Anselamimab

本周四，阿斯利康旗下负责罕见病领域的Alexion，与瑞士一家处于临床阶段的公司Neurimmune达成全球独家合作与授权协议，共同开发和商业化用于治疗轻链（AL）淀粉样变性的在研药 NI009。这是双方在淀粉样变性领域的第二次深度合作，距离首次合作已近四年。 NI009 是一款处于晚期临床前开发阶段的人源单克隆抗体，靶向并清除 AL 淀粉样变性患者体内的lambda轻链原纤维及沉积物。根据协议，阿斯利康将获得该药物全球独家的研究、开发、生产和商业化权利，向Neurimmune支付包括预付款在内的最高 7.8 亿美元款项，涵盖开发、监管和商业化里程碑达成后的潜在付款。若 NI009 成功上市，Neurimmune还将获得基于净销售额的分级特许权使用费。 Neurimmune首席执行官Roger M. Nitsch 示，NI009 展现出广泛的活性，能够应对不同患者体内多种 lambda 轻链亚型的淀粉样蛋白，即便该疾病存在高度克隆异质性这一治疗挑战。 此次合作是双方已有合作的扩充。在 2022 年初，Alexion就以 3000 万美元引进了Neurimmune的候选药物 NI006（现更名为 cliramitug），NI006用于治疗转甲状腺素蛋白淀粉样变性心肌病（ATTR-CM）。该药目前已进入 III 期临床，其 I 期研究数据显示，高剂量使用时可显著减少心脏淀粉样沉积物。 在 AL 淀粉样变性领域，阿斯利康此前还通过2021年收购 Caelum Biosciences 获得了另一款候选药物 anselamimab。不过，该药物在今年7月公布的 III 期研究中未能达到主要终点。Alexion高管表示，anselamimab 作为首款原纤维清除剂，在晚期 AL-kappa 淀粉样变性患者的生存和心脏结局改善方面具有潜力，公司计划将该研究中的关键经验应用于 NI009 的开发，使其成为互补性的原纤维清除剂，惠及更多 AL 淀粉样变性患者。AL 淀粉样变性是一种罕见的全身性进行性疾病，由骨髓中缺陷浆细胞异常产生异常的 kappa（κ）或 lambda（λ）轻链蛋白所致。这些异常蛋白会发生错误折叠并聚集形成淀粉样原纤维，沉积在心脏、肾脏等多个组织和器官中。若不及时治疗，这些有毒沉积物的累积将导致进行性器官损伤和功能障碍，严重时可引发过早死亡，其中最常见的死因是心力衰竭。 Neurimmune 是一家专注于开发下一代抗体疗法的临床阶段生物制药企业，开创性地将淀粉样蛋白清除作为治疗中枢神经系统及相关蛋白聚集疾病的新型治疗机制，其研发管线涵盖阿尔茨海默病、肌萎缩侧索硬化症、ATTR 心肌病等多个领域。除了cliramitug和NI009，该公司还拥有用于肌萎缩侧索硬化症的 II 期候选药物AP-101、用于脊髓损伤的 I 期药物NG004等多款在研资产。 参考消息： https://www.neurimmune.com/news/neurimmune-expands-collaboration-with-astrazeneca-to-develop-and-commercialize-fibril-depleter-ni009-for-al-amyloidosis 本文旨在行业资讯和知识分享，无任何商业用途。文章仅代表作者观点，不代表本站立场。   往期推荐 1.药明康德再次被五角大楼质疑！或对美有国家安全风险 2.减肥药第二轮降价谈判公布！司美格鲁肽降幅领衔，但其发言人明确反对持续降价 3.诺华裁到“大动脉”！ 4.诺和诺德阴霾渐散，在研新药减重无平台期！真·瘦成一道“闪电” 5.新晋院士最新Nature！无创透皮递送胰岛素，像护肤一样降糖 Being科学公众号目前已经有多个交流群（好学，有趣的生物医药人才在这里聚集）。进群请扫描下方二维码，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。 发现“分享”和“赞”了吗，戳我看看吧

The accumulation of toxic amyloid deposits, notably in the heart and kidneys, can cause progressive organ damage and dysfunction.\n Almost four years after penning its first amyloidosis collaboration with Neurimmune, AstraZeneca has returned to pick up a second asset.The latest licensing deal involves NI009, a preclinical monoclonal antibody that targets lambda light chain fibrils and deposits from affected tissues and organs in light chain (AL) amyloidosis. In return for the exclusive rights, AstraZeneca’s Alexion Pharmaceuticals rare disease unit is liable to pay up to $780 million in a combination of upfront and potential development, regulatory and commercial milestone payments.NI009 is currently in “advanced preclinical development,” according to Neurimmune, which will also oversee the first clinical trial of the drug before handing the process over to Alexion.Should NI009 make it to market, Neurimmune will also be in line for tiered royalties on net sales.AL amyloidosis is a rare, progressive disorder caused by defective plasma cells in the bone marrow. The accumulation of these toxic amyloid deposits, notably in the heart and kidneys, can cause progressive organ damage and dysfunction, Neurimmune explained in a Dec. 4 release.NI009 has so far exhibited “broad activity against amyloids of diverse lambda light chain subtypes across patients despite the high clonal heterogeneity of the disease,” Neurimmune’s CEO Roger Nitsch said in the release.This morning’s deal follows AstraZeneca’s $30 million payment to the biotech at the start of 2022 to license the ATTR amyloidosis candidate NI006. Since then, Neurimmune has read out data from a phase 1 study of NI006 that it claimed showed “substantial” reductions in cardiac amyloid deposition at higher doses. AstraZeneca already has a more advanced AL amyloidosis candidate in its pipeline in the form of anselamimab, which it acquired when it bought out Caelum Biosciences back in 2021. However, the pharma’s hopes of turning anselamimab into a potential blockbuster appeared dampened in July of this year, when the phase 3 Cares study showed the light chain depleter antibody failed to reduce deaths and hospitalizations.The U.K.-based drugmaker claimed at the time that anselamimab had demonstrated a “highly clinically meaningful improvement” in an unspecified subgroup of patients, and the upbeat rhetoric was maintained in this morning’s release.“This announcement follows the high-level results from Alexion\'s CARES phase 3 clinical program which demonstrated anselamimab\'s potential as a first-in-class fibril depleter to improve survival and cardiac outcomes in patients living with advanced AL-kappa amyloidosis, a debilitating progressive rare disease,” Gianluca Pirozzi, head of development, regulatory and safety at Alexion, said.“In expanding our collaboration with Neurimmune, we aim to apply key learnings from the CARES program to develop NI009 as a complementary fibril depleter to potentially benefit more patients living with AL amyloidosis,” Pirozzi added.