Summary of Merus (MRUS) FY Conference Call - August 13, 2025 Company Overview - Merus is an oncology-focused biotechnology company with a portfolio of clinical assets, including collaborations with partners like Insight, Loxo, and Gilead [4][3] - The company specializes in bispecific and multispecific antibodies, leveraging over a decade of experience in monoclonal antibody development [4][5] Key Product: Pitocetimab - **Pitocetimab** is a bispecific antibody targeting EGFR and LGR5, designed to enhance cancer cell targeting and improve therapeutic efficacy [8][9] - The mechanism of action involves internalization and degradation of EGFR, enhancing the immune response against cancer cells [10][11] Clinical Data Highlights - At ASCO 2025, Merus reported a **63% response rate** in a cohort of 43 patients with recurrent metastatic head and neck cancer treated with pitocetimab in combination with pembrolizumab [13] - The median progression-free survival (PFS) was **9 months**, significantly longer than the **3 months** typically seen with pembrolizumab alone [14] - **Overall survival** data showed that **80%** of patients were alive at 12 months, indicating a substantial improvement over existing therapies [16][34] Regulatory Strategy - Merus plans to pursue **accelerated approval** for pitocetimab in both first-line and second-line settings based on early endpoints like overall response rate (ORR) [17][24] - The company is in discussions with the FDA regarding the Project Front Runner paradigm, which allows for potential approval based on early clinical endpoints [18][22] Future Trials and Enrollment - A randomized trial for second and third-line treatment is ongoing, comparing pitocetimab to investigator's choice therapies, with expected near-complete enrollment by the end of 2025 [20][21] - The first-line trial will randomize pitocetimab plus pembrolizumab against pembrolizumab alone, following successful precedents [24][25] Colorectal Cancer Development - Merus is also exploring pitocetimab in colorectal cancer, with plans to report data in the second half of 2025 [36] - The focus is on genetically wild-type metastatic colorectal cancer, with ongoing cohorts evaluating the drug's efficacy in first, second, and third-line settings [42][44] Market Context - Current therapies for head and neck cancer show response rates of **19-21%** for pembrolizumab alone, and **34-35%** when combined with chemotherapy, highlighting the potential competitive advantage of pitocetimab [15][33] - The company aims to provide broad access to its therapies globally, emphasizing the importance of international registration strategies [45] Conclusion - Merus is positioned as a promising player in the oncology space, with innovative bispecific antibody therapies showing significant clinical efficacy and a strategic approach to regulatory approval and global market access [4][16][45]

Group 1: Earnings Performance - Merus N.V. reported a quarterly loss of $2.23 per share, significantly worse than the Zacks Consensus Estimate of a loss of $1.17, representing an earnings surprise of -90.60% [1] - The company posted revenues of $8.83 million for the quarter ended June 2025, missing the Zacks Consensus Estimate by 15.41%, but showing an increase from $7.33 million year-over-year [2] - Over the last four quarters, Merus has surpassed consensus EPS estimates only once [2] Group 2: Stock Performance and Outlook - Merus shares have increased by approximately 59.2% since the beginning of the year, outperforming the S&P 500's gain of 7.6% [3] - The company's earnings outlook is crucial for assessing future stock performance, with current consensus EPS estimates at -$1.15 for the coming quarter and -$4.86 for the current fiscal year [7] - The Zacks Rank for Merus is currently 3 (Hold), indicating expected performance in line with the market in the near future [6] Group 3: Industry Context - The Medical - Biomedical and Genetics industry, to which Merus belongs, is currently ranked in the bottom 43% of over 250 Zacks industries, which may impact stock performance [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, suggesting that investors should monitor these revisions closely [5]

