OnKure Therapeutics Conference Call Summary Company Overview - **Company**: OnKure Therapeutics (NasdaqGM: OKUR) - **Focus**: Development of selective PI3K alpha inhibitors for cancer treatment, particularly breast cancer and vascular malformations Key Points Industry and Market Context - **Targeted Area**: PI3K alpha mutations in cancer, which is the most frequently mutated gene in cancer [2][3] - **Market Opportunity**: Significant potential in treating breast cancer and other solid tumors, including colon, lung, endometrial, cervical, and ovarian cancers [7][12] Product Pipeline - **Lead Product**: OKI-219, a highly selective inhibitor for the H1047R mutation, currently in the PIKture-01 study [4][10] - **Development Focus**: - Monotherapy and combination studies with fulvestrant and ribociclib in breast cancer [12][16] - Triplet studies involving OKI-219 with trastuzumab and tucatinib in HER2-positive breast cancer [12][16] - **Future Plans**: Anticipation of moving pan-mutant selective molecules through preclinical development by 2026 [5][6] Clinical Development and Efficacy - **Selectivity and Efficacy**: OKI-219 shows an 80-fold selectivity over wild-type PI3K alpha, significantly higher than competitors [10][35] - **Combination Therapy**: Emphasis on the importance of combinability with existing therapies, which is crucial for market acceptance [11][21] - **Patient Population**: Targeting specific patient populations, including those who have failed prior lines of therapy, with a focus on understanding the impact of prior treatments on efficacy [29][30] Financial Position - **Cash Reserves**: As of September 30, the company reported $70 million in cash and cash equivalents, providing a solid foundation for ongoing development [22] Strategic Vision - **Balanced Portfolio**: The company aims to maintain a balanced, risk-adjusted portfolio of molecules, allowing for flexibility based on emerging data [25][26] - **Long-term Goals**: Focus on establishing OKI-219 as a key treatment in breast cancer and exploring opportunities in vascular malformations [22][24] Upcoming Milestones - **Data Reporting**: Expectation of significant data updates in the first quarter of 2026, including efficacy, tolerability, and combinability results from ongoing studies [19][42] - **Regulatory Considerations**: Plans to provide insights into progression-free survival (PFS) and overall response rates (ORR) in future disclosures [47][49] Additional Insights - **Vascular Malformations**: Recognition of the potential for OnKure's selective molecules to address vascular anomalies, presenting a compelling opportunity in a niche market [22][23] - **Competitive Landscape**: The company is aware of the competitive dynamics and is focused on demonstrating superior tolerability and efficacy compared to existing treatments [41][49] This summary encapsulates the key aspects of OnKure Therapeutics' conference call, highlighting the company's strategic focus, product pipeline, and market opportunities within the oncology sector.

OnKure Therapeutics FY Conference Summary Company Overview - **Company**: OnKure Therapeutics - **Ticker**: NasdaqGM:OKUR - **Location**: Boulder, Colorado - **Focus**: Development of selective PI3K alpha inhibitors, particularly targeting mutant forms of the enzyme [2][4] Key Product: OKI-219 - **Description**: OKI-219 is the most advanced candidate targeting the PI3K alpha H1047R mutation, which represents approximately two-thirds of mutations in patient populations with mutated PI3K alpha [3][4] - **Selectivity**: OKI-219 exhibits greater than 80-fold selectivity for mutant over wild type PI3K alpha, allowing for effective dosing without significant side effects associated with wild type inhibition [5][7] - **Comparison with Competitors**: Other approved drugs like alpelisib show no selectivity, while inavolisib has only four-fold selectivity. OKI-219's high selectivity minimizes common side effects such as hyperglycemia and rash [6][7] Clinical Studies - **Current Studies**: OKI-219 is involved in three clinical studies: - Monotherapy basket study - Doublet study in combination with fulvestrant for breast cancer - Triplet studies in ER-positive and HER2-positive breast cancer [11][12] - **Data Reporting**: Efficacy data from these studies is expected to be reported in the first quarter of 2026 [13][25] Differentiation and Market Strategy - **Differentiation**: The company aims to differentiate itself by moving into front-line therapy with a well-tolerated regimen, focusing on tolerability and combinability with existing treatments [12][20] - **Target Patient Population**: The HER2-positive breast cancer cohort is noted to have a significant opportunity, despite a lower mutation frequency compared to ER-positive breast cancer [18] CNS Penetration - **Importance**: OKI-219 has a high brain-to-plasma ratio (Kp,uu of 0.6), which is crucial for treating cancers with CNS involvement, particularly HER2-positive breast cancer [15][16] Future Development Plans - **Pan-PI3K Mutant Inhibitor**: The company is also developing a pan-PI3K mutant inhibitor with greater than 10-fold selectivity across all mutants, with plans to report on these developments in the first quarter of 2026 [32] - **Regulatory Strategy**: The company is focused on minimizing risks and ensuring that their drugs do not lead to significant drug-drug interactions (DDIs) with existing therapies [34][35] Conclusion - **Overall Strategy**: OnKure Therapeutics is positioning itself to compete effectively in the oncology market by focusing on high selectivity, tolerability, and strategic partnerships in clinical studies, with a clear timeline for data disclosure and future development [31][32]

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 September 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 ...

-- 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 PI3Ka pan-mutant inhibitor program; multiple candidates identified - announcement planned for the first quarter of 2026 Exhibit 99.1 OnKure Therapeutics Reports Third Quarter 2025 Financial Results and Provides a Business Update -- First patients ...

