UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 (Mark One) FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-40315 ONKURE THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware 47-2309515 (State or other juris ...

Exhibit 99.1 OnKure Therapeutics Reports Second Quarter 2025 Financial Results and Provides a Business Update -- Cash position of $83.4M expected to provide cash runway into Q4 2026 -- PIKture-01, a phase 1 clinical trial assessing OKI-219 in patients with advanced solid tumors, including breast cancer, is on track for single agent and fulvestrant combination data in Q4 2025 -- Initiated a new expansion arm of PIKture-01 to evaluate OKI-219 in combination with fulvestrant and ribociclib in HR+ metastatic br ...

-- PIKture-01, a phase 1 clinical trial assessing OKI-219 in patients with advanced solid tumors, including breast cancer, is on track for single agent and fulvestrant combination data in Q4 2025 -- Initiated a new expansion arm of PIKture-01 to evaluate OKI-219 in combination with fulvestrant and ribociclib in HR+ metastatic breast cancer -- Initiated a new expansion arm of PIKture-01 to evaluate OKI-219 in combination with trastuzumab and tucatinib in HER2+ metastatic breast cancer -- Cash position of $ ...

OnKure Therapeutics Overview - OnKure is developing mutant-selective PI3Kα inhibitors, targeting the majority of PI3Kα-mutated cancers while preserving wild-type PI3Kα [6, 9, 11] - The company's cash and investments are expected to provide funding through multiple clinical milestones and runway into Q4 2026 [6, 55] - OKI-219 is a PI3KαH1047R mutant selective inhibitor being evaluated in a Phase 1 trial as a monotherapy and in combination with fulvestrant in breast cancer [6] OKI-219 Clinical Development - OKI-219 is in Phase 1 clinical trials (PIKture-01) with data update expected in 2H 2025 [6, 9] - PIKture-01 trial includes Part A (monotherapy) and Part B (Fulvestrant Combination) [39, 51] - Initial combination data with fulvestrant expected in 2H 2025 [52] - As of March 31, 2025, OnKure had approximately $96.7 million in cash and investments [55] PI3Kα and Market Opportunity - PI3Kα is the most frequently mutated oncogene [6, 10] - PI3KαH1047R is present in approximately 15% of breast cancers and 4% of all human cancers [15] - OKI-219 exhibits approximately 80X selectivity for PI3KαH1047R vs PI3KαWT [17, 27]

Financial Data and Key Metrics Changes - The meeting confirmed the election of two class one directors and the ratification of KPMG as the independent registered public accounting firm for the fiscal year ending December 31, 2025 [5][13]. Business Lines Data and Key Metrics Changes - No specific data or metrics related to individual business lines were discussed in the meeting [1]. Market Data and Key Metrics Changes - No specific market data or metrics were provided during the meeting [1]. Company Strategy and Development Direction and Industry Competition - The company is focused on maintaining strong governance by electing qualified directors and ensuring reliable financial oversight through the appointment of KPMG [5][13]. Management's Comments on Operating Environment and Future Outlook - Management did not provide specific comments on the operating environment or future outlook during this meeting [1]. Other Important Information - The meeting was conducted virtually, and a sufficient number of shares were present to constitute a quorum [3][4]. Summary of Q&A Session - There were no questions or comments from attendees during the Q&A session [7].

Financial Performance - For the three months ended March 31, 2025, total operating expenses were $17.0 million, an increase of $7.2 million from $9.8 million in the same period in 2024[122]. - The net loss for the three months ended March 31, 2025, was $15.9 million, compared to a net loss of $9.5 million for the same period in 2024, representing an increase of $6.4 million[122]. - Cash used in operating activities for the three months ended March 31, 2025, was $14.0 million, compared to $10.6 million for the same period in 2024, reflecting a net loss of $15.9 million in 2025[137][139]. Expenses Breakdown - Research and development expenses were $13.0 million for the three months ended March 31, 2025, compared to $8.6 million for the same period in 2024, reflecting a $4.4 million increase[123]. - General and administrative expenses increased to $4.0 million for the three months ended March 31, 2025, from $1.3 million in the same period in 2024, a rise of $2.7 million[125]. Cash and Capital Requirements - As of March 31, 2025, the accumulated deficit was $170.6 million, with cash and cash equivalents amounting to $96.7 million[111]. - The company anticipates needing additional capital to fund operations, which may be sourced from equity or debt financings, collaborations, or licensing arrangements[129]. - The company anticipates requiring substantial additional capital to complete the development of its product candidates and to build necessary sales and marketing infrastructure[133]. - The company may need to raise additional capital through equity or debt financing, which could dilute existing stockholders' ownership interests[133]. Revenue and Product Development - The company has never generated any revenue from product sales and does not expect to do so until regulatory approval is obtained for its product candidates[132]. - The company expects research and development expenses in 2025 to be higher than in 2024 due to ongoing clinical and preclinical program advancements[124]. - Future funding requirements will depend on various factors, including the success of product candidates and the costs associated with regulatory reviews[135]. - The company may be required to license rights to product candidates at earlier stages of development if sufficient capital is not obtained[134]. Other Financial Activities - Other income for the three months ended March 31, 2025, was $1.1 million, up from $0.3 million in the same period in 2024, primarily due to increased interest income[127]. - Cash flows from investing activities were $18 thousand for the three months ended March 31, 2025, compared to $9 thousand for the same period in 2024, primarily related to the purchase of property and equipment[140]. - Cash flows from financing activities showed a cash outflow of $77 thousand in 2025 related to transaction costs, while there was a cash inflow of $10 thousand in 2024 from the sale of common stock[141]. Risks and Obligations - The company is subject to risks inherent in the development of new biopharmaceutical products, which may lead to unforeseen expenses and delays[132]. - The company has significant contractual obligations and commitments, including future operating lease minimum payments[142]. - Following the merger, shares received by Legacy OnKure stockholders represented approximately 53.6% of the outstanding Common Stock[109]. - The company completed a private placement of 2,839,005 shares at approximately $22.895 per share for an aggregate of approximately $65.0 million[109].

