2022 年随着 Enhertu 亮眼的临床试验数据披露，有更多企业开始进军 ADC 领域。截至目前，据 Insight 数据库显示，全球已有 317 款 ADC 新药进入临床阶段。在国内，也有 99 款 ADC 新药进入临床阶段，而在 2022 年截止目前，有 9 款进入 III 期临床阶段以及 2 款申报上市。此外，有 20 款 ADC 新药首次启动临床。2022 年国内 20 款 ADC 新药首次公示临床试验来自：Insight 手动整理（如有纰漏，请指正）在 20 款产品中，从靶点分布来看，热门靶点 TOP3 仍是 HER2（3 款）、TROP2（2 款）以及 CLDN-18.2（2 款）。此外，CD38、CD70、MUC1 等潜力靶点也有了首款 ADC 出线。来自：Insight 数据库网页版（http://db.dxy.cn/v5/home/）从企业布局来看，百奥泰今年 5 款 ADC 新药新进入临床阶段，杭州多禧生物有 3 款，苏州宜联生物以及四川百利药业有 2 款。此外，还涉及到科伦药业、基石药业、浙江医药等。来自：Insight 数据库网页版百奥泰：迭代技术平台，5 款 ADC 新进临床具体从单个企业来看，百奥泰今年有 5 款 ADC 新药新进入临床阶段。百奥泰 2022 年 5 款 ADC 首次启动临床试验来自：Insight 数据库网页版值得一提的是，百奥泰基于旧有 ADC 平台布局的两款分别靶向 HER2 以及 TROP2 ADC BAT8001、BAT8003 此前已被终止。此后，百奥泰自主研发了新的 ADC 平台，将毒素由 MMAE 更替为拓扑异构酶，Linker 采用定点偶联酶切可裂解，由此重新申报临床多个 ADC 项目，并在今年 8 月和 10 月，启动了 HER2 ADC BAT8010 以及 TROP2 ADC BAT8008。除布局 HER2、TROP2 热门靶点外，百奥泰还布局了 Nectin-4、CD276（B7H3）以及 FRα。针对 Nectin-4 ADC，从全球来看安斯泰来/seagen 同类产品 Enfortumab vedotin 已上市，不过，其 Payload 为 MMAE，而百奥泰采用的则是拓扑异构酶，有差异化布局。CD276 为当前未成药靶点。全球进展较快的为 MacroGenics vobramitamab duocarmazine 以及第一三共 DS-7300，目前已进入 II/III 期或 II 期临床阶段，后者已于今年 8 月在国内同步启动 II 期临床用于 NSCLC（登记号：CTR20222027）。全球进入 II 期临床 CD276 ADC来自：Insight 数据库网页版多禧生物：首款 Muc1 ADC 进临床，实体瘤、血液肿瘤两手抓多禧生物目前已有 5 款 ADC 进入临床阶段，今年首次启动临床的就有 3 款。多禧生物 2022 年首次启动临床 ADC来自：Insight 数据库网页版在这 3 款 ADC 新药中除 DXC004A 未披露靶点信息外，其余 2 款为分别靶向 CD33 DXC007 和 Muc1 DXC005，其中，后者为国内首款进入临床阶段的 Muc1 ADC 新药，而同类产品中，齐鲁从韩国 Peptron 公司独家授权引进 PAB001，目前尚未进入临床。在适应症方面，除实体瘤外，多禧生物也在布局血液肿瘤，DXC007 针对复发/难治性急性髓系白血病的 I 期临床研究已于今年 7 月完成首例受试者入组工作（登记号：CTR20221074）。此外，今年 10 月，多禧生物另一款 ADC 新药 DXC009 的临床试验申请已获 CDE 受理，靶点尚未披露，拟用于治疗多发性骨髓瘤。在医药交易方面，多禧生物今年也有新进展。今年 6 月，强生与多禧生物达成合作。根据该协议，多禧生物将应用其独有的 ADC 创新平台与杨森所提供的独有抗体，双方将就至多 5 个靶点开发新型 ADC 药物。强生 JJDC 同时对多禧生物进行了股权投资。多禧生物将获得预付款、成本报销和里程碑付款，以及产品全球销售额的特许权使用费。苏州宜联生物：国际化布局，2 款 ADC 中美同步开展临床苏州宜联生物在今年有 2 款 ADC 新药首次启动临床试验，这 2 款新药是基于其自有平台 TMALIN™ 技术平台所开发的，也是宜联生物目前唯一进入临床阶段的产品。苏州宜联生物 2 款 ADC 新药来自：Insight 数据库网页版据悉宜联生物的 ADC 技术，采用高亲和力易内吞的 IgG1、作用于 DNA 的中低毒性毒素 payload、高 DAR 值设计、可裂解 Linker。宜联生物已经完成了毒素 Linker 技术平台的国际专利布局，目前 LY201、LY202 这 2 个项目已在中美同步开展 I 期临床研究。这家 ADC 新秀企业在今年可谓是收获不少，今年 3 月，宜联生物完成 7000 万美元 B 轮融资。