Petosemtamab

- Petosemtamab in combination with pembrolizumab in 1L PD-L1+ r/m HNSCC interim clinical data selected for poster presentation - Conference call on Thursday, May 22 at 5:30 p.m. ET to discuss full ASCO® data set UTRECHT, The Netherlands and CAMBRIDGE, Mass., April 23, 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 the acceptance of an abstract for presentation at the 2025 American Society of Clinical Oncology® (ASCO®) Annual Meeting, being held in Chicago, Illinois on May 30- June 3, 2025. An updated analysis of the interim clinical data from the phase 2 trial of petosemtamab with pembrolizumab as 1L treatment of PD-L1+ recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) will be presented in a poster at 2025 ASCO®. 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®. “We continue to believe that petosemtamab has the potential to be a first and best-in-class, practice-changing medicine for the treatment of r/m HNSCC. While the decision to have a poster presentation at 2025 ASCO® was based on the limited data included in the submitted abstract, we are very much looking forward to sharing the robust updated interim phase 2 data, on the entire 45 patient data set, on the upcoming investor conference call and in our presentation at the conference,” said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. “We believe petosemtamab continues to demonstrate substantial clinical activity superior to historical controls, based on the magnitude and consistency of efficacy, not just on one endpoint, but across ORR, PFS and OS in the overall population and within important subgroups of HPV disease and PD-L1 expression levels. On the back of these data, and the strong execution of our phase 3 trials, we believe petosemtamab has the potential to become a new standard of care for r/m HNSCC.” Poster presentation: Title: Petosemtamab (MCLA-158) with pembrolizumab as first-line (1L) treatment of PD-L1+ recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase 2 trial Abstract #: 6024 Poster Board: 432 Session Title: Head and Neck Cancer Session Date and Time: June 2, 2025, 9:00-12:00 CT The abstracts will be available on the ASCO® website on May 22, 2025 at 5:00 p.m. ET. The full presentation will be available on the Merus website at the start of the session. Company Conference Call and Webcast Information 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. ET Webcast link: Available on our website Dial-in: Toll Free: (800) 715-9871 / International: (646) 307-1963 Conference ID: 7517301 or Merus NV call About Petosemtamab Petosemtamab, or MCLA-158, is a Biclonics® low-fucose human full-length IgG1 antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). Petosemtamab is designed to exhibit three independent mechanisms of action including inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity. About Head and Neck Cancer Head and neck squamous cell carcinoma (HNSCC) describes a group of cancers that develop in the squamous cells that line the mucosal surfaces of the mouth, throat, and larynx. These cancers begin when healthy cells change and grow in an unchecked manner, ultimately forming tumors. HNSCC is generally associated with tobacco consumption, alcohol use and/or HPV infections, depending on where they develop geographically. HNSCC is the sixth most common cancer worldwide and it is estimated that there were more than 930,000 new cases and over 465,000 deaths from HNSCC globally in 2020.1 The incidence of HNSCC continues to rise and is anticipated to increase by 30% to more than 1 million new cases annually by 2030.2 HNSCC is a serious and life-threatening disease with poor prognosis despite currently available standard of care therapies. 1 Sung et al. CA Cancer J Clin, 71:209-49, 2021; 2 Johnson, D.E., Burtness, B., Leemans, C.R. et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 6(1):92, 2020 About LiGeR-HN1 LiGeR-HN1, a phase 3 trial, will evaluate the safety and efficacy of petosemtamab in combination with pembrolizumab, compared to pembrolizumab in 1L PD-L1+ r/m HNSCC patients. The trial is open to adult patients eligible to receive pembrolizumab as 1L monotherapy with tumors expressing PD-L1, CPS ≥1. The primary endpoints are overall response rate as assessed by BICR based on RECIST v1.1 and overall survival. Secondary endpoints are duration of response and progression free survival. Merus plans to enroll approximately 500 patients in the trial. 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 clinical development of our clinical candidates, including petosemtamab, future clinical trial results or interim data, clinical activity and safety profile, and development plans in the on-going trials and described in forthcoming posters or presentations; our belief that petosemtamab has the potential to be a first and best-in-class, practice-changing medicine for the treatment of r/m HNSCC; our sharing the robust updated interim phase 2 data, on the entire 45 patient data set, on the upcoming investor conference call and in our presentation at the conference; our belief that petosemtamab continues to demonstrate substantial clinical activity superior to historical controls, based on the magnitude and consistency of efficacy, not just on one endpoint, but across ORR, PFS and OS in the overall population and within important subgroups of HPV disease and PD-L1 expression levels; our execution of our phase 3 trials; and our belief that petosemtamab has the potential to become a new standard of care for r/m HNSCC. 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 Annual Report on Form 10-K for the period ended December 31, 2024, filed with the Securities and Exchange Commission, or SEC, on February 27, 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® and Triclonics® are registered trademarks of Merus N.V. Source: Merus N.V.