Financial Performance - OnKure Therapeutics reported cash and cash equivalents of approximately $96.7 million as of March 31, 2025, expected to fund operations through multiple anticipated milestones into Q4 2026[5][17]. - The net loss for Q1 2025 was $15.9 million, or $1.19 per share, compared to a net loss of $9.5 million, or $30.37 per share, in Q1 2024[8][18]. - Interest income for Q1 2025 was $1.1 million, compared to $0.3 million in Q1 2024, reflecting improved cash management[18]. - Total operating expenses for Q1 2025 were $17.0 million, significantly higher than $9.8 million in Q1 2024, indicating increased investment in R&D and G&A[18]. Research and Development - Research and development (R&D) expenses increased to $13.0 million for Q1 2025, up from $8.6 million in Q1 2024, primarily due to higher personnel-related costs and clinical trial expenses[6]. - The PIKture-01 trial has completed dose escalation in Part A, with only one patient experiencing dose limiting toxicities, and a mature clinical update is expected in the second half of 2025[4][11]. - OnKure is actively enrolling patients in Part B of the PIKture-01 trial, evaluating OKI-219 in combination with fulvestrant, with no dose limiting toxicities observed to date[11]. - The company plans to announce a pan-mutant selective development candidate in Q2 2025, targeting approximately 10-fold selectivity against common PI3Ka mutations[3][11]. - OnKure aims to solidify its leadership in developing PI3K inhibitors with the ongoing PIKture-01 trial and the advancement of its pan-mutant program[2][3]. General and Administrative Expenses - General and Administrative (G&A) expenses rose to $4.0 million in Q1 2025, compared to $1.3 million in Q1 2024, driven by increased personnel-related costs and legal expenses[7].

Core Insights - OnKure Therapeutics is making progress in its PIKture-01 trial, with additional data expected in the second half of 2025, including mature single-agent and initial combination data [1][2] - The company plans to expand its PI3Ka franchise with a pan-mutant selective development candidate announcement anticipated in Q2 2025 [1][3] - As of March 31, 2025, OnKure has approximately $96.7 million in cash and cash equivalents, which is expected to fund operations through multiple anticipated milestones into Q4 2026 [1][4] Business Highlights and Upcoming Milestones - The PIKture-01 trial Part A has completed dose escalation, with only one patient experiencing dose-limiting toxicities at the highest dose level [3] - Preliminary data from Part A showed that OKI-219 was well tolerated across all dose levels, with no significant adverse events reported [3] - In Part B of the PIKture-01 trial, OnKure is actively enrolling patients to evaluate OKI-219 in combination with fulvestrant for treating PI3Kα mutated HR+/HER2- metastatic breast cancer, with initial combination data expected in the second half of 2025 [6] Financial Results - Research and development expenses for Q1 2025 were $13.0 million, an increase from $8.6 million in Q1 2024, primarily due to higher personnel-related costs and clinical trial expenses [5] - General and administrative expenses for Q1 2025 were $4.0 million, up from $1.3 million in Q1 2024, driven by increased personnel-related costs and legal expenses [7] - The net loss for Q1 2025 was $15.9 million, compared to a net loss of $9.5 million in Q1 2024, with a net loss per share of $1.19 [8][16]

Financial Performance - OnKure reported approximately $110.8 million in cash and cash equivalents as of December 31, 2024, an increase from $29.9 million in 2023[5][15]. - The net loss for Q4 2024 was $17.4 million, or $1.37 per share, compared to a net loss of $9.5 million, or $30.14 per share, in Q4 2023[7][16]. - Total operating expenses for the year ended December 31, 2024, were $54.4 million, compared to $36.9 million in 2023, representing a 47.2% increase[16]. Research and Development - Research and development (R&D) expenses for Q4 2024 were $14.4 million, up from $8.8 million in Q4 2023, reflecting a 63.6% increase[5][16]. - OnKure has completed patient enrollment in the Part A monotherapy arm of the PIKture-01 trial, with no dose limiting toxicities observed[4]. - The company initiated patient dosing in Part B of the PIKture-01 trial in Q4 2024, evaluating OKI-219 in combination with fulvestrant[8]. Administrative Expenses - General and Administrative (G&A) expenses rose to $4.3 million in Q4 2024, compared to $1.1 million in Q4 2023, marking a 290.9% increase[6][16]. Future Plans and Updates - OnKure expects to provide a clinical update on the PIKture-01 trial in the second half of 2025, with additional data from the OKI-219 program anticipated[4][3]. - OnKure plans to announce a pan-mutant development candidate in Q2 2025, targeting key mutations with approximately 10-fold selectivity[8]. Mergers and Financing - The merger with Reneo Pharmaceuticals closed on October 4, 2024, along with a $65 million financing[8].

