Muc18

▎药明康德内容团队编辑中国国家药监局药品审评中心（CDE）官网公示，普众发现（Multitude Therapeutics）申报的1类新药注射用AMT-562获批临床，拟开发治疗晚期实体瘤。公开资料显示，这是一款靶向HER3的新型抗体偶联药物（ADC）。截图来源：CDE官网HER3是受体酪氨酸激酶EGFR家族的成员之一，其在实体瘤中广泛表达，与肿瘤生长扩散、耐药和不良预后相关。根据文献报道，AMT-562由一种新型抗HER3抗体Ab562和一种增强了亲水性的连接子MC-VA-PABC结合有效载荷exatecan（依喜替康）构成。其中，抗体部分Ab562具有降低潜在毒性、改善肿瘤渗透性的潜力，有效载荷exatecan具有比其衍生物deruxtecan（DXd）更高的细胞毒性效力。根据发表在Molecular Cancer Therapeutics上的一项研究，无论是单药治疗还是联合治疗，AMT-562在HER3低表达患者来源异种移植物/类器官模型（包括具有较大未满足临床需求的消化系统和肺肿瘤）中均显示出强效和持久的抗肿瘤反应。在食蟹猴中，AMT-562的药代动力学和安全性特征良好，无严重毒性的最高剂量为30mg/kg。研究表明AMT-562有可能成为一种具有更宽治疗窗口的HER3靶向ADC，可以克服耐药性。此外，在针对另一款靶向HER3的ADC产品不敏感的肿瘤中，AMT-562也产生了更高的应答百分比和更持久的缓解。ClinicalTrials官网信息显示，AMT-562正在澳大利亚进行一项针对晚期实体瘤的非随机、开放标签、多中心首次1期临床研究。此外，根据CDE官网信息，普众发现已有多款ADC产品获批临床用于治疗晚期实体瘤，除了本次获批临床的AMT-562，还有AMT-707（靶向CDH6）、AMT-253（靶向MUC18）和AMT-151（靶向FRα）等。参考资料：[1] 中国国家药监局药品审评中心（CDE）官网. Retrieved Feb 26, 2024,  from https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d[2] Weng W, Meng T, Pu J, et al. (2023) AMT-562, a Novel HER3-targeting Antibody-Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors. Mol Cancer Ther. https://pubmed.ncbi.nlm.nih.gov/37302522/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。

「  本文共：16条资讯，阅读时长约：3分钟 」今日头条康方PD-1单抗报鼻咽癌NDA。康方生物PD-1单抗派安普利单抗注射液(安尼可®)的新适应症上市申请获CDE受理，联合化疗一线治疗复发或转移鼻咽癌（NPC）。目前，该新药在国内已获批两项适应症：派安普利单抗联合化疗一线治疗局部晚期或转移性鳞状非小细胞肺癌，以及派安普利单抗治疗至少经过二线系统化疗的复发或难治性经典型霍奇金淋巴瘤。派安普利单抗三线治疗NPC的上市申请正接受CDE的监管审查。国内药讯1.绿叶引进肺癌新药澳门获批上市。绿叶制药宣布其引进新药“注射用芦比替定”获得澳门药监部门批准上市，用于治疗接受铂类药物化疗期间或期后出现疾病进展的转移性小细胞肺癌（SCLC）成人患者。这是一款RNA聚合酶II抑制剂，能够选择性地抑制多种肿瘤所依赖的致癌基因转录。值得一提的是，该产品目前正在接受CDE和香港药监部门的上市监管审查。2.士泽iPS衍生细胞疗法获ALS孤儿药资格。士泽生物开发的诱导多能干细胞（iPSC）衍生亚型神经前体细胞疗法获FDA授予孤儿药资格，拟用于治疗肌萎缩侧索硬化症（ALS，又称“渐冻症”）。这是该公司首个候选产品，旨在通过iPSC在体外再生健康的细胞进行替代性疗法，为神经系统疾病患者提供全新的治疗选择。目前，该公司已完成超2亿元A1轮融资及A2轮追加投资。3.科济GPRC5D靶向CAR-T获批临床。科济药业靶向GPRC5D的自体CAR-T细胞候选产品CT071获FDA批准，即将在美国开展用于治疗复发/难治多发性骨髓瘤(MM)或复发/难治原发性浆细胞白血病(PCL)的临床研究。CT071正在国内开展一项研究者发起的用于MM或PCL治疗的临床试验（IIT）。初步数据显示，CT071具有可接受的安全性和初步疗效。4.百济神州HPK1抑制剂国内获批临床。百济神州HPK1抑制剂BGB-26808获国家药监局临床试验默示许可，拟开发单药治疗晚期实体瘤。HPK1是T细胞受体（TCR）信号通路下游的一种激酶，被认为在激活T细胞的过程中起到关键作用。目前，该新药正在澳大利亚、新西兰开展一项Ⅰ期临床，评估单药或与替雷利珠单抗联用治疗晚期实体瘤的安全性、耐受性、药代动力学和初步抗肿瘤活性。5.普众发现MUC18靶向ADC获批临床。普众发现医药（上海）1类生物药“注射用AMT-253”获国家药监局临床默示许可，拟用于晚期实体瘤的治疗。AMT-253是一款靶向MUC18的ADC药物，旨在通过DNA损伤和细胞凋亡表现出MUC18特异性的细胞毒性和强大的旁观者杀伤效应。在临床前研究中，AMT-253在黑色素瘤、宫颈鳞癌、头颈鳞癌、食管鳞癌、肺鳞癌、小细胞肺癌、卵巢癌、肝癌等多种CDX或PDX模型中均显示出积极的抑肿效果。6.再鼎DLL3靶向ADC报IND。再鼎医药1类生物制品注射用ZL-1310（YL212）的临床申请获CDE受理。YL212是基于宜联生物自有的TMALIN®平台所开发的DLL3 ADC。DLL3是一种在小细胞肺癌 (SCLC) 和神经内分泌肿瘤中过度表达的Notch配体抑制剂。今年4月，再鼎医药与宜联生物达成战略合作和许可协议，获得YL212的全球开发及商业化独家权益。国际药讯1.吸入性mRNA疗法获批英国Ⅰ期临床。Ethris GmbH公司编码III型干扰素（IFN）的吸入性mRNA疗法获英国药品和保健品监管局（MHRA）批准，即将在健康受试者中开展Ⅰ期临床，评估用于治疗和预防呼吸道病毒感染的安全性与初步疗效。ETH47旨在诱导病毒进入部位的粘膜产生先天性免疫防御反应，并抑制病毒复制。ETH47有望广泛用于季节性和新出现的呼吸道病毒感染，包括由病毒引起的哮喘等慢性呼吸道疾病的恶化。2.FASN抑制剂联合治疗NASH临床前研究积极。Sagimet公司新型脂肪酸合成酶（FASN）抑制剂TVB-3664与semaglutide联合治疗非酒精性脂肪性肝炎（NASH）的临床前研究结果积极。