OnKure Therapeutics (OKUR) Investor Presentation summary

Strategic focus and leadership

• Developing precision medicines targeting PI3Kα mutations in cancer, especially breast cancer and vascular malformations.

• Emphasis on mutant-selective inhibitors to improve efficacy and safety over existing therapies.

• Led by an experienced team with backgrounds in major pharmaceutical and biotech companies.

• Targeting large, underserved patient populations with significant unmet needs.

• Ongoing expansion into additional indications and combination therapies.

Pipeline and clinical development

• Lead candidate OKI-219 is in Phase 1 trials for PI3KαH1047R-mutant breast cancer and solid tumors.

• PIKture-01 trial includes single agent and multiple combination arms with fulvestrant, trastuzumab, tucatinib, and ribociclib.

• Dose escalation for monotherapy and doublet arms completed; triplet arms enrolling with data expected Q1 2026.

• Additional mutant-selective inhibitor programs in preclinical and discovery stages.

• Expansion into vascular malformations planned, with further updates in 2026.

Preclinical and clinical data highlights

• OKI-219 demonstrates high mutant selectivity (~80x for H1047R vs. wild type) and strong preclinical efficacy.

• Shows excellent brain penetration, wide therapeutic margin, and combinability with standard-of-care agents.

• Well-tolerated in early clinical data, with only mild, infrequent Grade 1 adverse events and no dose-limiting toxicities.

• Sustained reduction in ctDNA and prolonged stable disease observed in patients at ≥600 mg BID.

• Overcomes resistance in preclinical models when combined with other targeted therapies.