Pamvatamig

- Petosemtamab in combination with pembrolizumab in 1L PD-L1+ r/m HNSCC phase 2 trial ongoing with clinical data update at 2025 ASCO® Annual Meeting - Based on the Company’s current operating plan, existing cash, cash equivalents and marketable securities expected to fund Merus’ operations into 2028 UTRECHT, The Netherlands and CAMBRIDGE, Mass. , May 07, 2025 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), an oncology company developing innovative, full-length multispecific antibodies and antibody drug conjugates (Biclonics®, Triclonics® and ADClonics®), today announced financial results for the first quarter and provided a business update. “We are very much looking forward to sharing the robust updated interim phase 2 data, on the entire 45 patient data set at 2025 ASCO®. We believe based on these interim data that petosemtamab continues to demonstrate substantial clinical activity superior to historical controls based on the magnitude and consistency of efficacy across ORR, PFS and OS in the overall population and within important subgroups of HPV disease and PD-L1 expression levels,” said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. “Additionally, I’m thrilled by the team’s execution in our two phase 3 trials and expect both trials to be substantially enrolled by year end 2025.” Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics®): Solid TumorsLiGeR-HN1 phase 3 trial in 1L recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) and LiGeR-HN2 phase 3 trial in 2/3L r/m HNSCC enrolling – with both trials expected to be substantially enrolled by YE25; clinical update on phase 2 trial in combination with pembrolizumab in 1L PD-L1+ HNSCC at 2025 ASCO®; phase 2 trial in 1L, 2L and 3L+ metastatic colorectal cancer (mCRC) enrolling; mCRC initial clinical data planned for 2H25 An updated analysis of the interim clinical data from the phase 2 trial of petosemtamab with pembrolizumab as 1L treatment of PD-L1+ r/m HNSCC will be presented at the 2025 American Society of Clinical Oncology ® Annual Meeting (ASCO®) as detailed in our press release, Merus Announces Abstract Accepted for Presentation at the 2025 ASCO® Annual Meeting. The presentation will include data on the entire 45 patient dataset and follows the early clinical efficacy and encouraging safety data previously presented at 2024 ASCO®, which was detailed in our 2024 press release, Merus’ Petosemtamab in Combination with Pembrolizumab Interim Data Demonstrates Robust Response Rate and Favorable Safety Profile in 1L r/m HNSCC ( May 28, 2024 ). Merus will hold a conference call and webcast for investors on Thursday, May 22, 2025 at 5:30 p.m. ET. A replay will be available after the completion of the call in the Investors and Media section of our website for a limited time. Date & Time: May 22, 2025 at 5:30 p.m. ETWebcast link: Available on our websiteDial-in: Toll Free: (800) 715-9871 / International: (646) 307-1963Conference ID: 7517301 or Merus NV call In February 2025 , the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation (BTD) to petosemtamab in combination with pembrolizumab for the first-line treatment of adult patients with recurrent or metastatic programmed death-ligand 1 (PD-L1) positive HNSCC with combined positive score (CPS) ≥ 1. This designation was detailed in our press release, Petosemtamab granted Breakthrough Therapy designation by the U.S. FDA for 1L PD-L1 positive head and neck squamous cell carcinoma ( February 18, 2025 ). BTD was also granted for petosemtamab monotherapy for the treatment of patients with recurrent or metastatic HNSCC whose disease has progressed following treatment with platinum based chemotherapy and an anti-programmed cell death receptor-1 (PD-1) or anti-programmed death ligand 1 (PD-L1) antibody, detailed in our press release, Petosemtamab granted Breakthrough Therapy Designation by the U.S. FDA ( May 13 , 2024). Merus provided updated interim clinical data on petosemtamab in 2L+ r/m HNSCC at the European Society for Medical Oncology Asia Congress , demonstrating a 36% response rate among 75 evaluable patients. The oral presentation was detailed in our press release, Merus’ Petosemtamab Monotherapy Interim Data Continues to Demonstrate Clinically Meaningful Activity in 2L+ r/m HNSCC ( Dec. 7 , 2024). LiGeR-HN1, a phase 3 trial evaluating the efficacy and safety of petosemtamab in combination with pembrolizumab in 1L PD-L1+ (CPS≥1) r/m HNSCC compared to pembrolizumab, and LiGeR-HN2, a phase 3 trial evaluating the efficacy and safety of petosemtamab in 2/3L HNSCC compared to standard of care, are enrolling and we expect both trials to be substantially enrolled by YE25. Further, the Company manufactures both drug substance and drug product in the United States and Europe , with a plan to focus on potential commercial manufacturing in the United States . Merus believes a