Core Insights - Merus N.V. announced promising clinical trial results for petosemtamab in combination with pembrolizumab, showing a 63% response rate among 43 evaluable patients and a 79% overall survival rate at 12 months in a phase 2 trial for PD-L1+ recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) [1][3][6] Clinical Trials and Efficacy - The ongoing LiGeR-HN1 and LiGeR-HN2 phase 3 trials are expected to be substantially enrolled by the end of 2025, with potential interim readouts in 2026 [4][5] - Initial clinical data for petosemtamab in metastatic colorectal cancer (mCRC) is anticipated in the second half of 2025 [2][8] Financial Overview - The company completed a public offering raising $345 million in gross proceeds, which, along with existing cash and marketable securities, is expected to fund operations at least into 2028 [17][18] - Total revenue for Q2 2025 increased by $1.5 million compared to Q2 2024, driven by collaboration revenues [19] - Research and development expenses for Q2 2025 rose by $44.8 million, primarily due to increased clinical trial support related to petosemtamab [20] Collaborations and Licensing - Merus has established collaborations with several companies, including Incyte, Eli Lilly, Gilead Sciences, and Biohaven, focusing on the development of bispecific antibodies and novel therapies [11][12][15][16] - The company has licensed BIZENGRI for commercialization in the U.S. for specific cancer types, enhancing its market presence [9] Cash Position and Runway - As of June 30, 2025, Merus reported $892 million in cash, cash equivalents, and marketable securities, providing a strong financial position to support ongoing and future clinical trials [18]

PART I — FINANCIAL INFORMATION [Item 1. Financial Statements](index=6&type=section&id=Item%201.%20Financial%20Statements) Presents unaudited condensed consolidated financial statements, including balance sheets, statements of operations, cash flows, and equity changes, with detailed notes [Notes to Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Provides detailed accounting policies, segment information, investments, and key collaborations, alongside ongoing patent litigation with Xencor - The company operates in a **single reportable segment**: the discovery and development of innovative therapeutics, with Petosemtamab (MCLA-158) being the **largest R&D expense**[33](index=33&type=chunk)[35](index=35&type=chunk)[36](index=36&type=chunk) - The company is involved in **patent litigation with Xencor, Inc.**, regarding alleged infringement of three U.S. patents[52](index=52&type=chunk)[53](index=53&type=chunk) - In March 2024, a collaboration with Gilead resulted in a **$56.0 million upfront payment** and **$25.0 million from a share purchase** for trispecific T-cell engaging antibodies[58](index=58&type=chunk)[61](index=61&type=chunk) - In November 2024, Merus licensed zenocutuzumab (BIZENGRI®) to Partner Therapeutics, Inc. (PTx) for U.S. commercialization, with Merus eligible for up to **$130.0 million in commercial milestones** and tiered royalties[65](index=65&type=chunk)[66](index=66&type=chunk) - In January 2025, a research collaboration with Biohaven to co-develop three novel bispecific antibody drug conjugates (ADCs) included a **$5.0 million upfront payment** in Biohaven shares[72](index=72&type=chunk)[73](index=73&type=chunk) - In June 2025, a public offering of 6,052,631 common shares generated net proceeds of approximately **$326.0 million**[103](index=103&type=chunk) Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $442,791 | $293,294 | | Total current assets | $768,282 | $569,072 | | Total assets | $980,176 | $782,693 | | Total current liabilities | $91,579 | $87,076 | | Total liabilities | $138,440 | $134,766 | | Total shareholders' equity | $841,736 | $647,927 | Condensed Consolidated Statements of Operations Highlights (in thousands, except per share data) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Total revenue | $8,828 | $7,332 | $35,316 | $15,221 | | Research and development | $93,926 | $49,119 | $174,042 | $87,703 | | Total operating expenses | $119,178 | $71,706 | $221,406 | $126,404 | | Operating loss | $(110,350) | $(64,374) | $(186,090) | $(111,183) | | Net loss | $(158,218) | $(50,042) | $(254,692) | $(84,498) | | Net loss per share | $(2.23) | $(0.81) | $(3.64) | $(1.41) | Condensed Consolidated Statements of Cash Flows Highlights (in thousands) | Cash Flow Activity | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(165,692) | $(38,755) | | Net cash provided by (used in) investing activities | $(16,175) | $(8,847) | | Net cash provided by financing activities | $340,024 | $475,051 | | Net increase in cash | $149,498 | $425,213 | [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=31&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management's analysis of financial condition and operations, covering business overview, clinical programs, financial performance, and liquidity - As of June 30, 2025, the company held **$892.0 million** in cash, cash equivalents, and marketable securities, expected to fund operations at least **into 2028**[113](index=113&type=chunk)[150](index=150&type=chunk) - BIZENGRI® (zenocutuzumab-zbco) received **FDA accelerated approval** for NRG1 gene fusion positive pancreatic or non-small cell lung cancer, with U.S. commercialization rights **exclusively licensed to Partner Therapeutics, Inc. (PTx)**[109](index=109&type=chunk)[120](index=120&type=chunk)[121](index=121&type=chunk) [Clinical Programs](index=33&type=section&id=Clinical%20Programs) Updates on key clinical programs including petosemtamab, zenocutuzumab (BIZENGRI®) with FDA accelerated approval, and MCLA-129 - **Petosemtamab (MCLA-158):** **Phase 3 registrational trials** in HNSCC are enrolling, with potential interim readouts in **2026**, and initial clinical data for mCRC planned for H2 2025[114](index=114&type=chunk)[116](index=116&type=chunk)[118](index=118&type=chunk) - **Zenocutuzumab (MCLA-128):** BIZENGRI® has obtained **FDA accelerated approval** for NRG1+ cancers, with exploration of other potential development opportunities beyond NRG1+ cancer[120](index=120&type=chunk)[122](index=122&type=chunk) - **MCLA-129:** The **Phase 1/2 trial** in MET ex14 NSCLC and in combination with chemotherapy in 2L+ EGFR mutant NSCLC is ongoing, with global rights retained outside of China[123](index=123&type=chunk)[124](index=124&type=chunk)[125](index=125&type=chunk) [Results of Operations](index=35&type=section&id=Results%20of%20Operations) Details financial performance for Q2 and H1 2025 vs 2024, showing increased revenue and significantly higher operating expenses due to R&D Revenue Comparison (in millions) | Period | 2025 | 2024 | Change | | :--- | :--- | :--- | :--- | | **Three Months Ended June 30** | $8.8 | $7.3 | $1.5 | | **Six Months Ended June 30** | $35.3 | $15.2 | $20.1 | - The **$20.1 million increase** in revenue for the six-month period was primarily due to **$13.3 million in commercial material revenue** sold to PTx and a **$6.8 million increase in collaboration revenue** from Biohaven and Gilead[129](index=129&type=chunk) Operating Expenses Comparison (in millions) | Period | 2025 | 2024 | Change | | :--- | :--- | :--- | :--- | | **Three Months Ended June 30** | $119.2 | $71.7 | $47.5 | | **Six Months Ended June 30** | $221.4 | $126.4 | $95.0 | - R&D expenses for the six months ended June 30, 2025, increased by **$86.3 million** year-over-year, primarily driven by a **$73.7 million increase in external costs** related to petosemtamab clinical trials[134](index=134&type=chunk) - Net loss for the six months ended June 30, 2025, was **$254.7 million**, compared to a net loss of **$84.5 million** for the same period in 2024, driven by higher operating expenses and foreign exchange losses[141](index=141&type=chunk) [Liquidity and Capital Resources](index=39&type=section&id=Liquidity%20and%20Capital%20Resources) Discusses the company's strong liquidity, bolstered by a recent public offering, expected to fund operations into 2028 - In June 2025, the company raised net proceeds of approximately **$326.0 million** from a public offering of its common shares[144](index=144&type=chunk) Summary of Cash Flows (in millions) | Cash Flow Activity | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(165.7) | $(38.8) | | Net cash provided by (used in) investing activities | $(16.2) | $(8.8) | | Net cash provided by financing activities | $340.0 | $475.1 | - The **increase in net cash used in operating activities** was primarily due to higher operating expenses and lower cash inflows from revenues compared to the prior year period[151](index=151&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=41&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) Addresses market risks from interest rates, foreign exchange rates (primarily USD/Euro), and inflation, with currency risk being the most significant - The company's primary market risk is **foreign currency exchange risk**, particularly between the **U.S. dollar and the euro**, as a significant portion of operating costs are in euros[157](index=157&type=chunk) - A hypothetical **20% weakening** of the U.S. dollar against the euro would have increased the net loss for the quarter ended June 30, 2025, by approximately **$32.3 million**[157](index=157&type=chunk) - Interest rate risk is **not expected to be material** due to the short-term nature of the company's **$449.2 million investment portfolio**[156](index=156&type=chunk) [Item 4. Controls and Procedures](index=43&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded disclosure controls and procedures were effective as of June 30, 2025, with no material changes to internal controls - Based on an evaluation, the principal executive officer and principal financial officer concluded that the company's **disclosure controls and procedures were effective**[160](index=160&type=chunk) - There were **no changes in internal control over financial reporting** during the quarter ended June 30, 2025, that have materially affected, or are reasonably likely to materially affect, internal controls[161](index=161&type=chunk) PART II — OTHER INFORMATION [Item 1. Legal Proceedings](index=44&type=section&id=Item%201.%20Legal%20Proceedings) Refers to Note 6 for details on ongoing patent litigation with Xencor, confirming no other material legal proceedings - The company refers to Note 6 of the financial statements for details on legal proceedings, which describes **patent litigation with Xencor, Inc.