Tucatinib

-- 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 PI3Kα H1047 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 , 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 , 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 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 daniel@lifesciadvisors.com ONKURE THERAPEUTICS, INC. Condensed Consolidated Balance Sheets (In thousands, unaudited) March 31, 2026 December 31, 2025 Assets Current assets: Cash and cash equivalents $ 192,106 $ 59,050 Prepaid expenses and other current assets 5,376 1,789 Total current assets 197,482 60,839 Property and equipment, net 519 618 Operating lease, right-of-use asset 288 387 Other assets 405 273 Total assets $ 198,694 $ 62,117 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable, accrued expenses, and other liabilities $ 13,920 $ 5,372 Operating lease liabilities, current portion 409 549 Total current liabilities 14,329 5,921 Long-term liabilities 12 12 Total liabilities 14,341 5,933 Stockholders’ equity 184,353 56,184 Total liabilities and stockholders’ equity $ 198,694 $ 62,117 ONKURE THERAPEUTICS, INC. Condensed Consolidated Statements of Operations and Comprehensive Loss (In thousands, except share and per share data, unaudited) Three Months Ended March 31, 2026 2025 Operating expenses: Research and development $ 11,707 $ 13,012 General and administrative 3,908 3,988 Total operating expenses 15,615 17,000 Loss from operations (15,615) (17,000) Other income: Interest income 458 1,075 Net loss and comprehensive loss $ (15,157) $ (15,925) Net loss per share attributable to common stockholders: Basic and diluted $ (1.11) $ (1.19) Weighted average shares outstanding: Basic and diluted 13,674,577 13,424,335

BBO-10203 physically and allosterically disrupts the interaction between RAS and PI3Kα, leading to signaling inhibition without inhibiting the kinase activity of PI3Kα and with no observed hyperglycemia BBO-10203 displays strong in vivo combination effects with HER2 inhibitors tucatinib or trastuzumab in HER2 AMP models Updated clinical data are expected in the second half of 2026 SOUTH SAN FRANCISCO, Calif., April 21, 2026 (GLOBE NEWSWIRE) -- BridgeBio Oncology Therapeutics, Inc. (“BBOT”) (Nasdaq: BBOT), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, today presented new preclinical data in an oral presentation for BBO-10203, a first-in-class covalent small molecule RAS:PI3Kα breaker that selectively blocks the physical interaction between RAS and PI3Kα resulting in the inhibition of RAS-driven PI3Kα-AKT signaling in tumors with no observed hyperglycemia. The data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2026. "The interaction between RAS and PI3Kα plays a critical role in malignant cells,” said Pedro J. Beltran, PhD, Chief Scientific Officer of BBOT. “BBO-10203 physically disrupts the interaction between RAS and PI3Kα, leading to signaling inhibition and tumor regressions. Importantly, unlike competing approaches, no hyperglycemia has been observed to date. In addition, BBO-10203’s ability to block RAS-mediated activation of PI3Kα is independent of the mutational status of either RAS or PI3Kα, which may enable treatment of a broader patient population. These data suggest that non-canonical RAS proteins play a key role in PI3K α activation in HER2 AMP cell lines. Furthermore, BBO-10203 demonstrates strong in vivo combination activity with HER2-targeted therapies, including tucatinib and trastuzumab, in HER2 AMP models.” Highlights from the oral presentation include: BBO-10203 physically and allosterically disrupts the interaction between RAS and PI3Kα, leading to signaling inhibition without inhibiting the kinase activity of PI3Kα BBO-10203 induces tumor regressions at 30 mg/kg QD and no hyperglycemia observed at 100 mg/kg QD BBO-10203 shows that PI3Kα activity in HER2 AMP cells is RAS-dependent RAS RBD mutations recapitulate the pAKT and viability effects of breaker activity in HER2 AMP cell lines Non-canonical RAS signaling appears to be the dominant driver of pAKT in HER2 AMP cell lines BBO-10203 displays strong in vivo combination effects with HER2 inhibitors tucatinib or trastuzumab in HER2 AMP models The oral presentation is titled “ The RAS:PI3Kα breaker BBO-10203 inhibits PI3Kα/AKT activity in HER2 AMP models through non-canonical RAS signaling blockade .” A copy of the presentation will be available on the “ Publications ” page of the BBOT website following the conference. About BBO-10203 BBO-10203 is an orally bioavailable small molecule with a novel mechanism of action designed to inhibit the physical interaction between RAS and PI3Kα, inhibiting RAS-driven PI3Kα-AKT signaling in tumors. BBO-10203 binds directly and covalently to the RAS-binding domain of PI3Kα, preventing its activation by KRAS, HRAS and NRAS, reducing downstream signaling and tumor growth. It is a protein-protein inhibitor and not a kinase inhibitor, enabling inhibition of RAS-driven PI3Kα-AKT signaling in tumors without the risk of hyperglycemia. Importantly, BBO-10203’s ability to block RAS activation of PI3Kα is agnostic to the mutational status of either RAS or PI3Kα . In addition to a potentially differentiated safety profile, BBO-10203 could be combined with direct KRAS inhibitors, such as BBO-8520 and BBO-11818, or drugs that target HER2 or ER receptors. BBO-10203 is being evaluated in the Phase 1 BREAKER-101 trial (NCT06625775) for patients with locally advanced or metastatic HER2+ breast cancer, HR+/HER2- breast cancer, KRAS -mutant colorectal cancer, and KRAS -mutant non-small cell lung cancer. Updated Phase 1 clinical data are expected in the second half of 2026. About BBOT BBOT is a clinical-stage biopharmaceutical company advancing a next-generation pipeline of novel small molecule therapeutics targeting RAS and PI3Kα malignancies. BBOT has the goal of improving outcomes for patients with cancers driven by the two most prevalent oncogenes in human tumors. For more information, please visit and follow us on LinkedIn . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, and other federal securities laws. Any statements in this press release that are not historical facts may be deemed forward-looking statements, which generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends. These statements are based on various assumptions, whether or not identified in this press release, and are the current expectations of BBOT’s management and are not predictions of actual performance. Many actual events and circumstances are beyond the control of BBOT. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to the timing of expected regulatory and business milestones, including the progress of enrollment in clinical trials and availability of data from ongoing and planned clinical trials; and those factors discussed in documents BBOT has filed or will the U.S. Securities and Exchange Commission. In addition, forward-looking statements reflect BBOT’s expectations, plans, or forecasts of future events and views as of the date of this press release and are qualified in their entirety by reference to the cautionary statements herein. BBOT anticipates that subsequent events and developments will cause BBOT’s assessments to change. These forward-looking statements should not be relied upon as any guarantee, assurance, prediction or definitive statement of fact or probability or as representing BBOT’s assessments as of any date subsequent to the date of this press release. Neither BBOT, nor any of its affiliates undertake any obligation to update these forward-looking statements, except as required by law. BBOT Contacts: Investor Contact: Heather Armstrong, Head of Investor Relations BBOT Investors@BBOTx.com Media Contact: Jake Robison Inizio Evoke Comms Jake.robison@inizioevoke.com