Ikena Oncology, Inc. announced preclinical data in the Company's novel investigational Hippo pathway inhibitor, IK-930. The Company also updated its corporate presentation. IK-930 is currently being studied in a Phase 1 clinical trial as a monotherapy in patients with advanced solid tumors with or without gene alterations in the Hippo pathway, including NF2-deficient malignant mesothelioma, Epithelioid Hemangioendothelioma (EHE) with documented TAZ/CAMTA1 fusion genes as well as other solid tumors with either NF2 deficiency or with YAP/TAZ genetic fusions (NCT05228015).

Data being shared today reveals that IK-930 selectively binds and inhibits TEAD1 and further describes the mechanism for its antitumor activity. Key advantages demonstrated in the nonclinical studies include IK-930's superior tolerability and comparable antitumor activity compared to panTEAD inhibition, resulting in a significantly improved projected therapeutic window in cancer patients. IK-930 was designed as a TEAD1-selective inhibitor to avoid on-target renal toxicity expected from panTEAD inhibition.

TEAD1 is the most highly expressed TEAD paralog in mesothelioma and epithelioid hemangioendothelioma (EHE). The data being presented support the ongoing IK-930 Phase 1 program in patients with Hippo mutated cancers and the planned expansion into combinations of IK-930 with other targeted therapies in multiple cancer types, including across EGFR and RAS mutated cancers, to potentially delay or even reverse therapeutic resistance. In nonclinical models and species, IK-930 demonstrated selective inhibition of TEAD1 with equivalent activity to broad TEAD inhibitors and a significantly improved tolerability profile.

IK-930 promotes repressive TEAD1 activity by driving interactions with VGLL4, a signaling partner that reduces expression of pro-growth and anti-apoptotic genes. Through its binding with TEAD1 and VGLL4, IK-930 potentially blocks chromatin binding of other TEAD paralogs. In assessing the potential on-target renal toxicity of targeting TEAD, average urinary protein-to-creatinine ratios and histopathology in non-human primates predicted a therapeutic index of less than one for panTEAD inhibitions and a broad therapeutic window for IK-930.