Onkure Therapeutics, Inc. · NASDAQ:OKUR
Onkure Therapeutics — Investor Presentation (August 2026)
18 slides from Onkure Therapeutics's investor presentation, August 2026
Slide 1: OnKure Therapeutics August 2026
OnKure Therapeutics August 2026 1
Slide 2: Legends
Legends 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 statements regarding our future
Slide 3: OnKure is Developing a Differentiated Portfolio
OnKure is Developing a Differentiated Portfolio OnKure Therapeutics Pipeline • Developing PI3Kα PAN-mutant inhibitors Two Lead PI3KαPAN Programs with the highest known selectivity on helical • OKI-355 in Vascular Anomalies and kinase mutations • OKI-345 in Cancer • Two distinct candidates designed f
Slide 4: Led by a Team with Proven Experience
Led by a Team with Proven Experience Nicholas Samuel Agresta, Saccomano, Ph.D. M.D., MPH President and Chief Medical Officer Kevin S. Litwiler, Ph.D. Robbie Alton, Pharm.D. Chief Executive Officer SVP of DMPK and SVP of Clinical Operations Clinical Pharmacology James Blake, Ph.D. David Mareska, Ph.D
Slide 5: A Differentiated Portfolio
A Differentiated Portfolio Next Program Program Initial Indication Discovery Preclinical Clinical Anticipated Status Milestone OKI-355 Vascular IND-Enabling IND PI3KαPAN Anomalies Studies Ongoing (1H 2027) mutant-selective inhibitor OKI-345 Breast IND-Enabling IND PI3KαPAN Cancer Studies Ongoing (1H
Slide 6: PI3Kα Pathway is Pleiotropic: Central to Normal & Disease Signaling
PI3Kα Pathway is Pleiotropic: Central to Normal & Disease Signaling Disrupted cellular homeostasis due to mutant PI3Kα drives cancers & vascular anomalies OKI-355 OKI-345 Vascular Anomalies Oncology 6
Slide 7: Sequential Innovation Creates Durable Competitive Advantage
Sequential Innovation Creates Durable Competitive Advantage Best-in-class franchises emerge from iterative gains in potency, selectivity, resistance coverage, & safety Targeted 1st Gen 2nd Gen 3rd Gen 4th Gen Higher Potency, Enhanced Therapies First-in-Class Mutant Target Coverage Improved Therapeut
Slide 8: OnKure's Structure-Based Drug Design Platform Enables Discovery of Allosteric PI3Kα Pan-Mutant Inhibitors
OnKure’s Structure-Based Drug Design Platform Enables Discovery of Allosteric PI3Kα Pan-Mutant Inhibitors Allosteric pan-inhibitor design ATP Site • Targeting regions proximal to PI3Kα H1047 Allosteric mutations: Mutant Site − H1047 allosteric mutant site (lead) − OnKure-discovered E-mutant site (pr
Slide 9: Candidate Profile for Potential BIC PI3Kα Pan-Inhibitors
Candidate Profile for Potential BIC PI3Kα Pan-Inhibitors Discovering pan-mutant inhibitors vs. the current landscape Selectivity Efficacy Safety Coverage Comparison of cellular selectivity of OnKure vs. competitor pan-mutant At least 10X Potential Best- Broad mutant PI3Kα inhibitors in-class anti- B
Slide 10: Selectivity Provides Deeper Responses when Dosed to MTD
Selectivity Provides Deeper Responses when Dosed to MTD A wider therapeutic window allows for greater mutant target coverage OKI-345 Drives Regressions in MCF7 Cellular Selectivity vs. SK-BR-3 WT Helical (E545K) Domain Mutant Xenograft Model PI3Kα Mutation OKI-345 MCF7 TGI selectivity 700 compound H
Slide 11: OnKure's Thesis: Best-in-Class Selectivity Enables Greater Target Coverage
OnKure’s Thesis: Best-in-Class Selectivity Enables Greater Target Coverage to Unlock an Expanded Therapeutic Index inavolisib & alpelisib RLY-2608 STX-478 OKI-345 1x selectivity 2x selectivity 3x selectivity 18x selectivity Greater separation between the red & blue lines reflects an expanded therape
Slide 12: Vascular Anomalies Patients Deserve Precision Therapies
Vascular Anomalies Patients Deserve Precision Therapies Vascular anomalies are PI3Kα is a clinically validated Vascular Anomalies target monogenic targetable diseases that cause measurable functional OKI-355 – PI3Kα pan-mutant selective impairment and burden candidate; IND 1H 2027 Our approach resto
Slide 13: Available Therapies for Vascular Anomalies are Inadequate
Available Therapies for Vascular Anomalies are Inadequate Alpelisib & Rapamycin Validate PI3Kα as Target, but Wildtype Toxicity Limits Activity ALPELISIB (VIJOICE) SIROLIMUS (RAPAMYCIN) • Clinical efficacy limited by tolerably. • Not approved in any subset of vascular EPIK-P2 confirmatory study show
Slide 14: Vascular Anomalies: 86,000 Target U.S. Patient Population
Vascular Anomalies: 86,000 Target U.S. Patient Population Multi-Billion-Dollar Opportunity, Significant Patient Burden, and Inadequate Treatment Options Prevalence (U.S.)1 Approved Therapies Disease Presentation Neurologic Venous Malformations None Seizures, cognitive delays ~ 22,000 PIK3CAm Infecti
Slide 15: PIK3CA Mutated MBC Represents A Major Market Opportunity
PIK3CA Mutated MBC Represents A Major Market Opportunity A Multi-Billion-Dollar Market Opportunity ~38% of breast cancers harbor PIK3CA mutations1 OnKure’s Target Population Total Addressable Differentiation Patient Population (U.S. Patient Incidence)2 Market (TAM)2 Best-in-Class 1L HR+/HER2- mBC 10
Slide 16: Financial Overview
Financial Overview Stock Symbol NASDAQ: OKUR $176 million cash, cash equivalents, and marketable Cash securities as of June 30, 2026 Cash Runway Cash, cash equivalents, and marketable securities as of June 30, 2026 expected to fund operations into 2029 40.5 million shares of common stock plus pre-fu
Slide 17: OnKure is Developing a Differentiated Portfolio
OnKure is Developing a Differentiated Portfolio OnKure Therapeutics Pipeline • Developing PI3Kα PAN-mutant inhibitors Two Lead PI3KαPAN Programs with the highest known selectivity on helical • OKI-355 in Vascular Anomalies and kinase mutations • OKI-345 in Cancer • Two distinct candidates designed f
Slide 18: OnKure Therapeutics
OnKure Therapeutics August 2026 18
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