Study Overview - The MINOTAUR study investigates the combination of Lunresertib (Lunre), a PKMYT1 inhibitor, with FOLFIRI in advanced gastrointestinal cancers[1] - The study is ongoing but closed to enrollment (NCT05147350)[8, 10] - The primary objectives are to assess the safety, tolerability, recommended phase II dose (RP2D), and schedule of the combination[8] Preclinical Rationale - CCNE1 amplification and deleterious FBXW7 mutations, present in approximately 20% of GI cancers, are associated with poor prognoses and lack matched targeted therapies[5] - Lunre synergizes with irinotecan (iri) to enhance DNA damage and anti-tumor activity by abrogating iri-induced CDK1 phosphorylation[5] Clinical Trial Demographics - The study included 38 patients, with 18 (47.4%) having colorectal cancer (CRC) and 20 (52.6%) with other tumor types[10] - Among CRC patients, 77.8% (14/18) had RAS mutations, and 100% (18/18) had FBXW7 alterations[10] - Among other tumor patients, 35% (7/20) had RAS mutations, 60% (12/20) had CCNE1 amplification, and 40% (8/20) had FBXW7 alterations[10] Safety and Tolerability - The RP2D was established at 60mg BID (twice daily) of continuous daily dosing of Lunre[12] - The safety profile was consistent with FOLFIRI alone, with neutropenia being the most common Grade 3+ hematologic treatment-related adverse event (TRAE) observed in 31.6% (12/38) of patients[12, 13, 15] Efficacy - The overall response rate (ORR) was 18.2% (95% CI: 7-35.5)[17] - The clinical benefit rate (CBR) in CRC patients was 55.6% (10/18)[17] - 40% (2/5) of irinotecan-naïve CRC patients had a duration of treatment (DOT) greater than 9 months[17] - ctDNA molecular response rate (MRR) was 61% (14/23)[17]

PART I. FINANCIAL INFORMATION This section provides the unaudited condensed consolidated financial statements, management's discussion and analysis, and disclosures on market risk and controls [Item 1. Financial Statements (Unaudited)](index=6&type=section&id=Item%201.%20Financial%20Statements%20%28Unaudited%29) This section presents the unaudited condensed consolidated financial statements, including balance sheets, statements of operations, and cash flows, highlighting the impact of the Roche collaboration termination and restructuring charges [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets decreased to **$144.0 million** from **$176.5 million** due to reduced cash and marketable securities, while total liabilities also declined Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Total Current Assets** | $140,343 | $171,149 | | Cash and cash equivalents | $84,455 | $84,717 | | Marketable securities | $39,773 | $68,074 | | **Total Assets** | **$144,023** | **$176,506** | | **Total Current Liabilities** | $18,926 | $25,287 | | **Total Liabilities** | **$18,926** | **$25,375** | | **Total Shareholders' Equity** | $125,097 | $151,131 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The company reported a **$30.0 million** net loss in Q1 2025, a significant shift from **$13.2 million** net income in Q1 2024, primarily due to zero collaboration revenue and a new restructuring charge Q1 2025 vs. Q1 2024 Statement of Operations (in thousands, except per share data) | Metric | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Collaboration Revenue | $0 | $52,404 | | Research and Development | $20,270 | $32,970 | | General and Administrative | $7,652 | $8,618 | | Restructuring | $3,265 | $0 | | **Total Operating Expenses** | **$31,187** | **$41,588** | | (Loss) Income from Operations | ($31,187) | $10,816 | | **Net (Loss) Income** | **($30,043)** | **$13,162** | | Basic Net (Loss) Income per Share | ($0.71) | $0.31 | | Diluted Net (Loss) Income per Share | ($0.71) | $0.30 | [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities was **$29.1 million** in Q1 2025, a significant change from **$11.9 million** provided in Q1 2024, mainly due to the absence of a Roche milestone payment Cash Flow Summary (in thousands) | Activity | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash (used in) provided by operating activities | ($29,133) | $11,932 | | Net cash provided by (used in) investing activities | $28,792 | ($20,316) | | Net cash provided by financing activities | $79 | $375 | | **Net Decrease In Cash And Cash Equivalents** | **($262)** | **($8,051)** | [Notes to Unaudited Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) Key notes detail the financial impact of the Roche agreement termination, BMS revenue recognition, **$3.3 million** in restructuring costs, and the subsequent out-licensing of discovery platforms - In February 2024, Roche elected to terminate its collaboration agreement for camonsertib, with the termination becoming effective May 7, 2024. The company regained global rights to the product. Revenue of **$49.8 million** was recognized in Q1 2024 from this agreement, with **no revenue in Q1 2025**[51](index=51&type=chunk)[53](index=53&type=chunk) - In March 2024, Bristol-Myers Squibb exercised its final option under the BMS Agreement, leading to the recognition of **$2.6 million in revenue in Q1 2024**. **No revenue** was recognized from this agreement in Q1 2025[58](index=58&type=chunk)[59](index=59&type=chunk) - The company initiated a phased reorganization plan in Q1 2025 to reduce its workforce by approximately **75%**. This resulted in restructuring costs of **$3.3 million** for the quarter, consisting of **$2.3 million** in severance benefits and **$0.9 million** in accelerated depreciation[44](index=44&type=chunk)[45](index=45&type=chunk) - Subsequent to the quarter end, on May 1, 2025, the company out-licensed its early-stage discovery platforms to DCx Biotherapeutics. The deal includes **$4.0 million** in upfront and near-term payments, a **9.99% equity stake** in DCx, and potential future milestones and royalties[83](index=83&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=26&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the strategic shift to focus on Phase 1 clinical programs, a **$52.4 million** revenue decrease, and the sufficiency of **$124.2 million** cash to fund operations through 2027 [Overview and Pipeline](index=26&type=section&id=Overview%20and%20Pipeline) Repare re-prioritized its portfolio to focus on Phase 1 programs RP-3467 and RP-1664, involving a **75% workforce reduction** and out-licensing discovery platforms, with key data expected in Q3 and Q4 2025 - Strategic re-prioritization announced in January 2025 to focus resources on Phase 1 clinical programs **RP-3467** and **RP-1664**[87](index=87&type=chunk) - A phased workforce reduction of approximately **75%** was approved in February 2025, with remaining employees focused on the prioritized clinical programs[88](index=88&type=chunk) - Upcoming milestones include topline safety and efficacy data for **RP-3467 in Q3-2025** and initial