TGFBR2

超15亿美元！吉利德强化多抗布局2024年3月6日，吉利德宣布与Merus达成合作，双方将共同开发多款靶向新型肿瘤相关抗原（TAA）的三特异性抗体。根据协议，Merus需将选定的两个项目推行至目标阶段，并可选择性开展第三个项目。吉利德将负责选定项目的额外研究、开发和商业化活动，即权益锁定。一旦行权，Merus将获得5600万美元的首付款以及2500万美元的股权投资，潜在交易金额超15亿美元。此次合作，是吉利德继Tentarix之后的又一次多抗布局。两笔交易主体均为多个临床前项目，Tentarix则将获得6600万美元的股权融资。有趣的是，Merus官网公示的管线中均为双抗产品，具体包括EGFR×LGR5、HER2×HER3、EGFR×c-MET、CD137×PD-L1、PD-1×CD3、LAG3×PD-1、TGFBr2×PD-1，7个不重复靶点组合。其中，CD137×PD-L1双抗MCLA-145权益于2022年1月被Incyte退回，但Incyte仍保留该项目未来商业化分红。2016年，Incyte与Merus就11个双特异性抗体达成合作。Incyte将支付1.2亿美元的预付款，并购买Merus8000万美元的普通股。此外，Merus还与礼来、先声药业、贝达药业等药企均有合作。先声药业获得三款双特异性抗体的中国权益，贝达药业获得MCLA-129（EGFR×c-MET）的中国权益。虽然Merus的研发管线多停留在1/2期，但由于MCLA-158、MCLA-128等核心资产临床进展顺利，二级市场近期表现良好。Merus股价（NASDAQ：MRUS）数据来源：雪球截止2024年3月7日，Merus的股价较去年同比增长152.7%，报48.72美元/股，市值为28.2亿美元。吉利德为何加注多抗？近年来，吉利德通过HCV治愈性药物索非布韦（Sofosbuvir）、HIV系列产品Biktarvy（必妥维）等重磅炸弹成功跻身pharma后大举转型，欲通过M&A进入肿瘤领域。170亿美元收购Kite，获得Yescarta、Tecartus等CAR-T细胞疗法；210美元收购Immunomedics获得Trop-2 ADC药物Trodelvy；49亿美元收购Forty Seven获得CD47单抗Magrolimab……重金之下，吉利德并未获得令自己满意的回报。2023年，吉利德抗肿瘤管线总销售额为29.32亿美元（同比增长8%）。其中，Yescarta、Tecartus两款产品的销售额分别为3.70亿美元和14.98亿美元，Trodelvy销售额为10.63亿美元。据不完全统计，自2023年以来，吉利德在肿瘤投资超85亿美元。而双抗在近两年进入了收获期，强生、罗氏、康方、艾伯维、辉瑞等玩家陆续携自家产品上市。在双抗可及性得以充分验证之际，吉利德直接入局多抗也较为合理。据不完全统计，截止日前，国内已有8款多抗进入临床阶段。普米斯、恩沐/博锐、嘉和生物、贝达药业、惠和生物各申报了一款三抗，百利药业申报了3款四抗。多抗奇迹：药时代的BD项目从美国《生物安全法案》（S.3558）正式通过“二读”，国内CXO如履薄冰；到本土药企掘金中东北非，东南亚，最终闯关FDA；本质均是为了寻求更大市场，延伸生态链，打造全球化及在地化，避免“内卷”，扩大自身产品份额。而BD在此过程中扮演着尤为重要的角色。过去2年，境内BD交易屡创新高。2022年，康方的双抗PD-1/VEGF双抗AK112，以50亿美元的交易总额问鼎当年创新药出海榜首；2023年，百利天恒的EGFRxHER3双抗ADC BL-B01D1，又以84亿美元的交易总额再次刷新了我国创新药出海记录！多抗创造奇迹，药时代也拥有优质诸多优质的多抗产品。药时代BD | 与康方50亿美元项目同靶点（PD-1xVEGF），进度全球第二！药时代BD-041项目 | 高结合力、高效能PD-1xPD-L1双抗I期项目药时代BD-043项目 | 安全、高效PD-1xTGF-β双抗肿瘤项目寻求合作如果您对该项目感兴趣，欢迎与我们联系！请注明项目代号：BP-20240229-L-EE-13我们将与您详细探讨。谢谢！联系人：Richard电话：17821449819微信：DrugTimes_BD邮箱：qi.yang@drugtimes.cn其他BD项目药时代BD-112项目 | 急性痛风、化疗引发的腹泻（CID）领域临床Ⅱ期重组人白介素-1受体拮抗剂寻求合作药时代BD-093项目 | 全球首创治疗r/r T-ALL/LBL及AML的自体CD7-CAR-T寻求合作药时代BD-092项目 | 高活性，低风险THRβ靶向NASH新药寻求合作药时代BD-038项目 | VEGF靶向单抗III期眼病蓝海项目药时代BD-041项目 | 高结合力、高效能PD-1xPD-L1双抗I期项目药时代BD-043项目 | 安全、高效PD-1xTGF-β双抗肿瘤项目寻求合作药时代BD-052项目 | FLT3靶向临床III期口服小分子寻求合作药时代BD-需求011 | 寻找肿瘤（实体瘤）或自免疫领域的创新药资产药时代BD-需求012 | 寻找宫腔镜和子宫内膜异位的相关资产药时代BD-需求014 | 寻找前列腺癌和儿童罕见病相关的创新药资产药时代BD-需求015 | 寻找消化道疾病相关的资产药时代BD-需求016 | 寻找呼吸、免疫、心脑血管、代谢、肿瘤等相关创新药资产药时代BD需求 | TOP10跨国药企寻找GLP-1、JAK、肥胖、心血管、类风湿等差异化后期产品药时代BD-需求 | 资金充足的biotech寻找眼科相关的优质创新药资产及公司药时代BD-需求 | 知名上市公司寻找BIC潜力ADC项目药时代BD | 药企Co-development需求对接药时代BD | 企业出售或兼并购需求对接了解更多好项目，请点击阅读原文