今年 12 月，复宏汉霖与苏州宜联生物达成战略合作，复宏汉霖将获得基于宜联生物自主知识产权的 ADC 技术平台针对两个指定靶点在全球范围内开发、生产和商业化等相应 ADC 产品的独家许可和分许可权益。四川百利药业：2 款新药进入临床，布局热门靶点四川百利药业在今年也有 2 款 ADC 新药进入临床，是百利药业提交 IND 的第二款和第三款 ADC 药物，分别靶向热门靶点 TROP2、HER2 。来自：Insight 数据库网页版而其首款 ADC 新药 BL-B01D1 为国内首个申报临床的双抗 ADC 新药，可同时靶向 EGFR/HER3，于去年 11 月首次启动临床。基石药业：超 3.6 亿元引进 ROR1 ADC 启动临床今年 11 月，基石药业超 3.6 亿元引进的 ROR1 ADC 项目 CS5001 在国内首次公示临床试验。CS5001 权益流转情况来自：Insight 数据库网页版CS5001 具有连接子加前毒素的双控机制，从而有效解决了与传统 PBD 载荷有关的典型毒性问题，拥有更好的安全性。此外，CS5001 利用定向偶联技术获得精准的药物抗体比率（DAR），便于实现均质生产及大规模生产。在 2021 年国际分子靶标与癌症治疗大会上，CS5001 的临床前研究数据作为重磅研究摘要（LBA）通过海报形式展示研究结果（Poster ID：LBA008）。该项结果表明，CS5001 在多种表达 ROR1 的细胞系展现出了较强的选择性细胞毒性，并在异种移植小鼠模型中显示出显著的体内抗肿瘤活性。在一组癌症细胞系中，ROR1 的表达似乎可以预测对 CS5001 的敏感性。艾森药业：国内首款 CD38 ADC 启动临床艾森药业 CD38 ADC STI-6129 在今年首次启动临床。STI-6129 为国内首款进入临床的靶向 CD38 ADC 新药，使用了 Sorrento Therapeutics 公司的技术平台筛选出的 CD38 特异性抗体，及独有专利小分子毒素 Duostatin 5。艾森药业早先被 Sorrento 收购，成为其全资子公司。2020 年 5 月，STI-6129 获得 FDA 批准临床，用于治疗轻链淀粉样变性。在国内，其临床试验申请于去年 11 月获 CDE 受理，于今年 9 月首次获批临床，并于今年 10 月首次公示临床试验，正在开展用于治疗复发性或难治性多发性骨髓瘤的 I 期临床研究（登记号：CTR20222476）。STI-6129 国内项目开发概览来自：Insight 数据库网页版浙江医药：国内首款 CD70 ADC 启动临床浙江医药 ADC 新药 ARX305 在今年 8 月首次启动临床试验，并于今年 11 月完成针对晚期实体瘤患者 I 期临床中的首例受试者的入组工作（登记号：CTR20222161）。CTR20222161 试验历史时光轴来自：Insight 数据库网页版ARX305 也是国内首款进入临床阶段的 CD70 ADC。ARX305 由一种人源化抗 CD70 单克隆抗体共价结合 2 个微管抑制剂 AS269 而成。ARX305 与细胞膜上 CD70 特异性结合，通过内吞作用进入细胞，经蛋白酶水解释放微管蛋白抑制剂，通过抑制细胞有丝分裂杀死 CD70 阳性细胞。早在 2019 年 10 月，浙江医药与美国 Ambrx 公司就共同研发 ARX305 达成合作浙江医药将负责 ARX305 在中国的开发和商业化，而 Ambrx 保留 ARX305 在中国境外的商业权利。截至 2021 年 11 月 30 日，浙江医药在 ARX305 项目上已累计投入研发费用 6502 万元人民币。科伦药业：1 款 ADC 首次启动临床；三次牵手默沙东除此以外，对部分企业而言，虽然今年可能只有 1 款 ADC 新进入临床阶段，但其本身早已布局了多款，并已实现了海外授权。最典型的就是科伦药业。今年除靶向 CLDN-18.2 的 SKB315 首次启动临床外，其靶向 Nectin-4 SKB410 临床试验申请也已于今年 12 月获受理（受理号：CXSL2200608）。而在今年，对科伦药业来说，在 ADC 领域最引人瞩目的要数与默沙东达成 3 次合作，总额超 100 亿美元，9 个 ADC 项目出海。详见 Insight 往期报道>>>超 90 亿美元！科伦第 3 次牵手默沙东，7 个临床前 ADC 项目出海此外，君实、石药集团等国产企业均有 ADC 新药在今年首次启动临床。点击卡片进入 Insight 小程序点此查看「ADC」新药布局…随时随地查！👇👇👇免责声明：本文仅作消息分享，并不构成投资建议，也不代表 Insight 数据库的立场，文章观点仅供分享行业见解，请广大投资者谨慎。编辑：HebePR 稿对接：微信 insightxb投稿：微信 insightxb；邮箱 insight@dxy.cn点击阅读原文免费试用 Insight 数据库

