OnKure Therapeutics (OKUR) Stifel 2025 Healthcare Conference summary

Strategic focus and portfolio development

• Targeting PI3K alpha mutations in cancer, with a focus on breast cancer and emerging opportunities in vascular malformations.

• Developing highly selective molecules to improve efficacy and tolerability, including OKI-219 and pan-mutant selective candidates.

• Portfolio includes assets for H1047R and E542K mutations, with a risk-adjusted approach to advance the most promising candidates based on data.

• Team has deep kinase inhibitor expertise, leveraging experience from Array BioPharma.

• $70 million in cash and equivalents as of September 30, supporting ongoing and future development.

Clinical development and trial updates

• OKI-219 is in advanced clinical trials, including monotherapy, doublet, and triplet studies in breast cancer.

• Dose escalation for monotherapy completed; combination studies with fulvestrant, ribociclib, trastuzumab, and tucatinib are ongoing.

• Triplet studies in HR-positive and HER2-positive breast cancer are enrolling, with data on combinability, tolerability, and early efficacy expected in Q1 2026.

• Tablets introduced to improve dosing consistency and cost-effectiveness for registrational studies.

• Inclusion criteria allow prior PI3K inhibitor exposure, with strategic focus on patient populations most likely to benefit.

Differentiation and competitive positioning

• OKI-219 demonstrates over 80-fold selectivity for mutant PI3K alpha, surpassing competitors and reducing wild-type toxicity.

• High brain penetration and favorable safety profile, with no notable adverse events at any dose level to date.

• Designed for combinability with standard-of-care agents, addressing a key requirement for adoption in treatment regimens.

• Competitive benchmarking will focus on efficacy, tolerability, and combinability versus other agents in cross-trial analyses.

• Success defined by achieving similar or better efficacy with improved side effect profile and regimen compatibility.