Ikena Oncology, Inc. announced that the Company is presenting preclinical data on its newest program in next-generation MEK-RAF inhibition, IK-595, at the American Association for Cancer Research (AACR) Special Conference: Targeting RAS, taking place this week in both a poster presentation and a plenary session talk. Ikena's MEK-RAF inhibitor, IK-595, the Company's lead candidate in the RAS pathway, is designed to achieve more comprehensive inhibition of MAPK signaling than existing inhibitors by trapping MEK-RAF in an inactive complex, including ARAF, BRAF, and CRAF. Specifically, the stabilization of the inactive MEK-CRAF complex by IK-595 potentially provides two key advantages: First, it relieves the well-recognized CRAF-mediated bypass that leads to the reactivation of MAPK signaling and resistance to first-generation MEK inhibitors in RAS mutant cancer cells.

Second, sequestering CRAF in a complex with MEK also blocks the kinase-independent anti-apoptotic function of CRAF in RAS and RAF mutated cancers, which is not addressable with first generation MEK or pan-RAF inhibitors. Highlights of the poster and Dr. Zhang's oral presentation include: IK-595 stabilizes the MEK-RAF complex in an inactive conformation to stop CRAF bypass; IK-595 potently blocks MEK phosphorylation in RAS mutant cancer cells; IK-595 achieves deeper and more durable inhibition of MAPK signaling andERK phosphorylation across multiple KRAS mutant, NRAS mutant, and CRAF altered cancer cell lines, compared to existing MEK inhibitors; IK-595 drives robust anti-tumor efficacy and tumor regression in mouse models of KRAS mutant, NRAS mutated, and CRAF amplified cancers, across pancreatic, lung, bladder, and AML; Strong synergy of IK-595 in combination with therapies targeting multiple key mechanisms in vitro, including in combination with KRAS G12C, EGFR,PI3K, mTOR, SHP2, and SOS1 inhibitors; IK-595 is designed to have a shorter projected half-life in humans that allows a differentiated dosing st.