Ribociclib Succinate

上个周末，A股休市，但产业没有休息。 两天里攒下来的事，放在一起看，恰好是一条线：中国创新药的数据，在全球舞台上越来越硬；而出海的路，两边都在同步收口。 一边，ESMO主席论坛上，中国药企的III期数据登台、甚至直接上了《新英格兰医学杂志》；另一边，美国财政部把"生物技术"正式写进对外投资限制清单，NewCo模式的枪口被抬起来了。数据往上走，规则往下压。 一、ESMO主席论坛：中国数据连点开花 第一份、和黄医药SAFFRON全球III期（赛沃替尼+奥希替尼对比铂类双药化疗）于10月25日在ESMO主席论坛公布（摘要#LBA6），并同步发表于《新英格兰医学杂志》: 1.人群：EGFR突变非小细胞肺癌、MET高表达或扩增、泰瑞沙治疗后进展的患者，338例。 2.PFS：中位7.6个月 vs 5.4个月，HR 0.55，进展或死亡风险降低45%（p<0.001）；12个月无进展率36% vs 10%。 3.OS：中位17.8个月 vs 12.9个月，延长近5个月，HR 0.68，死亡风险降低32%（p=0.010）；12个月生存率70% vs 53%。 4.安全：≥3级治疗相关不良事件64% vs 63%，试验组治疗暴露时长中位数是对照的两倍多（8.5 vs 3.5个月）。 这意味着什么？这是全球首个在这个场景里PFS和OS双阳性的III期——MET驱动耐药一直是被忽略的一块硬骨头，现在有了全口服的靶向方案证据，还同步上了顶刊。基于此，和黄与阿斯利康已向FDA提交上市申请，欧洲、日本也在推进。 值得留意的是不良反应：两组发生率几乎一样，但试验组暴露时间更长，这些数字需要长期随访继续盯。另外，这是vs化疗的头对头，别拿去和别的方案跨试验比数字。 第二份、康方生物HARMONi-GI1（依沃西联合化疗 vs 度伐利尤联合化疗，一线晚期胆道癌III期，682例）入选ESMO主席论坛LBA，完整数据随公司10月26日公告披露： 1.OS：中位14.9 vs 12.1个月，HR 0.75，死亡风险降低25%（P=0.0031）；12个月OS率59.7% vs 50.7%，18个月OS率44.0% vs 32.5%。 2.PFS：中位8.4 vs 5.8个月，HR 0.61，进展或死亡风险降低39%（P<0.0001）。 3.ORR：53.8% vs 32.5%，绝对差值21.3%。 这是依沃西首个消化道肿瘤III期阳性，意味着"双抗一哥"的叙事从肺癌开始向泛实体瘤铺开。国内已拟授予优先审评，海外伙伴Summit也启动了全球注册性II/III期EA2251。 要小心一个误区：对照组是度伐利尤联合化疗，这是当前国际标准之一，但不是"最强"组合；OS HR 0.75、P=0.0031算不错，但胆道癌预后差、随访时间还不长，18个月OS率已经出现分离，继续看长期数据才是正事。 二、FDA与全球临床：一份分量不轻的周末清单 1.首款儿童每周一次胰岛素获批。FDA于10月23日批准诺和诺德Awiqli（依柯胰岛素），用于10岁及以上2型糖尿病儿童，每周皮下注射一次。基础胰岛素注射频次从每年365次降到52次——对小孩和家长来说，这是实打实的生活质量改善。但这一变化针对的是基础胰岛素注射，并不意味不需要其他治疗和血糖监测。 2.直肠癌免疫治疗加速批准，但适用边界很窄。FDA加速批准多塔利单抗，用于II/III期、局部晚期、错配修复缺陷（dMMR）或微卫星高度不稳定（MSI-H）的直肠癌患者。基于一项II期研究，中位随访超两年，近四分之三患者无需放化疗或手术。注意两个词：加速批准、特定人群，不是对所有直肠癌都有效，后续仍需确证。 3.几个值得记的临床数据。礼来FRα靶向ADC（Sofe-M）I期：铂敏感卵巢癌中联合贝伐的确认客观缓解率79.3%、疾病控制率100%，III期选了3mg/kg——早期数据，别当结论。诺华NATALEE六年随访：瑞波西利在部分高危HR阳性/HER2阴性早期乳腺癌中死亡风险相对降低19.1%。默沙东与Moderna的个体化mRNA癌症疫苗intismeran：高危黑色素瘤术后III期，复发或死亡风险相对降低42%，入组超1100人；注意"每人一款定制疫苗"不等于"一人只打一针"，方案里共9剂、每三周一次。 三、AI制药：周末也有动静 Pathos AI完成2.37亿美元E轮融资。10月23日，Pathos AI宣布完成E轮融资，融资将用于扩展"agentic AI"药物开发平台并推进肿瘤管线。同一天它还宣布与百时美施贵宝（BMS）、Tempus AI达成合作。融资和合作挤在同一天，这家公司的节奏相当快。 英矽智能披露2026年上半年收入约1.06亿美元、同比增287%，经调整净利润超5100万美元，据称是上市以来首个盈利半年度，年内签约总额约73亿美元。"AI制药能不能赚钱"一直是个悬案，英矽这组数字至少提供了一个正面样本——但要小心，这是单一公司的口径，行业整体还在验证期。 四、政策线：出海通道在中美两侧同步收口 如果说ESMO是"产业证据"的暖场，那这条线就是"交易规则"的凉风。 10月16日，商务部、科技部就修订《中国禁止出口限制出口技术目录》征求意见，拟新增人工智能、生物医药等40项技术；10月22日，美国财政部发布拟议规则制定通知（NPRM），落实《综合对外投资国家安全法》（COINS Act），首次把"生物技术"正式纳入美国对外投资安全监管的敏感技术领域；10月23日，外交部回应称美方泛化国家安全概念、人为设限不符合任何一方利益。 美方新规把相关投资分成"禁止交易"和"须申报交易"两类，违反者不仅面临民事处罚，财政部还握有强制"清算退出"的权力。目前仍在征求意见期（截止2026年12月7日），尚未生效。 谁最受影响？NewCo、Co-Co这类"管线授权+股权投资+联合开发"深度绑定的出海模式首当其冲——中国药企既输出资产又持股，恰好踩在"药物授权"与"资本投资"的交叉地带。美国生物技术产业组织BIO当天就警告，监管过宽可能反而削弱美国自身竞争力。 有意思的地方在于：中国创新药BD正在证明自己的价值，而它的主要买家市场，正在给自己的钱包上锁。 五、两条线并看 把周末的事放到一起看：一边是SAFFRON上了NEJM、依沃西在胆道癌交出OS阳性，一边是美国财政部NPRM的征求意见期还在走。数据在变硬，规则在变紧。 中国创新药正在完成从"卖管线"到"提供全球标准疗法候选"的叙事升级，而这个升级恰好撞上地缘博弈的窗口期。 前两周我们反复说"情绪归情绪，数据归数据"。这个周末的版本是：数据归数据，规则归规则，两边都会继续走自己的路。

Evidence Post & News 26 Oct , 2026 Newswise — More than 30 years after the direct connection was established between the molecular machinery controlling cell division and cancer, a new paper traces the evolution of cyclin-dependent kinase research and outlines the next generation of CDK-targeted therapies. Published in Molecular Medicine, the article, “Cyclin/CDK inhibition in cancer therapy: from small molecules and macrocycles to advanced drug delivery systems,” provides a comprehensive analysis of established and emerging strategies for targeting cyclin-dependent kinases, or CDKs. CDKs are enzymes that regulate cell-cycle progression, but their biological influence extends well beyond cell division. They also participate in gene transcription, DNA-damage responses, DNA repair, metabolism, immune regulation and cellular senescence. Their dysregulation is a defining feature of many malignancies, making them important, but highly complex