在NASH小鼠模型中，与TVB-3664单药相比，semaglutide治疗组动物体重减轻更多，其肝损伤的生物标志物水平较低；与TVB-3664或semaglutide单药相比，TVB-3664+semaglutide治疗在改善肝纤维化生物标志物上效果更佳。研究成果日前公布于肥胖和NASH药物研发峰会上。3.FIC抗炎药治疗痴呆的III期临床失败。Biovie公司靶向结合细胞外信号调节激酶的“first-in-class”口服抗炎候选药物NE3107，在治疗潜在轻中度阿尔茨海默病（AD）的III期NM101研究未达到主要终点。在修正后的意向性治疗（MITT）人群中，与安慰剂相比，NE3107治疗改善了患者的CDR-SB评分、ADAS-Cog 12评分、MMSE评分、ADCS-ADL评分、ADCS-CGIC评分和ADCOMS评分等指标，但不具统计学意义。受此影响，当天该公司股价下跌65%。4.辉瑞终止小分子GLP-1R激动剂III期开发。辉瑞口服小分子GLP-1受体激动剂Danuglipron（PF-06882961）每日两次（BID）给药治疗肥胖（非2型糖尿病）患者的IIb期临床（NCT04707313）达到主要终点。与安慰剂相比，Danuglipron治疗组患者第32周和第26周时体重下降幅度分别为8%-13%，和5%-9.5%；研究中没有新的安全性信号，Danuglipron治疗与肝酶升高发生率增加无关。但辉瑞表示，不计划将Danuglipron（BID）推进至III期临床阶段。5.罗氏31亿美元收购Carmot Therapeutics。罗氏宣布收购Carmot公司，并获得该公司开发拟用于治疗糖尿病和非糖尿病患者肥胖症的临床期肠促胰岛素产品组合（GLP-1/GIP受体双激动剂CT-388；口服小分子GLP-1R激动剂CT-996；皮下注射双重GLP-1/GIP受体激动剂CT-868），以及多项临床前资产。根据协议，罗氏将支付27亿美元的预付款和高达4亿美元的里程碑后期付款。该项交易预计明年第一季度完成。6.强生医疗科技收购Laminar公司。强生医疗科技宣布完成对私营医疗器械公司Laminar的收购。Laminar专注于开发用于左心耳封堵(LAA closure) 以降低非瓣膜性房颤(AFib)患者卒中风险的创新研究装置。Laminar的创新研究装置旨在非药物替代慢性口服抗凝药物，有望为不能耐受长期血液稀释剂的AFib患者提供新的治疗选择。根据协议，Laminar公司获得4亿美元的预付款，以及临床和监管里程碑潜在后期付款。医药热点1.国家卫健委建立全国地贫防控协作网。为进一步加大地贫防控力度，近期国家卫健委印发通知，在10个省份遴选101家医疗机构组建全国协作网，旨在进一步发挥优质医疗资源辐射带动作用，推进落实防控、诊疗、协作、保障、病例登记和科学研究6项任务。协作网以南方医科大学南方医院、广西医科大学第一附属医院为国家级牵头单位，四川大学华西第二医院为全国信息管理依托单位。2.我国未发现新病毒或细菌导致的新发传染病。12月2日，国家卫健委举行新闻发布会，介绍冬季呼吸道疾病防治有关情况。国家卫健委新闻发言人、宣传司副司长米锋在会上表示，根据监测，目前流行的急性呼吸道疾病均由已知病原体引起，都有相应的成熟治疗手段，未发现新病毒或细菌导致的新发传染病。3.超声波技术实现无创“读脑”。美国加州理工学院研究人员最新发表于《自然·神经科学》上一项新研究显示，无需开颅植入电极的功能性超声（FUS）技术可以成为一种“在线”脑机接口（BMI）的基础，这种BMI可以读取大脑活动，通过用机器学习编程的解码器破译其含义，从而控制一台延时极短、可准确预测运动的计算机。神经元活动的变化会引起它们对氧气等代谢资源的利用发生变化。这些资源通过血液重新补充，这是功能性超声波的关键。评审动态  1. CDE新药受理情况（12月04日) 2. FDA新药获批情况（北美12月01日）股市资讯上个交易日 A 股医药板块 -0.89%涨幅前三     跌幅前三振东制药+14.73%  凯莱英-10.00%通化金马+10.03%  九洲药业-8.89%益盛药业+10.02%  神奇B股-7.77%【海思科]全资孙公司西藏海思科制药有限公司产品创新药 HSK36357胶囊收到国家药品监督管理局下发的《药物临床试验批准通知书》。【通化东宝]公司产品利拉鲁肽注射液收到国家药品监督管理局核准签发的《药品注册证书》。【成大生物]公司产品水痘减毒活疫苗进入I期临床试验。- The End -戳“阅读原文”，了解更多医药研发及股市资讯。

Results of this MD Anderson study were recently published in Cancers and indicate the relevance of enumeration of Circulating Tumor Cells (CTCs) with the minimally invasive liquid biopsy-based CELLSEARCH® system to gain significantly earlier information, compared to standard imaging techniques, on the evolution of advanced skin cancer. BOLOGNA, Italy and HUNTINGDON VALLEY, Pa., Oct. 3, 2023 /PRNewswire/ -- Menarini Silicon Biosystems, a pioneer of liquid biopsy technology, announced today the publication, in the peer-reviewed journal Cancers, of the results of a clinical study on the utility of CTCs to detect disease relapse substantially earlier than what is currently possible with routine surveillance imaging, in patients with stage III melanoma. This study included 325 patients who were mainly enrolled upon diagnosis of their stage III melanoma status. Blood was collected at different time points