OKUR

-- Executing IND-enabling activities for next-generation PI3Kα pan-mutant selective candidates OKI-345 in breast cancer and OKI-355 in vascular anomalies, with IND submissions planned for 1H 2027 -- Hosted a Key Opinion Leader event highlighting the evolving PI3Kα treatment landscape and the scientific rationale supporting OnKure's next-generation PI3Kα pan-mutant inhibitor programs -- Participated as an exhibitor and sponsor at the ISSVA World Congress 2026 in Philadelphia, supporting engagement with leading vascular anomalies clinicians and researchers -- $176 million of cash, cash equivalents and marketable securities expected to fund operations into 2029 BOULDER, Colo., Aug. 04, 2026 (GLOBE NEWSWIRE) -- OnKure Therapeutics, Inc. (Nasdaq: OKUR), a clinical-stage biopharmaceutical company focused on developing novel precision medicines, today reported financial results for the second quarter ended June 30, 2026, and provided recent business highlights. “Following our strategic transformation earlier this year, we continue to advance our next-generation PI3Kα pan-mutant selective inhibitor pipeline, which we believe represents the most compelling opportunity to deliver differentiated therapies across PI3Kα-driven diseases,” said Nicholas Saccomano, Ph.D., President and Chief Executive Officer of OnKure. “Both OKI-355 and OKI-345 continue to advance through IND-enabling activities and remain on track for planned IND submissions in the first half of 2027. We believe the combination of our chemistry platform and deep understanding of PI3Kα biology positions us to develop differentiated therapies with the potential to meaningfully improve outcomes for patients. Our recent Key Opinion Leader event reinforced the scientific rationale underpinning our strategy and highlighted the significant opportunity for next-generation PI3Kα pan-mutant selective inhibitors to overcome the limitations of current therapies across multiple disease settings.” Vascular Anomalies OnKure continues to advance OKI-355, a next-generation PI3Kα pan-mutant-selective inhibitor candidate announced in March 2026 to lead its development pipeline in vascular anomalies. OKI-355 has been designed to selectively inhibit mutant PI3Kα while sparing wildtype PI3Kα, potentially enabling a wider therapeutic index and avoidance of class-limiting toxicities. High and sustained target coverage across all hotspot PI3Kα mutations can support the potential for deep and durable responses in vascular anomalies. OnKure plans to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for OKI-355 in the first half of 2027. Additionally, earlier this year, OnKure initiated a discovery research program to expand its vascular anomalies pipeline beyond targeting PI3Kα. Breast Cancer In breast cancer, OnKure continues to advance OKI-345, a next-generation PI3Kα pan-mutant-selective inhibitor candidate selected in March 2026. OKI-345 has been designed to selectively inhibit mutant PI3Kα while sparing wildtype PI3Kα, potentially enabling a wider therapeutic index and avoidance of class-limiting toxicities. High and sustained target coverage across all hotspot PI3Kα mutations can support the potential for deep and durable responses in breast cancer, both as monotherapy and in combination. OnKure plans to submit an IND application to the FDA for OKI-345 in the first half of 2027. Scientific Engagement OnKure recently hosted a virtual Key Opinion Leader event titled "Selectivity Matters and Pan-Mutant Allosteric Inhibition Delivers," featuring Benjamin F. Cravatt, Ph.D., of Scripps Research, and Robert Abraham, Ph.D., Chief Scientific Officer of Engine Biosciences. The discussion explored the scientific rationale supporting next-generation PI3Kα pan-mutant selective inhibitors, including the importance of PI3Kα selectivity, the potential to overcome limitations of current therapies, and the Company's structure-based drug design approach. OnKure also participated as an exhibitor and sponsor at the International Society for the Study of Vascular Anomalies (ISSVA) World Congress 2026 in Philadelphia, held in May. Financial Results Cash position: As of June 30, 2026, the Company reported cash, cash equivalents, and marketable securities of $176.4 million, which is expected to provide cash runway into 2029. Research and development (R&D) expenses: R&D expenses were $12.6 million for both the second quarter of 2026 and the second quarter of 2025. During the second quarter of 2026, an increase in clinical trial and outsourced manufacturing expenses was offset by a decrease in outsourced preclinical R&D expenses. General and Administrative (G&A) expenses: G&A expenses were $4.3 million for the second quarter of 2026, compared to $3.7 million for the second quarter of 2025. The increase of $0.6 million was primarily driven by increases in personnel-related and consulting costs. Net loss and net loss per share were $15.3 million, or $0.31 per share, for the second quarter of 2026, compared to $15.4 million, or $1.14 per share, for the second quarter of 2025. About OnKure Therapeutics OnKure Therapeutics (Nasdaq: OKUR) is a clinical-stage biopharmaceutical company focused on the discovery and development of best-in-class precision medicines that target biologically validated drivers of vascular anomalies and cancers that are underserved by available therapies. Using a structure and computational chemistry-driven drug design platform, OnKure is committed to improving clinical outcomes for patients by building a pipeline of small molecule drugs designed to selectively target specific mutations thought to be key drivers of vascular anomalies and cancer. OnKure aims to become a leader in targeting PI3Kα and has multiple programs designed to enable best-in-class targeting of this important molecular target. For more information about OnKure, visit us at www.onkure.com and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding, OnKure’s product candidates and programs, including OKI-355 and OKI-345; OnKure’s ability to discover, develop and advance additional programs; expected milestones and the timing of such milestones, including the submission of IND applications for OKI-355 and OKI-345; OnKure’s expected cash runway; and statements by OnKure’s President and Chief Executive Officer. In some cases, you can identify forward-looking statements by terminology such as “believe,” “expect,” “estimate,” “intend,” “may,” “plan,” “potentially,” “will” or the negative of these terms or other similar expressions. These forward-looking statements are based largely on OnKure’s current expectations and projections about future events and trends that OnKure believes may affect its financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: OnKure’s limited operating history; the significant net losses incurred since inception; the ability to raise additional capital to finance operations; the risk that actual uses of cash and cash equivalents differ from the assumptions underlying OnKure’s expected cash runway; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize, OnKure’s product candidates; the outcome of preclinical testing and early clinical trials for OnKure’s product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements and the potential that the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials; OnKure’s limited resources; the risk of adverse events, toxicities or other undesirable side effects; potential delays or difficulties in the enrollment or maintenance of patients in clinical trials; the decision to develop or seek strategic collaborations to develop OnKure’s current or future product candidates in combination with other therapies and the cost of combination therapies; OnKure’s limited experience in designing clinical trials and lack of experience in conducting clinical trials; the substantial competition OnKure faces in discovering, developing, or