therapeutic targets. A scientific journey beginning in 1989 The new publication carries particular historical significance for its senior and co-corresponding author, Antonio Giordano, M.D., Ph.D., Founder and Director of the Sbarro Health Research Organization (SHRO) and Professor at Temple University. In 1989, Giordano was the first author of a landmark study published in Cell that provided one of the earliest direct experimental links between the cyclin/CDK machinery and oncogenic transformation. The researchers demonstrated that a cdc2-associated protein complex interacted with the adenovirus E1A oncoprotein in infected and transformed human cells. The p60 component of that complex was subsequently identified as cyclin A. Five years later, in 1994, Giordano’s laboratory at Temple University identified a previously unknown nuclear kinase, initially named PITALRE and now recognized as CDK9. The original study, published in the Proceedings of the National Academy of Sciences, showed that PITALRE was associated with kinase activity directed against the retinoblastoma protein. CDK9 has since emerged as a crucial regulator of transcription, DNA-damage responses and cancer-cell survival, as well as an increasingly important target for anticancer therapy. “This review closes a scientific circle that began for me in 1989, when we helped demonstrate that the machinery controlling normal cell division could be directly connected to oncogenic transformation, and continued in 1994 with the identification of PITALRE, the kinase now known as CDK9,” says Antonio Giordano, who also serves as Director of the Sbarro Institute for Cancer Research and Molecular Medicine at Temple. “Today, we understand that cyclin-dependent kinases are not merely molecular switches driving cell proliferation. They are central regulatory hubs connecting cell division with gene transcription, DNA repair, metabolism, immune responses and cellular senescence. CDK9, in particular, stands at the intersection of transcription, genome stability and cancer-cell survival,” Giordano concludes. Beyond conventional CDK inhibition Several small-molecule CDK inhibitors have already been approved for cancer treatment, particularly drugs targeting CDK4 and CDK6. However, their broader clinical application can be limited by acquired resistance, insufficient selectivity, poor solubility, suboptimal biodistribution and toxicity resulting from exposure of healthy tissues. The new review focuses particularly on CDK4/6 and CDK9, the most clinically advanced examples of CDK targeting, as well as the emerging, context-dependent role of CDK10 in cancer progression and resistance to endocrine therapy. The authors analyze multiple mechanisms through which tumors can escape CDK-targeted treatment. These include loss or inactivation of the retinoblastoma protein, activation of alternative cyclin-CDK pathways, increased CDK2 activity, adaptive oncogenic signaling, metabolic reprogramming and transcriptional recovery. The review identifies three major areas that could shape the future of CDK-targeted oncology: Macrocycles: These ring-shaped molecules can interact with large and complex protein surfaces that are often inaccessible to conventional small molecules. Macrocycles may therefore disrupt interactions between cyclins and CDKs with greater selectivity. Their development must still overcome challenges involving synthesis, membrane permeability and bioavailability. Targeted protein degradation: PROTACs and molecular glues are designed not simply to inhibit CDKs but to recruit the cell’s protein-disposal machinery and eliminate them. This approach may produce more durable biological effects and help overcome certain forms of