randomized registration trial in HNSCC with an overall response rate endpoint could potentially support accelerated approval and the overall survival results from the same study could potentially verify its clinical benefit to support regular approval for the Company’s phase 3 trial in 1L, and in phase 3 trial in 2/3L HNSCC. A phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 1L and 2L mCRC, and as monotherapy in heavily pretreated (3L+) mCRC, is enrolling. We expect to provide initial clinical data for petosemtamab in mCRC in 2H25. BIZENGRI® (zenocutuzumab-zbco: HER2 x HER3 Biclonics®)Approved by FDA for adults with pancreatic adenocarcinoma or non–small cell lung cancer (NSCLC) that are advanced unresectable or metastatic and harbor a neuregulin 1 (NRG1) gene fusion who have disease progression on or after prior systemic therapy Merus has exclusively licensed to Partner Therapeutics, Inc. (PTx) the right to commercialize BIZENGRI® for the treatment of NRG1+ cancer in the U.S. This was detailed in our press release, Merus and Partner Therapeutics Announce License Agreement for the U.S. Commercialization of Zenocutuzumab in NRG1 Fusion-Positive Cancer ( December 2 , 2024). MCLA-129 (EGFR x c-MET Biclonics®): Solid TumorsInvestigation of MCLA-129 is ongoing in METex14 NSCLC; phase 2 trial in combination with chemotherapy in 2L+ EGFR mutant (EGFRm) NSCLC enrolling MCLA-129 is subject to a collaboration and license agreement with Betta Pharmaceuticals Co. Ltd. (Betta), which permits Betta to develop MCLA-129, and potentially commercialize exclusively in China, while Merus retains global rights outside of China. Collaborations Incyte CorporationSince 2017, Merus has been working with Incyte Corporation (Incyte) under a global collaboration and license agreement focused on the research, discovery and development of bispecific antibodies utilizing Merus’ proprietary Biclonics® technology platform. For each program under the collaboration, Merus receives reimbursement for research activities and is eligible to receive potential development, regulatory and commercial milestones and sales royalties for any products, if approved. Eli Lilly and CompanyIn January 2021, Merus and Eli Lilly and Company (Lilly) announced a research collaboration and exclusive license agreement to develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies utilizing Merus’ Biclonics® platform and proprietary CD3 panel along with the scientific and rational drug design expertise of Lilly. The collaboration is progressing well with three programs advancing through preclinical development. Gilead SciencesIn March 2024, Merus and Gilead Sciences announced a collaboration to discover novel antibody based trispecific T-cell engagers using Merus’ patented Triclonics® platform. Under the terms of the agreement, Merus will lead early-stage research activities for two programs, with an option to pursue a third. Gilead will have the right to exclusively license programs developed under the collaboration after the completion of select research activities. If Gilead exercises its option to license any such program from the collaboration, Gilead will be responsible for additional research, development and commercialization activities for such program. Ono PharmaceuticalIn 2018, the Company granted Ono Pharmaceutical Co., Ltd. (Ono) an exclusive, worldwide, royalty-bearing license, with the right to sublicense, research, test, make, use and market a limited number of bispecific antibody candidates based on Merus’ Biclonics® technology platform directed to an undisclosed target combination. BiohavenIn January 2025 , Merus and Biohaven announced a research collaboration and license agreement to co-develop three novel bispecific antibody drug conjugates (ADCs), leveraging Merus’ leading Biclonics® technology platform, and Biohaven’s next-generation ADC conjugation and payload platform technologies. Under the terms of the agreement, Biohaven is responsible for the preclinical ADC generation of three Merus bispecific antibodies under mutually agreed research plans. The agreement includes two Merus bispecific programs generated using the Biclonics® platform, and one program under preclinical research by Merus. Each program is subject to mutual agreement for advancement to further development, with the parties then sharing subsequent external development costs and commercialization, if advanced. Cash Runway, existing cash, cash equivalents and marketable securities expected to fund Merus’ operations into 2028 As of March 31, 2025, Merus had $638 million cash, cash equivalents and marketable securities. Based on the Company’s current operating plan, the existing cash, cash equivalents and marketable securities are expected to fund Merus’ operations into 2028. First Quarter 2025 Financial ResultsCollaboration revenue for the three months ended March 