Financial Performance - The company has incurred significant net losses of $52.7 million and $35.3 million for the years ended December 31, 2024 and 2023, respectively, with an accumulated deficit of $154.7 million as of December 31, 2024[182]. - The company expects to incur losses for the foreseeable future and might never achieve profitability, with substantial increased operating losses projected for at least the next several years[369]. - The market price of the company's Class A Common Stock has been volatile and is expected to continue to fluctuate significantly[366]. - Market volatility may adversely affect the trading price of the company's Class A Common Stock, especially during economic downturns[368]. Revenue Generation - The company has never generated any revenue from product sales and does not anticipate doing so for many years, if ever[184]. - The company expects to continue incurring significant expenses and increasing operating losses for the foreseeable future, with net losses fluctuating significantly from quarter to quarter[183]. Product Development and Regulatory Approval - The company is currently evaluating its product candidate OKI-219 in a Phase 1 clinical trial, which requires demonstrating safety and efficacy before seeking regulatory approvals[194]. - The company has not previously submitted a New Drug Application (NDA) to the FDA or similar regulatory authority for any product candidate, which is necessary for marketing approval[188]. - The regulatory approval processes for the company's product candidates are lengthy and unpredictable, and failure to obtain such approvals would significantly harm the business[202]. - The company is substantially dependent on the success of OKI-219, and any delays or failures in its clinical development could materially harm the business[193]. - The FDA's approval process for product candidates is unpredictable and can take many years, influenced by various factors including trial design and data interpretation[203]. - Regulatory authorities may require additional clinical data or disagree with trial results, potentially delaying or preventing marketing approval[204]. - Delays in patient enrollment for clinical trials can significantly impact the timeline for obtaining regulatory approvals[211]. - The company has not yet submitted for regulatory approval for any product candidates, and there is a risk that none will ever receive approval[203]. - The company plans to provide updated data from ongoing trials in the second half of 2025, with preliminary data indicating potential for further development[218]. Funding and Financial Needs - The company will need substantial additional funding to complete the development of its product candidates, with cash expected to fund operations into the fourth quarter of 2026[189]. - The company may seek to raise additional funds through equity and debt financings or strategic collaborations, but there are no assurances that sufficient funds will be secured[190]. Competition and Market Risks - There is substantial competition in the pharmaceutical industry, with competitors having greater financial resources and established market presence, which may hinder the company's ability to obtain regulatory approvals[232]. - Multiple PI3Kα-pathway targeted agents are either approved or in clinical development, posing competitive threats to OKI-219 and the company's portfolio[233]. Intellectual Property Risks - The company relies on a combination of patents and trade secrets for intellectual property protection, which is critical for the commercialization of product candidates[253]. - The patent application process is expensive and time-consuming, with no guarantee that patents will be issued or enforced effectively[256]. - There is a risk of litigation from third parties claiming infringement of their intellectual property rights, which could delay product development and commercialization[273]. - The company may face significant litigation expenses and resource diversion in defending against intellectual property claims[277]. - The company may struggle to prevent misappropriation of its intellectual property rights, especially in jurisdictions with weaker protections, which could adversely affect its operations[282]. Compliance and Regulatory Challenges - The company is subject to user fees and periodic inspections by the FDA to ensure compliance with Good Manufacturing Practices (cGMPs)[316]. - Non-compliance with regulatory requirements could result in marketing restrictions, product recalls, or withdrawal from the market[317]. - Changes in FDA policies or government regulations could delay or prevent regulatory approval of product candidates[318]. - The company may face ongoing regulatory requirements for product candidates, including safety monitoring and potential costly post-market studies[314]. Operational Risks - The company relies on third parties for clinical trials and studies, and any failure by these parties could delay regulatory approval and commercialization of product candidates[347]. - The company relies on third-party manufacturers for the production of its product candidates, which increases the risk of supply shortages and delays in clinical trials[352]. - The company does not have internal manufacturing capabilities and does not intend to develop such infrastructure, relying entirely on external partners[353]. Management and Personnel - The company is highly dependent on attracting and retaining skilled executives, with significant competition in the biotechnology field[356]. - The company may struggle to attract and retain key personnel due to intense competition in the biotechnology sector[371]. Legal and Compliance Risks - The company may face challenges in protecting its trademarks and trade names, which could adversely affect its ability to build brand recognition and compete effectively in its markets[298]. - The company may face claims regarding the wrongful use of confidential information by employees or contractors, which could result in costly litigation and loss of intellectual property rights[296].