commercializing products; OnKure’s ability to protect its intellectual property and proprietary technologies; developments relating to OnKure’s competitors and its industry, including competing product candidates and therapies; reliance on third parties, contract manufacturers, and contract research organizations; legislative, regulatory, political and economic developments and general market conditions; and those risks described in the section entitled “Risk Factors” in documents that OnKure files from time to time with the SEC, including its Annual Report on Form 10-K filed with the SEC on March 12, 2026, its Quarterly Report on Form 10-Q for the quarter ended June 30, 2026 filed with the SEC on August 4, 2026, and any subsequent filings with the SEC. These risks are not exhaustive. New risk factors emerge from time to time, and it is not possible for OnKure’s management to predict all risk factors, nor can OnKure assess the impact of all factors on OnKure’s business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although OnKure believes that the expectations reflected in the forward-looking statements are reasonable, OnKure cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, OnKure undertakes no obligation to update publicly any forward-looking statements for any reason after the date of this press release. Contact: Dan FerryLifeSci [email protected]

-- Announced nomination of OKI-355, a next-generation PI3Kα pan-mutant selective inhibitor candidate, in vascular anomalies -- Initiated a discovery research program to expand the company’s pipeline in vascular anomalies -- Announced nomination of OKI-345, a next generation PI3Kα pan-mutant selective inhibitor candidate, in breast cancer -- Closed $150 million private placement to advance next-generation PI3Kα pan-mutant programs into clinical development in 2027 -- $192 million cash and cash equivalents as of March 31, 2026, expected to fund operations into 2029 BOULDER, Colo., May 05, 2026 (GLOBE NEWSWIRE) -- OnKure Therapeutics, Inc. (Nasdaq: OKUR), a clinical-stage biopharmaceutical company focused on developing novel precision medicines, today reported financial results for the first quarter ended March 31, 2026, and provided recent business highlights. “During the first quarter, we sharpened our strategic focus on advancing our next generation PI3Kα pan-mutant selective inhibitor programs, which we believe represent the most compelling opportunity to deliver differentiated therapies across PI3Kα-driven diseases,” said Nicholas Saccomano, Ph.D., President and Chief Executive Officer of OnKure. “Building on insights gained from our earlier clinical and translational work, we have advanced two highly selective pan-mutant development candidates that were purpose designed to achieve robust target coverage while avoiding class limiting toxicities. As we move forward with OKI-355 in vascular anomalies and OKI-345 in breast cancer, our focus is on translating the strengths of our chemistry platform and deep understanding of PI3Kα biology into programs with the potential to deliver meaningful, differentiated, and durable benefit to patients.” Vascular Anomalies OnKure recently announced the selection of OKI-355, an advanced next-generation PI3Kα pan-mutant selective inhibitor candidate, to lead its development pipeline in vascular anomalies. OKI-355 has been designed to selectively inhibit mutant PI3Kα while sparing wildtype PI3Kα, potentially enabling a wider therapeutic index and avoidance of class-limiting toxicities. High and sustained target coverage across all hotspot PI3Kα mutations can support the potential for deep and durable responses in vascular anomalies. Additionally, the Company initiated a discovery research program to expand OnKure’s pipeline in vascular anomalies. OnKure plans to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for OKI‑355 in the first half of 2027. Breast Cancer OnKure recently announced the selection of OKI-345, an advanced next-generation PI3Kα pan-mutant selective inhibitor candidate in breast cancer. Like OKI-355, OKI-345 has been designed to selectively inhibit mutant PI3Kα while sparing wildtype PI3Kα, potentially enabling a wider therapeutic index and avoidance of class-limiting toxicities. High and sustained target coverage across all hotspot PI3Kα mutations can support the potential for deep and durable responses in breast cancer, both as monotherapy and in combination. OnKure plans to submit an IND application to the FDA for OKI‑345 in the first half of 2027. Given the Company’s strategic focus on advancing its next-generation PI3Kα pan-mutant inhibitors, OnKure is not planning to independently pursue further clinical development of OKI-219, a highly selective PI3KαH1047 mutant-specific inhibitor, at this time. The Company plans to report data from PIKture-01 by the end of 2026. Additional information about PIKture-01 may be found at www.ClinicalTrials.gov, using Identifier: NCT06239467. Upcoming Conference OnKure will participate as an exhibitor and sponsor in the International Society and Study of Vascular Anomalies (ISSVA) World Congress 2026 in Philadelphia, May 19-22, 2026. Financial Results Cash and cash equivalents were $192.1 million as of March 31, 2026, including proceeds from the oversubscribed $150 million private placement, which closed on March 31, 2026. Research and development (R&D) expenses were $11.7 million for the first quarter of 2026, compared to $13.0 million for the first quarter of 2025. The decrease of $1.3 million was primarily driven by a decrease in outsourced R&D related expenses, partially offset by increased clinical trial costs. General and Administrative (G&A) expenses were $3.9 million for the first quarter of 2026, compared to $4.0 million for the first quarter of 2025. The decrease of $0.1 million was primarily driven by a decrease in legal and filing service costs, partially offset by increased personnel-related costs. Net loss and net loss per share were $15.2 million, or $1.11 per share, for the first quarter of 2026, compared to $15.9 million, or $1.19 per share, for the first quarter of 2025. About the PIKture-01 Study PIKture-01 is a global, multi-center, dose-escalation, first-in-human phase 1a/1b study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and efficacy of OKI-219 as monotherapy and in combination with other anti-cancer drugs for the treatment of HR+ and HER2+ advanced breast cancer. As of March 26, 2026, the PIKture-01 trial has completed enrollment in single-agent OKI-219 dose escalation (n=38) and OKI-219 + fulvestrant dose escalation (n=33). Phase 2 dose evaluation in the OKI-219 + tucatinib and trastuzumab triplet and the OKI-219 + ribociclib and fulvestrant triplets will be completed in 2026. Given the progress of the Company’s PI3Kα pan-mutant inhibitors, OnKure is not planning to pursue further clinical development of OKI-219 independently at this time. Additional information about PIKture-01 may be found at www.ClinicalTrials.gov, using Identifier: NCT06239467. About OnKure Therapeutics OnKure Therapeutics (Nasdaq: OKUR) is a clinical-stage biopharmaceutical company focused on the discovery and development of best-in-class precision medicines that target biologically validated drivers of vascular anomalies and cancers that are underserved by available therapies. Using a structure and computational chemistry-driven drug design platform, OnKure is committed to improving clinical outcomes for patients by building a pipeline of small molecule drugs designed to selectively target specific mutations thought to be key drivers of vascular anomalies and cancer. OnKure aims to become a leader in targeting PI3Kα and has multiple programs designed to enable best-in-class targeting of this key oncogene. For more information about OnKure, visit us at www.onkure.com and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding, OnKure’s product candidates