FN Media Group Presents USA News Group News Commentary VANCOUVER, BC, Feb. 7, 2024 /PRNewswire/ -- USA News Group - One of the more worrying storylines of 2023 was the rising incidence of early-onset pancreatic cancer. As well, the deadly disease showed pancreatic cancer rates rising faster among women, causing increased alarm amongst doctors. Thankfully, 2023 also gave a lot of hope in terms of new treatments for the market that could reach US$36 billion by 2036, such as a potential mRNA vaccine, and other developments from biotech companies to lead into 2024, like O ncolytics Biotech Inc. (NASDAQ:ONCY) (TSX:ONC), Incyte Corporation (NASDAQ:INCY), Tango Therapeutics, Inc. (NASDAQ:TNGX), RayzeBio, Inc. (NASDAQ:RYZB) and its buyer Bristol-Myers Squibb Company (NYSE:BMY). After closing out 2022 with another fast track designation, O ncolytics Biotech Inc. (NASDAQ:ONCY) (TSX:ONC) and its flagship asset pelareorep continues to make strides in the battle against pancreatic cancer. This recognition came after pelareorep plus atezolizumab with gemcitabine and nab-paclitaxel achieved an impressive objective response rate (ORR) of 69%. The results were enough to garner the support of the Pancreatic Cancer Action Network (PanCAN), who selected pelareorep to receive the US$5 million Therapeutic Accelerator Award. "2023 was an outstanding year for Oncolytics and the development of pelareorep as a potential cancer therapy," said Dr. Matt Coffey, President and CEO of Oncolytics. "To date, we have studied pelareorep in more than 1,100 patients, and it has been shown to be well-tolerated with mild side effects. We believe our cash balance and strong data, supported by our active business development program, position us well for 2024." Most recently, Oncolytics added accomplished biopharmaceutical executive Pat Andrews to its Board of Directors. She comes with a track record of success in corporate strategy, first-in-class and first-for-the-company new product commercializations and business development, and a resume that includes 17 years with Pfizer leading a $900-million portfolio at the time, and later serving as CEO of Sumitomo Pharma Oncology (SMP), and as the Chief Commercial Officer for Incyte Corporation (NASDAQ:INCY), where she led the company through the launch of Jakafi, Incyte's first commercial product. "I am honored to join the Oncolytics board at this exciting time for the organization as it advances pelareorep toward registrational studies," said Ms. Andrews. "Promising recent results from the BRACELET-1 and GOBLET studies suggest that pelareorep has the potential to make an important contribution to cancer care, and I look forward to working with my fellow board members in addition to Dr. Coffey and the Executive Team to execute Oncolytics' clinical and corporate development plans." Andrews's previous employer Incyte Corporation (NASDAQ:INCY) also continues to be active in the pancreatic cancer space itself. Like Oncolytics Biotech, Incyte