**[52](index=52&type=chunk)[53](index=53&type=chunk)[162](index=162&type=chunk) [Item 1A. Risk Factors](index=44&type=section&id=Item%201A.%20Risk%20Factors) Outlines numerous risks across business, clinical development, regulatory approval, commercialization, third-party dependence, IP, personnel, and common shares [Risks Related to Our Business and Industry](index=44&type=section&id=Risks%20Related%20to%20Our%20Business%20and%20Industry) Highlights risks including a history of net losses, need for substantial funding, and the unproven nature of novel technology platforms - The company has a history of **significant net losses**, with an **accumulated deficit of $1,223.1 million** as of June 30, 2025, and expects to incur losses for the foreseeable future[164](index=164&type=chunk) - **Substantial additional funding will be required** to complete the development of antibody candidates and commercialize products, with capital raising potentially affected by market volatility[169](index=169&type=chunk) - The company's Biclonics®, Triclonics®, and ADClonics® technology platforms are **novel and largely unproven** approaches for therapeutic intervention beyond the single accelerated approval for BIZENGRI®[179](index=179&type=chunk)[181](index=181&type=chunk) [Risks Related to the Development and Clinical Testing of Our Antibody Candidates](index=51&type=section&id=Risks%20Related%20to%20the%20Development%20and%20Clinical%20Testing%20of%20Our%20Antibody%20Candidates) Focuses on the lengthy, expensive, and uncertain nature of clinical trials, potential side effects, and patient enrollment challenges - Clinical drug development is a **lengthy, expensive process with uncertain outcomes**, where failure can occur at any stage, and early trial results may not predict later success[195](index=195&type=chunk) - Antibody candidates may cause **serious or unacceptable side effects**, potentially leading to trial delays, halts, or denial of regulatory approval for both monotherapy and combination studies[207](index=207&type=chunk)[210](index=210&type=chunk) - The company **depends on timely patient enrollment** in its clinical trials, which can be challenging due to competition, strict eligibility, and availability of other therapies[217](index=217&type=chunk)[218](index=218&type=chunk)[219](index=219&type=chunk) [Risks Related to Regulatory Approval of Our Antibody Candidates](index=58&type=section&id=Risks%20Related%20to%20Regulatory%20Approval%20of%20Our%20Antibody%20Candidates) Details hurdles in obtaining and maintaining regulatory approval, including unpredictable processes and legislative impacts like the IRA - The regulatory approval process is **lengthy, time-consuming, and inherently unpredictable**, with a high degree of discretion from regulatory authorities like the FDA[226](index=226&type=chunk) - BIZENGRI® was approved under the **FDA's accelerated approval pathway**, with continued approval **contingent upon verification of clinical benefit** in confirmatory trials, risking withdrawal if not met[237](index=237&type=chunk)[239](index=239&type=chunk) - Enacted and future legislation, such as the **Inflation Reduction Act (IRA)**, may increase the difficulty and cost of marketing approval and could **negatively affect drug pricing and reimbursement**[257](index=257&type=chunk)[259](index=259&type=chunk) [Risks Related to Commercialization of Our Antibody Candidates](index=71&type=section&id=Risks%20Related%20to%20Commercialization%20of%20Our%20Antibody%20Candidates) Discusses challenges of commercialization, such as intense competition, reimbursement, market acceptance, and limited sales infrastructure - The biopharmaceutical industry is **highly competitive**, with competitors potentially possessing greater resources to develop and commercialize products more rapidly or successfully[290](index=290&type=chunk)[291](index=291&type=chunk) - Successful commercialization heavily depends on obtaining **adequate coverage and reimbursement** from government and private payors, who are increasingly challenging drug prices[298](index=298&type=chunk) - The company has **limited marketing, sales, and distribution infrastructure** and **relies on its licensee, PTx**, for BIZENGRI® commercialization in the U.S., making future capability building expensive and time-consuming[306](index=306&type=chunk)[309](index=309&type=chunk) [Risks Related to Our Dependence on Third Parties](index=75&type=section&id=Risks%20Related%20to%20Our%20Dependence%20on%20Third%20Parties) Emphasizes reliance on CROs, CMOs, and collaboration partners, whose performance is beyond direct company control - The company **relies on third-party CROs** to conduct pre-clinical studies and clinical trials, where poor performance or non-compliance could delay or compromise development programs[315](index=315&type=chunk)[316](index=316&type=chunk) - The company **depends on collaboration partners** like