Plinabulin

In DUBLIN-3 non-squamous EGFR WT NSCLC patients who progressed after anti-PD-(L)1, Plinabulin + docetaxel showed consistent and clinically meaningful improvements in OS, PFS, and ORR, reinforcing Plinabulin as a late-stage therapy with consistent survival benefit in anti-PD-(L)1-progressed NSCLC patients. Supported by anti-cancer efficacy and safety in significant reduction exposure-adjusted grade 3/4 adverse events in DUBLIN-3, BeyondSpring will conduct DUBLIN-4, a global, double-blind Phase 3 registrational trial. This study will evaluate Plinabulin + docetaxel vs. docetaxel in non-squamous EGFR wild-type NSCLC after progression on anti-PD-(L)1 and chemotherapy, and is intended to serve as the global confirmatory study. FLORHAM PARK, N.J., Dec. 11, 2025 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI), a clinical-stage biopharmaceutical company developing first-in-class immune-modulating cancer therapies, today announced new post-hoc analyses from its global Phase 3 DUBLIN-3 Study (Lancet Resp Med 12:775, 2024), showing that Plinabulin plus docetaxel provides clinically meaningful benefit for patients with EGFR wild-type (WT) non-squamous (NSQ) non-small cell lung cancer (NSCLC) who progressed after anti-PD-(L)1 immunotherapy. The findings were presented by Dr. Trevor Feinstein of Piedmont Cancer Center and acting chair of the Lung Disease Group for the OneOncology network at the 2025 IASLC/ASCO North America Conference on Lung Cancer (NACLC). More than 60% of NSCLC patients eventually develop resistance to anti-PD-(L)1 therapy, yet no new treatments have been approved in a decade. Nine late-stage trials, including ADC and anti-PD-(L)1combination regimens, have failed to show overall survival improvement over docetaxel. Plinabulin is a late-stage therapeutic candidate that has demonstrated consistent survival benefit in this rapidly growing population with major unmet medical need. In a mechanism-driven, post-hoc subset analysis of DUBLIN-3, non-squamous EGFR WT NSCLC patients who progressed after anti-PD-(L)1 therapy with at least 3 months of prior clinical benefit, Plinabulin + docetaxel (DP) combination showed clinically meaningful improvement compared to docetaxel alone (D). Median overall survival (OS): DP 15.8 months vs. D 11.7 months (HR=0.55), Median progression-free survival (PFS): DP 5.6 vs. D 3.8 months (HR=0.67),Objective response rate (ORR): 18.2% vs. 8.0%. These benefits reflect Plinabulin’s first-in-class dendritic-cell maturation mechanism, which helps to restore antigen presentation and T-cell function after acquired resistance to checkpoint inhibitors. BeyondSpring plans to initiate a global Phase 3 DUBLIN-4 trial following its End-of-Phase 2 meeting with the U.S. FDA. DUBLIN-4, together with DUBLIN-3, is expected to support a future NDA submission in non-squamous EGFR wild-type NSCLC following progression on anti-PD-(L)1 therapy. Post-hoc analysis of DUBLIN-3 intent-to-treat (ITT, N=559) EGFR WT NSCLC population showed additional clinically meaningful benefits for the Plinabulin + docetaxel combination compared to docetaxel. Meaningful