Core Insights - OnKure Therapeutics has initiated triplet expansion arms in the PIKture-01 trial for its lead product candidate, OKI-219, targeting metastatic breast cancer [1][2] - Initial clinical data from the single agent and combination arms of the trial is expected to be reported in the first quarter of 2026 [1][5] - The company is advancing its next-generation PI3Kα pan-mutant inhibitor program and plans to provide further details in 2026 [1][3] Company Developments - OKI-219 is being evaluated in the PIKture-01 phase 1 clinical trial for HR+ and HER2+ metastatic breast cancer, with a focus on its selectivity and safety profile [3][4] - The triplet arms of the trial include combinations of OKI-219 with fulvestrant and ribociclib, as well as trastuzumab and tucatinib, with initial data expected in early 2026 [5][6] - OnKure is also expanding into vascular malformations, leveraging its PI3Kα inhibitors to address this underserved population, with more information to be shared in 2026 [6] Financial Performance - As of September 30, 2025, OnKure reported cash and cash equivalents of approximately $70.3 million, sufficient to fund operations into the fourth quarter of 2026 [12] - Research and development expenses for Q3 2025 were $11.9 million, an increase from $10.1 million in Q3 2024, primarily due to higher personnel-related costs [12][17] - The net loss for Q3 2025 was $14.7 million, compared to a net loss of $11.6 million in Q3 2024, with a net loss per share of $1.09 [12][17]

BOULDER, Colo., Nov. 04, 2025 (GLOBE NEWSWIRE) -- OnKure Therapeutics, Inc. (Nasdaq: OKUR), a clinical-stage biopharmaceutical company focused on the development of novel precision medicines, today announced that Nichoals Saccomano, Ph.D., President and Chief Executive Officer, will present and be available for one-on-one investor meetings at the following investor conferences: A fireside chat at the Guggenheim Healthcare Innovation Conference, in Boston on Monday, November 10, 2025, at 4:00 p.m. ET. A live ...

Core Insights - Premarket trading is showing notable activity with significant price movements indicating potential trading opportunities before the market opens [1] Premarket Gainers - Artiva Biotherapeutics, Inc. (ARTV) has increased by 124% to $6.22 [3] - Akanda Corp. (AKAN) is up 39% at $3.10 [3] - Kezar Life Sciences, Inc. (KZR) has risen 38% to $5.80 [3] - Carbon Revolution Public Limited Company (CREV) is also up 38% at $5.15 [3] - Safe & Green Holdings Corp. (SGBX) has increased by 28% to $3.96 [3] - Achieve Life Sciences, Inc. (ACHV) is up 23% at $3.80 [3] - Revolution Medicines, Inc. (RVMD) has risen 8% to $53.90 [3] - Erayak Power Solution Group Inc. (RAYA) is up 8% at $5.76 [3] - ProQR Therapeutics N.V. (PRQR) has increased by 7% to $3.00 [3] - Bio Green Med Solution, Inc. (BGMS) is up 6% at $4.04 [3] Premarket Losers - American Rebel Holdings, Inc. (AREB) has decreased by 41% to $2.09 [4] - Sadot Group Inc. (SDOT) is down 25% at $5.35 [4] - AVITA Medical, Inc. (RCEL) has fallen 24% to $4.04 [4] - Soluna Holdings, Inc. (SLNH) is down 23% at $3.22 [4] - American Battery Technology Company (ABAT) has decreased by 17% to $4.70 [4] - CID HoldCo, Inc. (DAIC) is down 17% at $2.16 [4] - Pinnacle Food Group Limited (PFAI) has fallen 12% to $3.12 [4] - OnKure Therapeutics, Inc. (OKUR) is down 12% at $2.52 [4] - Whitehawk Therapeutics, Inc. (WHWK) has decreased by 12% to $2.29 [4] - Aqua Metals, Inc. (AQMS) is down 7% at $14.50 [4]

PART I — FINANCIAL INFORMATION [Item 1. Condensed Consolidated Financial Statements (Unaudited)](index=6&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements%20(Unaudited)) This section presents OnKure Therapeutics, Inc.'s unaudited condensed consolidated financial statements and accompanying notes [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) | ASSETS (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------- | :------------ | :---------------- | | Cash and cash equivalents | $83,374 | $110,761 | | Total current assets | $84,552 | $113,003 | | Total assets | $86,070 | $114,907 | | LIABILITIES AND STOCKHOLDERS' EQUITY (in thousands) | June 30, 2025 | December 31, 2024 | | Total current liabilities | $7,597 | $10,530 | | Total liabilities | $7,904 | $11,079 | | Total stockholders' equity | $78,166 | $103,828 | | Total liabilities and stockholders' equity | $86,070 | $114,907 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) | (in thousands, except share and per share amounts) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $12,613 | $10,752 | $25,625 | $19,318 | | General and administrative | $3,711 | $3,591 | $7,699 | $4,857 | | Total operating expenses | $16,324 | $14,343 | $33,324 | $24,175 | | Loss from operations | $(16,324) | $(14,343) | $(33,324) | $(24,175) | | Interest income | $934 | $230 | $2,009 | $526 | | Net loss and comprehensive loss | $(15,390) | $(14,139) | $(31,315) | $(23,675) | | Net loss per share (Basic and diluted) | $(1.14) | $(44.82) | $(2.33) | $(75.22) | | Weighted average shares outstanding (Basic and diluted) | 13,509,080 | 315,478 | 13,466,942 | 314,747 | [Condensed Consolidated Statements of Changes in Stockholders' Equity](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Changes%20in%20Stockholders'%20Equity) - Total stockholders' equity decreased from **$103.8 million** at December 31, 2024, to **$78.2 million** at June 30, 2025, primarily due to a net loss of **$31.3 million** for the six months ended June 30, 2025, partially offset by share-based compensation[28](index=28&type=chunk) - The accumulated deficit increased from **$(154.7) million** at December 31, 2024, to **$(186.0) million** at June 30, 2025, reflecting ongoing net losses[28](index=28&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) | Cash Flows (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------ | :----------------------------- | :----------------------------- | | Operating activities | $(27,279) | $(17,102) | | Investing activities | $(31) | $(19) | | Financing activities | $(77) | $5,878 | | Net decrease in cash and cash equivalents | $(27,387) | $(11,243) | | Cash and cash equivalents, beginning of period | $110,761 | $29,876 | | Cash and cash equivalents, end of period | $83,374 | $18,633 | [Notes to Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) [1. Organization and Business](index=10&type=section&id=1.