Siglec-10

·ATN-031（又名ATG-031）是在美国进入肿瘤临床研究的首款抗CD24单克隆抗体药物。·正在美国的4个临床研究中心开展的I期PERFORM研究旨在评估ATN-031治疗晚期实体瘤或B细胞非霍奇金淋巴瘤（B-NHL）患者的安全性和初步疗效。美国宾夕法尼亚州多尔斯敦，2024年3月20日 – 德琪医药的美国全资子公司Antennova今日宣布，已完成抗CD24单克隆抗体药物ATN-031（又名ATG-031）的I期临床研究的首个剂量水平队列。这项剂量爬坡研究（NCT06028373）正在晚期实体瘤或B细胞非霍奇金淋巴瘤（B-NHL）患者中对ATN-031展开评估。PERFORM研究由MD安德森癌症中心牵头，其他三个美国临床研究中心共同参与开展。按照研究的贝叶斯最优区间（BOIN）设计，共有5例晚期癌症患者入组至第一剂量组。5例患者中均未观察到剂量限制毒性（DLT）。1例既往接受过7线治疗的患者已获得影像学确认的肿瘤体积缩小。德琪医药创始人、董事长兼首席执行官梅建明博士表示：“在美国开展针对首款治疗晚期癌症患者的抗CD24单抗的临床研究对于Antennova而言具有里程碑意义，我们非常感谢所有参与这项临床研究的患者和研究中心。临床评估和转化医学数据显示，研究已在这个既往接受过多线治疗的患者群体中观察到初步临床活性，这让我们对研究的前景充满信心。我们将继续与MD安德森癌症中心、旧金山加州大学、科罗拉多大学和耶鲁大学癌症中心的研究者们保持密切合作，并将在研究过程中定期公布阶段性进展，期待在国际学术会议上公布最新数据。”PERFORM研究是一项针对ATN-031用于治疗晚期实体瘤或B-NHL患者的首次人体、多中心、开放性I期剂量探索/剂量爬坡试验。该研究的主要目的为评估ATN-031单药的安全性和耐受性，并确定II期研究的使用剂量。该研究的次要目的为确定ATN-031的药理特性和免疫原性，并评估该药物的初步疗效。关于ATN-031ATN-031是一款可在抑制“别吃我”信号的同时激活“来吃我”信号并强化由巨噬细胞介导的肿瘤细胞吞噬的全球首创（first-in-class）人源化抗CD24单克隆抗体。肿瘤细胞通过过度表达让其免于被巨噬细胞发现和吞噬的“别吃我”细胞表面蛋白实现免疫逃逸。CD24是一个主要的 “别吃我” 信号，它通过抑制由巨噬细胞介导的肿瘤细胞吞噬，在肿瘤免疫逃逸中起着关键作用。与另一个“别吃我”靶点CD47相比，CD24具有更局限的健康组织分布和更高的肿瘤组织表达，在实体瘤中的表达尤为明显。此外，CD24并不在人红细胞上表达，这使得CD24靶向疗法具有更低的在靶脱瘤毒性以及更大的安全窗。作为一个新型固有免疫检查点，CD24通过与表达于肿瘤相关巨噬细胞（TAM）上的抑制受体Siglec-10（唾液酸结合性免疫球蛋白样凝集素10）的相互作用，实现肿瘤细胞的免疫逃逸。在2023年美国癌症研究协会年会（AACR 2023）和2022年癌症免疫治疗学会年会（SITC 2022）上公布的临床前数据显示，ATN-031可以纳摩尔级别亲和力与CD24特异性结合并阻断CD24与Siglec-10的互动。此外，ATN-031可诱导皮摩尔EC50水平的高效吞噬作用，并促进巨噬细胞分泌促炎细胞因子。关于Antennova德琪医药的美国全资子公司Antennova成立于美国特拉华州。作为一家已进入临床阶段的生物技术公司，Antennova致力于开发可改善肿瘤微环境、强化现有疗法疗效、逆转对于检查点抑制剂（CPI）耐药并可靶向作用于现有CPI药物不敏感的“冷肿瘤”的创新疗法。至今，Antennova已在推进抗CD24单克隆抗体药物ATN-031、CD73小分子抑制剂ATN-037、Claudin 18.2抗体偶联药物ATN-022和抗PD-L1/4-1BB双特异性抗体ATN-101这四款临床阶段资产的开发方面实现多项里程碑进展。此外，美国食品药品管理局（FDA）已授予ATN-101一项孤儿药资格认定，用于治疗胰腺癌；授予ATN-022一项孤儿药资格认定，用于治疗胰腺癌和胃癌。前瞻性陈述本文所作出的前瞻性陈述仅与本文作出该陈述当日的事件或资料有关。除法律规定外，于作出前瞻性陈述当日之后，无论是否出现新资料、未来事件或其他情况，我们并无责任更新或公开修改任何前瞻性陈述及预料之外的事件。请细阅本文，并理解我们的实际未来业绩或表现可能与预期有重大差异。本文内有关任何董事或本公司意向的陈述或提述乃于本文刊发日期作出。任何该等意向均可能因未来发展而出现变动。点击这里，更多了解德琪医药！

ATN-031 (also known as ATG-031), is the first anti-CD24 antibody to advance to the clinic in oncology in the United States The Phase I PERFORM trial, ongoing at four major U.S. cancer centers, is evaluating the safety and preliminary efficacy of ATN-031 in patients with advanced solid tumors or B-cell non-Hodgkin's lymphoma (B-NHL) DOYLESTOWN, Pa., March 20, 2024 /PRNewswire/ -- Antennova, a clinical-stage biotech company focused on oncology today announced completion of the first dosing cohort in the Phase I study for the anti-CD24 antibody, ATN-031 (also known as ATG-031). The dose escalation trial is