improvement in metastasis-free survival: Metastasis-free survival improved to 15.34 months (DP) versus 7.7 months (D, HR=0.52, p=0.0012), consistent with Plinabulin’s DC maturation and durable anti-cancer benefit.Reduction in new brain metastasis: The incidence of new brain metastasis was reduced to 4.32% (DP) vs. 7.83% (D), consistent with Plinabulin’s brain-penetrant properties which demonstrated survival benefit in glioblastoma anal model as a monotherapy.Improved safety: Plinabulin significantly reduced docetaxel-induced grade 4 neutropenia (5.13% vs. 33.58%, p<0.0001). Plinabulin combination had significantly decreased exposure-adjusted grade 3/4 adverse events vs. docetaxel (p=0.0235), supporting prolonged treatment exposure and contributing to improved clinical outcomes. “Patients who relapse after anti-PD-(L)1 therapy represent one of the most significant unmet needs in NSCLC, with docetaxel as the only treatment option while multiple late-stage clinical trials have failed to improve upon it,” said Dr. Trevor Feinstein. Dr. Lan Huang, Co-Founder, Chairman, and CEO of BeyondSpring, said, “These new analyses suggest Plinabulin’s unique ability to potentially reinvigorate anti-tumor immune function and improve outcomes in patients who have developed resistance to checkpoint inhibitors. The post-hoc analysis data from DUBLIN-3 are consistent with our findings from the prospective 303 study in similar patients, as presented at the Society for Immunotherapy of Cancer (SITC) 2025 Annual Meeting. The observed reductions in brain metastasis and the substantial improvement in metastasis-free survival further highlight Plinabulin’s differentiated clinical profile. These findings provide strong momentum as we move forward with our global confirmatory Phase 3 DUBLIN-4 trial.” About PlinabulinPlinabulin is a first-in-class, brain-penetrating, dendritic -cell maturation small molecule. It has been used in over 700 cancer patients, with good tolerability and showed durable anti-cancer benefit across multiple clinical studies. As a reversible binder at a distinct tubulin pocket, plinabulin does not change tubulin dynamics or antagonize tubulin stabilizing agents, such as docetaxel, which contributes to its differentiated activity and tolerability compared to other tubulin binders. In addition, plinabulin significantly reduces chemotherapy-induced neutropenia and could thereby increase docetaxel tolerability. About DUBLIN-3 Study (103 Study)DUBLIN-3 (n=559, NCT02504489) was a multicenter, single-blinded (patient) and randomized, phase 3 trial in 58 medical centers (US, China, and Australia). Only patients with EGFR wild-type NSCLC who had progressed after first-line platinum-based therapy were enrolled. Patients were randomized (1:1) to receive docetaxel (75 mg/m2) on Day 1 and either plinabulin (30 mg/m2) or placebo on Days 1 and 8 in 21-day cycles until progression, unacceptable toxicity, withdrawal, or death. Treated patients were included in the safety analysis and ITT population in the primary efficacy analyses. The primary endpoint for the study was OS, and