%20Organization%20and%20Business) - OnKure Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on discovering and developing precision medicines for underserved cancers, utilizing a structure- and computational chemistry-driven drug design platform[33](index=33&type=chunk)[109](index=109&type=chunk) - On October 4, 2024, Reneo Pharmaceuticals, Inc. completed a reverse recapitalization merger with Legacy OnKure, Inc., with Legacy OnKure being the accounting acquirer. Reneo changed its name to OnKure Therapeutics, Inc. and effected a 1:10 reverse stock split[8](index=8&type=chunk)[9](index=9&type=chunk)[34](index=34&type=chunk)[35](index=35&type=chunk) - The company reported recurring losses from operations and an accumulated deficit of **$186.0 million** as of June 30, 2025, with cash and cash equivalents of **$83.4 million**. Management believes current cash resources are sufficient to fund operations for at least the next 12 months[38](index=38&type=chunk)[41](index=41&type=chunk)[114](index=114&type=chunk)[115](index=115&type=chunk) [2. Summary of Significant Accounting Policies](index=11&type=section&id=2.%20Summary%20of%20Significant%20Accounting%20Policies) - The unaudited Condensed Consolidated Financial Statements are prepared in accordance with GAAP for interim financial information and SEC rules, consolidating the Company and its wholly-owned subsidiary, OnKure, Inc[42](index=42&type=chunk) - The Company operates in a single operating segment: clinical research, with all equipment and property located in the United States[44](index=44&type=chunk)[71](index=71&type=chunk) - Key accounting estimates include accruals for external research and development expenses and the fair value of stock options and restricted stock units[45](index=45&type=chunk) - Research and development costs are expensed as incurred, including employee-related expenses, third-party activities, manufacturing costs, and license fees[47](index=47&type=chunk) - Share-based compensation is measured at grant date fair value using the Black-Scholes model for options and recognized over the vesting period[49](index=49&type=chunk)[50](index=50&type=chunk) - Cash and cash equivalents, primarily money market funds, are reported at cost approximating fair value and are classified as Level 1 inputs[54](index=54&type=chunk)[82](index=82&type=chunk) - The Company recognizes right-of-use (ROU) assets and lease liabilities for operating leases with terms greater than one year, measured at the present value of unpaid lease payments using the estimated incremental borrowing rate[57](index=57&type=chunk)[58](index=58&type=chunk) - The Company is evaluating the impact of recently issued accounting pronouncements, ASU 2023-09 (Income Taxes) and ASU 2024-03 (Expense Disaggregation), but does not anticipate a material impact from other pronouncements[59](index=59&type=chunk)[60](index=60&type=chunk)[61](index=61&type=chunk)[62](index=62&type=chunk) [3. Merger Agreement and Concurrent Financing](index=15&type=section&id=3.%20Merger%20Agreement%20and%20Concurrent%20Financing) - On October 4, 2024, Reneo Pharmaceuticals, Inc. completed a merger with Legacy OnKure, Inc., with Legacy OnKure surviving as a wholly-owned subsidiary and being treated as the accounting acquirer in a reverse recapitalization[63](index=63&type=chunk)[67](index=67&type=chunk) - In connection with the merger, 6,470,281 shares of Class A Common Stock and 686,527 shares of Class B Common Stock were issued to Legacy OnKure stockholders, and Reneo's common stock was reclassified into approximately 3,343,604 shares of Class A Common Stock[64](index=64&type=chunk) - A Concurrent Financing closed simultaneously with the merger, raising approximately **$65.0 million** in gross proceeds from the sale of 2,839,005 shares of Class A Common Stock, including the conversion of **$6.0 million** in convertible promissory notes and accrued interest[65](index=65&type=chunk) | Net Assets Acquired (in thousands) | Amount | | :--------------------------------- | :----- | | Cash and cash equivalents | $57,736 | | Short-term investments | $15,979 | | Other current assets | $690 | | Other assets | $553 | | Accrued expenses | $(9,072)| | Long-term operating lease liability| $(387) | | Net assets acquired | $65,499 | [4. Segment](index=16&type=section&id=4.%20Segment) - The Company operates as a single reportable segment focused on clinical research, with no generated revenue and anticipated substantial expenses and operating losses[71](index=71&type=chunk)[72](index=72&type=chunk) - The Chief Operating Decision Maker (CODM), comprised of the CFO and CEO, assesses financial performance using operating expenses and internal models, with segment assets and losses mirroring the Company's overall financial position[73](index=73&type=chunk)[74](index=74&type=chunk) | Clinical Research Segment Operating Expenses (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Direct program expense | $7,491 | $5,680 | $15,363 | $11,033 | | Indirect program expense | $432 | $525 | $958 | $1,042 | | Workforce salaries and benefits | $4,343 | $3,832 | $8,750 | $7,188 | | Share-based compensation expense | $2,908 | $1,813 | $5,653 | $1,920 | | General corporate expenses | $1,150 | $2,493 | $2,600 | $2,992 | | Interest and other expense | $— | $26 | $— | $26 | | Segment net loss | $16,324 | $14,369 | $33,324 | $24,201 | [5. Leases](index=17&type=section&id=5.%20Leases) - The Company leases office and lab facilities in Boulder, Colorado, expiring in December 2026 with a five-year extension option. An Irvine, California lease, assumed in the Reneo merger, was subleased in January 2025[76](index=76&type=chunk) | Lease Information (in thousands) | June 30, 2025 | December 31, 2024 | | :------------------------------- | :------------ | :---------------- | | Operating lease right-of-use assets | $581 | $770 | | Current operating lease liabilities | $556 | $536 | | Noncurrent operating lease liabilities | $267 | $549 | | Total lease liabilities | $823 | $1,085 | | Lease Expense (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Operating lease cost | $45 | $43 | $96 | $87 | | Variable lease expense | $29 | $47 | $74 | $94 | [6. Net Loss Per Share](index=18&type=section&id=6.