and programs, including OKI-355 and OKI-345; OnKure’s ability to advance additional programs; expected milestones and the timing of such milestones, including additional data from, and completion of enrollment in, the PIKture-01 trial, and the submission of IND applications for OKI-355 and OKI-345; OnKure’s expected cash runway; and statements by OnKure’s President and Chief Executive Officer. In some cases, you can identify forward-looking statements by terminology such as “expect,” “estimate,” “intend,” “may,” “plan,” “potentially,” “will” or the negative of these terms or other similar expressions. These forward-looking statements are based largely on OnKure’s current expectations and projections about future events and trends that OnKure believes may affect its financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: OnKure’s limited operating history; the significant net losses incurred since inception; the ability to raise additional capital to finance operations; the risk that actual uses of cash and cash equivalents differ from the assumptions underlying OnKure’s expected cash runway; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize, OnKure’s product candidates; the outcome of preclinical testing and early clinical trials for OnKure’s product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements and the potential that the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials; OnKure’s limited resources; the risk of adverse events, toxicities or other undesirable side effects; potential delays or difficulties in the enrollment or maintenance of patients in clinical trials; the decision to develop or seek strategic collaborations to develop OnKure’s current or future product candidates in combination with other therapies and the cost of combination therapies; OnKure’s limited experience in designing clinical trials and lack of experience in conducting clinical trials; the substantial competition OnKure faces in discovering, developing, or commercializing products; OnKure’s ability to protect its intellectual property and proprietary technologies; developments relating to OnKure’s competitors and its industry, including competing product candidates and therapies; reliance on third parties, contract manufacturers, and contract research organizations; legislative, regulatory, political and economic developments and general market conditions; and those risks described in the section entitled “Risk Factors” in documents that OnKure files from time to time with the SEC, including its Report on Form 10-Q filed with the SEC on May 5, 2026 and any subsequent filings with the SEC. These risks are not exhaustive. New risk factors emerge from time to time, and it is not possible for OnKure’s management to predict all risk factors, nor can OnKure assess the impact of all factors on OnKure’s business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although OnKure believes that the expectations reflected in the forward-looking statements are reasonable, OnKure cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, OnKure undertakes no obligation to update publicly any forward-looking statements for any reason after the date of this press release. Contact: Dan Ferry LifeSci Advisors [email protected] ONKURE THERAPEUTICS, INC. Condensed Consolidated Balance Sheets (In thousands, unaudited) ONKURE THERAPEUTICS, INC. Condensed Consolidated Statements of Operations and Comprehensive Loss (In thousands, except share and per share data, unaudited)

Thermo Fisher Scientific TMO is set to release first-quarter 2026 results on April 23, before the market opens. In the last reported quarter, the company posted adjusted earnings per share (EPS) of $6.57, which surpassed the Zacks Consensus Estimate by 2.18%. The company’s earnings topped estimates in each of the trailing four quarters, the average surprise being 2.78%. The Zacks Consensus Estimate for revenues is pegged at $10.83 billion, indicating an increase of 4.5% from the year-ago reported figure. The same for the company’s EPS implies a 1.2% year-over-year rise to $5.21. Estimates for Thermo Fisher’s Q1 earnings have remained constant at $5.21 in the past 30 days. Here’s a brief review of the company’s performance leading up to the announcement. Similar to recent quarters, the segment’s revenues are likely to have been driven by the Bioproduction business. Within this, Thermo Fisher expanded the single-use portfolio with the launch of the Thermo Scientific 5-liter DynaDrive single-use bioreactor, which might have improved workflow efficiencies for the pharma and biotech customers. Other recent high-impact innovations include two chemically-defined formulations within the Gibco Bacto CD portfolio and the Gibco Efficient-Pro Medium (+) Insulin for insulin-dependent CHO cell lines. The company also expanded its bioprocessing capabilities across Asia, an emerging global hub for biopharmaceutical innovation. Further, the addition of the Filtration and Separation business from Solventum has further strengthened the Bioproduction offerings with advanced filtration technologies and industrial filtration and membrane solutions. We expect all these developments to have positively boosted revenues in the first quarter of 2026. Per the Zacks Consensus Estimate, the Life Sciences Solutions revenues are expected to increase 7.9% year over year. In the first quarter, the segment’s revenues might have been aided by robust growth in the chromatography and mass spectrometry business. On the innovation front, Thermo Fisher introduced the Scios 3 and Talos 12 electron microscopes and an enterprise-ready compliance-focused software platform called Chromeleon 7.4 that unifies chromatography and mass spectrometry workflows. Thermo Fisher Scientific Inc. price-eps-surprise | Thermo Fisher Scientific Inc. Quote The company also launched Orbitrap Exploris EFOX Mass Detector, aimed at detecting per- and polyfluoroalkyl substances, pesticides and other pollutants in food and water quality testing. In addition, TMO and NVIDIA have teamed up to leverage the NVIDIA Artificial Intelligence platform and Thermo Fisher Scientific solutions to progressively increase the automation, accuracy and speed of laboratories. Combined, these developments are likely to have supported the quarter’s revenue performance. Per the Zacks Consensus Estimates, revenues in this segment are projected to increase 1.3% year over year. The segment’s revenues in the first quarter are likely to have been led by the clinical diagnostics, transplant diagnostics and immunodiagnostics businesses. Recent launches include the Thermo Scientific Brilliance Candida 2 Agar and Spectra Candida Agar, new color-based (chromogenic) culture media to help quickly detect and differentiate clinically important Candida species. The company also introduced a new laboratory-developed test to help transplant patients receive the right dose of critical anti-rejection medication faster. Further, Thermo Fisher’s Ion Torrent Oncomine Dx Target Test has been FDA-approved as a companion diagnostic (CDx) to identify patients who may be eligible for treatment with Bayer’s HYRNUO (sevabertinib). The test is already widely accessible thanks to its broad reimbursement coverage. We expect Thermo Fisher’s top-line in the first quarter of 2026 to have been positively impacted by these factors. The Zacks Consensus Estimate projects the segment’s revenues to grow 1.2% year over year. The segment’s organic revenues are expected to have benefited from the strength across the research and safety market channel and the pharma services and clinical research businesses. Besides, the 2023 acquisition of CorEvitas has added highly complementary real-world evidence solutions to the segment’s portfolio, enhancing decision-making as well as the time and cost of drug development. In February, the PPD clinical research business announced a