• OK-2268: A selective Class I HDAC inhibitor in clinical development for various cancers.
• OK-1144: A selective PI3Kα H1047R inhibitor in clinical development for solid tumors with specific mutations.
• Discovery Programs: Early-stage research and development efforts for novel small-molecule drug candidates targeting cancer.

As a clinical-stage biopharmaceutical company, OnKure Therapeutics (OKUR) is primarily focused on the discovery and development of precision medicines for cancer. The company does not currently have any commercialized products approved for sale on the market.

Therefore, OnKure Therapeutics does not have "major customers" in the traditional sense of companies or individuals purchasing its products or services at this stage of its business operations.

Nicholas A. Saccomano, Ph.D., President & Chief Executive Officer

Dr. Saccomano is a biopharmaceutical professional with nearly 35 years of experience leading pharmaceutical research and development across multiple therapeutic areas. Prior to joining OnKure, he served as the Chief Science Officer and Site Head at Pfizer's Boulder facility, where he led a team of 170 research scientists focused on small molecule drug programs. He oversaw the discovery and progression of several central nervous system drugs, including ziprasidone (Geodon®), donepezil (Aricept®), and varenicline (Chantix®). Dr. Saccomano also held the position of Chief Science Officer at Array BioPharma Inc., where he was instrumental in creating and advancing ten clinical-stage compounds, leading to seven drug approvals. Furthermore, he served as Chief Technology Officer at SomaLogic Inc., managing scientific and technical teams focused on advancing the company's proteomic platform.

Jason Leverone, CPA, Chief Financial Officer

Mr. Leverone brings over 25 years of strategic finance and operational experience, with more than 19 years in the life sciences sector. Before his role at OnKure, he served as Chief Financial Officer and Secretary of miRagen Therapeutics, Inc., a publicly traded biotechnology company that was acquired in 2021 (merged with Viridian Therapeutics, Inc. in 2020). At miRagen, he played key roles in public offerings, strategic license transactions, and mergers and acquisitions. Prior to miRagen, Mr. Leverone was the Senior Director of Finance and Controller for Replidyne, Inc., another publicly traded biotechnology company acquired in 2009. He also served as Corporate Controller for CreekPath Systems, Inc., a private international software development company. He is a Certified Public Accountant (CPA) and began his professional career in public accounting at Ernst and Young LLP and Arthur Andersen LLP.

Samuel Agresta, M.D., M.P.H., Chief Medical Officer

Dr. Agresta serves as the Chief Medical Officer for OnKure Therapeutics.

Dylan Hartley, Ph.D., Chief Scientific Officer

Dr. Hartley holds the position of Chief Scientific Officer at OnKure Therapeutics.

Rogan Nunn, J.D., General Counsel & Secretary

Mr. Nunn is the General Counsel and Secretary for OnKure Therapeutics.

OnKure Therapeutics (NASDAQ: OKUR) is a clinical-stage biopharmaceutical company focused on developing precision medicines for cancers. Its lead product candidate is OKI-219, a selective inhibitor of phosphoinositide 3 kinase alpha (PI3Kα) harboring the H1047R mutation, currently in Phase 1 clinical trials for solid tumors, including breast cancer.

The addressable market for OnKure's main product, OKI-219, primarily focuses on patients with PIK3CA H1047R-mutated breast cancer and potentially other solid tumors and vascular malformations.

For breast cancer, the estimated addressable market is:

• United States (US): Approximately 140,000 patients with HR+/HER2- breast cancer have a PI3Kα mutation per year. The H1047R mutation is one of the most prevalent PIK3CA hotspot mutations, accounting for about 35%-41% of PIK3CA mutations in ER+/HER2- breast cancer and 43%-61% in HER2+ breast cancer. Based on these percentages, the number of patients with the H1047R mutation within the PI3Kα-mutated HR+/HER2- breast cancer population in the US is estimated to be tens of thousands annually.
• Global: The World Health Organization reported 2.3 million women diagnosed with breast cancer globally in 2020. PIK3CA mutations are identified in approximately 36% of all breast cancers. With the H1047R mutation being one of the most common PIK3CA mutations, often representing around 45% of all PIK3CA mutations across various studies, the global annual incidence of H1047R-mutated breast cancer is estimated to be in the hundreds of thousands of patients.

