Plinabulin

如果你潜入深邃的海洋，会看到一个与陆地截然不同的世界。这里压力巨大、光线幽暗、温度极低，却孕育着比陆地上更古老、更多样的生命。为了在充满病原体和激烈生存竞争的极端环境中活下去，海洋生物——从微小的藻类到庞大的鲸鱼，从柔软的海绵到剧毒的锥形蜗牛——在漫长的进化中，锻造出了一套独一无二的化学防御体系。 在这个武器库里，最引人注目的并非庞大的蛋白质，而是一类被称为“生物活性肽”的微观分子。为什么将它们称为“微观猎手”？因为它们就像一群经过亿万年进化的、极度精准的纳米级刺客或猎手：在海洋生物体内，它们主动出击，追踪并消灭入侵的病菌；而在现代医学的视野中，它们被人类发掘出来，转而去“猎杀”引发人类疾病的炎症因子、耐药细菌、癌细胞以及异常升高的血糖和血压。它们个头极小（通常由2到20个氨基酸残基组成），却拥有极高的靶向精准度和致命的杀伤力。 从20世纪70年代科学家从芋螺毒液中分离出“芋螺毒素”开始，海洋多肽就向人类展示了其巨大的药用潜力。今天，这些来自深海的“分子猎手”，正按照一条严密的科学逻辑，一步步重塑现代医学的版图。 第一道关卡：如何在混沌中“捕获”并“驯化”猎手？ 要利用这些猎手，科学家面临的第一道挑战是如何从复杂的海洋生物体中将它们“捕获”出来。这犹如在浩瀚的沙海中淘金，传统方法往往显得粗暴。 早期的“溶剂提取”和“化学水解”就像是用大网捞鱼或用大锤砸核桃，虽然能破坏组织释放出肽段，但容易破坏猎手的“武器”（有效结构），甚至产生有害残留。随后，更精准的“生物剪刀”登场了。“酶解法”利用蛋白酶按照特定位点精确切割，例如用碱性蛋白酶处理江蓠藻，能精准释放出三种新型的抗氧化“猎手”。更巧妙的是“借力打力”的“微生物发酵法”，利用微生物分泌的复杂酶系，不仅能低成本（降低50%）地将渔业废弃的鱼皮、鱼骨转化为高价值活性肽，还能赋予产物独特的风味。 然而，最贴近生理现实的制备方式是“胃肠道模拟”。科学家在试管里模拟人体的消化过程，用胃蛋白酶、胰蛋白酶等处理金枪鱼心、海参等，直接“预测”并捕获那些在我们吃下海鲜后、在肠道内产生的活性猎手，比如从金枪鱼心中得到了11种抗氧化肽。 捕获粗品后，还需要进行严密的“分拣与筛选”。这像是一个精密的流水线：先通过“膜分离技术”，根据分子大小用纳米级的筛网过滤；再利用“色谱技术”，根据分子的亲水性、电荷等细微性格差异，在柱子中将它们一一分离；最后借助“毛细管电泳”，在电场中快速区分那些带电荷的微量猎手。正是这些技术的组合拳，让我们能够从海洋的混沌中，一步步接近那些价值连城的活性分子。 Figure 1. Advanced production technologies for marine peptides.  六大“超能力”：微观猎手的精准打击战术 经过层层筛选纯化出的海洋多肽，展现出了令人惊叹的、多维度的“狩猎”技巧。它们不仅是全能卫士，更是各自领域的狙击手。 1. 炎息狙击手（抗炎）： 慢性炎症是许多疾病的温床，传统药物往往“敌我不分”。而海洋多肽能精准调控炎症信号通路，平息“细胞因子风暴”。比如来自南极磷虾的猎手，能激活Nrf2通路，精准抑制肝脏中的炎症因子，保护小鼠免受酒精性肝损伤。 2. 细菌穿透者（抗菌）： 面对日益严重的耐药菌危机，海洋抗菌肽（AMPs）提供了新希望。它们往往带正电，能像磁铁一样吸附到带负电的细菌表面，然后物理性地穿透细胞膜，形成孔洞导致细菌爆裂。来自南极冰鱼和珍珠贝的猎手，不仅能直接破坏细菌膜，还能摧毁细菌的“堡垒”——生物膜，甚至能调节人体免疫系统增强吞噬作用。 3. 自由基清道夫（抗氧化）： 过量的活性氧自由基是导致衰老和疾病的元凶。海洋抗氧化猎手能通过提供电子中和自由基，或者像螃蟹钳子一样“螯合”金属离子（如铁离子）来切断自由基的产生源头。来自鲟鱼软骨的肽能精准保护细胞免受氧化损伤。 4. 癌细胞终结者（抗癌）： 与传统化疗“杀敌一千自损八百”的无差别轰炸不同，海洋抗癌猎手具有“智能靶向”能力。它们能识别癌细胞表面的特异性标志，直接诱导其凋亡（程序性死亡），或者抑制其转移。例如从绿藻中发现的猎手MP06，能精准抑制非小细胞肺癌细胞的迁移，而对正常细胞毒性极低。 5. 血管减压阀（降压）： 高血压的元凶之一是血管紧张素转化酶（ACE）。海洋多肽能像塞子一样精准堵住ACE的活性位点，阻止血管收缩。从鲭鱼、黄鳍东方鲀等多种海产中发现的猎手，都能在体内显著且平稳地降低血压。 6. 血糖调节器（降糖）： 海洋猎手能精准狙击导致糖尿病的关键酶，如DPP-IV和α-淀粉酶。从罗非鱼皮提取的肽能改善糖尿病肾病的线粒体功能障碍；从鲳鱼中鉴定的猎手则能像钥匙一样开启胰岛素的分泌通道。 Figure 2. Biological activities of marine-derived peptides.  数字“炼丹术”：AI如何辅助猎手进化？ 传统的“大海捞针”式研究效率低下。如今，生物信息学技术如同数字时代的“炼丹术”，正在彻底改变猎手的发现与进化方式。 首先是“虚拟猎捕”（虚拟酶解）。利用计算机程序模拟各种酶在海洋蛋白数据库上的切割，瞬间生成成千上万种理论上的肽段序列。接着是“透视眼”（结构预测）。借助AlphaFold等革命性的AI工具，无需复杂的实验，就能高精度预测这些猎手在三维空间中的折叠形态和武器构造。 最神奇的是“战术预演”（生物活性预测）。通过建立数学模型（QSAR）或分析氨基酸偏好，计算机可以预测某个序列是否具有杀菌或降压能力。通过“分子对接”技术，科学家甚至能在屏幕上看到预测出的肽猎手如何与人体内的靶标蛋白（如ACE酶）像“钥匙和锁”一样完美契合。例如，研究人员通过虚拟筛选深海动物蛋白，成功预测并合成了两种新型抗凝血猎手。这套流程让人类从“盲目实验”转变为“理性设计”，在成千上万的候选者中，快速锁定最致命、最精准的“王牌猎手”。 