Incyte, Lilly, Gilead, and Biohaven for antibody candidate development, and their failure to perform or agreement termination would adversely affect the business[322](index=322&type=chunk)[327](index=327&type=chunk)[333](index=333&type=chunk)[336](index=336&type=chunk) - The company **relies on third-party CMOs** for manufacturing antibody candidates, and any failure in production, quality, or regulatory approval of facilities could halt or delay clinical trials and commercialization[340](index=340&type=chunk)[341](index=341&type=chunk) [Risks Related to Intellectual Property and Information Technology](index=83&type=section&id=Risks%20Related%20to%20Intellectual%20Property%20and%20Information%20Technology) Covers risks related to patent protection, third-party IP infringement, trade secret disclosure, and cybersecurity vulnerabilities - The company's success depends on **obtaining and maintaining patent protection** for its technology and candidates, which is a costly, time-consuming, and uncertain process[347](index=347&type=chunk)[348](index=348&type=chunk) - **Third-party intellectual property rights** could create obstacles, potentially requiring costly litigation or licensing agreements to commercialize antibody candidates[357](index=357&type=chunk) - The company's information technology systems are **vulnerable to cybersecurity attacks**, which could lead to the loss of trade secrets, disclosure of sensitive data, and disruption of operations[395](index=395&type=chunk) [Risks Related to Employee Matters and Managing Growth](index=92&type=section&id=Risks%20Related%20to%20Employee%20Matters%20and%20Managing%20Growth) Addresses risks in attracting and retaining key personnel and effectively managing organizational growth - The company's success depends on **retaining key senior leaders and scientific personnel** and recruiting additional qualified individuals in a highly competitive biopharmaceutical field[399](index=399&type=chunk) - **Expected growth in operations**, particularly in development and commercialization, may present management difficulties and could disrupt operations if not handled effectively[400](index=400&type=chunk) [Risks Related to Our Common Shares](index=93&type=section&id=Risks%20Related%20to%20Our%20Common%20Shares) Details investor risks including share price volatility, dilution, anti-takeover provisions, and potential PFIC classification - **Future sales of common shares** could adversely affect the market price[401](index=401&type=chunk) - Provisions in the company's articles of association and Dutch corporate law, including **anti-takeover measures**, could deter acquisition bids or prevent changes in the board of directors[402](index=402&type=chunk)[403](index=403&type=chunk) - The company may be classified as a **Passive Foreign Investment Company (PFIC)** for U.S. federal income tax purposes, which could result in adverse tax consequences for U.S. investors[412](index=412&type=chunk) [Item 5. Other Information](index=101&type=section&id=Item%205.%20Other%20Information) Confirms no director or officer adopted or terminated Rule 10b5-1 trading arrangements during Q2 2025 - **No director or officer adopted or terminated a Rule 10b5-1 trading arrangement** during the second quarter of 2025[434](index=434&type=chunk) [Item 6. Exhibits](index=101&type=section&id=Item%206.%20Exhibits) Lists exhibits filed with the Form 10-Q, including Articles of Association and CEO/CFO certifications - The report includes several exhibits, such as the **Articles of Association, CEO and CFO certifications, and interactive data files (XBRL)**[435](index=435&type=chunk)

Core Insights - Merus N.V. has granted non-statutory stock options to two new employees as an inducement award outside the 2016 Incentive Award Plan, in compliance with Nasdaq Listing Rule 5635(c)(4) [1] - A total of 240,000 shares of common stock were granted, with an exercise price of $65.56 per share, the closing price on August 1, 2025 [1] - The stock options have a ten-year term and vest over four years, with 25% vesting on the first anniversary of the hire date and the remainder vesting in equal monthly installments over the following three years [1] Company Overview - Merus is an oncology company focused on developing innovative full-length human bispecific and trispecific antibody therapeutics, known as Multiclonics® [2] - Multiclonics® are produced using industry-standard processes and have demonstrated features similar to conventional human monoclonal antibodies, including long half-life and low immunogenicity [2]