%20Net%20Loss%20Per%20Share) - Basic loss per share is calculated by dividing net loss by the weighted average common shares outstanding. Diluted net loss per share includes common stock equivalents unless their inclusion would be anti-dilutive[78](index=78&type=chunk) | Anti-Dilutive Securities Outstanding | June 30, 2025 | June 30, 2024 | | :----------------------------------- | :------------ | :------------ | | Outstanding common stock options | 3,054,036 | 195,841 | | Unvested restricted stock units | 59,983 | 213,819 | | Total | 3,114,019 | 409,660 | [7. Fair Value Measurements](index=18&type=section&id=7.%20Fair%20Value%20Measurements) - The Company classifies its money market funds as Level 1 in the fair value hierarchy, using quoted prices in active markets, and these are included in cash and cash equivalents[82](index=82&type=chunk) - No assets or liabilities were transferred into or out of their fair value classifications during the six months ended June 30, 2025 and 2024[82](index=82&type=chunk) [8. Property and Equipment, Net](index=19&type=section&id=8.%20Property%20and%20Equipment,%20Net) | Property and Equipment, Net (in thousands) | June 30, 2025 | December 31, 2024 | | :--------------------------------------- | :------------ | :---------------- | | Lab equipment | $706 | $705 | | Leasehold improvements | $1,090 | $1,090 | | Computer hardware and software | $219 | $189 | | Furniture and fixtures | $160 | $160 | | Property and equipment, gross | $2,175 | $2,144 | | Less: accumulated depreciation and amortization | $(1,354) | $(1,119) | | Property and equipment, net | $821 | $1,025 | - Depreciation and amortization expense for the three months ended June 30, 2025, was **$117 thousand**, and for the six months ended June 30, 2025, was **$235 thousand**[85](index=85&type=chunk) [9. Accrued Expenses](index=19&type=section&id=9.%20Accrued%20Expenses) | Accrued Expenses (in thousands) | June 30, 2025 | December 31, 2024 | | :------------------------------ | :------------ | :---------------- | | Accrued compensation | $2,103 | $3,173 | | Accrued contract manufacturing costs | $1,384 | $1,565 | | Accrued clinical trial costs | $309 | $1,302 | | Accrued other | $864 | $986 | | Total accrued expenses | $4,660 | $7,026 | [10. Share-Based Compensation](index=19&type=section&id=10.%20Share-Based%20Compensation) | Stock Options Activity | Number of Options | Weighted Average Exercise Price | | :--------------------- | :---------------- | :------------------------------ | | Outstanding - Dec 31, 2024 | 2,393,824 | $23.54 | | Granted | 774,400 | $4.98 | | Expired | (114,188) | $37.30 | | Outstanding - Jun 30, 2025 | 3,054,036 | $18.32 | | Exercisable - Jun 30, 2025 | 898,273 | $29.18 | | Restricted Stock Units (RSUs) Activity | Number of Shares | Weighted Average Grant Date Fair Value | | :------------------------------------- | :--------------- | :------------------------------------- | | Unvested balance - Dec 31, 2024 | 213,254 | $22.88 | | Granted | 17,054 | $3.07 | | Vested and released | (170,325) | $20.90 | | RSUs outstanding - Jun 30, 2025 | 59,983 | $22.89 | | Share-Based Compensation Expense (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :---------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $1,410 | $1,518 | $2,727 | $1,555 | | General and administrative | $1,498 | $295 | $2,926 | $365 | | Total | $2,908 | $1,813 | $5,653 | $1,920 | - The 2024 Employee Stock Purchase Plan (ESPP) was adopted in October 2024, incurring **$55 thousand** in share-based compensation expense for the three and six months ended June 30, 2025, despite no shares being issued yet[93](index=93&type=chunk) [11. Income Taxes](index=21&type=section&id=11.%20Income%20Taxes) - The Company has recorded a full valuation allowance against its net deferred tax assets due to the uncertainty of future profitable operations and taxable income[96](index=96&type=chunk) - The recently signed One Big Beautiful Bill Act, a tax reform legislation, is not expected to have a material impact on the consolidated financial statements for the six months ended June 30, 2025, given the existing full valuation allowance[97](index=97&type=chunk) [12. Commitments and Contingencies](index=21&type=section&id=12.%20Commitments%20and%20Contingencies) - Two complaints were filed in the Supreme Court of New York alleging misrepresentation and omission in the Proxy Statement/Prospectus related to the merger, seeking injunction or damages. The Company intends to vigorously defend against these actions[98](index=98&type=chunk)[99](index=99&type=chunk) - The Company provides indemnification to its officers and directors, which in many cases is unlimited, but has not incurred material costs to date and has not accrued related liabilities[101](index=101&type=chunk)[102](index=102&type=chunk) - Severance payments for a former officer totaled **$622 thousand** in R&D expense for the three months ended June 30, 2024, with **$43 thousand** remaining unpaid as of June 30, 2025[103](index=103&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=22&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides management's analysis of OnKure Therapeutics, Inc.'s financial condition, operating results, liquidity, and critical accounting policies [Overview](index=23&type=section&id=Overview) - OnKure is a clinical-stage biopharmaceutical company developing precision medicines for cancer, with its lead product candidate, OKI-219 (a PI3Kα H1047R inhibitor), currently in a Phase 1a/1b clinical trial for advanced breast cancer[109](index=109&type=chunk) - The Company completed a reverse stock split, name change, and stock reclassification as part of the merger with Legacy OnKure on October 4, 2024, and concurrently raised approximately **$65.0 million** through