data for **RP-1664 in Q4-2025**[92](index=92&type=chunk)[100](index=100&type=chunk) - On May 1, 2025, the company out-licensed its early-stage discovery platforms to **DCx Biotherapeutics**[100](index=100&type=chunk) [Results of Operations](index=37&type=section&id=Results%20of%20Operations) Revenue declined to zero from **$52.4 million** due to collaboration terminations, while R&D expenses decreased by **$12.7 million**, and a new **$3.3 million** restructuring expense was recorded Comparison of Results of Operations (in thousands) | Line Item | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | Revenue | $0 | $52,404 | ($52,404) | | R&D Expenses | $20,270 | $32,970 | ($12,700) | | G&A Expenses | $7,652 | $8,618 | ($966) | | Restructuring | $3,265 | $0 | $3,265 | | **(Loss) Income from Operations** | **($31,187)** | **$10,816** | **($42,003)** | - The **$52.4 million decrease in revenue** was due to a **$49.8 million decrease** from the terminated Roche agreement and a **$2.6 million decrease** from the concluded BMS agreement[133](index=133&type=chunk) - The **$12.7 million decrease in R&D expenses** was driven by a **$3.8 million decrease** in lunresertib program costs, a **$3.2 million decrease** in personnel costs, and a **$1.7 million decrease** in camonsertib program costs[132](index=132&type=chunk)[140](index=140&type=chunk) [Liquidity and Capital Resources](index=39&type=section&id=Liquidity%20and%20Capital%20Resources) The company held **$124.2 million** in cash and equivalents, projected to fund operations through 2027, despite a **$29.1 million** net cash outflow from operations in Q1 2025 - Cash, cash equivalents, and marketable securities totaled **$124.2 million** as of March 31, 2025[96](index=96&type=chunk)[142](index=142&type=chunk) - The company believes its current cash position is sufficient to fund anticipated operating and capital expenditure requirements through **2027**, after accounting for restructuring and other strategic changes[96](index=96&type=chunk)[142](index=142&type=chunk) - Net cash used in operating activities was **$29.1 million** for Q1 2025, a **$41.0 million decrease** in cash flow compared to Q1 2024, primarily due to the **$40.0 million milestone payment** received from Roche in Q1 2024[146](index=146&type=chunk)[149](index=149&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=45&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a "smaller reporting company," the company is exempt from providing quantitative and qualitative disclosures about market risk - As a "smaller reporting company," Repare Therapeutics is exempt from providing quantitative and qualitative disclosures about market risk[157](index=157&type=chunk) [Item 4. Controls and Procedures](index=45&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of March 31, 2025, with no material changes to internal control over financial reporting - The company's management, including the CEO/CFO, concluded that disclosure controls and procedures were **effective** as of March 31, 2025[159](index=159&type=chunk) - No changes in internal control over financial reporting occurred during the quarter that have materially affected, or are reasonably likely to materially affect, internal controls[160](index=160&type=chunk) PART II. OTHER INFORMATION This section covers legal proceedings, risk factors, equity sales, other information, and a list of exhibits filed with the report [Item 1. Legal Proceedings](index=46&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings and is unaware of any pending or threatened actions - The company is not currently involved in any material legal proceedings[163](index=163&type=chunk) [Item 1A. Risk Factors](index=46&type=section&id=Item%201A.%20Risk%20Factors) No material changes to risk factors were noted, except for a new risk concerning adverse effects of international trade policies, tariffs, and supply chain disruptions - A new risk factor was added concerning the potential adverse impact of international trade policies, tariffs, and trade barriers on the business[165](index=165&type=chunk) - The company relies on international suppliers, including from China, for active pharmaceutical ingredients (APIs) and precursor chemicals, making it vulnerable to trade tensions[166](index=166&type=chunk) - Current or future tariffs could significantly increase manufacturing costs, raise R&D expenses, and cause delays to clinical development timelines[166](index=166&type=chunk)[167](index=167&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=47&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No unregistered sales of equity securities or issuer purchases of equity securities were reported during Q1 2025 - There were no unregistered sales of equity securities or issuer purchases of equity securities in Q1 2025[169](index=169&type=chunk)[170](index=170&type=chunk) [Item 5. Other Information](index=47&type=section&id=Item%205.%20Other%20Information) No directors or officers adopted, terminated, or modified Rule 10b5-1 trading arrangements during Q1 2025 - No directors or officers adopted, terminated, or modified a Rule 10b5-1 trading plan during the first quarter of 2025[173](index=173&type=chunk) [Item 6. Exhibits](index=48&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Form 10-Q, including employment agreements, separation agreements, and required certifications - Exhibits filed include an amendment to an employment agreement, separation agreements, and CEO/CFO certifications pursuant to Sarbanes-Oxley Act Sections 302 and 906[177](index=177&type=chunk)

Core Viewpoint - Repare Therapeutics Inc. (RPTX) has received a Zacks Rank 2 (Buy) upgrade, indicating a positive outlook driven by an upward trend in earnings estimates, which significantly influences stock prices [1][4]. Earnings Estimates and Revisions - The Zacks rating system is based on the changing earnings picture of a company, specifically tracking the Zacks Consensus Estimate for EPS from sell-side analysts [2]. - The correlation between earnings estimate revisions and near-term stock price movements is strong, making the Zacks rating system valuable for investors [3][7]. - For the fiscal year ending December 2025, Repare Therapeutics is expected to earn -$2.24 per share, reflecting a -13.7% change from the previous year [9]. - Over the past three months, the Zacks Consensus Estimate for Repare Therapeutics has increased by 28.3%, indicating a positive trend in earnings estimates [9]. Zacks Rating System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a proven track record of Zacks Rank 1 stocks generating an average annual return of +25% since 1988 [8]. - The upgrade of Repare Therapeutics to a Zacks Rank 2 places it in the top 20% of Zacks-covered stocks, suggesting potential for market-beating returns in the near term [10][11].

