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

[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]

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

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

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

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

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

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

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