GEN-3017

PART 01核心提要管线调整：丹麦生物技术巨头 Genmab 宣布停止其 III 期肺癌药物 Acasunlimab 的临床开发。合作伙伴：该药物曾是 Genmab 与 BioNTech 的合作项目，但 BioNTech 已于去年退出了该资产的开发。决策突变：这一决定颇为突然，就在本月初，Genmab 高管还曾公开表示该项目“进展顺利”且拥有“10 亿美元潜力”。战略聚焦：在近期斥资 80 亿美元 收购 Merus 后，Genmab 正重新评估竞争格局，集中资源于更具价值的管线。在生物制药领域，果断“砍管线”往往比坚持到底更考验决策者的勇气。本周一， Genmab 正式宣布，将终止其双特异性抗体 Acasunlimab （PD-L1 x 4-1BB）的临床开发工作，该药物此前正处于针对肺癌的 III 期临床阶段。这一决定是在 Genmab 完成对 Merus 的 80 亿美元巨额收购后做出的。公司表示，经过对“不断演变的竞争格局”进行彻底评估后，决定将资源集中在晚期产品组合中“最具价值创造机会”的项目上。PART 02BioNTech早已退出，CFO言论遭“打脸”？Acasunlimab 的开发之路可谓坎坷。早在去年，Genmab 的合作伙伴 BioNTech 就已决定放弃该资产。当时，Genmab CEO Jan van de Winkel 曾信心满满地表示，Genmab 处于“非常有利的位置”，有信心将 Acasunlimab 推向后期开发阶段。更令人意外的是，这一终止决定与公司管理层近期的表态形成了鲜明反差。就在本月初的花旗全球医疗健康大会上，Genmab 首席财务官 Anthony Pagano 还告诉与会者，Acasunlimab 的 III 期临床“进展顺利”，并代表着一个“约 10 亿美元 的机会”。根据美国联邦试验数据库的信息，该试验原计划还需要三年时间才能完成。PART 03止损是正确的决定随着随访时间的延长，该药物在 II 期试验中的 总生存期（OS）曲线出现了恶化 。 这或许是导致 Genmab 最终放弃该药的关键科学原因。PART 04管线大清洗与未来展望今年以来，Genmab 在消化收购（包括此前收购 ADC 制造商 ProfoundBio）的同时，进行了一系列管线清理。在过去 13 个月中，Genmab 已先后终止了 GEN1047、GEN1056、GEN3017、GEN1107、GEN1160 和 GEN1055/BNT315 的开发，并未将 GEN1042 推进至针对实体瘤的 II 期临床。Genmab 与 BioNTech 的长期合作中目前仅剩一个活跃资产——GEN1059/BNT314 （EpCAM x 4-1BB 双抗），目前正处于针对实体瘤的 I 期临床阶段。随着 Merus 的融入，Genmab 的晚期管线重心将转移至 Rina-S 和 Epkinly 等更具潜力的项目上。 .cls-1{fill:#001e36;}.cls-2{fill:#31a8ff;} .cls-1{fill:#001e36;}.cls-2{fill:#31a8ff;}

Genmab is culling a trio of early oncology assets to focus on upcoming milestones for its late-stage programs that include an ADC from its purchase of ProfoundBio. After “careful consideration,” Genmab has decided to end development of GEN1047 and GEN1056 for solid tumors, as well as GEN3017 for Hodgkin and non-Hodgkin lymphoma, CEO Jan van de Winkel said on its third-quarter earnings call Wednesday. The programs “didn’t meet the high bar we have set internally for really having a truly differentiated therapeutic candidate,” he added. GEN1047 and GEN3017 are both bispecific antibodies that Genmab was advancing by itself. GEN1056 is also an antibody asset, but is part of the company’s cancer immunotherapy pact with BioNTech that dates back to 2015. The partners initiated a Phase 1 trial in 2022. Genmab also pulled the plug on plans to start Phase 3 studies of its ADC Tivdak in previously-treated head and neck cancer. The drug won FDA accelerated approval for metastatic cervical cancer in 2021, which was converted to a full approval earlier this year. The changes mean the company will be “very focused on maximizing the potential” of its Phase 3 programs Epkinly, Rina-S, and acasunlimab, van de Winkel said. Genmab and partner AbbVie are testing Epkinly in Phase 3 trials in various B cell lymphomas. Epkinly is already approved for certain forms of diffuse large B cell lymphoma and follicular lymphoma. The CD3xCD20 bispecific reached $82 million in Q3 sales. Elsewhere, Genmab’s ADC Rina-S is in a Phase 3 trial in platinum resistant ovarian cancers after it paid $1.8 billion in April to buy ProfoundBio. At the time of the deal, van de Winkel told Endpoints News there was a “lot to digest” in terms of deciding pipeline priorities. “We need time to rank all of our internal programs versus the ProfoundBio programs,” he said. The Danish drugmaker is also advancing acasunlimab, its PD-L1x4-1BB bispecific antibody, into a Phase 3 trial for NSCLC by itself after BioNTech pulled out of a collaboration in August. Earlier in its pipeline, Genmab said it plans to share data for its Phase 2 anti-CD38 monoclonal antibody dubbed GEN3014 with partner Johnson & Johnson later this year. J&J is expected to decide whether to exercise its option for the drug in the first quarter of next year.