evaluating ATN-031 in patients with advanced solid tumors or B-cell non-Hodgkin's lymphoma (B-NHL), (NCT06028373). The PERFORM trial is being conducted at four cancer centers in the U.S., led by The University of Texas MD Anderson Cancer Center. A total of five late stage cancer patients have been enrolled based on the Bayesian Optimal Interval (BOIN) design of the trial in the first dosing cohort. To date, no dose-limiting toxicities (DLTs) have been reported among the 5 patients. Tumor shrinkage based on CT scan was observed in one heavily pre-treated patient (7 prior lines of therapy). "Introducing the first anti-CD24 program for late stage cancer patients in the U.S. is a very important milestone for Antennova. We are especially grateful to the participation in the study by our patients and study centers, and encouraged to observe early clinical activity in this heavily pre-treated patient population based on clinical evaluation and translational data. We are working closely with study sites and investigators at MD Anderson, the University of California, San Francisco, the University of Colorado, and Yale University Cancer Center and look forward to providing periodic updates and presentations at major international medical conferences throughout the study." commented by Jay Mei, M.D., Ph. D., Founder and Chairman of the Board. The PERFORM trial is a first-in-human, multi-center, open-label, Phase I dose-finding/escalation study of ATN-031 in patients with advanced solid tumors or B-NHL. The study's primary objective is to evaluate the safety and tolerability of ATN-031 as a monotherapy, and determine the appropriate dose for Phase II studies. The secondary objective is to characterize the pharmacology, evaluate the immunogenicity, and assess the preliminary efficacy of ATN-031. About ATN-031 ATN-031 is a first-in-class humanized anti-CD24 monoclonal antibody which inhibits the "don't eat me" signal while stimulating the "eat me" signal, and enhances macrophage-mediated phagocytosis of cancer cells. Tumor cells evade the surveillance of the human immune system by over-expressing "don't eat me" surface proteins that signal macrophages to prevent the detection and phagocytosis of cancer cells. CD24 is a prominent "don't eat me" signal that plays a significant role in tumor immune evasion by suppressing macrophage-mediated phagocytosis. Compared to CD47, another "don't eat me" target, CD24, has a more markedly restricted distribution in normal tissues and higher expression in cancerous tissues, especially