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]

Core Insights - Repare Therapeutics (RPTX) shares increased by 8% following the announcement of dosing the first patient in an early-stage study for the combination of RP-3467 and AstraZeneca's Lynparza to treat advanced solid tumors [1] - The combination of RP-3467 and Lynparza has shown promising preclinical results, leading to complete and durable tumor regressions without additional toxicities, indicating potential to improve patient outcomes by addressing PARP inhibitor resistance [2] - The ongoing phase I POLAR study aims to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of RP-3467, targeting 52 patients with specific advanced solid tumors [3][4] Company Pipeline - Repare utilizes its CRISPR-enabled SNIPRx platform to develop targeted cancer therapies focusing on genomic instability and DNA damage repair [5] - The company is also evaluating lunresertib, a PKMYT1 inhibitor, in combination with camonsertib, an ATR inhibitor, in a phase I study for ovarian and endometrial cancer, with top-line data expected soon [6] - RP-1664, an oral PLK4 inhibitor, is currently in a phase I study for advanced solid tumors, indicating a diverse clinical-stage pipeline [7] Market Context - Year to date, RPTX shares have decreased by 53.6%, contrasting with a 2% decline in the broader industry [3] - Repare currently holds a Zacks Rank 3 (Hold), while ANI Pharmaceuticals and Alnylam Pharmaceuticals are ranked 1 (Strong Buy) [8]

Core Viewpoint - Repare Therapeutics is approaching a significant milestone with the upcoming results from its phase 1 MYTHIC trial, which is testing the combination of lunresertib and camonsertib for treating platinum-resistant ovarian and endometrial cancers. The data expected in Q4 2024 will be crucial in determining the viability of its SNIPRx platform for developing Synthetic Lethality drugs [2][3]. Company Overview - Repare Therapeutics is focused on developing lunresertib in combination with camonsertib for patients with specific genetic mutations in platinum-resistant ovarian and endometrial cancers. The MYTHIC trial is currently ongoing to evaluate this combination [3]. - The global ovarian cancer market is projected to reach $11.18 billion by 2029, indicating a substantial market opportunity for effective treatments targeting this disease [3]. Clinical Trials and Data - The MYTHIC trial aims to assess the efficacy of lunresertib and camonsertib in a patient population with genetic alterations. Data from 20 to 30 patients is expected to be released in Q4 2024 [3]. - Preliminary results from a cohort of 26 pre-treated gynecologic cancer patients showed an objective response rate of 38.5% and a clinical benefit rate of 57.7% when treated with lunresertib and camonsertib [3]. Financials - As of June 30, 2024, Repare Therapeutics reported cash, cash equivalents, and marketable securities totaling $208.1 million. The company anticipates its cash runway to extend into the second half of 2026 due to a strategic reprioritization of its pipeline and a reduction in workforce by 25% [4][5]. Strategic Focus - The company is narrowing its pipeline to focus on lunresertib, camonsertib, RP-1664, and RP-3467, while reducing preclinical research and discovery activities. This strategic shift is expected to yield annual savings of $15 million [5]. Future Catalysts - The next significant catalyst for Repare Therapeutics will be the data release from the MYTHIC trial in Q4 2024. If the results are positive, it could lead to the initiation of a phase 3 study in 2025 targeting patients with genomic alterations [7]. - Additionally, the company is exploring other opportunities, including a monotherapy program for camonsertib in non-small cell lung cancer, with initial results expected in 2025 [7].

Repare Therapeutics Inc. (RPTX) came out with a quarterly loss of $0.82 per share versus the Zacks Consensus Estimate of a loss of $0.85. This compares to loss of $0.28 per share a year ago. These figures are adjusted for non-recurring items. This quarterly report represents an earnings surprise of 3.53%. A quarter ago, it was expected that this company would post a loss of $0.10 per share when it actually produced earnings of $0.30, delivering a surprise of 400%. Over the last four quarters, the company ha ...