31, 2025 increased by $18.6 million as compared to the three months ended March 31, 2024 , primarily as a result of commercial material revenue this quarter and higher deferred revenue amortization. Research and development expense for the three months ended March 31, 2025 increased by $41.5 million as compared to the three months ended March 31, 2024 . The increase is primarily driven by an increase of $35.6 million in clinical trial support provided by contract manufacturing and development organizations and contract research organizations, most of which is related to the petosemtamab clinical trials. General and administrative expense for the three months ended March 31, 2025 increased by $6.0 million as compared to the three months ended March 31, 2024 , primarily as a result of increases in personnel related expenses including share-based compensation of $5.3 million ; increases in consulting expenses, facilities and depreciation expense also contributed. Other income (loss), net consists of interest earned and fees paid on our cash and cash equivalents held on account, accretion of investment earnings and net foreign exchange (losses) gains on our foreign denominated cash, cash equivalents and marketable securities. Other gains or losses relate to the issuance and settlement of financial instruments. About Merus N.V. Merus is an oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics®. Multiclonics® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus’ website, and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding the content and timing of clinical trials, data readouts and clinical, regulatory, strategy and development updates for our product candidates; our ongoing LiGeR-HN1, LiGeR-HN2 and phase 2 mCRC trials for petosemtamab, our planned update at 2025 ASCO® on the phase 2 cohort of 1L PD-L1+ r/m HNSCC; our planned initial clinical data update on the phase 2 investigation of petosemtamab in mCRC; the potential impact, if any, on the receipt of BTD by the FDA for petosemtamab in combination with pembrolizumab in 1L PD-L1+ r/m HNSCC; our expectation that the LiGeR-HN1 and LiGeR-HN2 trials will be substantially enrolled by year-end; our belief that a randomized registration trial in HNSCC with an overall response rate endpoint could potentially support accelerated approval and the overall survival results from the same study could potentially verify its clinical benefit to support regular approval in our phase 3 trial in 1L, and in phase 3 trial in 2/3L HNSCC; our looking forward to sharing the robust updated interim phase 2 data, on the entire 45 patient data set at 2025 ASCO® ; our belief based on these interim data that petosemtamab continues to demonstrate substantial clinical activity superior to historical controls, based on the magnitude and consistency of efficacy across ORR, PFS and OS in the overall population and within important subgroups of HPV disease and PD-L1 expression levels; our statements regarding the sufficiency of our cash, cash equivalents and marketable securities, and expectation that it will fund the Company into 2028; the continued investigation of MCLA-129 and enrolling of patients in the investigation of MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC; the benefits of the license from Merus to PTx for the commercialization of Bizengri® in the US for NRG1+ cancer, collaborations between Incyte and Merus, Lilly and Merus, Gilead and Merus, Biohaven and Merus, and license agreement between Ono and Merus; and the potential of those licenses and collaborations for future value generation, including whether and when Merus will receive any future payments, including milestones or royalties, and the amounts of such payments; whether any programs under the collaboration will be successful; and our collaboration and license agreement with Betta, which permits Betta to develop MCLA-129 and potentially commercialize exclusively in China , while Merus retains full ex- China rights, including any future clinical development by Betta of MCLA-129. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the volatility in the global economy, including global instability, including the ongoing conflicts in Europe and the Middle East ; we may not identify suitable Biclonics® or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; and our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the period ended March 31, 2025 , filed with the Securities and Exchange Commission , or SEC , on May 7, 2025 , and our other reports filed with the SEC , could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Multiclonics®, Biclonics®, Triclonics®, ADClonics® and BIZENGRI® are registered trademarks of Merus N.V. Please see full Prescribing Information, including Boxed WARNING, at BIZENGRI.com/pi. Reference: 1. BIZENGRI. Prescribing information. Merus N.V.; 2024. Source: Merus N.V.