a private placement[110](index=110&type=chunk)[111](index=111&type=chunk)[112](index=112&type=chunk) - OnKure has incurred significant operating losses since inception, with net losses of **$31.3 million** for the six months ended June 30, 2025, and an accumulated deficit of **$186.0 million**. Cash and cash equivalents stood at **$83.4 million** as of June 30, 2025, deemed sufficient for the next 12 months[114](index=114&type=chunk)[115](index=115&type=chunk) [Components of Our Results of Operations](index=24&type=section&id=Components%20of%20Our%20Results%20of%20Operations) - Research and development (R&D) expenses, which are expensed as incurred, include employee-related costs, fees for CROs and CMOs, non-clinical activities, regulatory operations, and facilities costs. These expenses are expected to increase substantially as product candidates advance through clinical trials[116](index=116&type=chunk)[117](index=117&type=chunk)[118](index=118&type=chunk) - General and administrative (G&A) expenses cover salaries, bonuses, share-based compensation, severance, professional fees, and other administrative costs. G&A expenses are anticipated to rise due to business growth and public company operating requirements[120](index=120&type=chunk)[121](index=121&type=chunk) - Other income primarily consists of interest income from cash equivalents, while interest expense, previously from convertible notes, was eliminated upon their conversion in 2024[123](index=123&type=chunk)[124](index=124&type=chunk) [Results of Operations](index=26&type=section&id=Results%20of%20Operations) | (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | $ Change | | :------------- | :------------------------------- | :------------------------------- | :------- | | R&D Expenses | $12,613 | $10,752 | $1,861 | | G&A Expenses | $3,711 | $3,591 | $120 | | Other Income | $934 | $204 | $730 | | Net Loss | $(15,390) | $(14,139) | $(1,251) | - For the three months ended June 30, 2025, R&D expenses increased by **$1.9 million**, mainly due to higher clinical trial and outsourced manufacturing costs. G&A expenses saw a slight increase of **$0.1 million**, driven by personnel costs and share-based compensation, partially offset by reduced legal expenses related to the 2024 merger[126](index=126&type=chunk)[127](index=127&type=chunk) | (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | $ Change | | :------------- | :----------------------------- | :----------------------------- | :------- | | R&D Expenses | $25,625 | $19,318 | $6,307 | | G&A Expenses | $7,699 | $4,857 | $2,842 | | Other Income | $2,009 | $500 | $1,509 | | Net Loss | $(31,315) | $(23,675) | $(7,640) | - For the six months ended June 30, 2025, R&D expenses rose by **$6.3 million**, primarily due to increased personnel, share-based compensation, clinical trial, and outsourced manufacturing and research expenses. G&A expenses increased by **$2.8 million**, driven by higher personnel costs and public company operating expenses, partially offset by lower non-recurring legal fees[130](index=130&type=chunk)[132](index=132&type=chunk) - Other income significantly increased for both periods due to higher average cash and cash equivalents available for investment[128](index=128&type=chunk)[134](index=134&type=chunk) [Liquidity and Capital Resources](index=27&type=section&id=Liquidity%20and%20Capital%20Resources) - The Company has no product revenue and expects continued significant operating losses, necessitating additional capital from equity, debt financings, or collaborations to fund ongoing R&D and future commercialization efforts[135](index=135&type=chunk)[136](index=136&type=chunk)[140](index=140&type=chunk) - Current cash and cash equivalents are projected to fund operations for at least the next 12 months from the issuance date of the financial statements[137](index=137&type=chunk) | Cash Flows (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------ | :----------------------------- | :----------------------------- | | Operating activities | $(27,279) | $(17,102) | | Investing activities | $(31) | $(19) | | Financing activities | $(77) | $5,878 | - Cash used in operating activities increased to **$27.3 million** for the six months ended June 30, 2025, from **$17.1 million** in the prior year, primarily due to higher net loss and changes in operating assets and liabilities[145](index=145&type=chunk)[146](index=146&type=chunk) - Cash used in financing activities for the six months ended June 30, 2025, was **$77 thousand**, related to merger and financing issuance costs, a decrease from **$5.9 million** provided in 2024 from convertible notes[149](index=149&type=chunk) [Critical Accounting Policies and Estimates](index=30&type=section&id=Critical%20Accounting%20Policies%20and%20Estimates) - The Company's financial statements rely on estimates and judgments, particularly for accrued research and development expenses and the fair value of stock options and restricted stock units. No material changes to critical accounting policies were reported from the prior annual report[151](index=151&type=chunk)[152](index=152&type=chunk) [Recent Accounting Pronouncements](index=30&type=section&id=Recent%20Accounting%20Pronouncements) - The Company refers to Note 2 for a description of recent accounting pronouncements applicable to its condensed consolidated financial statements[153](index=153&type=chunk) [Item 3. Quantitative and Qualitative Disclosures about Market Risk](index=30&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20about%20Market%20Risk) As a smaller reporting company, OnKure Therapeutics, Inc. is not required to provide quantitative and qualitative disclosures about market risk - OnKure Therapeutics, Inc. is a smaller reporting company and is therefore not required to provide quantitative and qualitative disclosures about market risk[154](index=154&type=chunk) [Item 4. Controls and Procedures](index=30&type=section&id=Item%204.