Figure 3. Bioinformatics approaches for marine bioactive peptides research.  从深海到临床：驯服猎手的挑战与希望 尽管战术华丽，但将这些野性的微观猎手真正带入临床，仍面临严峻的“驯化”挑战。 首先是安全性隐患。海洋环境污染（重金属、微塑料）可能通过食物链富集在原料中。更棘手的是，某些猎手天生带有“毒性反噬”。例如某些海葵肽虽然能镇痛，但过度使用会导致免疫抑制；某些蓝细菌肽会严重损害肝脏。 其次是药代动力学瓶颈。多肽分子在体内极易被酶降解，导致“半衰期”极短（有的仅2-3小时）；它们口服生物利用度低，很难穿透肠壁或血脑屏障。这导致许多临床试验受挫，比如一种名为plinabulin的海洋环肽，就因半衰期过短而在非小细胞肺癌III期试验中失败。 然而，希望同样存在。科学家们正在用化学“魔法”改造这些猎手：通过“环化”或替换特殊氨基酸来增强其抗酶解的“铠甲”；通过“PEG化”为其披上隐身衣以延长在血液中的存活时间；通过连接“细胞穿膜肽”赋予其穿越血脑屏障的技能。同时，人工智能正被用于更精准地预测多肽的毒性和体内代谢行为，从源头筛选出更温顺、更持久的候选药物。智能纳米递送系统，则有望将多肽猎手精准空投到肿瘤等病灶，避免误伤平民细胞。 结语 海洋，覆盖地球71%的表面，却蕴藏着超过90%未被探索的生物多样性。海洋多肽，正是这片未知疆域送给人类的珍贵礼物。 扫码阅读原文 Citation: Cheng Xiangyu, Tang Ziqi, Li Zhongqi, Hu Shuaijie, Qin Kehan, Zhao Yindi, Hao Baoming, Hu Qinghua. Marine-derived products as pharmaceutical treasure troves: a focus on recent research techniques and potential bioactive activities of marine peptides[J]. Chinese Journal of Natural Medicines, 2026, 24(5): 543-558. DOI: 10.1016/S1875-5364(26)61178-8 原文链接：https://www.cjnmcpu.com/article/doi/10.1016/S1875-5364(26)61178-8 10 作者简介 胡庆华 胡庆华，教授，博士生导师，现任中国药科大学生命科学与技术学院院长。国家级高层次青年人才项目入选者，十四五国家重点研发计划首席青年科学家，江苏省“青蓝工程”中青年学术带头人，中国药理学会抗炎免疫药理专业委员会常务委员。 2002-2006年在南京大学匡亚明学院学习获学士学位，2006-2011年在南京大学硕博连读并获博士学位，研究方向为疾病治疗原创靶标发现和新药研发，先后主持国家重点研发计划、国家自然科学基金项目、江苏省自然科学基金项目等纵向项目和多项企事业横向合作课题。以第一作者或通讯作者在Eur Heart J、Nature Commun、Acta Pharm Sin B、J Adv Res、J Med Chem等期刊发表论文60余篇；作为第一发明人申请发明专利12项，授权9项，完成专利转化2项，其中1项抗痛风新药专利以2000万转化；CJNM青年编委、《药理学》编委。获国家级教学成果奖二等奖1项，江苏省教学成果奖二等奖1项，获第十三届全国大学生创新创业年会优秀指导教师。 往期推荐 【CJNM优秀论文】中国中医科学院梁爱华|探秘“莪术”精华：莪术二酮——一味古老中药的现代科学解读 【CJNM优秀论文】中国药科大学郝海平、郑啸|解密“记忆守护者”石杉碱甲的脑内之旅 【CJNM优秀论文】中国药科大学黄庆、吴建新|香附根茎提取物在体内外促进毛发生长并调节毛发周期 【CJNM封面论文】中国药科大学孔令义、王凯波|TMPRSS2基因启动子区G-四链体结构解析及其与小分子黄连素的复合物研究 【CJNM优秀论文科普解读】天津中医药大学徐强|当心脏遭遇“电量危机”：中医药如何通过修复线粒体拯救心衰？ 【CJNM优秀论文】上海中医药大学田建辉|中药单体组合TSZAF mc抑制肺癌转移的机制研究 【CJNM优秀论文】中国药科大学张尊建、黄寅|黄芪甲苷与毛蕊异黄酮组合治疗阿霉素诱导的心肌病 【CJNM优秀论文】中科院微生物研究所刘玲|基于分子网络技术从青霉属真菌中分离出蒽酮-环戊烯酮杂二聚体 CJNM是由中国药科大学主办的学术期刊，主要刊载天然药物相关研究，包括药理学、天然药物化学、天然产物生物合成、药物分析与代谢、药物靶点研究等。科睿唯安JCR2024年影响因子4.9，位于补充与替代医学一区（6/45）,药学一区（48/352）。2019年入选中国科技期刊卓越行动计划一期梯队期刊，2024入选中国科技期刊卓越行动计划二期英文梯队期刊，2025年入选江苏科技期刊卓越行动计划领军期刊。 期刊官网：https://www.cjnmcpu.com/ 期刊邮箱：cpucjnm@163.com 期刊电话：025-83271565 欢迎点击关注，欢迎转载，留言开白。 点击下方  “阅读全文” 查看文章全文