无论是ADC还是TCE，如何解决On target off tumor毒性一直以来都是业界的难题，庆幸的是在TCE领域，该问题逐渐已经获得突破，条件性激活TCE经过多年的探索已经初见疗效，并且在实体瘤的临床治疗中已经展现疗效，但是在ADC领域，目前还在探索中，作为条件下激活的先驱cytomax的Probody已经停止相关探索。最近，BioAtla开发了靶向ROR2的条件激活型ADC。BioAtla的条件性激活平台（CABs）是利用肿瘤微环境偏酸性的特点，对抗体进行筛选，改造后，使得其对pH具有一定敏感性，改造的CAB抗体在酸性条件下可以有效的结合靶点，并发挥作用，但是当抗体循环到正常组织（PH值7.4以下）时，其不会与靶标蛋白结合，因此该激活是可逆的，抗体只有在肿瘤微环境酸性条件下激活，从而在一定程度上避免On target off tumor毒性。利用该平台，BioAtla开发了靶向ROR2的条件激活型ADC BA3021，并且最近在线发表了临床前相关成果。该ADC采用MC-Val-Cit-PAB linker，payload为MMAE，DAR值为4。临床前研究结果表明，其在pH 6.0的酸性环境条件下，可以有效地结合ROR2，但是在中性条件下，基本上完全丧失结合活性。在体外不同的靶标细胞杀伤研究中，无论是在ROR2高表达还是低表达的细胞株中，BA3021都展现了剂量依赖的杀伤。而且在高表达细胞株中，pH 6.0的条件下，IC50仅是pH 7.0条件下的1/30。虽然在ROR2低表达的LCLC103H和HT1080肿瘤中，其窗口没有高表达显著，但是两者约有2倍的差异。在体内动物模型研究中，在SK-MEL5和LCLC103H的CDX模型中，BA3021展现了剂量依赖的肿瘤抑制活性，甚至在PDX模型中，其也展现了强大的抑制肿瘤活性。其中在肉瘤SA13179模型中，其甚至能够完全清除肿瘤。临床进展临床中，Ozuriftamab Vedotin已经开展了治疗SCCHN的临床研究（头颈部鳞状细胞癌，squamous cell carcinoma of the head and neck），研究表明，ROR2在SCCHN中有较高的表达几率，并且在HPV病毒驱动的SCCHN中高表达，最近的研究证明，ROR2的高表达受HPV E6和E7的驱动临床中入组患者如基线如下图所示，多数患者在接受Ozuriftamab Vedotin治疗前已经接受过至少2线治疗，超过50%的患者之前接受过3线及以上治疗，并且所有患者都接受过免疫检查点治疗，在HPV感染方面，患者中有26位为HPV p16阳性。疗效方面，截止2025年3月24日，35位患者接受治疗并进行评估，治疗的总体相应率为40%（已经证实的响应率为23%），其中在1.8 mg/kg Q2W治疗组中，治疗的总体相应率同样为40%（已经证实的响应率为27%），疾病控制率为93%，略高于总体的86%。PFS和OS目前还不成熟，正在评估中。而在HPV阳性治疗组中，虽然所有患者之前平均接受过3线治疗，但是Ozuriftamab Vedotin治疗也展现了良好的治疗效果，治疗的总体响应率为45%（已经证实的响应率为27%），疾病控制率高达100%。作为对比，Merus的EGFR/LER5双抗Petosemtamab在临床中也在探索头颈癌的治疗，在平均接受过2线治疗的患者中，其总体ORR为36%，DCR为64%。对比两者的临床患者基线，Ozuriftamab Vedotin入组患者平均接受过3线治疗，而Petosemtamab入组的患者先前平均接受过2线治疗，另外Ozuriftamab Vedotin入组患者有50%接受过EGFR抗体疗法，而Petosemtamab入组患者中仅2%接受过EGFR抗体疗法。虽然其响应率略低于Petosemtamab，但是考虑到其患者更难治，因此疗效总体上还是不错的。在来对比一下目前的免疫检查点疗法，无论是O药还是K药，两者在SCCHN的治疗中都没有展现疗效，总体响应率K药为7.2%，而O药为5.8%,同样对于抗血管治疗，Cetuximab单独治疗的总体响应率也仅有13%，大幅度低于Ozuriftamab Vedotin，总的来说，Ozuriftamab Vedotin疗法目前还是相对比较成功的。安全性方面，1.8 mg/kg Q2W治疗组有90%的患者发生副作用，其中有15%的患者发生3级或者4级副作用，要低于1.8 mg/kg 2Q3W治疗组。总结在解决On target off tumor毒性方面，cytomax作为先行者开发的Probody已经被拍死在沙滩上，之后鲜有biotech涉猎条件激活型ADC，BioAtla以条件激活型抗体平台CABs起家，后续坚持深耕该领域，随着ADC的爆火，其也开始探索将CABs与ADC结合，从而解决On target off tumor毒性。 BA3021是利用CABs平台构建的靶向ROR2的ADC，在3线及以上的SCCHN临床研究中已经展现了初步的临床疗效，而且与现有的免疫检查点疗法或者抗血管疗法相比，其都展现了更好的治疗效果，期待其后续的表现。我们已经建立抗体密码读者交流群，有兴趣的可以扫描下方二维码添加微信进群，请主动备注姓名-公司-职位（高校-专业），非诚勿扰！往期精彩回顾抗体密码文章合集双特异抗体平台靶点相关双特异抗体作用机制综述，行业概览抗体筛选技术相关公司技术汇总医药资讯因为你的分享、点赞、在看我足足的精气神儿！声明本公众号所发表文章以宣传知识为目的，因此不构成投资，病人用药等建议。如果文章侵您的权益及时联系小编进行删除！欢迎扫码交流/咨询/合作等参考文献：1、https://doi-org.libproxy1.nus.edu.sg/10.1080/19420862.2025.2490078