OnKure Therapeutics, Inc.

OnKure Therapeutics, Inc. (Nasdaq: ONKR) is a clinical-stage biopharmaceutical company focused on discovering and developing precision medicines that target biologically validated drivers of cancers and other diseases underserved by available therapies. The company utilizes a structure-based drug design platform employing x-ray crystallography and computational chemistry to create small molecule drugs designed to selectively target specific mutations shown to be key drivers of disease while sparing wild-type proteins, thereby aiming to achieve improved efficacy and tolerability with reduced toxicity.

The company's lead product candidate, OKI-219, is a highly selective inhibitor of phosphoinositide 3-kinase alpha harboring the H1047R mutation (PI3KαH1047R), demonstrating approximately 80-fold selectivity for the mutated form over wild-type PI3Kα. OKI-219 is currently being investigated in the PIKture-01 Phase 1 open-label multi-arm clinical trial evaluating safety, tolerability, pharmacokinetics, and efficacy in patients with solid tumors including breast cancer. The trial includes multiple arms testing OKI-219 as monotherapy and in combination with standard-of-care therapies including fulvestrant, ribociclib, trastuzumab, and tucatinib. The company plans to initially focus development on advanced breast cancer patients with hormone receptor positive/HER2-negative and HER2-positive subtypes harboring PI3KαH1047R mutations.

OnKure is also pursuing additional discovery programs targeting other common PI3Kα mutations and has initiated a program in vascular malformations where PI3Kα pathway mutations are implicated. The company plans to announce a pan-mutant development candidate targeting the most common PI3Kα mutations in the first quarter of 2026.

In December 2024, preliminary data from PIKture-01 demonstrated that OKI-219 was well tolerated across all dose levels with no hyperglycemia, stomatitis, or rash observed, with all treatment-related adverse events being grade 1. The company retains worldwide rights to all programs and plans to pursue regulatory approval and commercialization in the United States and internationally. More information is available at www.onkuretherapeutics.com.