抗体药物偶联物临床2期临床3期申请上市临床成功

2022-11-10

·Business Wire

Ambrx Announces NovoCodex’s Dosing of First Patient with ARX305, Ambrx’s Investigational Antibody Drug Conjugate Targeting CD70

SAN DIEGO--(BUSINESS WIRE)--Ambrx Biopharma Inc., or Ambrx, (NYSE: AMAM), a clinical stage biopharmaceutical company using its proprietary Engineered Precision Biologics (EPBs) platform to create antibody drug conjugates (ADCs), today announced the first patient has been dosed by Ambrx’s partner, NovoCodex Biopharmaceuticals, Inc. (NovoCodex) in its Phase 1 trial of ARX305 in patients with advanced solid tumors. ARX305 is the only anti-CD70 ADC in active development that targets CD70, a protein that is overexpressed in a broad range of solid and hematologic tumors, giving it the potential to treat a range of liquid and solid tumor cancers, where CD70 is overexpressed. 'The dosing of the first patient with ARX305 by NovoCodex represents an important strategic benchmark that will not only advance another Ambrx-generated ADC asset into the clinic, but also will allow us to leverage findings from the study to inform our own clinical trial' According to their development agreement, NovoCodex and Ambrx will collaborate in the development of ARX305 up until the completion of Phase 1 clinical trials. Under the terms of the development agreement, Ambrx is eligible to receive up to $4.0 million in clinical milestones, as well as tiered royalties in the low teens percentage range of aggregate net sales of ARX305 in China from NovoCodex. As a result of the first patient being dosed in NovaCodex’s Phase 1 clinical trial in China, Ambrx will now receive a significant portion of the $4.0 million milestones payments. Ambrx plans to leverage the safety data from NovoCodex’s Phase 1 dose escalation clinical trial to inform its own Phase 1a trial, thereby efficiently using the company’s cash and resources. Specifically, using the data gained from NovoCodex’s dose escalation trial, Ambrx can reduce the expense of conducting its own initial dose escalation clinical trial. Building on the NovoCodex Phase 1 data, Ambrx plans to expedite its Phase 1a trial of ARX305 by starting at higher doses (i.e., doses closer to a recommended Phase 2 dose). Following the completion of NovoCodex’s Phase 1 clinical trial, Ambrx’s Phase 1a clinical trial for ARX305 is expected to initiate in the second half of 2023. NovoCodex is also responsible for funding a majority of Ambrx’s development of ARX305 through the end of Phase 1 clinical trials, up to a certain cap, and will be able to leverage Ambrx’s data in its own development of ARX305. "The dosing of the first patient with ARX305 by NovoCodex represents an important strategic benchmark that will not only advance another Ambrx-generated ADC asset into the clinic, but also will allow us to leverage findings from the study to inform our own clinical trial,” said Daniel O’Connor, Chief Executive Officer of Ambrx. “Leveraging partner data will both expedite internal development and cut costs, establishing a strong foundation from which to begin our own Phase 1 trial.” Mr. O’Connor added, “CD70 is highly expressed on the surface of a variety of hematological and solid tumor cells, and I believe the stability of ARX305 conferred by our proprietary EBP platform uniquely positions it as a potential best-in-class treatment for CD70 expressing tumors. I want to thank NovoCodex for continuing our strong partnership and look forward to continued progress as they advance ARX305 through the clinic.” About Ambrx Biopharma Inc. (Ambrx) Ambrx is a clinical stage biopharmaceutical company using an expanded genetic code technology platform to discover and develop Engineered Precision Biologics. These include next generation antibody drug conjugates (ADCs) and other engineered therapies to modulate the immune system. Ambrx is advancing a focused portfolio of clinical and preclinical programs designed to optimize efficacy and safety in multiple cancer indications, including its lead product candidate ARX517, a prostate-specific membrane antigen (PSMA) targeting ADC. In addition, Ambrx has clinical collaborations with multiple partners on drug candidates generated using Ambrx technology. For more information, please visit www.ambrx.com.