2025年第116届美国癌症研究协会（AACR）年会于2025年4月25-30日在美国芝加哥举行。贝达药业BPI-572270、BPI-585725、BK-001（VM-001）、MCLA-129等四项研究成果亮相2025AACR年会。△贝达同事参加AACR年会BPI-572270KRAS突变是导致多种癌症发生（如胰腺癌，非小细胞肺癌和结直肠癌）的致癌驱动因素，在所有癌症中的突变频率为20%-30%。目前已有靶向KRASG12C突变的药物获批并显示出临床获益。但尚未有靶向其他常见KRAS突变（如 KRASG12D/G12V/G12R等）以及另外两种RAS亚型（NRAS和HRAS）突变的药物获批上市，具有极大未满足临床需求。BPI-572270是一种强效泛RAS抑制剂，对携带KRAS、NRAS和HRAS不同突变的多种肿瘤细胞具有强效杀伤作用，显示出纳摩尔级IC50的细胞活性。BPI-572270在KRASG12V和KRASG12D的人胰腺癌异种移植小鼠模型中，低剂量每天口服给药一次可实现肿瘤消退。BPI-572270在小鼠、大鼠和比格犬中具有出色的药代动力学特性和良好的口服生物利用度。大鼠和比格犬进行的重复给药安全性评估数据初步显示BPI-572270安全性良好，进一步增强其在临床开发潜力。BPI-572270有望为携带不同RAS突变的广大实体瘤患者提供新的治疗方案。BPI-585725△杭州研发中心副主任周全博士作口头报告目前，尽管已有数款KRASG12C抑制剂上市，但是由于易出现耐药等原因，其疗效有限且应答持续时间较短。通过降解而非抑制KRAS蛋白有望实现持久的临床疗效。BPI-585725是一个新的多KRAS突变（KRASmulti）靶向蛋白降解嵌合体（PROTAC）分子。在细胞水平的KRAS降解实验中，BPI-585725通过泛素-蛋白酶体系统（UPS）依赖机制，对KRAS G12C、G12D、G12V、G13D及野生型扩增（WT-Amp）均能展现出显著的KRAS降解能力。该化合物对多种KRAS驱动型肿瘤细胞系（包括G12X、G13D和WT-Amp）均具有很好的增殖抑制作用，在多种细胞系中的IC50小于10 nM。生物化学水平靶点结合实验显示，BPI-585725对KRAS的亲和力比N/HRAS高300倍以上。在PK-59（KRASG12D）异源移植瘤模型中，单次静脉注射30 mg/kg BPI-585725可使药物在肿瘤组织中维持长达6天的有效浓度，并伴随持续的KRAS降解及下游DUSP6抑制效应。在该模型上每周一次给药，呈现出良好的剂量依赖性的肿瘤抑制能力。综上，BPI-585725是一款高效、高选择性KRASmulti降解剂，具有优良的药代动力学特性，且在临床前研究中展现出良好的安全性。BK-001（VM-001）目前的癌症治疗药物，如抗体、CAR-细胞，以及XDC等药物，主要是针对肿瘤相关抗原，而非肿瘤特异性抗原进行开发的。尽管这些治疗药物在一定程度上提高了靶向特异性并降低了毒性，但仍无法避免对正常信号通路的干扰和脱靶效应的发生。为了解决这些挑战，贝达药业徐汶新博士带领贝达药业和康万达的科学家们联合开发了一种创新的肿瘤治疗策略，即抗体与溶瘤病毒的协同疗法。