Onkure Therapeutics, Inc. · NASDAQ:OKUR
Onkure Therapeutics — Investor Presentation (June 2025)
21 slides from Onkure Therapeutics's investor presentation, Jun 26, 2025
Slide 1: Corporate Overview June 2025
Corporate Overview June 2025 Exhibit 99.1
Slide 2: Forward-Looking Statements
Legends Forward-Looking Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties of OnKure Therapeutics, Inc. (“OnKure” or the “Company”). All statements other than statements of historical facts contained in this presentation, including state
Slide 3: Investment Highlights
Investment Highlights OnKure is developing a best-in-class portfolio of highly mutant-selective PI3Kα inhibitors designed to preserve wild-type PI3Kα while effectively targeting the majority of PI3Kα-mutated cancers PI3Kα is the most frequently mutated oncogene Highly selective, targeted therapies o
Slide 4: Leadership Team with Proven Experience
Nicholas Saccomano, Ph.D. President and Chief Executive Officer Leadership Team with Proven Experience Samuel Agresta, M.D., MPH Chief Medical Officer Rogan Nunn, J.D. General Counsel and Secretary Robbie Alton, Pharm SVP of Clinical Operations James Blake, Ph.D. SVP of Computational Drug Discovery
Slide 5: Mutant-Selective PI3Kα Inhibitors Targeting the Majority of PI3Kα-mutated Cancers
Mutant-Selective PI3Ka Inhibitors Targeting the Majority of PI3Ka-mutated Cancers While Preserving Wild-type PI3Ka Program/Target Indication(s) Discovery Preclinical Clinical Current Status Next Anticipated Milestone OKI-219 PI3KaH1047R mutant-selective inhibitor Breast cancer & solid tumors Phase 1
Slide 6: PI3Kα: A validated target in HR+ MBC
PI3Ka: A validated target in HR+ MBC Three approved drugs (alpelisib, capivasertib, and inavolisib) However, on-target toxicity of inhibiting wild type significantly limits dosing and decreases quality of life5,6 OnKure is developing mutant-selective inhibitors designed to preserve wild-type PI3KaH1
Slide 7: Next-Gen PI3Kα Mutant-Targeting Landscape
Alpelisib approved Inavolisib approved Phase 1: RLY-2608 & STX-478 Single-digit selectivity Initial proof of concept data Compound H1047R Alpelisib1 1 STX-4781 8.8 RLY-26082 3.8 OKI-2193 ~80 Next-Gen PI3Ka Mutant-Targeting Landscape Mutant-Selectivity is Necessary to Drive Improved Efficacy and Safe
Slide 8: PI3KαMUT Inhibitors: Potential Backbone Therapy in Combination with Approved Agents
PI3KaMUT Inhibitors: Potential Backbone Therapy in Combination with Approved Agents in Breast Cancer SERM: Selective Estrogen Receptor Modulator SERD: Selective Estrogen Receptor Degrader AI: Aromatase Inhibitor ADC: Antibody Drug Conjugate HER2 Cancer Cell Survival & Proliferation PI3Ka AKT Estroge
Slide 9: PI3Kα Mutated HR+ MBC: A Major Market Opportunity
1https://seer.cancer.gov/statfacts/html/breast-subtypes.html 2Third party research Current & Near-Term PI3Ki Treatments INAVOLISIB + palbociclib + fulvestrant ALPELISIB + fulvestrant CAPIVASERTIB + fulvestrant Treatable US Population2 ~25K ~9K ~5.5K NONE HR+ accounts for ~70% of all BrCa cases1 PI3K
Slide 10: OKI-219: Multiple Development Opportunities
Current & Near-Term PI3Ki Treatments PI3KaH1047R Mutant-Selective Drugs: Development into Poorly Served Markets INAVOLISIB + palbociclib + fulvestrant 2nd Line NONE (AI +/- CDK4/6) 1st Line OKI-219 vs. Placebo (SOC) (AI+CDK4/6 Combo) OKI-219 vs. alpelisib/capivasertib OKI-219 + next gen SERD OKI-219
Slide 11: Preclinical Safety and Efficacy Profile Shows High Potential