AACR 2026 Data Positions Plinabulin as a Potential Backbone Agent to Combine with Antibody-Drug Conjugate (ADC)-Based Therapies to Improve Anti-Cancer Efficacy and Tolerability SEED Advances First Molecular Glue Degrader into Clinical Development with Biomarker-Driven Strategy FLORHAM PARK, N.J., May 13, 2026 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI) (“BeyondSpring” or the “Company”), a clinical-stage company developing transformative therapies for the treatment of cancer and other diseases, today announced its financial results for the quarter ended March 31, 2026, and provided a corporate update highlighting significant scientific and clinical advancements across its pipeline. “Plinabulin continues to demonstrate the ability to enhance both efficacy and tolerability in ADC-based regimens, supporting its positioning as a potential backbone agent across a rapidly evolving treatment landscape,” said Dr. Lan Huang, Co-Founder, Chair, and Chief Executive Officer of BeyondSpring. “Data presented at AACR 2026 further highlights the expanding value of our pipeline and reinforces our strategy of advancing highly differentiated therapies with the potential to address significant unmet medical needs. We believe Plinabulin has the potential to become a foundational combination agent that unlocks the full clinical and commercial value of ADC therapies.” Dr. Huang continued, “At SEED, the advancement of ST-01156, a novel RBM39 molecular glue degrader, into clinical development in oncology indications, coupled with a biomarker-driven approach, underscores the strength and scalability of our RITE3™ platform. These milestones reflect disciplined execution across our portfolio and position us to unlock meaningful long-term value through multiple clinical and strategic partnership opportunities.” Recent Clinical Highlights Plinabulin: Expanding Role as a Potentially Foundational Combination Therapy AACR 2026 data demonstrated that Plinabulin significantly enhances both efficacy and tolerability of topoisomerase inhibitor–based ADC regimens, with or without immune checkpoint inhibitors Preclinical findings showed: Improved complete response rate and survival outcomes Improved tolerability Enhanced CD8+ T cell / Treg ratio - shifting the tumor immune environment from suppression to attack These preclinical results suggest Plinabulin’s potential to address key limitations of current ADC therapies, including limited durability and dose-limiting safety concerns, and support Plinabulin’s positioning as a potential backbone agent across a broad range of ADC combination regimens SEED Therapeutics: Advancing precision oncology through molecular glue degraders ST-01156 (RBM39 