该方法利用转基因溶瘤病毒（V113）在肿瘤细胞表面递呈人类不表达的靶抗原（TT3），随后，用CD3/TT3双特异性抗体（BK-001）靶向该抗原（TCE平台技术）。这一组合疗法不仅改变了肿瘤微环境，并具有精准靶向性和旁观者效应，显著提高了治疗效果，为癌症患者，特别是那些对现有治疗药物耐药或无药可医的患者，提供了全新的治疗选择。MCLA-129研究名称：《晚期非小细胞肺癌（NSCLC）中MET扩增/过度表达状态与MCLA-129响应的相关性：1期试验的生物标志物结果》背景：MCLA-129是一种靶向EGFR和c-MET的人源双特异性抗体，具有多种作用机制，包括抑制EGFR和c-MET信号传导、抗体依赖性细胞吞噬作用（ADCP）和增强抗体依赖性细胞毒性（ADCC）。在这项正在进行的针对晚期非小细胞肺癌患者的MET/EGFR双特异性抗体MCLA-129的1b期研究（NCT04930432）中，我们旨在更深入地探索MCLA-129与MET扩增（METamp）或蛋白质过表达（OE）人群疗效之间的关系。方法：符合条件的患者（≥18岁；ECOG PS 0-1；转移性或不可切除的非小细胞肺癌或其他实体瘤；EGFR或MET突变阳性）每两周接受一次静脉注射MCLA-129（1500 mg）。MET OE定义为IHC2+或IHC 3+（SP44抗体），METamp根据基因拷贝数（GCN）定义。我们使用不同的GCN截止值，旨在探索其与疗效结果的关系。结果：在数据截止日期（2024年3月31日），在24名NSCLC患者中，6名MET IHC 2+/3+患者和18名METamp患者的疗效可评估。6名MET IHC 2+/3+患者中有4名（中位既往治疗线数：1 [0-1]）达到了确认的部分缓解（PR）（总体缓解率[ORR]: 66.6% [95% CI 22.3-95.7]），所有这4名患者都存在共突变（3名METex14跳跃和1名EGFR exon20ins）。未达到中位反应持续时间（DOR）和无进展生存期（PFS）。18名METamp患者中有8名达到了确诊的PR（中位既往治疗线数：2 [1-7]）（ORR: 44.4% [95% CI 21.5-69.2]；DOR: NR [2.8-NR]；PFS: 4.8个月[2.7-9.6]）。在7名全身抗肿瘤治疗前检测到METamp的患者中，4名患者达到了确诊的PR，ORR为57.1%（95% CI 18.4-90.1），所有这4名患者都发生了共突变（2个EGFR exon20ins，1个METex14跳跃和1个L861Q）。在9名接受三代EGFR-TKI治疗的患者中，有3名患者达到了确诊的PR。不同MET临界值的患者表现出不同的ORR。结论：MCLA-129在携带MET OE或METamp的晚期非NSCLC患者中显示出具有临床意义的抗肿瘤活性，特别是在携带共突变的患者中。高GCN似乎与METamp的晚期NSCLC患者中更好的疗效呈现相关性，表明其预后特性。关于AACR年会AACR年会是世界上规模最大的癌症研究会议之一，每年都会吸引来自世界各地的近20000名专业人士出席会议。