Preclinical Safety and Efficacy Profile Shows High Potential Demonstrated excellent brain exposure & CNS activity OKI-219 highly mutant-selective (~80X for H1047R vs. wt) inhibition leads to superior efficacy Potential for superior target coverage at accessible tolerated doses Selectivity/ Efficacy
Slide 12: Preclinical Safety and Efficacy Profile Shows High Potential
Preclinical Safety and Efficacy Profile Shows High Potential Safety Combinability Overcomes Resistance Brain Penetration Selectivity/ Efficacy
Slide 13: PIKture-01 Study Design
PIKture-01 Study Design BOIN: Bayesian Optimal Interval Design; DOR: Duration of Response; ORR: Objective Response Rate; PFS: Progression Free Survival; PAD: Pharmacologically Active Dose; PD: Pharmacodynamics, PK: Pharmacokinetics; R: Randomization; RP2D: Recommended Phase 2 Dose; SOC: Standard of
Slide 14: Pharmacokinetics: Highly Developable Candidate Profile
Pharmacokinetics: Highly Developable Candidate Profile EC80 0.1 1.0 10.0 0 2 4 6 8 10 12 Time (hr) OKI-219 Plasma Concentration (µg/mL) 300 mg (n=3) 900 mg (n=4) 600 mg (n=4) Values are geometric means with 90% CI; 12 hr point based on Day 15 pre-dose 0 10 20 30 0 200 400 600 800 1000 AUC AUClast (h
Slide 15: Only Grade 1 TRAEs Observed Across All Dose Levels
Only Grade 1 TRAEs Observed Across All Dose Levels No Hyperglycemia, Stomatitis, or Rash Observed at Any Dose OKI-219 is well tolerated across all doses Adverse events were mild and infrequent No DLTs observed No dose interruptions, delays, reductions, or discontinuations for any AEs 300 mg BID n =
Slide 16: Time on Treatment
Time on Treatment As of October 28, 2024 Patient 1 Patient 2 13/14 patients at doses ≥600 mg BID remain on study 2/3 patients at 300 mg showed prolonged stable disease Sustained >95% reduction in PIK3CAH1047R ctDNA in 300 mg BID patient who remains on study after >7 months
Slide 17: PIKture-01 Update
PIKture-01 Update As of May 6, 2025 PIKture-01 trial Part A Monotherapy Completed dose escalating and closed enrollment in Part A Dose limiting toxicities observed in only one patient to date and at the highest dose level Mature clinical update expected 2H 2025 PIKture-01 Part B Fulvestrant Combinat
Slide 18: OKI-219 Strategy: Combine with Targeted Agents Across Breast Cancer
OKI-219 Strategy: Combine with Targeted Agents Across Breast Cancer HER2 Cancer Cell Survival & Proliferation PI3Ka AKT Estrogen Receptor Transcription G1 G2 M Cell Cycle S RTK Fulvestrant (generic) Camizestrant (AZ) Vepdegestrant (Pfizer) Palazestrant (Olema) Giredestrant (Roche) Imlunestrant (Lill
Slide 19: Financial Overview
Financial Overview Stock Symbol Common Stock 13.4 million shares of common stock outstanding March 31, 2025 Cash and investments expected to provided funding through multiple clinical data readouts and runway into 4Q 2026 Approximately $96.7 million as of March 31, 2025 NASDAQ: OKUR Cash Runway Cash
Slide 20: Summary: OnKure is Developing Innovative Precision Medicines for Patients
Summary: OnKure is Developing Innovative Precision Medicines for Patients Focused team with remarkable success in precision medicine Ongoing PIKture-01 trial evaluating OKI-219 single agent and in combination with other agents Supported by committed investors Mutation-specific approach to a validate
Slide 21: Writing the Next Chapter in Precision Medicines for Patients with Cancer
WRITING THE NEXT CHAPTER IN PRECISION MEDICINES FOR PATIENTS WITH CANCER
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