secondary endpoints were PFS, ORR, Duration of Response (DoR), Grade 4 neutropenia and Quality of Life. The study was published in Lancet Resp Med 12:775, 2024. About BeyondSpringBeyondSpring (NASDAQ: BYSI) is a clinical-stage biopharmaceutical company developing first-in-class therapies addressing high unmet medical needs. Its lead asset, Plinabulin, is in late-stage clinical development as an anti-cancer agent in NSCLC and other indications. Plinabulin’s novel mechanism as a dendritic cell maturation agent supports both anti-cancer activity and immune modulation, offering a unique approach to resensitizing tumors resistant to checkpoint inhibitors. Learn more at https://beyondspringpharma.com. Investor Contact: IR@beyondspringpharma.com Media Contact: PR@beyondspringpharma.com

药哥侃药 设为星标 在BD对外上，恒瑞已经日臻成熟，但是在BD进国产创新药上，恒瑞却老是踩坑。 继与万春医药合作普纳布林创新药踩坑失败后，又一个恒瑞BD合作的本土创新药企出状况。 2025年10月以来，有关恒瑞合作方璎黎药业的诉讼密集爆发。 天眼查信息显示，2025年10月以来，有关璎黎药业（被告身份）的开庭公告、买卖合同纠纷等诉讼信息大幅增加。与此同时，璎黎药业部分股权已遭冻结，公司在被未能给付康龙化成的相关费用，被列为失信被执行人同时被限制高消费。 与此同时，有多位患者及患者家属反映，林普利塞目前在部分医院以及药店已经无法采购，有关该药品的买赠活动也无法正常兑现。有关林普利塞停产、璎黎药业或将破产的消息已经在坊间广为流传。 璎黎药业由许祖盛于2011年在张江创立，是一家科技创新型生物医药企业并设有全功能覆盖的新药研发中心，公司专注于血液瘤、实体瘤及肾相关代谢疾病的小分子创新药物的研制及商业化。 许祖盛为中国科学院上海有机化学研究所博士、美国乔治亚大学和加拿大皇后大学博士后，曾任尚华医药集团副总裁，并且曾经就职于睿智化学，有超过15年新药研发和管理经验。 曾经，恒瑞医药与璎珞药业是紧密的合作方。 2021年2月8日，恒瑞医药公告拟以 2000 万美元认购璎黎药业 6.67% 的股份，同时获得璎黎药业在研的1类创新药 PI3Kδ 抑制剂林普利塞（研发代码 YY - 20394）在大中华地区的联合开发权益及排他性独家商业化权益。 当时璎黎药业虽处于亏损状态，但林普利塞作为高选择性 PI3Kδ 抑制剂，在抗肿瘤领域具备显著潜力，这也是恒瑞布局该领域的关键举措。 同年4月，双方合作进一步深化，林普利塞与恒瑞的 BTK 抑制剂 SHR - 1459 联合用药的临床方案获批，用于治疗复发 / 难治 B 细胞非霍奇金淋巴瘤，期望通过协同作用提升治疗效果。此后双方持续推进林普利塞的研发进程，凭借其良好的临床试验数据，该药物还获得了国家药监局的突破性疗法认定，为后续上市奠定基础。 202２年9月，林普利塞（商品名因他瑞 ®）正式获批上市，用于治疗既往接受过至少两种系统性治疗的复发或难治滤泡性淋巴瘤成人患者，这是璎黎药业首个商业化落地产品，恒瑞随即负责该药物的商业化推广。2023 年 1 月，该药物开出首批处方，正式进入临床应用阶段。 2023年9月，恒瑞披露林普利塞新适应症上市申请获国家药监局受理，用于治疗复发和 / 或难治性外周 T 细胞淋巴瘤，该适应症也让林普利塞成为全球同靶点药物中首个申报该病症的产品。不过到2024年6月，该新适应症上市申请未获批准，璎黎药业表示会加紧开展随机对照研究以准备重新提交申请。 2025年10月起，璎黎药业的经营状况急转直下，相关诉讼密集爆发，涵盖买卖合同纠纷等多个类型。与此同时，其部分股权被冻结，公司还被列为失信被执行人并被限制高消费，市场上关于璎黎药业或将破产的传言广为流传，为其与恒瑞医药的合作蒙上一层阴影。 不得不感叹，恒瑞医药在BD合作引进上踩坑频率有点高。  恒瑞医药此前就与万春医药因为一款名为普那布林的创新药合作陷入纠纷，核心是该药物中美上市接连失败后，恒瑞试图追回已支付的2亿元首付款，最终诉求被仲裁驳回。 具体而言，2021年，恒瑞医药正处于创新药研发转型阶段，开始重视外部合作模式。 同年8月26日，恒瑞与万春医药旗下的大连万春达成协议，恒瑞以2亿元首付款、1亿元入股大连万春，并承诺后续支付的里程碑款使得总交易额最高可达13亿元，以此获得创新药普那布林在大中华地区的联合开发及独家商业化权益。 当时普那布林兼具抗肿瘤和缓解化疗副作用的前景，被业界寄予厚望，甚至被预测可能成为年销售额超20亿美元的重磅药物。 合作后不久，问题便接踵而至。2021年9月，万春医药公布普那布林用于非小细胞肺癌的III期临床数据，随即被质疑入组患者不标准；更有机构指出其临床试验存在控制不足、未完整公布关键数据等问题。 当年12月1日，普那布林针对中性粒细胞减少症的上市申请被美国 FDA 拒绝，理由是单一三期注册临床无法充分证明治疗获益，要求补充第二项注册临床。 2023年3月10 日，该药物的国内新药上市申请也被国家药监局驳回，恒瑞见状明确后续不再有相关研发计划。 两次上市申请失败导致双方合作目标落空，而已支付2亿元首付款的恒瑞不愿接受损失。 2023年9月，恒瑞提出非诉财产保全申请，获北京市第二中级人民法院批准，大连万春名下2亿元财产被冻结。恒瑞的核心诉求是要求万春医药全额退还预付款，同时主张就未支付预付款按每日0.05% 计收违约罚款，并要求对方承担仲裁相关的所有费用和成本。 2024年1月10日，中国国际经济贸易仲裁委员会作出最终裁决，驳回了恒瑞的所有诉讼请求。 从行业惯例来看，这类创新药合作的 license in 协议中，通常会约定首付款不可退还，仲裁结果也契合这一行业常规。至此，这场曾引发行业广泛关注的医药合作纠纷正式落幕，恒瑞支付的2亿元首付款最终无法追回。 而如今，恒瑞医药的合作方璎黎药业也陷入纠纷中，后续情况如何？药哥也会持续跟踪和关注。 转载、合作、沟通请加药哥微信：Leon1985002 药哥侃药覆盖医药企业目录指引 上市医药公司： 恒瑞医药百济神州 药明生物药明康德  康方生物迈瑞医疗信达生物复星医药  复宏汉霖中国生物制药 免责声明：本微信文章仅根据公开信息进行总结、分析和/或推测，相关内容和观点仅供参考，不作为任何投资、立项以及就医、用药指南（若有）等各类用途的决策依据，药哥侃药及运营者不对任何个人或主体因使用本文内容而导致的任何过失、损失等后果承担责任。