is also involved with PanCAN in bringing potentially pioneering treatment options to patients. Now, the market is watching out for the potential future approval of Incyte's INCA-33890 for pancreatic cancer, which is currently in Phase I. INCA-33890 is a novel PD-1x TGFbR2 bispecific antibody designed to conditionally antagonize TGF signaling in primary immune cells co-expressing PD-1. Through a licensing deal with Swedish pharmaceutical company Medivir, Tango Therapeutics, Inc. (NASDAQ:TNGX) received FDA clearance on its Investigational New Drug application for TNG348 back in September 2023. Now, in early 2024, Tango has dosed the first patient for the drug in a phase 1/2 clinical study. Tango licensed TNG348 from Medivir back in 2020. TNG348 is a novel USP1 inhibitor for the treatment of BRCA1/2-mutant and other homologous recombination deficiency (HRD)+ cancers. HRD+ cancers, including BRCA1/2 mutations, represent 5% of pancreatic cancers. "The preclinical data generated by Tango for TNG348 is promising and dosing the first patient in a clinical study is encouraging for patients with HRD+ cancers," said Jens Lindberg, CEO of Medivir. "The efforts undertaken by Tango to develop TNG348 into a clinical-staged drug are impressive and we will continue to follow the clinical development of TNG348 with great anticipation." Closing out 2023, Bristol-Myers Squibb Company (NYSE:BMY) struck a deal for roughly $4.1 billion to buy RayzeBio, Inc. (NASDAQ:RYZB), with the highlight of the deal being RYZ101, which is being tested in late-stage studies for a rare type of pancreatic cancer. It's a drug that uses radioactive particles to kill tumor cells. "[The RayzeBio acquisition] further strengthens our growth opportunities in the back half of the decade and beyond," said Chris Boerner, newly-appointed CEO of BMY. "Acquiring RayzeBio's differentiated actinium-based radiopharmaceutical platform will establish Bristol Myers Squibb's presence in one of the most promising and fastest-growing new modalities for the treatment of patients with solid tumors – delivering radioactive payloads to cancer cells in a targeted manner," added Samit Hirawat, M.D., Executive Vice President, Chief Medical Officer, Drug Development of Bristol Myers Squibb. "In addition, RayzeBio's platform has the potential to be a significant IND engine, generating several therapeutic candidates in the future by leveraging our global drug development capabilities and infrastructure." Article Source: Article Source: USA News Group [email protected] DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. USA News Group is a wholly-owned subsidiary of Market IQ Media Group, Inc. ("MIQ"). MIQ has been paid a fee for Oncolytics