Part I [Business](index=8&type=section&id=Item%201.%20Business) Repare Therapeutics is a clinical-stage precision oncology company focused on developing synthetic lethality therapeutics via its SNIPRx® platform [Overview and Strategy](index=8&type=section&id=Item%201.%20Business%20-%20Overview%20and%20Strategy) Repare Therapeutics, a clinical-stage precision oncology company, restructured in January 2025 to focus on Phase 1 programs RP-3467 and RP-1664 - The company is a clinical-stage precision oncology firm using its proprietary SNIPRx® platform to develop novel therapeutics based on synthetic lethality[19](index=19&type=chunk) - In January 2025, the company announced a strategic re-prioritization to focus on its Phase 1 programs, RP-3467 and RP-1664[20](index=20&type=chunk) - As part of the restructuring, the company reduced its workforce by approximately **75%** on February 24, 2025, to focus on advancing RP-3467 and RP-1664[20](index=20&type=chunk) - The company plans to seek partnerships for its other clinical assets, lunresertib and camonsertib, before initiating pivotal development[20](index=20&type=chunk) [Development Programs](index=8&type=section&id=Item%201.%20Business%20-%20Development%20Programs) The company's pipeline focuses on Phase 1 trials for RP-3467 and RP-1664, with other candidates paused pending partnerships - **RP-3467 (Polθ inhibitor):** A potential best-in-class inhibitor for HRD tumors. A Phase 1 trial (POLAR) was initiated in Q4 2024, with the first patient dosed in combination with olaparib. Topline safety and early efficacy data are expected in Q3 2025[22](index=22&type=chunk)[23](index=23&type=chunk) - **RP-1664 (PLK4 inhibitor):** A potential first-in-class oral inhibitor for tumors with TRIM37 amplification. A Phase 1 trial (LIONS) in adults began in February 2024. A Phase 1/2 expansion in pediatric neuroblastoma is planned for Q3 2025, with initial LIONS data expected in Q4 2025[23](index=23&type=chunk) - **Lunresertib (PKMYT1 inhibitor) and Camonsertib (ATR inhibitor):** Further development of these candidates is paused, pending a partnership. An ongoing combination study of lunresertib with Debiopharm's Debio 0123 will continue[24](index=24&type=chunk)[26](index=26&type=chunk)[27](index=27&type=chunk) [Intellectual Property](index=9&type=section&id=Item%201.%20Business%20-%20Intellectual%20Property) The company protects its proprietary technologies and product candidates through patents, trade secrets, and confidentiality agreements Expected Patent Expiry Dates for Key Programs | Programs | Expected expiry dates | | :--- | :--- | | Polθ inhibitors, including RP-3467 | 2042-2044 | | PLK4 inhibitors, including RP-1664 | 2043 | | CCNE1-SL inhibitors, including lunresertib | 2041-2044 | | ATR inhibitors, including camonsertib | 2039-2044 | - The company's IP strategy involves seeking and maintaining patent rights, defending them, and protecting trade secrets and know-how through confidentiality and invention assignment agreements[28](index=28&type=chunk)[31](index=31&type=chunk) - Patent terms are generally 20 years from the earliest non-provisional filing date, with potential for extensions to compensate for FDA regulatory review delays[29](index=29&type=chunk) [Collaborations and License Agreements](index=11&type=section&id=Item%201.%20Business%20-%20Collaborations%20and%20License%20Agreements) Key agreements include the expired BMS collaboration with ongoing royalties and a NYU license for Polθ patents with milestone payments - **Bristol-Myers Squibb (BMS) Agreement:** The collaboration term for research and target identification expired in November 2023. BMS exercised options for five druggable and one undruggable target. Repare is eligible for up to **$301.0 million** in milestones per program and tiered royalties[33](index=33&type=chunk)[35](index=35&type=chunk)[36](index=36&type=chunk)[39](index=39&type=chunk) - **New York University (NYU) Agreement:** Repare holds an exclusive, worldwide license for Polθ patents. The agreement requires milestone payments (up to **$6.7 million** in aggregate for a product) and low single-digit royalties on net sales. A **$0.1 million** milestone was triggered in October 2024[40](index=40&type=chunk)[43](index=43&type=chunk)[45](index=45&type=chunk) [Competition](index=13&type=section&id=Item%201.%20Business%20-%20Competition) The company faces intense competition in precision oncology from major pharmaceutical and biotech firms, including specific rivals for its lead programs - The company faces substantial competition from large pharmaceutical companies and other biotechs with greater resources in R&D, manufacturing, and marketing[54](index=54&type=chunk) - Competitors in the precision oncology space include Loxo Oncology, Blueprint Medicines, and Tango Therapeutics. Competitors in the synthetic lethality space include AstraZeneca, GlaxoSmithKline, and IDEAYA Biosciences[55](index=55&type=chunk) - Specific competitors for Repare's pipeline include: - **Polθ (RP-3467):** Artios Pharma, IDEAYA Biosciences, MOMA Therapeutics - **PLK4 (RP-1664):** Exelixis, Oric Pharmaceuticals, Treadwell Therapeutics - **PKMYT1 (lunresertib):** Acrivon Therapeutics, Exelixis, Schrodinger[57](index=57&type=chunk)[58](index=58&type=chunk) [Government Regulation](index=14&type=section&id=Item%201.