strategic data collaboration with Datavant, under which its data linkage technology will be combined with Thermo Fisher’s deep clinical research expertise and infrastructure to bring richer, more connected patient data into the research process. Per the Zacks Consensus Estimate, revenues in this segment are projected to increase 2% year over year in the first quarter of 2026. Per our proven model, a stock with a Zacks Rank #1 (Strong Buy), 2 (Buy) or 3 (Hold), along with a positive Earnings ESP, has a higher chance of beating estimates, which is exactly the case here, as you can see below. Earnings ESP: Thermo Fisher has an Earnings ESP of +1.23%. You can uncover the best stocks to buy or sell before they’re reported with our Earnings ESP Filter. Zacks Rank: The company currently carries a Zacks Rank #3. You can see the complete list of today’s Zacks Rank #1 stocks here. Here are some other medical stocks worth considering, as these also have the right combination of elements to post an earnings beat this time: Agenus AGEN has an Earnings ESP of +7.69% and a Zacks Rank #1. The company is expected to release first-quarter 2026 results soon. In the trailing four quarters, AGEN delivered an average surprise of 31.42%. The Zacks Consensus Estimate for the company’s first-quarter EPS is expected to increase 289.3% from the year-ago quarter’s figure. The Ensign Group ENSG has an Earnings ESP of +2.38% and a Zacks Rank #1. The company is expected to release first-quarter 2026 results soon. ENSG’s earnings surpassed estimates in each of the trailing four quarters, the average surprise being 2.93%. The Zacks Consensus Estimate for the company’s first-quarter EPS calls for an increase of 17.8% from the year-ago quarter’s figure. OnKure Therapeutics OKUR has an Earnings ESP of +10.74% and a Zacks Rank #2. The company is expected to release first-quarter 2026 results soon. OKUR’s earnings beat estimates in each of the trailing four quarters, the average surprise being 10.06%. The Zacks Consensus Estimate for the company’s first-quarter loss per share is pegged at up 31.9% from the year-ago reported figure. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Thermo Fisher Scientific Inc. (TMO) : Free Stock Analysis Report Agenus Inc. (AGEN) : Free Stock Analysis Report The Ensign Group, Inc. (ENSG) : Free Stock Analysis Report OnKure Therapeutics, Inc. (OKUR) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

-- Data from the ongoing PIKture-01 trial is expected to be announced in March 2026; continued enrollment in breast cancer triplet combinations -- Next-generation PI3Kα pan-mutant inhibitor development candidate for HR+ metastatic breast cancer is expected to be announced in March 2026 -- Approximately $59M in cash and cash equivalents at the end of Q4 2025 BOULDER, Colo., March 12, 2026 (GLOBE NEWSWIRE) -- OnKure Therapeutics, Inc. (Nasdaq: OKUR), a clinical-stage biopharmaceutical company focused on developing novel precision medicines, today reported financial results for the fourth quarter and full year ended December 31, 2025, and provided recent business highlights. “We are pleased with the continued progress across our PI3Kα‑focused pipeline, including the steady execution of the PIKture‑01 trial of OKI-219. We look forward to sharing updated data from this trial later this month,” said Nicholas Saccomano, Ph.D., President and Chief Executive Officer of OnKure. “We are also excited to announce our next‑generation pan‑mutant inhibitor development candidate for HR+ metastatic breast cancer this month and provide additional information on our program in vascular malformations later this year. Overall, we believe our progress to date underscores the power of our mutation‑selective approach to PI3Kα inhibition and reinforces the momentum we are building as we work to deliver scientifically differentiated therapies to patients.” OKI-219 Program Highlights OnKure’s lead product candidate, OKI-219, is a highly selective PI3kαH1047 mutant specific inhibitor. OKI-219 is being evaluated in the PIKture-01 phase 1a/1b clinical trial for the treatment of patients with HR+ and HER2+ metastatic breast cancer. Parts A and B – Enrollment in both the monotherapy and fulvestrant combination dose escalation arms of the PIKture-01 trial has been completed and closed. A total of 71 patients have been dosed across both arms: 38 in monotherapy and 33 in combination with fulvestrant. The Company expects to report updated safety, tolerability, and clinical activity data from Parts A and B in March 2026. Part E – The Company continues to enroll patients with PI3KαH1047R mutated, HR+ metastatic breast cancer in the triplet expansion arm evaluating OKI-219 in combination with fulvestrant and ribociclib. A total of 17 patients have been dosed with OKI-219 in combination with fulvestrant and ribociclib. The Company expects to report initial safety, tolerability, and clinical activity data from Part E in March 2026. Part C – The Company continues to enroll patients with PI3KαH1047R mutated, HER2+ breast cancer in the triplet expansion arm evaluating OKI-219 in combination with trastuzumab and tucatinib. The Company expects to report initial data from Part C in 2026. Next-Generation PI3KαPAN Mutant Selective Program OnKure expects to announce its next-generation PI3Kα pan-mutant inhibitor candidate for HR+ metastatic breast cancer in March 2026. Additionally, PI3Kα mutations represent the most common driver alterations in key subtypes of vascular malformations, where activating PIK3CA variants lead to dysregulated signaling that promotes abnormal cell growth, proliferation, and survival. OnKure believes its differentiated portfolio of PI3Kα inhibitors has significant potential to address a large and underserved patient population. The Company expects to provide additional details on its PI3Kα pan‑mutant program in 2026. This progression reflects the Company’s strategic expansion into indications driven by PI3Kα biology. Financial Results Cash and cash equivalents were approximately $59.1 million as of December 31, 2025. Research and development (R&D) expenses were $10.7 million for the fourth quarter of 2025, compared to $14.4 million for the fourth quarter of 2024. The decrease of $3.6 million was primarily driven by a decrease in consulting, outsourced R&D, clinical trial, and manufacturing related expenses in addition to lower personnel-related costs. General and Administrative (G&A) expenses were $3.4 million for the fourth quarter of 2025, compared to $4.3 million for the fourth quarter of 2024. The decrease of $0.9 million was primarily driven by a decrease in personnel-related costs and consulting and professional service expenses including audit, tax, insurance, board of director compensation, and other consulting expenses. Net loss and net loss per share for the fourth quarter of 2025 were $13.5 million, or $0.99 per share, compared to $17.4 million, or $1.37 per share, for the fourth quarter of 2024. About PIKture-01 Study PIKture-01 is a global, multi-center, dose-escalation, first-in-human phase 1a/1b study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and efficacy of OKI-219 as monotherapy and in combination with other anti-cancer drugs. Phase 1a (Part A) of the study is investigating escalating doses of OKI-219 monotherapy, and Phase 1b is currently investigating OKI-219 (at a tolerated dose determined in Part A) in combination with fulvestrant (Part B), trastuzumab and tucatinib (Part C), and ribociclib and fulvestrant (Part E). Participants will continue to receive study treatment until disease progression, intolerable toxicity, or other study treatment withdrawal criteria are met. Additional information about PIKture-01 may be found at www.ClinicalTrials.gov, using Identifier: NCT06239467. About OnKure Therapeutics OnKure Therapeutics (Nasdaq: OKUR) is a clinical-stage biopharmaceutical company focused on the