OnKure Therapeutics (OKUR) Leerink's Global Healthcare Conference 2025 summary

Company background and scientific focus

• Shifted focus three years ago to PI3K alpha mutant selective drug discovery, deprioritizing earlier programs.

• Team includes experienced scientists from ARRAY, maintaining a strong drug discovery culture.

• Based in Boulder, Colorado, benefiting from a concentration of medicinal chemistry talent.

PI3K alpha landscape and therapeutic rationale

• PI3K alpha mutations are prevalent in many solid tumors, especially breast cancer, representing a significant market.

• Selectivity is crucial to avoid wild type inhibition and associated side effects like hyperglycemia.

• Combination therapies in hormone receptor-positive and HER2-positive breast cancer are key development areas.

Lead molecule OKI-219: profile and clinical progress

• OKI-219 is highly selective for the H1047R mutation, with over 80-fold selectivity over wild type.

• Demonstrated strong tolerability and target coverage in early dose escalation, with no significant on-target toxicity.

• Dose optimization ongoing, with monotherapy escalation up to 1500 mg b.i.d. and combination studies with fulvestrant underway.

• Early ctDNA data show promising reductions in some patients, supporting further development.