer types, including colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). When activated, EP4 affects the activity of a broad range of cells within the innate and adaptive immune system culminating in an immunosuppressive tumor microenvironment.
Ikena’s IK-007 (formerly ARY-007) is a first-in-class, oral, highly selective, and potent small-molecule EP4 receptor antagonist. Ikena is currently investigating IK-007 in two Phase 1b/2 clinical trials in combination with Merck’s anti-PD-1 antibody KEYTRUDA® (pembrolizumab) in patients with checkpoint-refractory and -resistant solid tumors, namely advanced or progressive microsatellite stable CRC (NCT03658772) and advanced or metastatic post PD-1/L-1 NSCLC (NCT03696212). For both trials, Ikena is employing a robust, retrospective biomarker strategy relevant to T cell checkpoint inhibitors and EP4 signaling. The objective of these correlative biomarker studies is to identify patients most likely to benefit from IK-007 combined with pembrolizumab going forward. Ikena expects to report preliminary data in 2020.
In clinical studies:
- Orally bioavailable
- Efficacy data obtained in non-oncology indications
- Well tolerated at therapeutic doses
- Favorable pharmaceutical properties
In pre-clinical studies:
- Highly potent and selective
- Shown to boost the immune response through modulation of multiple innate and adaptive immune cell types
- Demonstrated tumor reduction as a single agent and increased cures in combination with checkpoint inhibitors