FDA 放行 Biolojic 双靶抗体偶联药 BD200 进入临床：1期试验数周内启动
Biolojic Design 11月12日在华盛顿与以色列 Ness Ziona 宣布，美国食品药品监管局 FDA 已放行其多体药物偶联物 BD200 的新药临床试验（IND）申请。BD200 同时靶向 Trop2 与 Nectin-4 两个已被验证的肿瘤抗原，放行使该公司得以启动计划中的全球 1 期临床研究，美国部分将聚焦表达这两个抗原的特定实体瘤患者。
BD200 被称为多体（multibody）药物：抗体的每条臂都可以选择结合 Nectin-4 或 Trop2，既能双臂结合同一抗原，也能一臂结合一个抗原。公司称，这种可变的结合方式配合其独特的连接子与载荷设计，可以适应患者肿瘤局部的抗原表达差异，目标是克服肿瘤抗原表达不均一与耐药这两大难题，其治疗指数估计显著高于同类药物。BD200 携带强效拓扑异构酶抑制剂载荷，临床前研究显示，它能结合双靶并按肿瘤细胞异质性的抗原表达调整特异性，较标准单特异性抗体药物偶联物（ADC）与模板双特异性 ADC 提高疗效并克服耐药。
Biolojic 首席执行官兼创始人 Yanay Ofran 表示，FDA 放行 BD200 的 IND，是首个多体药物进入临床测试的重要一步，也是超级智能（SI）用于药物设计的又一成果，公司期待在未来数周内启动 1 期研究。首席医疗官 Roger Waltzman 表示，肿瘤抗原表达的异质性与耐药是改善癌症治疗的重大挑战，BD200 的灵活结合与连接子载荷设计正是为帮助跨过这些障碍、并可能改善疗效与安全性而设计。
BD200 的 1 期研究将在评估安全性、耐受性、药代动力学与初步疗效，在美国与全球开展。在选定最佳生物剂量后，研究将聚焦一种或多种合适的肿瘤类型，并探索单药与联合治疗两条开发路径。
Biolojic Design 是一家以超级智能（SI）与计算设计把抗体改造成靶向药物候选的生物技术公司，其平台生成的首个由超级智能（SI）设计的抗体 imneskibart 已进入 2 期临床。公司管线聚焦自身免疫疾病与肿瘤领域，并与多家生物制药公司建有合作。
需要说明的是，IND 放行只意味着 FDA 允许该药进入人体临床试验阶段，不等于认可其疗效，更不等于批准上市，BD200 能否成为可用药物要看后续各期试验结果。（来源：Biolojic Design）
FDA Clears Biolojic Dual-Target Antibody Conjugate BD200 for Clinical Testing: Phase 1 to Start Within Weeks
Biolojic Design announced in Washington and Ness Ziona, Israel, on November 12 that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for BD200, a multibody drug conjugate targeting both Trop2 and Nectin-4, two validated oncology antigens that may be expressed on cancer cells. The clearance enables the company to start its planned global Phase 1 clinical study in the United States, focusing on patients with select solid tumors known to express Trop2 and Nectin-4.
BD200 is a multibody drug conjugate in which each arm of the antibody can alternatively bind to either Nectin-4 or Trop2, bind one antigen with both arms, or bind each antigen with one arm. Combined with a unique linker and payload, the company says, BD200 can adapt to various local tumor expression profiles and potentially overcome resistance, and its therapeutic index is estimated to be substantially greater than comparators. BD200 carries a potent topoisomerase inhibitor payload. In preclinical studies it was able to bind both targets and adapt its specificity to heterogeneous antigen expression on tumor cells, increasing efficacy and overcoming resistance compared with standard monospecific antibody-drug conjugates (ADCs) or a template bispecific ADC.
Yanay Ofran, Biolojic's chief executive officer and founder, said the FDA clearance is a significant step toward advancing the first multibody into clinical testing and an important achievement in the application of super intelligence (SI) to drug design, showing that SI can support the creation of antibodies with unique properties, and that the company looks forward to starting the Phase 1 study in the coming weeks. Chief Medical Officer Roger Waltzman said the heterogeneity of tumor antigen expression and the development of resistance are significant challenges in improving cancer treatment, and that BD200's flexible binding profile and unique linker-payload profile were designed to help overcome these hurdles, potentially improving efficacy and safety.
The Phase 1 study will evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of BD200 in patients with tumors known to express these antigens, and will be conducted in the United States and globally. Once optimal biologic doses are selected, the study will focus on one or more appropriate tumor types, as well as potential monotherapy and combination therapy pathways.
Biolojic Design uses super intelligence (SI) and computational design to transform antibodies into targeted drug candidates. Its platform generated the first SI-designed antibody to enter the clinic, imneskibart, which is now in Phase 2 trials. The company's pipeline focuses on autoimmune diseases and oncology, and it has partnerships with several biopharmaceutical companies.
An IND clearance only allows a drug to enter human clinical testing. It is not a finding of efficacy and is not a marketing approval; whether BD200 becomes an available medicine depends on the results of its clinical trials. (Source: Biolojic Design)
来源：Biolojic Design
发布：GSM·美国（发布链接）
图片来源：图：美国食品药品监管局 FDA 总部入口。编辑部联邦固定图库。 / Image: Entrance of the U.S. Food and Drug Administration headquarters. GSM federal asset library.
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