OnKure Therapeutics FY Conference Summary Company Overview - **Company**: OnKure Therapeutics - **Ticker**: NasdaqGM:OKUR - **Location**: Boulder, Colorado - **Focus**: Development of selective PI3K alpha inhibitors, particularly targeting mutant forms of the enzyme [2][4] Key Product: OKI-219 - **Description**: OKI-219 is the most advanced candidate targeting the PI3K alpha H1047R mutation, which represents approximately two-thirds of mutations in patient populations with mutated PI3K alpha [3][4] - **Selectivity**: OKI-219 exhibits greater than 80-fold selectivity for mutant over wild type PI3K alpha, allowing for effective dosing without significant side effects associated with wild type inhibition [5][7] - **Comparison with Competitors**: Other approved drugs like alpelisib show no selectivity, while inavolisib has only four-fold selectivity. OKI-219's high selectivity minimizes common side effects such as hyperglycemia and rash [6][7] Clinical Studies - **Current Studies**: OKI-219 is involved in three clinical studies: - Monotherapy basket study - Doublet study in combination with fulvestrant for breast cancer - Triplet studies in ER-positive and HER2-positive breast cancer [11][12] - **Data Reporting**: Efficacy data from these studies is expected to be reported in the first quarter of 2026 [13][25] Differentiation and Market Strategy - **Differentiation**: The company aims to differentiate itself by moving into front-line therapy with a well-tolerated regimen, focusing on tolerability and combinability with existing treatments [12][20] - **Target Patient Population**: The HER2-positive breast cancer cohort is noted to have a significant opportunity, despite a lower mutation frequency compared to ER-positive breast cancer [18] CNS Penetration - **Importance**: OKI-219 has a high brain-to-plasma ratio (Kp,uu of 0.6), which is crucial for treating cancers with CNS involvement, particularly HER2-positive breast cancer [15][16] Future Development Plans - **Pan-PI3K Mutant Inhibitor**: The company is also developing a pan-PI3K mutant inhibitor with greater than 10-fold selectivity across all mutants, with plans to report on these developments in the first quarter of 2026 [32] - **Regulatory Strategy**: The company is focused on minimizing risks and ensuring that their drugs do not lead to significant drug-drug interactions (DDIs) with existing therapies [34][35] Conclusion - **Overall Strategy**: OnKure Therapeutics is positioning itself to compete effectively in the oncology market by focusing on high selectivity, tolerability, and strategic partnerships in clinical studies, with a clear timeline for data disclosure and future development [31][32]