Core Insights - Merus N.V. (MRUS) shares have increased by 29.9% over the past three months, driven by positive interim results from a phase II study of its bispecific antibody, petosemtamab (MCLA-158), in combination with Merck's Keytruda for treating PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) [1][4] Study Results - As of February 27, 2025, 45 patients were treated, with 43 deemed efficacy-evaluable, resulting in a confirmed overall response rate (ORR) of 63%, which included six complete responses and 21 partial responses [2] - The ORR varied with PD-L1 expression levels, showing a 73% ORR in patients with a combined positive score (CPS) greater than 20 and 47% in those with CPS 1–19 [2] - Median progression-free survival was reported at nine months, with an overall survival rate of 79% at 12 months [3] Safety Profile - The safety profile of the combination therapy was manageable, with no significant overlapping toxicities reported with Keytruda; treatment-related adverse events occurred in all patients, with infusion-related reactions observed in 38% [5][6] Future Prospects - The promising data suggests that the petosemtamab combination therapy could become a new standard of care for HNSCC, a cancer type with poor prognosis [6] - Merus is also conducting a registrational phase III study (LiGeR-HN1) for the combination therapy and another study (LiGeR-HN2) for petosemtamab monotherapy [7][8] Market Context - Merck's Keytruda, a leading anti-PD-1 therapy, generated $7.21 billion in sales in Q1 2025, reflecting a 6% year-over-year increase, and continues to expand into new indications and markets [8][10]

Summary of Merus Conference Call Company Overview - **Company**: Merus - **Industry**: Biotechnology, specifically focused on developing bispecific and multispecific antibodies for cancer treatment - **Key Product**: Pedosemtamab, a bispecific antibody targeting EGFR and LGR5 in head and neck cancer [3][7][10] Core Points and Arguments - **Technology Platform**: Merus utilizes a foundational platform technology to develop fully human IgG1 antibodies, which enhances the chances of success in drug development by relying on established methods [4][5] - **Clinical Success**: - Pedosemtamab has shown unprecedented efficacy in head and neck cancer, with a response rate of 63% when combined with Keytruda, significantly higher than the typical 20% response rate seen with standard immunotherapy [10] - One-year overall survival rate for patients treated with pedosemtamab is reported at 79%, with projections suggesting a median overall survival of over 30 months [20][22] - **Regulatory Designation**: Pedosemtamab has received breakthrough therapy designation from the FDA for both single-agent and combination therapy settings, indicating its potential to provide substantial benefits over existing therapies [11][12] - **Phase III Trials**: Enrollment for ongoing Phase III trials is progressing well, with over 125 sites activated. The company anticipates substantial enrollment by year-end and potential top-line results next year [32][33][46] Important but Overlooked Content - **Patient Population Insights**: The Phase II population is considered representative of the overall population, with no strong correlation observed between EGFR expression levels and response rates [16][13] - **Colorectal Cancer Development**: Merus is also exploring pedosemtamab in colorectal cancer, with ongoing cohorts aimed at assessing its efficacy in combination with chemotherapy and as a monotherapy [47][48] - **Financial Position**: As of the last quarter, Merus reported a cash balance of $638 million, bolstered by a recent financing of $300 million, which supports its ongoing clinical trials [63] Key Events to Watch - **Upcoming Data Releases**: Investors should look forward to the initial clinical update on colorectal cancer later this year and the top-line readout from the Phase III trials next year [63]

Core Viewpoint - Merus N.V. has announced a public offering of 5,263,158 common shares priced at $57.00 per share, aiming to raise approximately $300 million in gross proceeds to support its oncology product development and general corporate purposes [1][2]. Group 1: Offering Details - The offering includes a 30-day option for underwriters to purchase an additional 789,473 common shares [1]. - The expected closing date for the offering is around June 5, 2025, pending customary closing conditions [2]. - The offering is conducted under a shelf registration statement filed with the SEC, effective since February 28, 2024 [4]. Group 2: Use of Proceeds - The net proceeds from the offering will be utilized for advancing clinical development of product candidates, preclinical research, technology development, and general corporate purposes [2]. Group 3: Underwriters - Jefferies, BofA Securities, Leerink Partners, Guggenheim Securities, Truist Securities, and LifeSci Capital are serving as joint book-running managers for the offering, with Van Lanschot Kempen as the lead manager [3]. Group 4: Company Overview - Merus N.V. specializes in developing innovative full-length human bispecific and trispecific antibody therapeutics, known as Multiclonics, which exhibit features similar to conventional human monoclonal antibodies [12].

