EVOLVE-106

10月31日，艾伯维与EvolveImmune Therapeutics宣布达成合作，双方将结合艾伯维的肿瘤学专业知识与 EvolveImmune 专有的 EVOLVE T 细胞衔接器平台（T-Cell Engager Platform），针对多个靶点，开发用于癌症的新型多特异性治疗性抗体。 根据协议条款，EvolveImmune将从艾伯维获得总计6500万美元的前期费用和股权投资，并有资格获得高达14亿美元的期权费和里程金，以及净销售额的分层版税。 EvolveImmune成立于2018年，致力于开发下一代生物疗法，以克服癌细胞对当前免疫疗法的耐药性。Pfizer Ventures、Takeda Ventures、BMS等机构参与了该公司先前的融资。 EvolveImmune的核心技术平台为EVOLVE，目标是实现强效、选择性、集成的T细胞共刺激，增强及维持T细胞的肿瘤杀伤能力，以克服实体肿瘤和血液肿瘤的治疗挑战。 目前，EvolveImmune已布局了丰富的管线，包括EVOLVE-104（ULBP2/CD3/CD2三抗，潜在first-in-class）、EVOLVE-105（CD20/CD3/CD2多抗）、EVOLVE-106（CD2/B7-H4/CD3三抗）等。公司预计将于2025年进行首次人体临床试验。 EvolveImmune管线 “我们相信，具有差异化的CD2共刺激策略的EVOLVE平台代表了潜在的下一代best-in-class T细胞衔接器平台。” EvolveImmune首席执行官Stephen Bloch博士说道。 双抗/三抗（多抗）赛道在过去几个月势头火热，2024年，多家制药巨头在该领域发力。其中，近期国内公司的两项交易引人注目。10月29日，GSK宣布以3亿美元首付款从恩沐生物收购CMG1A46（一种靶向CD19、CD20和CD3的三特异性抗体）。GSK计划重点开发该候选药物在B细胞驱动的自身免疫性疾病领域的应用，例如系统性红斑狼疮（SLE）和狼疮性肾炎（LN），并有可能扩展到其他相关的自身免疫性疾病。恩沐生物还有资格获得总计5.5亿美元的开发和商业化里程碑付款。 此外，8月9日，默沙东与同润生物宣布达成一项最终协议，默沙东通过子公司收购同润生物临床阶段的新型CD3xCD19双抗CN201。交易现金预付款为7亿美元，里程碑付款高达6亿美元。默沙东计划评估CN201作为B细胞恶性肿瘤的治疗方法，并研究其作为一种新型自身免疫性疾病治疗方案的潜力 除艾伯维、GSK、默沙东外，2024年，诺华（与Dren Bio达成战略合作，潜在交易总额30亿美元）、强生（以约12.5亿美元收购Yellow Jersey Therapeutics）等MNC亦在双抗领域有加注。 双抗/三抗/多抗是过去近10年新药研发领域的热门赛道之一。据医药魔方NextPharma®数据库，截至2024年11月1日，全球有超1300个双抗/三抗/多抗项目同步在研，中国公司已成为“主力军”，一半的项目由国内公司开发。 全球获批上市的双抗药物 数据来源：医药魔方NextPharma®；数据截至2024-11-01（备注：2009年获欧盟批准上市的CD3/EpCAM双抗catumaxomab已退市） 过去3年，双抗在监管层面可以说是“大丰收”。自2022年以来，全球共有11款双抗获批上市，取得了包括适应症的突破（如CD3双抗拿下首个实体瘤适应症、首款眼科疾病双抗获批上市）、作用机制的突破（如两款基于PD-1的双抗获批上市）。市场表现方面，2022年1月获批的眼科双抗Vabysmo仅用两年的时间，年销售额就已突破20亿美元，而更早获批的A型血友病双抗Hemlibra 2023年销售峰值达到了44.85亿美元。未来，在肿瘤、自免等领域，双抗/三抗/多抗还能带来怎样的突破，值得期待。  -上下滑动查看参考资料-  [1]https://evolveimmune.com/abbvie-and-evolveimmune-therapeutics-announce-collaboration-and-option-to-license-agreement-to-develop-next-generation-cancer-biotherapeutics/ [2]https://www.gsk.com/en-gb/media/press-releases/gsk-enters-agreement-to-acquire-cmg1a46-from-chimagen-biosciences/ [3]https://www.businesswire.com/news/home/20240808638055/en/Merck-to-Acquire-Investigational-B-Cell-Depletion-Therapy-CN201-from-Curon-Biopharmaceutical [4]https://www.businesswire.com/news/home/20241001828681/en/Merck-Completes-Acquisition-of-Investigational-B-Cell-Depletion-Therapy-CN201-from-Curon-Biopharmaceutical [5]https://www.globenewswire.com/news-release/2024/08/26/2935368/0/en/Ordspono-odron Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。 免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

EV-104 and EV-106 Programs Demonstrate Potential for A Differentiated Precision Immunotherapy Approach Built on Novel Insights Into Solid Tumor FeaturesBRANFORD, Conn., Nov. 06, 2023 (GLOBE NEWSWIRE) -- EvolveImmune Therapeutics, an immuno-oncology company developing first-in-category, multifunctional biotherapeutics to overcome the therapeutic challenges of cancer cell resistance to current immune therapy agents, today announced that new preclinical and translational data highlighting EV-104 and EV-106, two programs utilizing EVOLVE, the company’s proprietary costimulatory T cell engager platform were presented at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). The company shared for the first time its pioneering insights into the regulation of tumor antigen expression in specific solid tumor lineages and the association of those lineages with immune infiltration. In addition, presented data highlighted the robust anti-tumor efficacy exhibited by lead molecules for the EV-104 and EV-106 programs in patient-derived solid tumor models. These findings illustrate the potential of the EVOLVE platform to enable a novel precision immunotherapy strategy for selecting patients who are most likely to benefit by treatment with each of these molecules. The EVOLVE platform uniquely unleashes potent, selective and integrated T cell costimulation, which amplifies and sustains the tumor killing capacity of these T cells. This approach bypasses low tumor immunogenicity, conditionally activates adaptive immunity and reduces T cell dysfunction to address unmet needs for the treatment of solid and hematologic tumors. The platform also takes advantage the company’s understanding of specific tumor cell characteristics to guide tumor antigen prioritization and program differentiation. By pairing its distinctive costimulation strategy with these critical tumor-intrinsic attributes, EvolveImmune is developing an innovative pipeline of first-in-category precision immuno-oncology agents with an enhanced likelihood of clinical success. EV-104: In a poster presentation at SITC, EvolveImmune spotlighted advances to the company’s first-in-class EV-104 program, a novel multi-functional T cell engager with integrated CD2 costimulation which conditionally targets ULBP2. Researchers found that