OnKure Therapeutics (OKUR) Corporate presentation summary

Portfolio and pipeline overview

• Developing PI3Kα pan-mutant inhibitors with high selectivity for helical and kinase mutations, targeting both vascular anomalies and cancer.

• Two lead programs: OKI-355 for vascular anomalies and OKI-345 for breast cancer, both with best-in-class drug properties and IND submissions expected in 1H 2027.

• OKI-219 clinical development not pursued independently; mature data to be presented in 2026.

• Estimated US total addressable market: $7–10B for vascular anomalies and $9B for breast cancer.

• $59M cash at end of 2025 and $150M expected from financing, providing runway into 2029.

Scientific and clinical differentiation

• Structure-based drug design enables discovery of allosteric pan-mutant PI3Kα inhibitors, targeting key regulatory domains and overcoming resistance.

• Best-in-class selectivity (~10x or greater) for mutant PI3Kα, minimizing wild-type toxicities and enabling broader combination strategies.

• Demonstrated anti-tumor activity and safety in preclinical and clinical models, including activity in patients with prior PI3K inhibitor exposure.

• OKI-219 showed clinical activity and safety in doublet and triplet combinations, with no significant wild-type toxicities.

• Only known PI3K inhibitor to combine with full-dose ribociclib without significant adverse events.

Market opportunity and unmet need

• Vascular anomalies affect 86,000 US patients, with no approved therapies for most subtypes; current options limited by toxicity and efficacy.

• PI3Kα is a validated target for vascular anomalies, but existing drugs like alpelisib and sirolimus are limited by wild-type toxicity and lack of durable efficacy.

• Breast cancer market opportunity is significant, with ~38% of cases harboring PIK3CA mutations and a US TAM of $7–9B for first-line HR+/HER2- metastatic breast cancer.

• OnKure’s mutant-selective approach aims to transform standard of care and enable longer duration of therapy.