%20Business%20-%20Government%20Regulation) The company's operations are subject to extensive FDA regulation for drug development and approval, alongside various healthcare laws and pricing reforms - The FDA drug approval process is lengthy and resource-intensive, requiring preclinical studies (GLP) and three phases of human clinical trials (GCP) before submitting a New Drug Application (NDA)[61](index=61&type=chunk)[62](index=62&type=chunk)[65](index=65&type=chunk)[70](index=70&type=chunk) - The FDA offers expedited review programs such as Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review for drugs treating serious conditions and addressing unmet medical needs[71](index=71&type=chunk) - The company is subject to numerous healthcare laws, including the federal Anti-Kickback Statute, the False Claims Act (FCA), and HIPAA, which regulate interactions with healthcare providers and protect patient information[98](index=98&type=chunk)[100](index=100&type=chunk)[101](index=101&type=chunk) - Healthcare reform measures, such as the Affordable Care Act (ACA) and the Inflation Reduction Act of 2022 (IRA), impact drug pricing, reimbursement, and market access, creating significant uncertainty[112](index=112&type=chunk)[114](index=114&type=chunk)[116](index=116&type=chunk) [Employees and Human Capital Resources](index=25&type=section&id=Item%201.%20Business%20-%20Employees%20and%20Human%20Capital%20Resources) The company reduced its workforce by 75% in February 2025, focusing on core values and competitive compensation to attract and retain talent - On February 24, 2025, the company reduced its workforce by approximately **75%**. Prior to this, as of February 10, 2025, it had **129** full-time employees[121](index=121&type=chunk) - The company's core values are: Patients come first; Respect and trust are core; We are empathetic; We are open, direct, and authentic; We embrace risk and thrive[123](index=123&type=chunk) - Repare offers competitive compensation packages including base salaries, annual equity and cash incentive plans, healthcare benefits, and an employee share purchase plan to attract and retain talent[125](index=125&type=chunk) [Risk Factors](index=27&type=section&id=Item%201A.%20Risk%20Factors) Investing in Repare Therapeutics involves significant financial, development, operational, commercial, and IP risks, including those from recent restructuring and regulatory changes - **Financial Risks:** The company has a limited operating history, has incurred significant losses since inception, and will require substantial additional funding to continue operations, which may not be available on acceptable terms[136](index=136&type=chunk)[139](index=139&type=chunk)[144](index=144&type=chunk) - **Development and Regulatory Risks:** The success of the business depends on advancing early-stage product candidates through uncertain clinical development and regulatory approval processes. The company's SNIPRx® platform is novel and may not prove effective[150](index=150&type=chunk)[155](index=155&type=chunk)[172](index=172&type=chunk) - **Operational Risks:** The company relies on third parties for manufacturing (CMOs) and clinical trials (CROs), and its recent corporate restructuring and **75%** headcount reduction could disrupt business and employee retention[133](index=133&type=chunk)[253](index=253&type=chunk)[260](index=260&type=chunk) - **Commercial and IP Risks:** The company faces substantial competition, may not achieve market acceptance for its products if approved, and its success depends on its ability to obtain and protect its intellectual property rights[211](index=211&type=chunk)[205](index=205&type=chunk)[270](index=270&type=chunk) [Unresolved Staff Comments](index=80&type=section&id=Item%201B.%20Unresolved%20Staff%20Comments) The company reports no unresolved staff comments from the Securities and Exchange Commission - None[379](index=379&type=chunk) [Cybersecurity](index=80&type=section&id=Item%201C.%20Cybersecurity) Repare Therapeutics manages cybersecurity through a formal risk management program, overseen by its audit committee, focusing on threat identification, mitigation, and vendor risk - The company has processes to identify, assess, and manage material cybersecurity risks, utilizing methods like automated scanning, third-party audits, and external intelligence[380](index=380&type=chunk)[381](index=381&type=chunk) - Cybersecurity governance is handled by the board of directors' audit committee, which oversees the risk management processes implemented by company management[387](index=387&type=chunk) - Management, including the EVP & CFO and VP of IT, is responsible for implementing the cybersecurity program and escalating significant incidents to the audit committee as per the incident response policy[388](index=388&type=chunk)[390](index=390&type=chunk) [Properties](index=82&type=section&id=Item%202.%20Properties) Repare Therapeutics leases headquarters in Montréal and U.S. operations in Cambridge, and is exploring lease options due to recent strategic realignment - Headquarters in Montréal, Québec consists of **24,039 sq. ft.** of leased lab and office space, with the lease expiring in August 2025[392](index=392&type=chunk) - U.S. operations are based in a leased **11,312 sq. ft.** office space in Cambridge, Massachusetts, with the lease expiring in January 2026[392](index=392&type=chunk) - The company is currently exploring its lease options due to the recent realignment of resources and strategic reprioritization[392](index=392&type=chunk) [Legal Proceedings](index=82&type=section&id=Item%203.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings or aware of any threatened legal actions - The company is not currently a party to any material legal proceedings[393](index=393&type=chunk) [Mine Safety Disclosures](index=82&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - Not applicable[394](index=394&type=chunk) Part II [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=83&type=section&id=Item%205.