OnKure Therapeutics (OKUR) Stifel 2025 Virtual Targeted Oncology Forum summary

Company overview and scientific background

• Pivoted to precision oncology, focusing on PI3Kα mutant selective molecules, with a team including ARRAY alumni.

• Built a portfolio of mutant selective inhibitors, with OKI-219 as the lead candidate in clinical expansion studies.

• ARRAY's legacy has contributed to a robust biotech ecosystem and talent pool.

Scientific rationale and drug development challenges

• PI3Kα is the most frequently mutated protein in solid tumors, especially breast cancer, and is a key oncogenic driver.

• Selectivity for mutant over wild-type PI3Kα is critical to avoid dose-limiting toxicities like hyperglycemia.

• Allosteric inhibitors offer higher selectivity due to the spatial separation of mutations from the active site.

• Allosteric sites are linked to protein function and can be exploited for pan-mutant selectivity.

OKI-219 development and clinical progress

• OKI-219 targets the H1047R mutant in breast cancer, aiming for high selectivity and brain penetration.

• Early clinical data show dose proportionality, good tolerability, and no wild-type inhibition toxicities.

• Monotherapy studies included heavily pretreated patients, some with prior PI3K inhibitor exposure and brain metastases.

• Stable disease observed at lower doses; more mature efficacy data expected in the second half of the year.