OnKure Therapeutics, Inc.

OnKure Therapeutics, Inc. is a clinical-stage biopharmaceutical company that discovers and develops precision medicines. These medicines target specific biological drivers of cancers and other diseases where current therapies are insufficient. The company uses a structure-based drug design platform to create a pipeline of small molecule drugs. These drugs are designed to selectively target specific mutations that drive cancer and vascular overgrowth syndromes, aiming for optimal efficacy and tolerability while sparing the non-mutated, or wild-type, enzyme. This approach seeks to improve safety and efficacy by reducing toxicity associated with non-selective inhibition. OnKure's product candidates are designed to inhibit specified mutated versions of phosphoinositide 3-kinase alpha ("PI3Kα"), a key disease-creating gene. The lead product candidate, OKI-219, is a highly selective inhibitor of PI3Kα harboring the H1047R mutation ("PI3Kα H1047R"). OKI-219 has approximately 80-fold selectivity for PI3Kα H1047R over wild-type PI3Kα ("PI3Kα WT"), meaning it has a much smaller impact on PI3Kα WT. This selectivity is intended to limit on-target toxicities such as hyperglycemia, gastrointestinal ("GI") effects, fatigue, and rash. OnKure plans to initially develop OKI-219 for patients with advanced breast cancer of genetic subtypes that are both hormone receptor positive ("HR+") and human epidermal growth factor receptor 2 negative ("HER2-"), as well as human epidermal growth factor receptor 2 positive ("HER2+").