%20Market%20for%20Registrant's%20Common%20Equity,%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) Repare Therapeutics' common shares trade on Nasdaq under "RPTX"; the company has never paid dividends and issued a warrant in November 2024 - The company's common shares trade on The Nasdaq Global Select Market under the symbol "RPTX"[397](index=397&type=chunk) - The company has never declared or paid cash dividends and does not plan to in the foreseeable future[399](index=399&type=chunk) - In November 2024, the company issued a warrant to a service provider to purchase **35,000** common shares at an exercise price of **$3.61** per share[400](index=400&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=84&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The company reported a net loss of $84.7 million in 2024, with $152.8 million cash expected to fund operations into late 2027 post-restructuring [Results of Operations](index=92&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations%20-%20Results%20of%20Operations) For 2024, revenue increased to $53.5 million due to a Roche milestone, while R&D and G&A expenses decreased, resulting in a net loss of $84.7 million Comparison of Results of Operations (2024 vs. 2023) | Financial Metric | 2024 (in thousands) | 2023 (in thousands) | Change (in thousands) | Key Driver(s) | | :--- | :--- | :--- | :--- | :--- | | **Revenue** | $53,477 | $51,133 | $2,344 | Increase from Roche milestone, offset by decreases from expired BMS and Ono agreements | | **R&D Expenses** | $115,941 | $133,593 | ($17,652) | Decrease in camonsertib program costs and discovery costs | | **G&A Expenses** | $29,680 | $33,764 | ($4,084) | Decrease in personnel costs and D&O insurance premiums | | **Restructuring Expenses** | $1,379 | $0 | $1,379 | Costs from August 2024 strategic refocus | | **Loss from Operations** | ($93,523) | ($116,224) | $22,701 | Lower operating expenses | | **Net Loss** | ($84,689) | ($93,796) | $9,107 | Lower operating loss and changes in income tax benefit/expense | [Liquidity and Capital Resources](index=94&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations%20-%20Liquidity%20and%20Capital%20Resources) As of December 31, 2024, Repare had $152.8 million in cash, expected to fund operations into late 2027 after recent restructuring and cost-saving measures - As of December 31, 2024, the company had **$152.8 million** in cash, cash equivalents, and marketable securities[464](index=464&type=chunk) - The current cash position is expected to fund operating and capital expenditure requirements into **late-2027**, factoring in recent cost-saving measures[464](index=464&type=chunk)[465](index=465&type=chunk) - The company has an active at-the-market (ATM) sales agreement to sell up to **$100.0 million** in common shares, but did not sell any shares under this program in 2024 or 2023[460](index=460&type=chunk) - In early 2025, the company implemented a significant realignment, including a **75%** workforce reduction, to extend its cash runway and focus on its Phase 1 programs, RP-3467 and RP-1664[461](index=461&type=chunk) [Critical Accounting Estimates](index=97&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations%20-%20Critical%20Accounting%20Estimates) Key accounting estimates include Revenue Recognition, Accrued and Prepaid R&D Expenses, and Share-Based Compensation, all requiring significant judgment - **Revenue Recognition:** Involves significant judgment in identifying performance obligations, determining the transaction price (including variable consideration like milestones), and allocating it based on relative stand-alone selling prices in complex collaboration agreements[481](index=481&type=chunk)[482](index=482&type=chunk)[483](index=483&type=chunk) - **Accrued and Prepaid Research and Development Expenses:** Requires estimating costs for services performed by third-party vendors (e.g., CROs) that have not yet been invoiced, based on contract terms and the level of service completed[491](index=491&type=chunk)[492](index=492&type=chunk) - **Share-Based Compensation:** The fair value of stock options is estimated using the Black-Scholes model, which requires subjective assumptions for expected volatility, expected term, risk-free interest rate, and dividend yield[494](index=494&type=chunk)[496](index=496&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=102&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a "smaller reporting company," Repare Therapeutics is not required to provide market risk disclosures - As a "smaller reporting company," Repare Therapeutics is not required to provide quantitative and qualitative disclosures about market risk[499](index=499&type=chunk) [Financial Statements and Supplementary Data](index=103&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) The consolidated financial statements, audited by Ernst & Young LLP, show a net loss of $84.7 million in 2024 and total assets of $176.5 million Consolidated Balance Sheet Data (in thousands) | | Dec 31, 2024 | Dec 31, 2023 | | :--- | :--- | :--- | | Cash, cash equivalents, and marketable securities | $152,791 | $223,627 | | Total Assets | $176,506 | $253,901 | | Total Liabilities | $25,375 | $41,819 | | Total Shareholders' Equity | $151,131 | $212,082 | Consolidated Statement of Operations Data (in thousands) | | Year Ended Dec 31, 2024 | Year Ended Dec 31, 2023 | | :--- | :--- | :--- | | Revenue | $53,477 | $51,133 | | Research and development expenses | $115,941 | $133,593 | | General and administrative expenses | $29,680 | $33,764 | | Net Loss | ($84,689) | ($93,796) | | Net Loss Per Share | ($2.00) | ($2.23) | Consolidated Statement of Cash Flows Data (in thousands) | | Year Ended Dec 31, 2024 | Year Ended Dec 31, 2023 | | :--- | :--- | :--- | | Net cash used in operating activities | ($76,445) | ($127,158) | | Net cash provided by investing activities | $49,468 | $78,041 | | Net cash provided by financing activities | $542 | $842 | - The independent auditor, Ernst & Young LLP, issued an unqualified opinion on the financial statements and identified 'Accrued and Prepaid Research and Development Expenses' as a critical audit matter due to the significant judgment and estimates involved[506](index=506&type=chunk)[510](index=510&type=chunk)[511](index=511&type=chunk) [Changes in and Disagreements With Accountants on Accounting and Financial Disclosure](index=143&type=section&id=Item%209.%20Changes%20in%20and%20Disagreements%20With%20Accountants%20on%20Accounting%20and%20Financial%20Disclosure) The company reports no changes in or disagreements with its accountants on accounting or financial disclosure matters - None[704](index=704&type=chunk) [Controls and Procedures](index=143&type=section&id=Item%209A.