%20Controls%20and%20Procedures) Management, with the participation of the principal executive and financial officers, evaluated the effectiveness of the Company's disclosure controls and procedures, concluding they were effective as of June 30, 2025. No material changes in internal control over financial reporting occurred during the quarter - Management concluded that the Company's disclosure controls and procedures were effective as of June 30, 2025, providing reasonable assurance that required information is recorded, processed, summarized, and reported timely[155](index=155&type=chunk)[156](index=156&type=chunk) - There were no material changes in the Company's internal control over financial reporting during the three months ended June 30, 2025[157](index=157&type=chunk) PART II — OTHER INFORMATION [Item 1. Legal Proceedings](index=31&type=section&id=Item%201.%20Legal%20Proceedings) The Company may be involved in legal proceedings in the ordinary course of business, which could adversely impact its operations and financial position due to defense costs, diversion of management resources, and potential negative publicity - The Company may become involved in legal proceedings arising in the ordinary course of business, which could have an adverse impact due to defense and settlement costs, diversion of management resources, and negative publicity[160](index=160&type=chunk) [Item 1A. Risk Factors](index=33&type=section&id=Item%201A.%20Risk%20Factors) This section details risks to OnKure's business, covering its early development stage, product dependence, clinical trials, competition, funding, intellectual property, and stock volatility - The Company is an early-stage biopharmaceutical company with no approved products, has incurred significant net losses since inception, and expects to continue incurring losses, making its future viability uncertain[163](index=163&type=chunk)[164](index=164&type=chunk)[167](index=167&type=chunk) - Success is highly dependent on OKI-219's clinical development, regulatory approval, and commercialization, which are subject to risks including trial failures, delays, and the inability to demonstrate safety and efficacy[163](index=163&type=chunk)[179](index=179&type=chunk)[181](index=181&type=chunk)[182](index=182&type=chunk) - The Company faces substantial competition from other pharmaceutical and biotechnology companies, with multiple PI3Kα-targeted agents already approved or in clinical development[219](index=219&type=chunk)[220](index=220&type=chunk)[221](index=221&type=chunk) - OnKure will need substantial additional funding to complete product development and commercialization, with current cash resources expected to last into Q4 2026. Failure to secure additional capital could force delays or discontinuation of programs[173](index=173&type=chunk)[175](index=175&type=chunk)[177](index=177&type=chunk) - The Company relies heavily on third parties for manufacturing and clinical trials, increasing risks related to supply, quality control, regulatory compliance, and potential delays or disruptions[346](index=346&type=chunk)[351](index=351&type=chunk)[352](index=352&type=chunk) - Maintaining and enforcing intellectual property rights is critical but challenging due to complex patent laws, potential infringement claims, and the risk of trade secret misappropriation[246](index=246&type=chunk)[247](index=247&type=chunk)[267](index=267&type=chunk)[285](index=285&type=chunk) - The market price of the Company's Class A Common Stock is expected to be volatile due to clinical trial results, regulatory actions, competition, and general market conditions[367](index=367&type=chunk)[368](index=368&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=85&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The Company reported no unregistered sales of equity securities or use of proceeds during the period - There were no unregistered sales of equity securities or use of proceeds to report[409](index=409&type=chunk) [Item 3. Defaults Upon Senior Securities](index=85&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The Company reported no defaults upon senior securities during the period - There were no defaults upon senior securities to report[410](index=410&type=chunk) [Item 4. Mine Safety Disclosures](index=85&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) The Company reported no mine safety disclosures during the period - There were no mine safety disclosures to report[411](index=411&type=chunk) [Item 5. Other Information](index=85&type=section&id=Item%205.%20Other%20Information) No officers or directors adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement during the last fiscal quarter - No officers or directors adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement during the last fiscal quarter[412](index=412&type=chunk) [Item 6. Exhibits](index=86&type=section&id=Item%206.%20Exhibits) This section lists all exhibits filed as part of the Form 10-Q, including the Agreement and Plan of Merger, Amended and Restated Certificate of Incorporation and Bylaws, Investors' Rights Agreement, and certifications from the Principal Executive Officer and Principal Financial Officer | Exhibit Number | Description

[Executive Summary & Business Update](index=1&type=section&id=OnKure%20Therapeutics%20Reports%20Second%20Quarter%202025%20Financial%20Results%20and%20Provides%20a%20Business%20Update) [Second Quarter 2025 Highlights](index=1&type=section&id=Highlights) OnKure Therapeutics reported its Q2 2025 financial results, highlighting a cash position of $83.4 million, expected to fund operations into Q4 2026, and continued progress in its lead asset, OKI-219 - Cash position of **$83.4 million** expected to provide cash runway into **Q4 2026**[2](index=2&type=chunk) - Continued progress in the development of lead asset, **OKI-219**, with **enrollment completed** for single agent and fulvestrant combination arms, and **initiation of two new triplet arms**[3](index=3&type=chunk) [CEO Commentary](index=1&type=section&id=CEO%20Commentary) President and CEO, Nick Saccomano, expressed encouragement regarding OKI-219's clinical performance and its potential in HR+ and HER2+ breast cancer, announcing new triplet arm initiations and plans to expand the PI3Kα franchise - **OKI-219** has the