to detect CTCs and results were compared with follow-up imaging, to detect disease recurrence. The Menarini Silicon Biosystems CELLSEARCH system and Celltracks® Circulating Melanoma Cell Kit* were used to analyze and enumerate CTCs. According to Dr. Anthony Lucci, MD, Professor of Surgery in the Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center: "In this study we were able to detect CTCs in over 75% of patients… at a median of nine months prior to a radiological relapse". This data suggests that a blood biomarker is now able to help assess which patients with melanoma are most at risk of experiencing a relapse. "In the future these findings could lead to earlier intervention before a clinical metastasis is formed." Melanoma is an aggressive cancer with both a propensity to spread to distant sites and poor prognosis when diagnosed at a late stage. Its prevalence has been increasing worldwide[1]. Despite the introduction of new targeted treatments and immunotherapies in the last decade, the risk of relapse continues to represent a major concern. The need, to improve the selection of high-risk patients who can most benefit from new immunotherapies and earlier intervention, is therefore quite urgent. The overall study cohort was comprised of 174 males (53.5%) and 151 females (46.5%), with a mean age of 54.3 years (range, 20–89 years). CTCs could, in 75% of cases, be identified many months prior to positive radiologic detection of disease relapse. Importantly, CTCs were detected at a median greater than 9 months before the radiological detection of progression, meaning that there is significant lead time available for treatment intervention. Moreover, patients, who had zero CTCs in their blood, were significantly less likely to develop disease relapse compared to those who had a presence of at least 1 CTC (HR: 0.37, 95% CI: 0.26–0.53, p-value < 0.001). This study opens the door to both an earlier detection of disease progression, compared to the current standard of care imaging modalities including PET/CT, MRI, CT or ultrasound, and better timing for the utilization of imaging techniques that are more expensive and represent a higher burden to patients and to the healthcare system. The study results further underline the fact that the CELLSEARCH CTC liquid biopsy test could be used not only to guide earlier intervention but also to regularly monitor patient response to medication. "We are thrilled by the fact that our CELLSEARCH technology has proven its value to guide early clinical intervention in a disease with a high unmet medical need," said Fabio Piazzalunga, President and CEO of Menarini Silicon Biosystems. "This study is another example of why we are so committed to working with clinical research teams in different oncology settings where our minimally invasive and