%20Controls%20and%20Procedures) Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2024, with no material changes - Management concluded that the company's disclosure controls and procedures were effective as of December 31, 2024[706](index=706&type=chunk) - Management's assessment concluded that the company's internal control over financial reporting was effective as of December 31, 2024, based on the COSO 2013 framework[708](index=708&type=chunk) - The company is exempt from the requirement for an auditor's attestation report on internal control over financial reporting because it is a smaller reporting company[709](index=709&type=chunk) [Other Information](index=145&type=section&id=Item%209B.%20Other%20Information) No directors or officers adopted, terminated, or modified Rule 10b5-1 or non-Rule 10b5-1 trading arrangements in Q4 2024 - No director or officer adopted, terminated, or modified a Rule 10b5-1 trading plan or other non-Rule 10b5-1 trading arrangement during the fourth quarter of 2024[712](index=712&type=chunk) [Disclosure Regarding Foreign Jurisdictions that Prevent Inspections](index=145&type=section&id=Item%209C.%20Disclosure%20Regarding%20Foreign%20Jurisdictions%20that%20Prevent%20Inspections) This item is not applicable to the company - None[713](index=713&type=chunk) Part III [Directors, Executive Officers and Corporate Governance](index=146&type=section&id=Item%2010.%20Directors,%20Executive%20Officers%20and%20Corporate%20Governance) Information on directors, executive officers, and corporate governance is incorporated by reference from the 2025 Annual Meeting proxy statement - The information required by this item is incorporated by reference from the company's definitive proxy statement for its 2025 Annual Meeting of Shareholders[715](index=715&type=chunk) [Executive Compensation](index=146&type=section&id=Item%2011.%20Executive%20Compensation) Executive and director compensation information is incorporated by reference from the 2025 Annual Meeting proxy statement - The information required by this item is incorporated by reference from the company's definitive proxy statement for its 2025 Annual Meeting of Shareholders[717](index=717&type=chunk) [Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters](index=146&type=section&id=Item%2012.%20Security%20Ownership%20of%20Certain%20Beneficial%20Owners%20and%20Management%20and%20Related%20Stockholder%20Matters) Security ownership and equity compensation plan information is incorporated by reference from the 2025 Annual Meeting proxy statement - The information required by this item is incorporated by reference from the company's definitive proxy statement for its 2025 Annual Meeting of Shareholders[718](index=718&type=chunk) [Certain Relationships and Related Transactions, and Director Independence](index=146&type=section&id=Item%2013.%20Certain%20Relationships%20and%20Related%20Transactions,%20and%20Director%20Independence) Information on related party transactions and director independence is incorporated by reference from the 2025 Annual Meeting proxy statement - The information required by this item is incorporated by reference from the company's definitive proxy statement for its 2025 Annual Meeting of Shareholders[719](index=719&type=chunk) [Principal Accounting Fees and Services](index=146&type=section&id=Item%2014.%20Principal%20Accounting%20Fees%20and%20Services) Information on principal accounting fees and services is incorporated by reference from the 2025 Annual Meeting proxy statement - The information required by this item is incorporated by reference from the company's definitive proxy statement for its 2025 Annual Meeting of Shareholders[720](index=720&type=chunk) Part IV [Exhibits and Financial Statement Schedules](index=147&type=section&id=Item%2015.%20Exhibits%20and%20Financial%20Statement%20Schedules) This section lists documents filed as part of the Annual Report, including consolidated financial statements and an index of exhibits - The company's Consolidated Financial Statements are filed under Part II, Item 8 of the report[723](index=723&type=chunk) - All financial statement schedules have been omitted because the information is not applicable or is already included in the financial statements or notes[723](index=723&type=chunk) - A detailed index of exhibits filed with or incorporated by reference into the Form 10-K is provided[725](index=725&type=chunk) [Form 10-K Summary](index=151&type=section&id=Item%2016.%20Form%2010-K%20Summary) The company has not provided a summary for this item - None[732](index=732&type=chunk)

Core Viewpoint - Repare Therapeutics Inc. (RPTX) has shown a downtrend recently, losing 7.6% over the past four weeks, but a hammer chart pattern suggests a potential trend reversal as buying interest may be emerging to counteract selling pressure [1][2]. Technical Analysis - The hammer chart pattern indicates a possible bottoming out, with reduced selling pressure, suggesting a bullish outlook for the stock [2][4]. - A hammer pattern forms when there is a small candle body with a long lower wick, indicating that despite a new low, buying interest has emerged to push the stock price up towards the opening price [3][4]. - This pattern is significant when it appears at the bottom of a downtrend, signaling that bears may be losing control and bulls are gaining strength [4]. Fundamental Analysis - There has been a positive trend in earnings estimate revisions for RPTX, which is a bullish indicator as it typically leads to price appreciation [6]. - Over the last 30 days, the consensus EPS estimate for the current year has increased by 3%, indicating that analysts expect better earnings than previously predicted [7]. - RPTX holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks, which historically outperform the market [8].

