OnKure Therapeutics (OKUR) KOL event summary

Introduction and agenda

• Focus on selectivity and pan-mutant allosteric inhibition in PI3Kα, with insights from two KOLs and a scientific presentation on molecule design and advancement.

• The event covered a differentiated portfolio targeting cryptic allosteric pockets, PI3Kα therapeutic selectivity, pipeline strategy, and included a Q&A session.

• Overview of portfolio progress, including two main candidates, OKI-355 for vascular anomalies and OKI-345 for cancer, with INDs targeted for the first half of 2027.

KOL background and credentials

• Ben Cravatt, Scripps professor and Wolf Prize recipient, is a pioneer in chemical biology, proteomics, and biotech entrepreneurship.

• Robert Abraham, Ph.D., is a leader in oncology drug development, former Pfizer Oncology R&D head, and expert in PI3K/mTOR biology, contributing to 11 FDA-approved drugs.

Market insights and analysis

• PI3Kα mutations are present in about 15% of all cancers and major subsets of vascular anomalies, nearing the prevalence of RAS mutations.

• The PI3Kα pathway is central to both normal and disease signaling, with mutant-selective inhibition offering improved therapeutic windows.

• Existing PI3Kα inhibitors like alpelisib are limited by side effects, leading to dose reductions and discontinuations.

• Next-generation inhibitors aim to reduce wild-type inhibition and associated toxicities, enabling better combination regimens.