cost-effective CELLSEARCH platform keeps demonstrating an ability to address unmet healthcare needs". About stage III melanoma Stage III melanoma is a form of skin cancer in which cancer cells have spread to the lymph nodes that are located throughout the body. The primary cause of melanoma is exposure to UV radiation from the sun. People with fair skin are more susceptible to developing this disease because they have less melanin, the pigment that gives the skin its color and, also, acts as a UV shield. Because melanoma is the deadliest form of skin cancer with survival rates dropping significantly after metastasis, early diagnosis is key to improve prognosis. About CELLSEARCH CELLSEARCH is the first and only clinically validated blood test cleared by the U.S. Food & Drug Administration (FDA) for detecting and counting CTCs to aid physicians in managing patients with metastatic breast, prostate, and colorectal cancers when used in conjunction with other clinical methods of monitoring. The test is also approved by the China National Medical Products Administration (NMPA) for use in monitoring patients with Metastatic Breast Cancer. For more information on the full intended use and limitations of the CELLSEARCH system, please refer to the Instructions for Use at . The Celltracks Circulating Melanoma Cell Kit* immunomagnetically captures CD146-positive cells from whole blood. Circulating melanoma cells are further identified using fluorescently labeled antibodies anti-MEL, anti-CD34, and anti-CD45. Circulating melanoma cells are defined as CD146+, MEL+, CD45-, CD34-. The Celltracks Circulating Melanoma Cell Kit is available as a Research Use Only product in Europe and Asia Pacific. In the USA only, the Celltracks Circulating Melanoma Cell test is available to clinicians, through Menarini Silicon Biosystems' CLIA registered clinical laboratory as a laboratory developed test. About Menarini Silicon Biosystems Menarini Silicon Biosystems offers unique rare cell technologies and solutions that provide clinical researchers with access to unparalleled resolution in the study of cells and their molecular characterization. Menarini Silicon Biosystems, based in Bologna, Italy, and Huntingdon Valley, Pa., U.S., is a wholly owned subsidiary of the Menarini Group, a multinational pharmaceutical, biotechnology and diagnostics company headquartered in Florence, Italy, with more than 17,000 employees in 140 countries. *The Celltracks® Circulating Melanoma Cell Kit is for research use only and is not FDA cleared or approved for use to guide treatment decisions. [1] Wada-Ohno M, Ito T, Furue M. Adjuvant Therapy for Melanoma. Curr Treat Options Oncol. 2019 Jun 24;20(8):63. doi: 10.1007/s11864-019-0666-x. PMID: 31236710. CONTACT: Linda PAVY, [email protected] Logo - SOURCE Menarini Silicon Biosystems