potential to become an important medicine in the first-line hormone receptor positive setting[4](index=4&type=chunk) - Initiated an arm to evaluate **OKI-219** in combination with fulvestrant and ribociclib in PI3KαH1047R mutated, metastatic HR+ breast cancer[4](index=4&type=chunk) - Initiated an arm to evaluate **OKI-219** in combination with trastuzumab and tucatinib in HER2+ breast cancer[4](index=4&type=chunk) [PI3Kα Portfolio Progress](index=1&type=section&id=PI3KaPortfolio%20Progress) [PIKture-01 Clinical Trial Updates](index=1&type=section&id=PIKture-01%20Clinical%20Trial%20Updates) The Phase 1 PIKture-01 clinical trial assessing OKI-219 in patients with advanced solid tumors is on track, with enrollment completed for monotherapy and fulvestrant combination arms, and new triplet combination arms initiated for HR+ and HER2+ metastatic breast cancer - **PIKture-01**, a phase 1 clinical trial assessing **OKI-219**, is on track for single agent and fulvestrant combination data in **Q4 2025**[6](index=6&type=chunk) [Monotherapy and Fulvestrant Combination](index=1&type=section&id=PIKture-01%20Monotherapy%20and%20Fulvestrant%20Combination) Enrollment for both monotherapy and fulvestrant combination dose escalation arms in the PIKture-01 trial has been completed and closed, with data expected in Q4 2025 - **Enrollment completed and closed** in both the monotherapy and fulvestrant combination dose escalation arms in the **PIKture-01** trial[7](index=7&type=chunk) **PIKture-01 Enrollment (as of August 5, 2025):** | Arm | Patients Dosed | | :--- | :--- | | Monotherapy | 36 | | Combination with Fulvestrant | 34 | | **Total** | **70** | - OnKure expects to report data from both arms in the **fourth quarter of 2025**[7](index=7&type=chunk) [Ribociclib Triplet Combination](index=1&type=section&id=PIKture-01%20Ribociclib%20Triplet%20Combination) A new arm of PIKture-01 has been initiated to evaluate OKI-219 in combination with fulvestrant and ribociclib for PI3KαH1047R mutated, HR+ metastatic breast cancer, with an initial focus on safety - Initiated a new expansion arm of **PIKture-01** to evaluate **OKI-219** in combination with fulvestrant and ribociclib in HR+ metastatic breast cancer[6](index=6&type=chunk)[7](index=7&type=chunk) - The initial phase of this arm will evaluate the safety of escalating doses of **OKI-219** as part of a triplet combination[7](index=7&type=chunk) [Tucatinib Triplet Combination](index=2&type=section&id=PIKture-01%20Tucatinib%20Triplet%20Combination) A new arm of PIKture-01 has been initiated to evaluate OKI-219 in combination with trastuzumab and tucatinib for PI3KαH1047R mutated, HER2+ breast cancer, with an initial focus on safety - Initiated a new expansion arm of **PIKture-01** to evaluate **OKI-219** in combination with trastuzumab and tucatinib in HER2+ metastatic breast cancer[6](index=6&type=chunk)[11](index=11&type=chunk) - The initial phase of this arm will evaluate the safety of escalating doses of **OKI-219** as part of a triplet combination[11](index=11&type=chunk) [Pan-mutant Selective Program](index=2&type=section&id=Pan-mutant%20Selective%20Program) OnKure is developing a third-generation PI3Kα compound targeting high selectivity against common PI3Kα mutations, aiming for a best-in-class pan-mutant inhibitor - Targeting approximately **10-fold selectivity** over PI3Kα wild type against each of the most common mutations (**PI3KαH1047X**, **PI3KαE542K**, and **PI3KαE545K**)[11](index=11&type=chunk) - OnKure plans to announce the nomination of a **development candidate** by the **end of 2025**[11](index=11&type=chunk) [Upcoming Investor Conferences](index=2&type=section&id=Upcoming%20Investor%20Conferences) [Cantor Global Healthcare Investor Conference](index=2&type=section&id=Cantor%20Global%20Healthcare%20Investor%20Conference) OnKure's President and CEO, Nicholas Saccomano, will participate in a fireside chat at the upcoming Cantor Global Healthcare investor conference on September 3, 2025, with a live audio webcast available - OnKure's President and CEO, **Nicholas Saccomano, Ph.D.**, will participate in a fireside chat at the **Cantor Global Healthcare investor conference** on **September 3, 2025**, at **3:20 P.M. ET**[9](index=9&type=chunk) - A live audio webcast can be accessed under 'News & Events' on the Investor section of OnKure's website, with a replay available for at least **90 days**[9](index=9&type=chunk) [Second Quarter 2025 Financial Results](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Results_Summary) [Financial Highlights](index=2&type=section&id=Financial%20Highlights) OnKure reported key financial figures for Q2 2025, including a cash position of $83.4 million, increased R&D and G&A expenses, and a net loss of $15.4 million, with a significantly lower net loss per share due to increased shares outstanding **Key Financial Highlights (Q2 2025 vs. Q2 2024):** | Metric | Q2 2025 (in millions) | Q2 2024 (in millions) | Change (YoY) | | :--- | :--- | :--- | :--- | | Cash and cash equivalents (as of June 30) | $83.4 | N/A (Dec 31, 2024: $110.8) | Decrease | | Research and development (R&D) expenses | $12.6 | $10.8 | +$1.8 (+16.7%) | | General and Administrative (G&A) expenses | $3.7 | $3.6 | +$0.1 (+2.8%) | | Net loss | $(15.4) | $(14.1) | +$1.3 (+9.2%) | | Net loss per share | $(1.14) | $(44.82) | Significant decrease in loss per share due to increased shares outstanding | - Increase in **R&D expenses** primarily due to increased clinical trial, outsourced manufacturing, and research expenses[12](index=12&type=chunk) - Increase in **G&A expenses** 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, partially offset by a decrease in legal expenses[12](index=12&type=chunk) [About OnKure Therapeutics](index=2&type=section&id=About%20OnKure%20Therapeutics) [Company Overview and Strategy](index=2&type=section&id=Company%20Overview%20and%20Strategy) OnKure Therapeutics is a clinical-stage biopharmaceutical company focused on developing best-in-class precision medicines that target biologically validated drivers of underserved cancers, utilizing a structure-based drug design platform with OKI-219 as its lead program - OnKure Therapeutics, Inc. 