discovery and development of best-in-class precision medicines that target biologically validated drivers of cancers and other diseases that are underserved by available therapies. Using a structure-based drug design platform, OnKure is building a pipeline of small molecule drugs designed to achieve optimal efficacy and tolerability by selectively targeting specific mutations shown to be key drivers of cancer and other diseases. OnKure is currently developing OKI-219, a highly selective PI3KαH1047R inhibitor, as its lead program. OnKure aims to become a leader in targeting oncogenic PI3Kα and has multiple programs designed to enable best-in-class targeting of this key oncogene. For more information about OnKure, visit us at www.onkure.com and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release, including statements regarding our future financial condition, results of operations, business strategy and plans, and objectives of management for future operations, as well as statements regarding industry trends, are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding, OnKure’s product candidates and programs, including OKI-219 and the pan-mutant program; OnKure’s ability to advance additional programs; the expected milestones and timing of such milestones, including additional data for OKI-219 from the PIKture-01 trial, the anticipated development candidate announcement and details on the pan-mutant program; statements regarding OnKure’s financial position, including its liquidity, cash runway and the sufficiency of its cash resources; and statements by OnKure’s President and Chief Executive Officer. In some cases, you can identify forward-looking statements by terminology such as “estimate,” “intend,” “may,” “plan,” “potentially” “will” or the negative of these terms or other similar expressions. We based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things, OnKure’s limited operating history; the significant net losses incurred since inception; the ability to raise additional capital to finance operations; the risk that actual uses of cash and cash equivalents differ from the assumptions underlying our expected cash runway; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize, OnKure’s product candidates; the outcome of preclinical testing and early clinical trials for OnKure’s product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements and the potential that the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials; OnKure’s limited resources; the risk of adverse events, toxicities or other undesirable side effects; potential delays or difficulties in the enrollment or maintenance of patients in clinical trials; the decision to develop or seek strategic collaborations to develop OnKure’s current or future product candidates in combination with other therapies and the cost of combination therapies; OnKure’s limited experience in designing clinical trials and lack of experience in conducting clinical trials; the substantial competition OnKure faces in discovering, developing, or commercializing products; OnKure’s ability to protect its intellectual property and proprietary technologies; developments relating to OnKure’s competitors and its industry, including competing product candidates and therapies; reliance on third parties, contract manufacturers, and contract research organizations; legislative, regulatory, political and economic developments and general market conditions; and those risks described in the section entitled “Risk Factors” in documents that OnKure files from time to time with the Securities and Exchange Commission (“SEC”), including our Annual Report on Form 10-K filed with the SEC on March 12, 2026 and any subsequent filings with the SEC. These risks are not exhaustive. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this press release. Contact: Dan Ferry LifeSci Advisors [email protected]

-- First patients dosed in triplet expansion arms of the PIKture-01 trial evaluating OKI-219 in combination with fulvestrant and ribociclib, and in combination with trastuzumab and tucatinib in patients with metastatic breast cancer -- Clinical data from OKI-219 PIKture-01 single agent and fulvestrant combination arms are maturing and is now expected to be reported together with initial data from the triplet expansion arms in the first quarter of 2026 -- Significant progress in next-generation PI3Kα pan-mutant inhibitor program; multiple candidates identified - announcement planned for the first quarter of 2026 -- Expansion into Vascular Malformations - additional information to be provided in 2026 BOULDER, Colo., Nov. 06, 2025 (GLOBE NEWSWIRE) -- OnKure Therapeutics, Inc. (Nasdaq: OKUR), a clinical-stage biopharmaceutical company focused on developing novel precision medicines, today reported financial results for the third quarter ended September 30, 2025 and provided a business update. “We have made steady progress advancing our lead clinical development program, OKI-219, and are committed to leading the advancement of selective PI3Kα inhibitors for the treatment of patients with breast cancer and rare diseases. Based on its selectivity and safety profile, the differentiated value of OKI-219 is best demonstrated in early lines of therapy. This fact is at the heart of our clinical strategy. It is important to note that the single agent and fulvestrant dose ranging combination arms of our PIKture-01 trial have supported the expanded development of OKI-219 with the recent initiation of two triplet arms of the trial, including an evaluation of OKI-219 in combination with fulvestrant and ribociclib. We are at an exciting time in our company’s history, and we look forward to sharing clinical data from several arms of our ongoing PIKture-01 trial of OKI-219 in the first quarter of 2026,” said Nick Saccomano, Ph.D., President and Chief Executive Officer of OnKure. “While the team has been hard at work advancing the development of OKI-219, we have also continued to fuel the future growth of OnKure, with important advancements in our next-generation PI3Kα pan-mutant inhibitor program and the beginnings of an expansion program in vascular malformations. We look forward to offering additional details on these programs as our activities ramp up over the next several months.” Program Highlights OKI-219 OnKure’s lead product candidate, OKI-219, is a highly selective PI3kαH1047 mutant specific inhibitor. OKI-219 is being evaluated in the PIKture-01 phase 1 clinical trial for the treatment of patients with HR+ and HER2+ metastatic breast cancer. In August 2025, the Company announced that it had completed and closed enrollment in the monotherapy and fulvestrant combination dose escalation arms of the PIKture-01 trial. As of October 14, 2025, a total of 71 patients have been dosed across both arms: 37 in monotherapy and 34 in combination with fulvestrant. The last patient in the monotherapy arm was dosed in September 2025 and the last patient in the fulvestrant combination arm was dosed in July 2025. The Company expects to announce initial data from these two arms of the trial in the first quarter of 2026. In September 2025, the first patient was dosed in a triplet expansion arm of PIKture-01 evaluating OKI-219 in combination with fulvestrant and ribociclib in patients with PI3KαH1047R mutated, HR+ metastatic breast cancer. The 600 and 900 mg BID cohorts are enrolled. Initial data is expected in the first quarter of 2026. In October 2025, the first patient was dosed in a triplet expansion arm of PIKture-01 evaluating OKI-219 in combination with trastuzumab and tucatinib in patients with PI3KαH1047R mutated, HER2+ breast cancer. Initial data is expected in the first quarter of 2026. Next-Generation PI3KαPAN Mutant Selective Program OnKure has identified a series of next-generation PI3Kα pan-mutant inhibitors. OnKure believes that to be truly “pan-mutant,” a candidate should be