solid tumors. Importantly, CD24 is differentiated from CD47 because it is not expressed on human red blood cells, allowing for a wider therapeutic window and minimal on-target-off-tumor toxicity. CD24 acts as a novel innate immune checkpoint, orchestrating immune evasion through its interaction with the inhibitory receptor Siglec-10 (sialic-acid-binding Ig-like lectin 10), expressed on tumor-associated macrophages (TAMs). Preclinical data presented at the American Association for Cancer Research Annual Meeting in 2023 (AACR 2023) and the Society for Immunotherapy in Cancer Annual Meeting in 2022 (SITC 2022) demonstrated that ATN-031 can specifically bind to CD24 with nM affinity and block the interaction of CD24 and Siglec-10. Furthermore, ATN-31 induces efficient phagocytosis with a picomolar EC50 and stimulates the pro-inflammatory cytokines production by macrophages. About Antennova Antennova, a Delaware corporation and a subsidiary of Antengene (HKEX: 6996), is a clinical-stage biotech company specialized in developing innovative therapeutics that re-educate the tumor microenvironment, enhancing the effectiveness of standard therapies and reversing checkpoint inhibitor (CPI) resistance, as well as targeting "cold tumors" that are not responsive to the current CPI therapies. Antennova has achieved significant milestones which include advancing and developing 4 clinical stage programs: ATN-031: anti-CD24 monoclonal antibody; ATN-037: CD73 small molecule inhibitor; ATN-022: Claudin 18.2 ADC; and ATN-101: anti-PD-L1/4-1BB bispecific antibody. The U.S. Food and Drug Administration (FDA) awarded an Orphan Drug Designation to ATN-101, for pancreatic cancer; and to ATN-022, for gastric and pancreatic cancers. Forward-Looking Statements The forward-looking statements made in this document relate only to the events or information as of the date on which the statements are made in this document. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this document completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this document, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this document. Any of these intentions may alter in light of future development. Investor Relations Email: ir@antennova.com

