OnKure Therapeutics is a clinical-stage biotech developing precision cancer drugs that selectively target mutated forms of the PI3Kα enzyme, one of the most commonly mutated oncogenes in cancer. The core thesis is that existing approved PI3Kα inhibitors cause significant toxicity because they inhibit both the mutated (oncogenic) and normal forms of PI3Kα. OnKure's approach is to design drugs that bind selectively to the mutated form and spare the normal enzyme, which it believes can improve both safety and efficacy. OnKure's lead candidate, OKI-219, is an oral small molecule that selectively inhibits the PI3KαH1047R mutation — the most common PI3Kα mutation in breast cancer — with roughly 80-fold selectivity over the normal enzyme. OKI-219 is currently in a Phase 1 trial enrolling patients with advanced solid tumors, primarily breast cancer, being tested as a monotherapy and in combination with standard-of-care drugs including fulvestrant, ribociclib, trastuzumab, and tucatinib. Early data show no hyperglycemia, rash, or stomatitis, which contrasts favorably with approved competitors. Beyond OKI-219, OnKure has two discovery-stage programs: a pan-mutant PI3Kα inhibitor targeting the three most common PI3Kα mutations simultaneously, and a vascular malformations program applying the same platform to a non-oncology indication. OnKure is pre-revenue, funds operations through equity, and retains worldwide rights to all programs. It has 45 employees and outsources all manufacturing.