Petosemtamab Clinical Trial Results in HNSCC - In 2L+ r/m HNSCC, petosemtamab monotherapy showed a confirmed overall response rate (ORR) of 36% (27 out of 75 patients) [24, 25] - Petosemtamab with pembrolizumab in 1L PD-L1+ r/m HNSCC achieved a confirmed overall response rate (ORR) of 63% [53, 58] - The median progression-free survival (mPFS) for petosemtamab with pembrolizumab in 1L PD-L1+ r/m HNSCC was 9 months, and the overall survival (OS) rate at 12 months was 79% [55, 58] Safety and Tolerability - In the petosemtamab monotherapy trial (1500 mg Q2W), all 82 patients experienced at least one treatment-emergent adverse event (TEAE), with 59% experiencing Grade ≥3 TEAEs [29, 30] - When petosemtamab was administered with pembrolizumab, all 45 patients experienced at least one TEAE, with 60% experiencing Grade ≥3 TEAEs [51] - Infusion-related reactions (IRRs) occurred in 38% of patients receiving petosemtamab with pembrolizumab, with 7% being Grade 3 [40, 52] Market Opportunity and Pipeline - Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer [65, 79] - Estimated sales for HNSCC and CRC in 2024 are $4 billion and $7.1 billion, respectively [73] - The company has patents expiring no earlier than October 2038 related to petosemtamab and a topoisomerase inhibitor [64]

Summary of Merus Investor Call Company Overview - Merus is an oncology-focused company with a proprietary technology platform for developing bispecific and multispecific antibodies, including pitocentimab and other clinical assets [6][8][35] - The company received its first FDA approval for BIZENGRI, validating its capabilities in oncology drug development [6] Clinical Data Presentation - The call focused on the phase two interim clinical data of pitocentimab in combination with pembrolizumab for first-line recurrent metastatic head and neck squamous cell carcinoma [2][5] - Data will be presented at the ASCO Annual Meeting on June 2, 2025 [2][5] Key Clinical Findings - **Efficacy of Pitocentimab**: - The overall response rate (ORR) for pitocentimab monotherapy was 36% with a median duration of response of 6.2 months [17] - In combination with pembrolizumab, the ORR was 63% (27 out of 43 patients) with a 95% confidence interval indicating a lower bound of 49% [27] - The median progression-free survival (PFS) was 9 months, significantly higher than historical data for pembrolizumab alone [29] - The 12-month overall survival (OS) rate was 79%, compared to 51% for pembrolizumab monotherapy [30] - **Safety Profile**: - The combination therapy was well tolerated with no significant overlapping toxicities observed [32][26] - The incidence of treatment-emerging adverse events was manageable, with 38% of patients reporting infusion-related reactions [26] Market Opportunity - The head and neck cancer market is estimated to be around $4 billion in 2024, with significant unmet medical needs [37][39] - Merus aims to position pitocentimab as a first and best-in-class treatment option, potentially changing clinical practice [38][39] Regulatory and Development Strategy - Merus is confident in the potential for accelerated approval based on strong ORR and survival data [66] - The company plans to substantially enroll both Phase III registration trials by the end of 2025, with top-line readouts expected in 2026 [42][34] Intellectual Property - Merus holds a robust patent estate covering its platform technologies and clinical assets, ensuring protection for its innovations [35] Additional Insights - The company emphasizes the importance of including both HPV positive and negative patients in clinical trials, with a focus on maintaining a consistent patient population across studies [101][102] - There is a strong belief that the combination of pitocentimab and pembrolizumab could provide a transformative treatment option for patients with recurrent metastatic head and neck cancer [41][42] Conclusion - Merus is advancing its clinical development of pitocentimab with promising efficacy and safety data, aiming to address significant unmet needs in the oncology market, particularly in head and neck cancer [41][43]