合作抗体抗体药物偶联物

2022-10-19

·FierceBiotech

Ambrx cuts 15% of staff and dumps lead HER2 asset after 'strategic review'

Ambrx Biopharma expects changes to extend its cash runway into 2025. Ambrx Biopharma has been mulling major changes since August. Now, it has confirmed what form these will take: narrowing its cancer pipeline to earlier-stage therapies and dumping its lead asset at the expense of 15% of its workforce. Change has been afoot at the biotech since July, when the company revealed that a relaxin heart failure collaboration with Bristol Myers Squibb had hit the buffers. CEO Feng Tian, Ph.D., headed for the exit two months ago, when the company also unveiled a “strategic review” of its pipeline. The search for a CEO remains ongoing, the company said in a release yesterday. Board member Kate Hermans is continuing to serve as CEO in an interim role and is overseeing the company’s new strategy. It turns out that new strategy will see Ambrx dropping its phase 3 HER2 antibody-drug conjugate (ADC) dubbed ARX788. The company has hit pause on trials of the therapy and will seek a development partner for the drug outside of China, where NovoCodex already owns the rights. With AstraZeneca and Daiichi Sankyo’s blockbuster Enhertu becoming the first approved therapy targeting patients with the HER2-low breast cancer subtype in August, Hermans referred in general terms to changes in the HER2 market as a reason for the strategic pivot. “There has been a significant shift this past year in the HER2 metastatic breast cancer competitive landscape,” the interim CEO said in the release. “As a result of our assessment, the board has endorsed the decision that the company should pause the internal development of ARX788 and seek a partner to further its development ex-China in order to extend the cash runway into 2025.” In its place, the phase 1 ADC therapy ARX517 will be promoted up to lead asset, Ambrx said. The company believes ARX517 has the potential to be the first ADC therapy to specifically target prostate-specific membrane antigen to treat prostate cancer. Safety data from the phase 1 study are due to read out in the second half of 2023. At that time, Ambrx can decide on a recommended dose and move into a phase 1b/2 trial. The San Diego-based biotech also has two other assets that will continue in development. ARX305 is an anti-CD70 ADC that is due to begin phase 1 trials in the second half of next year, subject to results from a study sponsored by NovoCodex. The other asset is the smart PEG-IL2 called ARX102, for which the company plans to seek FDA permission in the first half of 2024 to start human trials, subject to results from a Sino Biopharm-sponsored trial in China.