The broader market for PI3K & AKT & mTOR Pathway Inhibitors for Breast Cancer is estimated to be approximately $1,500 million globally in 2025, with a projected Compound Annual Growth Rate (CAGR) of around 18% over the forecast period of 2025-2033. OnKure Therapeutics highlights a "sizable commercial opportunity" specifically in PI3Kα-mutated HR+/HER2- and HER2+ breast cancer.

Additionally, OnKure is advancing programs in vascular malformations. A competitor's PI3Kα inhibitor is noted to have the potential to address an estimated 170,000 patients with vascular anomalies driven by a PI3Kα mutation per year in the United States.

Here are 3-5 expected drivers of future revenue growth for OnKure Therapeutics (OKUR) over the next 2-3 years:

1. Advancement of Lead Clinical Candidate (OKI-219): Successful progression and positive clinical data readouts from the PIKture-01 trial for OKI-219 are a primary driver. OnKure Therapeutics' lead product candidate, OKI-219, a selective inhibitor of phosphoinositide 3 kinase alpha (PI3Kα) harboring the H1047R mutation, is currently in Phase 1 clinical trials for solid tumors, including breast cancer. Completion of enrollment in Parts A and B, and ongoing dosing in the triplet Part E of the PIKture-01 trial, with expected updated safety, tolerability, and clinical activity data in March 2026, are critical milestones. Positive results could validate the drug's potential, attract further investment, and significantly enhance its value for future partnerships or commercialization efforts.

2. Development and Progression of Next-Generation PI3Kα Pan-Mutant Inhibitor: The planned announcement and subsequent development of a next-generation PI3Kα pan-mutant inhibitor candidate, especially for HR+ metastatic breast cancer, represents a significant expansion of OnKure's pipeline and a potential future market opportunity. The company anticipates providing additional details on this PI3Kα pan-mutant program in 2026. This new candidate, if successfully advanced, could lead to new collaborations and future revenue streams by addressing a large and underserved patient population.

3. Strategic Collaborations and Licensing Agreements: As a clinical-stage biopharmaceutical company with a pre-commercial status, OnKure Therapeutics' business model relies significantly on collaborations with larger pharmaceutical companies, licensing agreements, and milestone payments. The company actively seeks strategic partnerships to accelerate the development and potential commercialization of its innovative small-molecule therapies. Such agreements typically include upfront payments and milestone payments upon achieving specific development or regulatory goals, which would directly contribute to revenue growth over the next 2-3 years.

Share Issuance

• OnKure Therapeutics, Inc. filed a Follow-on Equity Offering in the amount of approximately $16.0 million on November 7 (likely 2024 or 2025).
• In connection with the merger that created OnKure Therapeutics (closing October 4, 2024), pre-merger OnKure, Inc. stockholders were expected to own approximately 69.4% of the combined company, and pre-merger Reneo Pharmaceuticals stockholders were expected to own approximately 30.6% on a fully-diluted basis.

Inbound Investments

• Reneo Pharmaceuticals, Inc. (the predecessor company to OnKure Therapeutics) entered into a subscription agreement for a $65 million Private Investment in Public Equity (PIPE) financing, which was expected to close concurrently with the merger in October 2024. This investment was made by a group of institutional investors including Acorn Bioventures, Cormorant Asset Management, Deep Track Capital, Perceptive Advisors, Samsara BioCapital, Surveyor Capital (a Citadel company), and Vestal Point Capital.
• The merger itself, which combined Reneo Pharmaceuticals, Inc. and OnKure, Inc. (a private company), formed the current public entity OnKure Therapeutics, Inc. The combined company was expected to have approximately $120 million of cash resources at closing.