OnKure Therapeutics, Inc.

OKI-219 Program Highlights

OnKure’s lead product candidate, OKI-219, is a highly selective PI3Kα H1047 mutant specific inhibitor. OKI-219 is being evaluated in the PIKture-01 phase 1a/1b clinical trial for the treatment of patients with HR+ and HER2+ metastatic breast cancer.

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Parts A and B – Enrollment in both the monotherapy and fulvestrant combination dose escalation arms of the PIKture-01 trial has been completed and closed. A total of 71 patients have been dosed across both arms: 38 in monotherapy and 33 in combination with fulvestrant. The Company expects to report updated safety, tolerability, and clinical activity data from Parts A and B in March 2026.

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Part E – The Company continues to enroll patients with PI3Kα H1047R mutated, HR+ metastatic breast cancer in the triplet expansion arm evaluating OKI-219 in combination with fulvestrant and ribociclib. A total of 17 patients have been dosed with OKI-219 in combination with fulvestrant and ribociclib. The Company expects to report initial safety, tolerability, and clinical activity data from Part E in March 2026.

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Part C – The Company continues to enroll patients with PI3Kα H1047R mutated, HER2+ breast cancer in the triplet expansion arm evaluating OKI-219 in combination with trastuzumab and tucatinib. The Company expects to report initial data from Part C in 2026.

Next-Generation PI3Ka PAN Mutant Selective Program

OnKure expects to announce its next-generation PI3Ka pan-mutant inhibitor candidate for HR+ metastatic breast cancer in March 2026.

Additionally, PI3Kα mutations represent the most common driver alterations in key subtypes of vascular malformations, where activating PIK3CA variants lead to dysregulated signaling that promotes abnormal cell growth, proliferation, and survival. OnKure believes its differentiated portfolio of PI3Kα inhibitors has significant potential to address a large and underserved patient population. The Company expects to provide additional details on its PI3Kα pan‑mutant program in 2026. This progression reflects the Company’s strategic expansion into indications driven by PI3Kα biology.