OnKure Therapeutics (OKUR) investor relations material

Differentiated portfolio and pipeline

• Developing PI3Kα pan-mutant inhibitors with high selectivity for helical and kinase mutations, targeting both vascular anomalies and cancer.

• Two lead candidates: OKI-355 for vascular anomalies and OKI-345 for cancer, both in IND-enabling studies with IND submissions expected in 1H 2027.

• Discovery programs are ongoing for novel targets beyond PI3Ka in vascular anomalies.

• $176 million in cash and marketable securities as of June 30, 2026, expected to fund operations into 2029.

• Experienced R&D team with backgrounds from leading biotech and pharma companies.

Scientific and clinical innovation

• Structure-based drug design platform enables discovery of allosteric PI3Kα pan-mutant inhibitors targeting key regulatory regions.

• Candidates demonstrate at least 10x selectivity in cell lines with major hotspot mutations, with broad mutant coverage and brain penetration.

• OKI-345 and OKI-355 show superior selectivity and efficacy over competitors, with potential to overcome resistance and minimize wild-type toxicities.

• Expanded therapeutic window expected to reduce risk of hyperglycemia and improve safety profile.

Market opportunities and unmet needs

• Vascular anomalies represent a target US patient population of ~86,000, with significant unmet need due to limited approved therapies and wild-type toxicity of current options.

• PIK3CA-mutated metastatic breast cancer (MBC) is a multi-billion-dollar market, with ~38% of breast cancers harboring these mutations.

• Current therapies like alpelisib and sirolimus are limited by toxicity and efficacy, highlighting the need for mutant-selective approaches.