highly selective against each of the most common PI3Kα mutations (PI3KαH1047X, PI3KαE542K, and PI3KαE545K), with a favorable safety and tolerability profile that enables combinability with other agents. The Company is evaluating a series of PI3Kα pan-mutant inhibitor development candidates shown preclinically to have an overall selectivity profile, combinability, and pharmaceutical attributes that the Company believes will produce best-in-class pan-mutant PI3Kα inhibitors. The Company plans to announce additional details in the first quarter of 2026. Vascular Malformations Expansion PI3Kα mutations are the most common driver mutations for specific sub-types of vascular malformations. These mutations in the PI3KCA gene lead to overactivation of the pathway, which controls cell growth, proliferation, and survival. OnKure believes its portfolio of PI3kα inhibitors have great potential to serve patients in this large, underserved population. The Company plans to announce additional information on its vascular malformations program in 2026. Financial Results Cash and cash equivalents were approximately $70.3 million as of September 30, 2025. The Company believes its current cash and cash equivalents will be sufficient to fund its planned clinical activities and corporate operations into the fourth quarter of 2026. Research and development (R&D) expenses were $11.9 million for the third quarter of 2025, compared with $10.1 million for the third quarter of 2024. The increase in R&D expenses was primarily due to increased personnel-related costs, including share-based compensation charges. General and Administrative (G&A) expenses were $3.6 million for the third quarter of 2025, compared with $1.4 million for the third quarter of 2024. The increase in G&A expenses was primarily due to increased personnel-related costs, including share-based compensation charges, and increases in director compensation, consulting, filing fees, franchise taxes, and other professional service fees. Net loss and net loss per share for the third quarter of 2025 were $14.7 million and $1.09 per share, compared with $11.6 million and $36.55 per share for the third quarter of 2024. About OnKure Therapeutics OnKure Therapeutics, Inc. (Nasdaq: OKUR) is a clinical-stage biopharmaceutical company focused on the discovery and development of best-in-class precision medicines that target biologically validated drivers of diseases that are underserved by available therapies. Using a structure-based drug design platform, OnKure is building a pipeline of tumor-agnostic candidates that are designed to achieve optimal efficacy and tolerability. OnKure is currently developing OKI-219, a selective PI3KαH1047R inhibitor, as its lead program. OnKure aims to become a leader in targeting oncogenic or pathologically activated PI3Kα and has multiple programs designed to enable best-in-class targeting of this key disease creating gene. For more information about OnKure, visit us at www.onkure.com and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release, including statements regarding our future financial condition, results of operations, business strategy and plans, and objectives of management for future operations, as well as statements regarding industry trends, are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding, OnKure’s current and potential future product candidates and programs, including OKI-219 and the pan-mutant program; OnKure’s ability to advance additional programs; OnKure’s ability to advance and expected timing of additional programs in vascular malformations; expected milestones and timing of such milestones, including additional data for OKI-219 from the PIKture-01 trial and an anticipated development candidate announcement; and statements regarding OnKure’s cash runway. In some cases, you can identify forward-looking statements by terminology such as “estimate”, “intend”, “expect”, “may”, “plan”, “potentially”, “will” or the negative of these terms or other similar expressions. We based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things, OnKure’s limited operating history; the significant net losses incurred since inception; the ability to raise additional capital to finance operations; the risk that actual uses of cash and cash equivalents differ from the assumptions underlying our expected cash runway; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize, OnKure’s product candidates; the outcome of preclinical testing and early clinical trials for OnKure’s product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements, timing of regulatory reviews and approvals, and the potential that the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials; OnKure’s limited resources; the risk of adverse events, toxicities or other undesirable side effects; potential delays or difficulties in the enrollment or maintenance of patients in clinical trials; the decision to develop or seek strategic collaborations to develop OnKure’s current or future product candidates in combination with other therapies and the cost of combination therapies; OnKure’s limited experience in designing clinical trials and lack of experience in conducting clinical trials; the substantial competition OnKure faces in discovering, developing, or commercializing products; OnKure’s ability to protect its intellectual property and proprietary technologies; developments relating to OnKure’s competitors and its industry, including competing product candidates and therapies; reliance on third parties, contract manufacturers, and contract research organizations; legislative, regulatory, political and economic developments and general market conditions; and those risks described in the section entitled “Risk Factors” in documents that OnKure files from time to time with the Securities and Exchange Commission (“SEC”), including our Quarterly Report on Form 10-Q filed with the SEC on November 6, 2025 and any subsequent filings with the SEC. These risks are not exhaustive. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this press release. Contact: Dan Ferry LifeSci Advisors [email protected]

-- 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 $83.4M expected to provide cash runway into Q4 2026 BOULDER, Colo., Aug. 12, 2025 (GLOBE NEWSWIRE) -- OnKure Therapeutics, Inc. (Nasdaq: OKUR), a clinical-stage biopharmaceutical company focused on developing novel precision medicines in oncology, today reported financial results for the second quarter ended June 30, 2025 and provided a business update. “We are encouraged by the continued progress in the development of our lead asset, OKI-219, as we have completed the enrollment of the single agent and the fulvestrant combination arms and have initiated two new triplet arms. Given the clinical performance of OKI-219 to date, we are eager to move broad and deep in both HR+ and HER2+ breast cancer with OKI-219,” said Nick Saccomano, Ph.D., President and Chief Executive Officer of OnKure. “We believe OKI-219 has the potential to become an important medicine in the first-line hormone receptor positive setting and have initiated an arm to evaluate OKI-219 in combination with fulvestrant and ribociclib in PI3KαH1047R mutated, metastatic HR+ breast cancer. We also see an opportunity for OKI-219 in HER2+ breast cancer and have initiated an arm to evaluate OKI-219 in combination with trastuzumab and tucatinib. We look forward to sharing OKI-219 monotherapy and fulvestrant combination data as well as announcing the expansion of our PI3Kα franchise with the nomination of a pan-mutant selective PI3Kα inhibitor later this year.” PI3Kα Portfolio Progress PIKture-01 Monotherapy and Fulvestrant Combination – The Company has completed and closed enrollment in both the monotherapy and fulvestrant combination dose escalation arms in the PIKture-01 trial. As of August 5, 2025, the Company dosed a total of 70 patients