ULBP2 expression is markedly enriched in cancers displaying molecular features of the basal-squamous tumor lineage and that these tumors show high levels of immune infiltrates. This profile is favorable to optimize clinical anti-tumor responses with EV-104 in these sizeable patient subpopulations which continue to experience high unmet needs despite current therapies. The expression pattern of ULBP2 is distinct from that of the solid tumor targets for a number of approved or investigational immunotherapies, suggesting opportunities for meaningful clinical differentiation. EV-104 showed robust single-agent anti-tumor activity in patient-derived tumor models of bladder and lung cancer and demonstrated promising activity in combination with anti-PD1 therapy in pre-clinical models with patient-derived tumors, providing rationale for combination treatment approaches with checkpoint inhibitors. EV-106: In a second SITC poster presentation, researchers shared the latest data on EV-106, a proprietary multi-functional T cell engager with integrated CD2 costimulation which conditionally targets B7-H4. EvolveImmune has identified advanced candidate leads for this best-in-class solid tumor program. The presentation unveiled new observations showing that B7-H4 expression is elevated in breast tumors that are estrogen receptor (ER)-low and in triple-negative breast cancers (TNBCs). New clinical, genetic and pharmacologic evidence indicates that a range of clinically relevant breast cancer therapeutics such as CDK4/6 inhibitors, selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) strongly induce surface B7-H4 levels following treatment. This profile suggests significant therapeutic potential for a B7-H4-targeting immunotherapy such as EV-106 to overcome therapeutic resistance in both breast cancer patient subpopulations, which are notable by their high unmet need. New findings demonstrated robust single-agent anti-tumor activity by EV-106 lead molecules in three different preclinical breast cancer cell assay systems that was superior to B7-H4-targeted CD3 T cell engagers being advanced by competitors which do not employ integrated CD2 costimulation. Additionally, combining EV-106 with either estrogen therapies (SERD + CDK4/6 inhibitor) or an anti-PD-1 antibody further heightened the anti-tumor activity of EV-106, suggesting the potential for effective combination therapy in these patient segments. “EvolveImmune’s intentional focus on integrating CD2 costimulation in their T cell engager platform continues to be a highly appealing approach to address the therapeutic challenges which result from impaired T cell effector function and T cell exhaustion in the solid tumor setting. With their new and unexpected observations describing the association of high levels of expression of their drug targets with specific cancer cell features, the company has broken new ground to enable a patient selection strategy to identify patients who may benefit most from these treatments. I look forward to closely following the progress of EvolveImmune’s programs, which have the potential to address unmet medical needs in the significant proportion of patients whose cancers do not respond to currently available immunotherapies,” said Susan Kaech, Ph.D., professor and director, NOMIS Center for Immunobiology and Microbial Pathogenesis at the Salk Institute for Biological Studies, and NOMIS Foundation Chair. “These new translational data presented at SITC build upon the strong pipeline and platform advances we have made at EvolveImmune, and provide a glimpse into the potential of EV-104 and EV-106, as well as other EVOLVE programs to come, to represent a next generation of differentiated precision immunotherapies,” said Jeremy Myers, Ph.D., senior vice president, research and development at EvolveImmune. “We are highly driven to continue our quest to leverage our team’s innovativeness and know-how to quickly bring our solid tumor programs to patients in need, and we remain on track to meet this goal.” Additional information on the 38th Annual Meeting of SITC is available through the conference website at: https://www.sitcancer.org/2023/home. About EvolveImmune Therapeutics EvolveImmune Therapeutics, Inc. is an immunotherapy platform company developing first-in-category, multifunctional biotherapeutics designed to overcome cancer-driven immunodeficiency in a range of solid tumors and hematological cancers. First-in-human clinical trials are anticipated in 2024. The company is supported by a syndicate of top-tier life science industry investors including Pfizer Ventures, Solasta Ventures, Takeda Ventures, Yonjin Ventures and Elm Street Ventures. For more information, please visit: www.evolveimmune.com