Group 1 - Repare Therapeutics Inc. (RPTX) has experienced a downtrend with a 5.2% decline over the past four weeks, but it is now in oversold territory, indicating a potential turnaround [1] - The Relative Strength Index (RSI) for RPTX is at 20.45, suggesting that the heavy selling pressure may be exhausting itself, which could lead to a reversal in the stock's trend [5] - Analysts have raised earnings estimates for RPTX by 3% over the last 30 days, indicating a consensus that the company may report better earnings than previously predicted, which typically correlates with price appreciation [6] Group 2 - RPTX holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate revisions and EPS surprises, further supporting the potential for a near-term turnaround [7]

[Form 8-K Current Report](index=1&type=section&id=Form%208-K) [Results of Operations and Financial Condition](index=2&type=section&id=Item%202.02.%20Results%20of%20Operations%20and%20Financial%20Condition.) Repare Therapeutics reported preliminary, unaudited cash, cash equivalents, and marketable securities of approximately $153 million as of December 31, 2024 Preliminary Financial Position | Metric | Value (Preliminary, Unaudited) | | :--- | :--- | | Cash, Cash Equivalents and Marketable Securities | Approx. $153 million | - The announced financial information is **preliminary, unaudited**, and represents a **management estimate**, subject to change upon completion of year-end financial closing procedures[5](index=5&type=chunk) - The company's independent registered public accounting firm has **not audited or reviewed** these preliminary results[5](index=5&type=chunk) [Regulation FD Disclosure](index=2&type=section&id=Item%207.01%20Regulation%20FD%20Disclosure.) The company re-aligned resources to focus on Phase 1 clinical programs RP-1664 and RP-3467, extending cash runway into mid-2027 - Announced a **re-alignment of resources** and **re-prioritization** of its clinical portfolio[8](index=8&type=chunk) - The strategic focus will be on advancing **Phase 1 clinical programs: RP-1664 and RP-3467**[8](index=8&type=chunk) - Planned **cost savings** and **headcount reductions** are projected to extend the company's **cash runway into mid-2027**[8](index=8&type=chunk) [Cautionary Note Regarding Forward-Looking Statements](index=2&type=section&id=Cautionary%20Note%20Regarding%20Forward-Looking%20Statements) Forward-looking statements on business plans and cash runway are subject to risks and uncertainties, potentially causing actual results to differ - The report includes **forward-looking statements** regarding **business plans**, expected **cost-savings**, and the estimated **cash runway**[10](index=10&type=chunk) - These statements are **not guarantees of future performance** and are subject to **risks and uncertainties** that could cause actual results to **differ materially**[10](index=10&type=chunk) - Identified risks include the successful implementation of **cost-cutting**, the impact on business and **employee retention**, and potential **litigation or regulatory actions**[10](index=10&type=chunk) [Financial Statements and Exhibits](index=3&type=section&id=Item%209.01%20Financial%20Statements%20and%20Exhibits.) This section lists exhibits filed with the Form 8-K, including a press release dated January 9, 2025 Filed Exhibits | Exhibit No. | Description | | :--- | :--- | | 99.1 | Press Release dated January 9, 2025 | | 104 | Cover Page Interactive Data File |

Core Insights - Repare Therapeutics Inc has released data from its MYTHIC Phase 1 trial evaluating the combination therapy of lunresertib and camonsertib for endometrial cancer and platinum-resistant ovarian cancer [1] Group 1: Clinical Findings - In the gynecologic cancer expansion cohort, 51 evaluable patients were enrolled as of the data cut-off date of November 14 [1] - For endometrial cancer, the overall response rate was 25.9%, with clinical benefit observed in 48.1% of patients, and a 24-week progression-free survival (PFS) rate of 43% [4] - In platinum-resistant ovarian cancer, the overall response rate was 37.5%, with clinical benefit in 79% of patients, and a 24-week PFS rate of 45% [5] Group 2: Safety Profile - Lunre+Camo therapy demonstrated a favorable tolerability profile compared to current and emerging therapies, with the most common adverse event being anemia at 26.9% (Grade 3) [2][3] Group 3: Regulatory and Development Plans - Repare has consulted with the FDA and the European Medicines Agency regarding registrational development plans for Lunre+Camo in gynecologic tumors [5] - The company plans to submit final Phase 3 trial protocols for regulatory clearance soon and aims to start the first Phase 3 trial in endometrial cancer in the second half of 2025 [6] Group 4: Market Reaction - Following the announcement, RPTX stock experienced a decline of 52.4%, trading at $1.89 [7]

Clinical Development - The company is a leading clinical-stage precision oncology firm utilizing a proprietary synthetic lethality approach for drug development [70]. - The company has developed four clinical therapeutic candidates, including Lunresertib, which is currently the only PKMYT1 inhibitor in clinical trials [71]. - Positive initial Phase 1 data for Lunresertib was presented, showing it to be well tolerated with a compelling safety profile [72]. - The company expects to provide updated MYTHIC data from endometrial cancer expansion cohorts in December 2024, with a registrational trial anticipated to start in 2025 [73]. - The first patient was dosed in the LIONS clinical trial for RP-1664 in February 2024, with plans to move into a Phase 1/2 trial for pediatric neuroblastoma [76]. - Initial data for RP-3467 demonstrated complete, sustained regressions in combination with PARP inhibitors, with the first patient dosed in the POLAR Phase 1 trial in October 2024 [77]. - The company is evaluating lunresertib in combination with camonsertib in a clinical trial, with data expected from approximately 20-30 patients in December 2024 [78]. - Initial data from the TRESR clinical trial evaluating camonsertib in NSCLC is expected to be reported in 2025 [80]. - The POLAR clinical trial for RP-3467 has commenced, evaluating its safety and preliminary clinical activity in advanced solid tumors [82]. Financial Performance - The company reported net losses of $93.8 million for the year ended December 31, 2023, and an accumulated deficit of $389.1 million as of September 30, 2024 [86]. - Revenue from collaboration agreements totaled $53.5 million for the nine months ended September 30, 2024, compared to $38.1 million for the same period in 2023 [95]. - The company