across both arms: 36 in monotherapy and 34 in combination with fulvestrant. OnKure expects to report data from both arms in the fourth quarter of 2025. PIKture-01 Ribociclib Triplet Combination – The Company recently initiated the evaluation of OKI-219 in combination with fulvestrant and ribociclib in patients with PI3KαH1047R mutated, HR+ metastatic breast cancer. The initial phase of this arm of the PIKture-01 trial will evaluate the safety of escalating doses of OKI-219 administered as part of a triplet combination, leveraging data from the completed single agent and fulvestrant doublet arms. Expansion of the ribociclib triplet arm will be determined after this run-in phase. PIKture-01 Tucatinib Triplet Combination – The Company recently initiated the evaluation of OKI-219 in combination with trastuzumab and tucatinib in patients with PI3KαH1047R mutated, HER2+ breast cancer. The initial phase of this arm of the PIKture-01 trial will evaluate the safety of escalating doses of OKI-219 administered as part of a triplet combination. Expansion of the tucatinib triplet combination arm will be determined after this run-in phase. Pan-mutant Selective Program – OnKure believes that to be truly “pan-mutant,” a candidate should be highly selective against each of the most common PI3Kα mutations, with a favorable safety and tolerability profile. OnKure is targeting approximately 10-fold selectivity over PI3Kα wild type against each of the most common mutations (PI3KαH1047X, PI3KαE542K, and PI3KαE545K). The Company has identified a series of promising third-generation PI3Kα compounds with an overall selectivity profile that the Company believes will produce a best-in-class pan-mutant inhibitor. OnKure plans to announce the nomination of a development candidate by the end of 2025. Upcoming Investor Conferences OnKure’s President and Chief Executive Officer, Nicholas Saccomano, Ph.D., will participate in a fireside chat at the upcoming Cantor Global Healthcare investor conference taking place in New York on September 3, 2025, at 3:20 P.M.ET. A live audio webcast can be accessed under “News & Events” on the Investor section of OnKure’s website at onkure.com. Following the event, a replay will be available for at least 90 days. Second Quarter 2025 Financial Results Cash and cash equivalents were approximately $83.4 million as of June 30, 2025. Research and development (R&D) expenses were $12.6 million for the second quarter of 2025, compared with $10.8 million for the second quarter of 2024. The increase in R&D expenses was primarily due to increased clinical trial, outsourced manufacturing, and research expenses. General and Administrative (G&A) expenses were $3.7 million for the second quarter of 2025, compared with $3.6 million for the second quarter of 2024. The increase in G&A expenses was primarily due to increased personnel-related costs, including share-based compensation charges, and increases in director compensation, consulting, filing fees, and other professional service fees. These increases were partially offset by a decrease in legal expenses during 2025. Net loss and net loss per share for the second quarter of 2025 were $15.4 million and $1.14 per share, compared with $14.1 million and $44.82 per share for the second quarter of 2024. About OnKure Therapeutics OnKure Therapeutics, Inc. (Nasdaq: OKUR) is a clinical-stage biopharmaceutical company focused on the discovery and development of best-in-class precision medicines that target biologically validated drivers of cancers that are underserved by available therapies. Using a structure-based drug design platform, OnKure is building a pipeline of tumor-agnostic candidates that are designed to achieve optimal efficacy and tolerability. OnKure is currently developing OKI-219, a selective PI3KαH1047R inhibitor, as its lead program. OnKure aims to become a leader in targeting oncogenic PI3Kα and has multiple programs designed to enable best-in-class targeting of this key oncogene. For more information about OnKure, visit us at www.onkure.com and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release, including statements regarding our future financial condition, results of operations, business strategy and plans, and objectives of management for future operations, as well as statements regarding industry trends, are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding, OnKure’s current and potential future product candidates and programs, including OKI-219 and the pan-mutant program; OnKure’s ability to advance additional programs; expected milestones and timing of such milestones, including additional data for OKI-219 from the PIKture-01 trial and an anticipated development candidate announcement; and statements regarding OnKure’s cash runway. In some cases, you can identify forward-looking statements by terminology such as “estimate”, “intend”, “expect”, “may”, “plan”, “potentially”, “will” or the negative of these terms or other similar expressions. We based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things, OnKure’s limited operating history; the significant net losses incurred since inception; the ability to raise additional capital to finance operations; the risk that actual uses of cash and cash equivalents differ from the assumptions underlying our expected cash runway; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize, OnKure’s product candidates; the outcome of preclinical testing and early clinical trials for OnKure’s product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements, timing of regulatory reviews and approvals, and the potential that the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials; OnKure’s limited resources; the risk of adverse events, toxicities or other undesirable side effects; potential delays or difficulties in the enrollment or maintenance of patients in clinical trials; the decision to develop or seek strategic collaborations to develop OnKure’s current or future product candidates in combination with other therapies and the cost of combination therapies; OnKure’s limited experience in designing clinical trials and lack of experience in conducting clinical trials; the substantial competition OnKure faces in discovering, developing, or commercializing products; OnKure’s ability to protect its intellectual property and proprietary technologies; developments relating to OnKure’s competitors and its industry, including competing product candidates and therapies; reliance on third parties, contract manufacturers, and contract research organizations; legislative, regulatory, political and economic developments and general market conditions; and those risks described in the section entitled “Risk Factors” in documents that OnKure files from time to time with the Securities and Exchange Commission (“SEC”), including our Quarterly Report on Form 10-Q filed with the SEC on August 12, 2025 and any subsequent filings with the SEC. These risks are not exhaustive. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this press release. Contact: Dan Ferry LifeSci Advisors [email protected]