▎药明康德内容团队编辑根据中国国家药监局药品审评中心（CDE）官网数据，本周有十余款1类新药获批临床，这些新药来自百奥泰、星盛新辉、靖因药业、默沙东、阿斯利康、强生等公司，涉及抗体药物、偶联药物、siRNA疗法、小分子靶向疗法等。本文将分享其中部分1类新药信息，仅供读者参阅（排名不分先后）。截图来源：CDE官网藤济生物：NM6606片作用机制：维甲酸X受体（RXRα）配体适应症：非酒精性脂肪性肝炎NM6606是藤济生物自主研发的一款RXRα口服药物。RXRα在肝脏组织的各种不同细胞中发挥着关键作用。NM6606选择性靶向修饰的RXRα，调控线粒体功能，进而有效的改善了脂肪变性，球样变性，炎症和纤维化等病理特征，综合药效好。该产品本次获批临床拟用于治疗非酒精脂肪性肝炎。上海莱士：SR604注射液作用机制：抑制人活化蛋白C抗凝血功能的单克隆抗体适应症：血友病及先天性凝血因子Ⅶ缺乏症患者出血发作的预防治疗SR604是上海莱士在研的一款特异性抑制人活化蛋白C抗凝血功能的单克隆抗体，人活化蛋白C具有抗血栓、抗炎和纤溶特性。该药本次获批临床拟用于血友病A/B及先天性凝血因子Ⅶ缺乏症患者出血发作的预防治疗。目前血友病常规预防治疗是每周2至3次静脉注射血源或重组凝血因子。SR604拟开展每4周一次的皮下注射预防治疗临床1期试验。该项目的部分临床前研究成果已在Blood上以封面文章的形式发表。百奥泰：注射用BAT7205作用机制：PD-L1/IL-15双功能抗体融合蛋白适应症：实体瘤BAT7205为百奥泰开发的一款PD-L1/IL-15双功能抗体融合蛋白。IL-15是一种多效细胞因子，对许多免疫功能的调节至关重要，并能促进PD-1抑制剂无响应的CD8+肿瘤浸润T细胞的活化增殖，有望显著提高PD-1/PD-L1类药物的临床疗效。BAT7205既可以阻断PD-1/PD-L1免疫抑制通路，又可以通过IL-15激活免疫细胞，从而达到解除免疫抑制和激活免疫抗肿瘤的协同效应。该产品本次获批临床拟开发用于治疗局部晚期或转移性实体瘤。图片来源：123RF默沙东（MSD）：注射用MK-1200作用机制：靶向Claudin18.2的抗体偶联药物（ADC）适应症：实体瘤MK-1200是默沙东在研的一款靶向Claudin18.2的ADC。Claudin18.2是正常组织紧密连接中一种重要的蛋白质，在包含胃癌在内的消化道癌症中高度表达，因此可能成为治疗胃癌等实体肿瘤的有效靶标。该产品本次获批临床拟用于治疗晚期实体瘤（含消化道肿瘤）。星盛新辉：XS-02胶囊作用机制：CHK1抑制剂适应症：实体瘤XS-02是星盛新辉在研的一款小分子CHK1抑制剂，且具有良好的口服生物利用度。CHK1在DNA损伤修复过程中发挥着重要的作用，在多种肿瘤中过度表达，其缺失可使肿瘤细胞对放疗或化疗敏感，并且与其它靶向DNA损伤修复系统的药物产生“合成致死”的效应。该产品本次获批临床拟开发用于治疗晚期实体瘤。靖因药业：SRSD107注射液作用机制：小干扰核酸（siRNA）疗法适应症：静脉血栓SRSD107是靖因药业在研的一款双链siRNA药物，属于新一代抗凝药物，正在澳大利亚开展1期临床试验。SRSD107可通过特异性肝靶向凝血因子XI（FXI）mRNA，抑制FXI的蛋白表达，阻断内源性凝血途径的激活，从而达到抗凝血/抗血栓的作用。该产品本次获批临床拟开发用于预防或治疗动静脉血栓。图片来源：123RF再生元（Regeneron）：Cemdisiran注射液作用机制：靶向C5补体的RNAi疗法药物适应症：阵发性夜间血红蛋白尿（PNH）Cemdisiran是再生元与Alnylam Pharmaceuticals联合开发的一种靶向C5补体的RNAi疗法药物。它在进入细胞后通过与靶标mRNA结合，从而使mRNA降解，避免功能性蛋白产生。抑制补体C5是具有显著临床症状的PNH患者的治疗标准。该产品本次获批临床拟与pozelimab联合用于治疗伴有活动性体征和溶血迹象的PNH。强生（Johnson&Johnson）：JNJ-80948543注射液作用机制：CD79bxCD20xCD3三特异性T细胞重定向抗体适应症：淋巴细胞恶性肿瘤JNJ-80948543是强生旗下强生创新制药（Johnson&Johnson Innovative Medicine）在研的一款新型CD79bxCD20xCD3三特异性T细胞重定向抗体。JNJ-80948543可与T细胞上的CD3抗原以及B细胞上的CD79b和CD20结合，从而导致恶性B细胞溶解。该产品本次获批临床拟开发用于治疗淋巴细胞恶性肿瘤。复融生物：FL115注射液作用机制：IL-15超级免疫激动剂适应症：实体瘤FL115是复融生物自主开发的一款IL-15超级免疫激动剂，此前已在美国进行1期临床试验。IL-15是一种多效性细胞因子，具有激活T细胞、B细胞和NK细胞，并可介导这些细胞的增殖和存活的功能。虽然与IL-2具有相似的激活功能，但IL-15并不会激活Treg细胞，理论上有着更小临床副作用，因此在肿瘤免疫治疗领域被赋予厚望。FL115本次获批临床针对的适应症为不可切除局部晚期或转移性实体瘤。图片来源：123RF阿斯利康（AstraZeneca）：AZD9829作用机制：靶向CD123的拓扑异构酶1抑制剂（TOP1i）-ADC适应症：恶性血液疾病AZD9829是阿斯利康在研的一款靶向CD123的TOP1i-ADC。CD123是一种细胞表面蛋白，在包括急性髓系白血病（AML）和骨髓增生异常综合征（MDS）在内的几种血液系统恶性肿瘤中过表达，在正常造血干细胞中表达受限。AZD9829的主要作用机制是将TOP1i载荷递送到表达CD123的癌细胞中，导致DNA损伤和细胞凋亡。该产品本次获批临床拟用于CD123阳性恶性血液疾病。康弘生物：KH801注射液作用机制：抗CD24人源化单克隆抗体适应症：晚期实体瘤KH801注射液是康弘生物自主研发的抗CD24人源化单克隆抗体。KH801能与肿瘤细胞上的CD24特异性结合，通过阻断CD24/Siglec-10“别吃我”信号，提高肿瘤相关巨噬细胞（TAM）对肿瘤细胞的吞噬作用。该产品本次获批临床拟开发用于晚期实体瘤。除了上述药物，还有一些其它药物也于本周在中国获批临床，限于篇幅，本文不再一一介绍。希望这些药物后续研究顺利进行，早日惠及广大病患。参考资料：[1] 中国国家药监局药品审评中心（CDE）官网.Retrieved Mar 9，2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c[2] 各公司官网及新闻稿本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。