received a $40 million milestone payment from Roche in February 2024 upon dosing the first patient with camonsertib in Roche's Phase 2 TAPISTRY trial [97]. - Revenue for the three months ended September 30, 2024, was nil, a decrease of $2.2 million compared to $2.2 million for the same period in 2023, primarily due to the termination of the Roche Agreement and expiration of the BMS Agreement [125]. - Revenue for the nine months ended September 30, 2024, was $53.5 million, an increase of $15.4 million compared to $38.1 million for the same period in 2023, driven by a milestone achievement under the Roche Agreement [132]. - The company reported a net loss of $56.0 million for the nine months ended September 30, 2024, compared to a net loss of $65.8 million for the same period in 2023 [150][152]. Research and Development Expenses - Total research and development costs for the nine months ended September 30, 2024, amounted to $91.446 million, compared to $98.327 million for the same period in 2023, reflecting a decrease [114]. - Research and development expenses for the three months ended September 30, 2024, were $28.4 million, down from $32.7 million in 2023, a decrease of $4.3 million attributed to reduced external costs and personnel-related costs [126]. - Research and development expenses for the nine months ended September 30, 2024, were $91.4 million, down from $98.3 million in 2023, a decrease of $6.9 million due to various program cost adjustments [134]. - The company plans to substantially increase research and development expenses in the long term, particularly for the potential registrational trial of lunresertib and camonsertib combination expected to commence in 2025 [116]. Cash and Funding - As of September 30, 2024, the company had cash and cash equivalents and marketable securities of $179.4 million, expected to fund operations into the second half of 2026 [85]. - Net cash used in operating activities for the nine months ended September 30, 2024, was $49.1 million, a decrease of $49.9 million compared to $99.0 million for the same period in 2023 [149][150][152]. - Cash provided by operating activities increased by $49.9 million primarily due to a $40.0 million milestone payment from Roche in Q1 2024 [153]. - The company has a cash balance of $179.4 million as of September 30, 2024, with $8.4 million earned in interest income during the same period [161]. - The company expects to finance its cash needs through equity offerings, debt financings, and collaborations, which may dilute shareholder ownership [148]. Workforce and Restructuring - The company has reduced its workforce by approximately 25% as part of a strategic reprioritization of R&D activities [83]. - The company incurred approximately $1.5 million in restructuring expenses due to a strategic reprioritization of research and development activities, resulting in a 25% workforce reduction [120]. - Restructuring expenses of $1.5 million were incurred in the three months ended September 30, 2024, as part of a strategic refocus [128]. Agreements and Collaborations - The company received a cumulative total of $182.6 million from Roche for the camonsertib collaboration, which included an initial $125 million upfront payment [73]. - The Roche Agreement was terminated on May 7, 2024, allowing the company to regain global development and commercialization rights for camonsertib [99]. - The company recognized approximately $10.5 million as revenue for the three and six months ended June 30, 2023, under the Ono Agreement, which has since concluded [104]. - The company recognized $2.6 million as revenue related to undruggable targets, including an option fee payment of $0.1 million, following the exercise of an option by Bristol-Myers Squibb [103]. - The company is eligible to receive up to $301.0 million in total milestones on a program-by-program basis, contingent upon achieving specified research, development, regulatory, and commercial milestones [102].

Clinical Trials - The company is on track to report data from the MYTHIC dose expansion clinical trial in December 2024, with plans to begin a registrational trial in 2025[1] - The first patient has been dosed in the Phase 1 POLAR trial evaluating RP-3467, a Polq ATPase inhibitor, alone and in combination with the PARP inhibitor, olaparib[1] - The company presented positive updated safety and tolerability data from the Phase 1 MYTHIC trial, showing a reduction in Grade 3 anemia to 22.6% from 51.4%[4] Financial Performance - Cash, cash equivalents, and marketable securities as of September 30, 2024, were $179.4 million, sufficient to fund operations into the second half of 2026[11] - Revenue from collaboration agreements was nil for the three months ended September 30, 2024, compared to $2.2 million for the same period in 2023[12] - Net R&D expenses were $28.4 million for the three months ended September 30, 2024, down from $32.7 million for the same period in 2023[13] - General and administrative expenses were $6.4 million for the three months ended September 30, 2024, compared to $7.9 million for the same period in 2023[14] - The net loss for the three months ended September 30, 2024, was $34.4 million, or $0.81 per share, compared to a net loss of $18.9 million, or $0.45 per share, for the same period in 2023[15] - Total operating expenses for Q3 2024 were $36,372,000, down from $40,577,000 in Q3 2023, a decrease of 5.4%[20] - Net loss for Q3 2024 was $34,406,000, compared to a net loss of $18,879,000 in Q3 2023, an increase of 82.7%[20] - Research and development expenses for the nine months ended September 2024 were $91,446,000, down from $98,327,000 for the same period in 2023, a decrease of 7%[20] - General and administrative expenses for Q3 2024 were $6,444,000, a decrease of 18.1% from $7,868,000 in Q3 2023[20] - Interest income for Q3 2024 was $2,512,000, compared to $3,312,000 in Q3 2023, a decrease of 24.1%[20] - Comprehensive loss for Q3 2024 was $34,132,000, compared to $18,707,000 in Q3 2023, an increase of 82.5%[20] - Net loss per share attributable to common shareholders for Q3 2024 was $(0.81), compared to $(0.45) in Q3 2023, a decrease of 80%[20] - Total other income for Q3 2024 was $2,451,000, down from $3,240,000 in Q3 2023, a decrease of 24.4%[20] - Restructuring expenses for Q3 2024 were $1,527,000, with no restructuring expenses reported in Q3 2023[20] Workforce and Strategic Changes - The company reduced its overall workforce by approximately 25% as part of a strategic reprioritization of its R&D activities[10] - Total assets as of September 30, 2024, were $206.4 million, down from $253.9 million as of December 31, 2023[19]