-- Continued progress in the PIKture-01 trial; on track to report additional data in the second half of 2025, including mature single agent and initial combination data -- Expansion of the Company’s PI3Ka franchise with the planned announcement of a pan-mutant selective development candidate in Q2 2025 -- $96.7M in cash and cash equivalents expected to be sufficient to fund operations through multiple anticipated milestones into Q4 2026 BOULDER, Colo., May 06, 2025 (GLOBE NEWSWIRE) -- OnKure Therapeutics, Inc. (Nasdaq: OKUR), a clinical-stage biopharmaceutical company focused on developing novel precision medicines in oncology, today reported financial results for the quarter ended March 31, 2025, and provided business highlights. “OnKure looks to define a new standard of performance for precision targeted agents. We designed OKI-219 and our ongoing PIKture-01 trial to set a high bar for achieving considerable selectivity in targeting oncogenic PI3KαH1047R. Late last year, we announced preliminary data that showed OKI-219 was well tolerated across all dose levels, allowing us to complete the dose escalation portion of the study up to 1500 mg BID. We anticipate presenting a mature clinical update in the second half of 2025 that could demonstrate a clear and meaningful benefit in treating this very challenging patient population. This exciting next step in our program would further solidify OnKure’s place as a leader in developing PI3Ka inhibitors,” said Nick Saccomano, Ph.D., President and Chief Executive Officer of OnKure. “Building on the advancement of our initial candidate, our research and development team is advancing towards a second development candidate in the second quarter of 2025; a true pan-mutant inhibitor with a selectivity profile that augurs well for rendering all major PI3Ka mutants actionable.” Business Highlights and Upcoming Anticipated Milestones PIKture-01 trial Part A Monotherapy – The Company has completed dose escalating and closed enrollment in Part A with dose limiting toxicities observed in only one patient to date and at the highest dose level. OnKure expects to provide a mature clinical update in the second half of 2025. OnKure previously announced encouraging preliminary safety, tolerability, and pharmacokinetic (“PK”) data from the part A single-agent arm of the PIKture-01 trial, with a data cut-off of October 28, 2024. These preliminary data showed OKI-219 was well tolerated across all dose levels, with no hyperglycemia, stomatitis, or rash observed. Additionally, only grade 1 treatment-related adverse events (“TRAEs”) were reported with no dose interruptions, delays, reductions, or discontinuations reported for any adverse events. PIKture-01 Part B Fulvestrant Combination – OnKure is actively enrolling patients in Part B of the PIKture-01 trial, evaluating OKI-219 in combination with fulvestrant in patients with PI3KαH1047R mutated HR+/HER2- metastatic breast cancer. The Company is nearing the end of the dose escalation portion of Part B, with no dose limiting toxicities observed to date. OnKure expects to report initial combination data with fulvestrant in the second half of 2025. It is anticipated that the dose escalation portion of Part B will be completed at the time of the presentation. Pan-mutant Program – OnKure believes that to be truly “pan-mutant”, a candidate should be highly selective against each of the most common PI3Ka mutations with a favorable safety and tolerability profile. OnKure is targeting approximately 10-fold selectivity against each of the most common mutations (PI3KαH1047X, PI3KαE542K, and PI3KαE545K) over wild type with its pan-mutant development candidate, which it expects to announce in the second quarter of 2025. First Quarter 2025 Financial Results Cash and cash equivalents were approximately $96.7 million as of March 31, 2025. Research and development (R&D) expenses were $13.0 million for the first quarter of 2025, compared with $8.6 million for the first quarter of 2024. The increase in R&D expenses was primarily due to increases in personnel-related costs, including share-based compensation charges, clinical trial and outsourced manufacturing expenses, and outsourced research as OnKure seeks to advance multiple programs. General and Administrative (G&A) expenses were $4.0 million for the first quarter of 2025, compared with $1.3 million for the first quarter of 2024. The increase in G&A expenses was primarily due to increased personnel-related costs, including share-based compensation charges, and increases in legal expenses, board, consulting, and other professional service fees. Net loss and net loss per share for the first quarter of 2025 were $15.9 million and $1.19 per share, compared with $9.5 million, and $30.37 per share, for the first quarter of 2024. About OnKure Therapeutics OnKure Therapeutics, Inc. (Nasdaq: OKUR) is a clinical-stage biopharmaceutical company focused on the discovery and development of best-in-class precision medicines that target biologically validated drivers of cancers that are underserved by available therapies. Using a structure-based drug design platform, OnKure is building a pipeline of tumor-agnostic candidates that are designed to achieve optimal efficacy and tolerability. OnKure is currently developing OKI-219, a selective PI3KαH1047R inhibitor, as its lead program. OnKure aims to become a leader in targeting oncogenic PI3Kα and has multiple programs designed to enable best-in-class targeting of this key oncogene. For more information about OnKure, visit us at www.onkure.com and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release, including statements regarding our future financial condition, results of operations, business strategy and plans, and objectives of management for future operations, as well as statements regarding industry trends, are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding, OnKure’s current and potential future product candidates and programs, including OKI-219 and the pan-mutant program; OnKure’s ability to advance additional programs; expected milestones and timing of such milestones, including additional data for OKI-219 from the PIKture-01 trial, anticipated development candidate announcements and advancement of OnKure’s discovery stage programs; and statements regarding OnKure’s financial position, including its liquidity, cash runway and the sufficiency of its cash resources. In some cases, you can identify forward-looking statements by terminology such as “estimate,” “intend,” “may,” “plan,” “potentially” “will” or the negative of these terms or other similar expressions. We based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things, OnKure’s limited operating history; the significant net losses incurred since inception; the ability to raise additional capital to finance operations; the risk that actual uses of cash and cash equivalents differ from the assumptions underlying our expected cash runway; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize, OnKure’s product candidates; the outcome of preclinical testing and early clinical trials for OnKure’s product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements, timing of regulatory reviews and approvals, and the potential that the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials; OnKure’s limited resources; the risk of adverse events, toxicities or other undesirable side effects; potential delays or difficulties in the enrollment or maintenance of patients in clinical trials; the decision to develop or seek strategic collaborations to develop OnKure’s current or future product candidates in combination with other therapies and the cost of combination therapies; OnKure’s limited experience in designing clinical trials and lack of experience in conducting clinical trials; the substantial competition OnKure faces in discovering, developing, or commercializing products; OnKure’s ability to protect its intellectual property and proprietary technologies; developments relating to OnKure’s competitors and its industry, including competing product candidates and therapies; reliance on third parties, contract manufacturers, and contract research organizations; legislative, regulatory, political and economic developments and general market conditions; and those risks described in the section entitled “Risk Factors” in documents that OnKure files from time to time with the Securities and Exchange Commission (“SEC”), including our Annual Report on Form 10-K filed with the SEC on March 10, 2025 and any subsequent filings with the SEC. These risks are not exhaustive. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this press release. Contact: Dan Ferry LifeSci Advisors [email protected]