Biotech Inc. advertising and digital media from the company directly. There may be 3rd parties who may have shares of Oncolytics Biotech Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ own shares of Oncolytics Biotech Inc. which were purchased in the open market, and reserve the right to buy and sell, and will buy and sell shares of Oncolytics Biotech Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved by Oncolytics Biotech Inc.; this is a paid advertisement, we currently own shares of Oncolytics Biotech Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. 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导读：肝内胆管癌 （ICC） 是原发性肝癌中第二常见的恶性肿瘤，总体发病率增加，预后不良。ICC的瘤间和瘤内异质性使得很难找到有效的药物治疗。因此，鉴定诱导ICC形成和进展的抑癌基因和癌基因至关重要。2014年1月11日，澳门大学邓初夏教授团队在期刊《Cell Death & Disease》上发表题为“The heterogeneity of signaling pathways and drug responses in intrahepatic cholangiocarcinoma with distinct genetic mutations”的研究论文，我们的研究研究数据提供了SPC小鼠的ICC模型。通过HTV将CRISPR文库引入小鼠肝脏，我们筛选了在4个月内加速ICC形成的基因。我们分析了不同基因突变调控的信号转导变化，并为ICC患者提供了潜在的药物治疗策略。https://www.nature.com/articles/s41419-023-06406-7研究背景 01 除肝细胞癌（HCC）外，胆管癌（CC）占所有原发性肝癌的10-15%，近年来其总体发病率和死亡率有所上升。CC 是一种胆道上皮肿瘤，根据其解剖部位分为三种亚型：肝内 CC （ICC）、肺门周围 CC （PCC） 或远端 CC（DCC）。ICC 位于肝内二级胆管的外围，而 PCC 和 DCC 都位于肝外。混合型HCC-ICC肿瘤具有HCC和ICC的特征，表现为侵袭性肿瘤生长和预后不良。ICC是恶性肿瘤，大多数患者在晚期被诊断出来。ICC在基因组和表观遗传学水平上的瘤间异质性使得很难找到有效的治疗方法。确定ICC形成和进展的复杂机制对于开发新的治疗策略至关重要。许多研究使用综合分析工具揭示了 ICC 的遗传和表观遗传变化。关键调节因子已被证明在 CC 中发生突变，并且与不同的信号通路有关。然而，在基因组改变的患者中，大多数鉴定出的基因具有低频率（<5%），这表明其中许多可能是 ICC 形成和进展过程中的突变而不是驱动突变。然而，在对 200 个人类 CC 标本的基因组分析中，大多数 （61.5%） 没有显示任何已知的突变，这表明许多癌症驱动突变仍未被发现。研究设计 02 为了确定加速ICC形成的其他驱动因素，我们之前在SPC小鼠中进行了CRISPR / Cas9介导的靶向20,611个基因的全基因组筛选，并将Cul3鉴定为肿瘤抑制因子，其破坏通过诱导肝脏炎症来加速ICC的形成。除了 Cul3 之外，我们的分析还检测到许多其他基因的 sgRNA，这些基因以高频率出现与 ICC 形成相关。在这项研究中，我们进一步分析了我们的顶级候选基因，发现 Trp53、Fbxw7、Inppl1 或 Tgfbr2 的缺陷可以显著增强 SPC 小鼠的 ICC 形成，并且这些基因与几种不同的信号通路相关。我们还对与这些突变相关的ICC衍生类器官进行了高通量药物筛选，为其治疗提供了潜在的治疗策略。研究结果 03 我们的研究确定了在具有不同基因突变的ICC肿瘤中调节的不同信号通路。先前对临床样本进行基因组分析的研究确定了ICC的炎症和增殖类别。结果表明，Trp53、Fbxw7、Inppl1和Tgfbr2突变增强了ICC细胞增殖。Cul3突变似乎会诱导免疫环境变化，从而促进肿瘤形成。增殖类通常显示经典致癌通路的富集，包括 RTK、VEGF、PDGF、RAS-MAPK、PI3K-AKT-mTOR 和 WNT-β-catenin 信号通路。我们的研究确定 FGFR 和 VEGF 通路上调。对于下游通路，由于我们的小鼠模型包含Pten突变背景，进一步的基因突变增强了PI3K信号通路，这可能是由于Fgfr、Vegfr或Igfr的信号转导升高。这些结果表明，PI3K是ICC中激活的主要信号通路。炎症类表现出增强的免疫反应相关通路。在 Fbxw7 突变肿瘤中，许多细胞因子和趋化因子上调，关键的细胞因子转导 Stat 家族也过表达。此外，Fbxw7突变肿瘤对免疫检查点抑制剂反应良好，表明Fbxw7缺陷可能诱导严重的免疫反应，从而加速肿瘤的形成和生长。已鉴定的基因突变在体外和体内促进癌症进展综上所述，使用SPC小鼠模型，结果验证了Trp53、Fbxw7、Inppl1、Tgfbr2和Cul3是ICC的抑癌基因。然而，这些基因启动ICC形成并诱导免疫微环境变化的详细机制需要进一步阐明。在这里，我们分析了受这些基因突变调控的多种信号通路，并研究了多种药物反应，为ICC肿瘤的新治疗策略提供了建议。参考资料：https://www.nature.com/articles/s41419-023-06406-7小编收集了254份参会药企在2024年JPM上的报告材料，以供业内参考，向【生物制品圈】公众号消息对话框内发送「2024JPM」即可获取下载2021-2024年四年JPM学习资料。资源清单识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。