resistance to conventional inhibitors. Advanced drug-delivery systems: Liposomes, polymeric nanoparticles, micelles, nanosponges, hydrogels and engineered extracellular vesicles may protect drugs from premature degradation, improve solubility and controlled release, and increase their accumulation within tumors while reducing systemic exposure. “The next step is not simply to produce more powerful inhibitors, but to achieve smarter inhibition,” adds Giordano. “We must select the appropriate CDK target, understand and anticipate resistance, and deliver the drug precisely where it is needed. The convergence of small molecules, macrocycles, targeted protein degradation and advanced drug-delivery systems gives us an important opportunity to attack tumor biology with greater precision while limiting damage to healthy tissues.” From laboratory innovation to patient benefit The authors emphasize that drug-delivery technologies should not be regarded as universal solutions. Each delivery platform must be selected according to the chemical properties of the individual inhibitor, the biology of the tumor and the specific therapeutic objective. The review examines delivery strategies under investigation for CDK inhibitors including abemaciclib, ribociclib, alvocidib, seliciclib and dinaciclib. Before these approaches can enter widespread clinical use, they will require rigorous comparisons with the corresponding free drugs, quantitative biodistribution studies, validation in appropriate in vivo models and careful assessment of efficacy and toxicity. Manufacturing scalability, reproducibility, storage stability and regulatory compliance will also be essential. “Translating this scientific potential into tangible benefits for patients will require rigorous validation, multidisciplinary collaboration and a continuous bridge between molecular discovery and clinical application,” Giordano says. “This is the path toward a new generation of more precise, effective and personalized cancer therapies.” The publication integrates current preclinical and clinical evidence, identifies unresolved challenges and proposes priorities for the future development of CDK-targeted treatments. International collaboration The review brings together researchers affiliated with the Sbarro Institute for Cancer Research and Molecular Medicine, at the Center for Biotechnology, College of Science and Technology, Temple University, the University of Siena, the University of Naples Federico II, the Scuola Superiore Meridionale, and the Istituto Nazionale Tumori IRCCS Fondazione G. Pascale. Simone Braccia and Giulio Mazzarotti contributed equally to the work. Luigi Alfano and Antonio Giordano are the corresponding authors. The study was supported by the Sbarro Health Research Organization and the Italian Ministry of Health, Ricerca Corrente 2025 Grant 3/29_25. Article information Title: Cyclin/CDK inhibition in cancer therapy: from small molecules and macrocycles to advanced drug delivery systems Journal: Molecular Medicine Publication date: October 3, 2026 Article type: Peer-reviewed, open-access review — Article in Press Authors: Simone Braccia, Giulio Mazzarotti, Maria Cuomo, Vrunda Satasiya, Canio Martinelli, Irene Miriello, Andrea Russo, Francesco Scippa, Stefania Galdiero, Luigi Alfano and Antonio Giordano DOI: https://doi.org/10.1186/s10020-026-01663-6 Article Credits Newswise.com An Italian Day in Philadelphia: Science, Medicine and a Transatlantic Bridge The Broken Brotherhood: The Science Behind the Loss of a Part of Oneself SHRO & NIAF One Health – Celebrating Italian-American Scientific Collaboration SHRO & NIAF “One Health – An Italian-American Scientific Forum: Shaping the Future of Medicine” The Program