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[11](index=11&type=chunk)[13](index=13&type=chunk) - The company uses a **structure-based drug design platform** to build a pipeline of tumor-agnostic candidates[11](index=11&type=chunk) - OnKure is currently developing **OKI-219**, a selective PI3KαH1047R inhibitor, as its lead program, aiming to become a leader in targeting oncogenic PI3Kα[13](index=13&type=chunk) [Cautionary Note Regarding Forward-Looking Statements](index=3&type=section&id=Cautionary%20Note%20Regarding%20Forward-Looking%20Statements) [Forward-Looking Statements and Risks](index=3&type=section&id=Forward-Looking%20Statements%20and%20Risks) This section warns that the press release contains forward-looking statements that involve substantial risks and uncertainties, and actual results may differ materially from expectations. Investors should not rely on these statements as predictions of future events, and the company undertakes no obligation to update them - This press release contains **forward-looking statements** that involve substantial risks and uncertainties, including statements regarding future financial condition, results of operations, business strategy, and product candidates[14](index=14&type=chunk) - Key risks include OnKure's limited operating history, significant net losses, ability to raise additional capital, clinical development and regulatory approval risks, competition, intellectual property protection, and reliance on third parties[15](index=15&type=chunk) - Readers should not rely upon forward-looking statements as predictions of future events, and the company undertakes no obligation to update them publicly for any reason after the date of the press release, except as required by law[16](index=16&type=chunk) [Financial Statements](index=5&type=section&id=Financial%20Statements_Detailed) [Condensed Consolidated Balance Sheets](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) The condensed consolidated balance sheets provide a snapshot of OnKure's financial position, showing total assets of $86.07 million and total liabilities of $7.90 million as of June 30, 2025, compared to December 31, 2024 **Condensed Consolidated Balance Sheets (in thousands, unaudited):** | Item | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $83,374 | $110,761 | | Prepaid expenses and other current assets | 1,178 | 2,242 | | Total current assets | 84,552 | 113,003 | | Property and equipment, net | 821 | 1,025 | | Operating lease, right-of-use asset | 581 | 770 | | Other assets | 116 | 109 | | **Total assets** | **$86,070** | **$114,907** | | **Liabilities and Stockholders' Equity** | | | | Accounts payable, accrued expenses, and other liabilities | $7,041 | $9,994 | | Operating lease liabilities, current portion | 556 | 536 | | Total current liabilities | 7,597 | 10,530 | | Long-term liabilities | 307 | 549 | | **Total liabilities** | **7,904** | **11,079** | | Stockholders' equity | 78,166 | 103,828 | | **Total liabilities and stockholders' equity** | **$86,070** | **$114,907** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The condensed consolidated statements of operations detail the company's financial performance for the three and six months ended June 30, 2025, showing increased operating expenses and net losses compared to the prior year, alongside a significant change in net loss per share due to increased weighted average shares outstanding **Condensed Consolidated Statements of Operations and Comprehensive Loss (in thousands, except share and per share amounts, unaudited):** | Item | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Operating expenses: | | | | | | Research and development | $12,613 | $10,752 | $25,625 | $19,318 | | General and administrative | 3,711 | 3,591 | 7,699 | 4,857 | | Total operating expenses | 16,324 | 14,343 | 33,324 | 24,175 | | Loss from operations | (16,324) | (14,343) | (33,324) | (24,175) | | Total other income and (expense), net | 934 | 204 | 2,009 | 500 | | **Net loss and comprehensive loss** | **$(15,390)** | **$(14,139)** | **$(31,315)** | **$(23,675)** | | Net loss per share, basic and diluted | $(1.14) | $(44.82) | $(2.33) | $(75.22) | | Weighted average shares outstanding, basic and diluted | 13,509,080 | 315,478 | 13,466,942 | 314,747 |

Core Insights - OnKure Therapeutics is advancing its lead asset, OKI-219, through the PIKture-01 clinical trial, with data expected in Q4 2025 for both monotherapy and combination treatments [1][2][6] - The company has initiated new expansion arms in the PIKture-01 trial to evaluate OKI-219 in combination with fulvestrant and ribociclib for HR+ metastatic breast cancer, as well as with trastuzumab and tucatinib for HER2+ metastatic breast cancer [1][3][6] - OnKure's cash position of approximately $83.4 million is projected to sustain operations into Q4 2026 [1][13] Clinical Development - Enrollment for the single agent and fulvestrant combination arms of the PIKture-01 trial has been completed, with a total of 70 patients dosed: 36 in monotherapy and 34 in combination with fulvestrant [6] - The new triplet combination arms will assess the safety of escalating doses of OKI-219 in conjunction with fulvestrant and ribociclib, and trastuzumab and tucatinib, specifically targeting PI3Kα mutated breast cancer [6][3] Financial Performance - For Q2 2025, OnKure reported R&D expenses of $12.6 million, up from $10.8 million in Q2 2024, primarily due to increased clinical trial and research costs [13][17] - General and Administrative expenses were $3.7 million for Q2 2025, slightly higher than $3.6 million in Q2 2024, attributed to increased personnel-related costs [13][17] - The net loss for Q2 2025 was $15.4 million, or $1.14 per share, compared to a net loss of $14.1 million, or $44.82 per share, in Q2 2024 [13][17] Strategic Outlook - OnKure aims to position OKI-219 as a significant treatment option in the first-line hormone receptor positive setting and is expanding its PI3Kα portfolio with plans to nominate a pan-mutant selective PI3Kα inhibitor by the end of 2025 [3][4]