molecular glue degrader) advanced into Phase 1 clinical development, with the first dose cohort completed AACR 2026 data demonstrated: Complete tumor eradication in a neuroblastoma in vivo model Identification of MYC overexpression and CDKN2A/B deletion as potential predictive biomarkers This program represents a biomarker-driven precision oncology approach and highlights the productivity of SEED’s proprietary RITE3™ platform for targeted protein degradation First Quarter Financial Results 1 Continuing operations: R&D expenses were $1.1 million for the three months ended March 31, 2026 compared to $0.9 million for the three months ended March 31, 2025. The $0.2 million increase was primarily driven by increased drug manufacturing activities to prepare for potential future study initiation, partially offset by lower regulatory filing advisory and personnel expenses G&A expenses were $1.1 million for the three months ended March 31, 2026 compared to $1.7 million for the three months ended March 31, 2025. The $0.6 million decrease was primarily driven by lower personnel and legal advisory expenses Net loss was $2.4 million for the three months ended March 31, 2026 compared to $2.6 million for the three months ended March 31, 2025 Cash, cash equivalents, and short-term investments were $7.9 million as of March 31, 2026 Discontinued operations: Net loss was $4.3 million for the three months ended March 31, 2026, compared to net income of $3.8 million for the three months ended March 31, 2025 Current assets were $5.3 million as of March 31, 2026 Note 1. As a result of BeyondSpring entering into definitive agreements to sell a portion of its Series A-1 Preferred Shares of SEED, SEED’s operations met the criteria as discontinued operations under ASC 205-20 for financial reporting purposes. About BeyondSpring BeyondSpring (NASDAQ: BYSI) is a clinical-stage biopharmaceutical company developing first-in-class therapies for cancers with high unmet need. Its lead asset, Plinabulin, has been studied in over 700 cancer patients and is in late-stage development across multiple cancer indications, with results published in The Lancet Respiratory Medicine. Learn more at beyondspringpharma.com. About SEED Therapeutics SEED Therapeutics is a clinical-stage biotechnology company pioneering targeted protein degradation. Its proprietary RITE3™ platform is advancing novel molecular glue degraders across oncology, neurodegeneration, and immunology. SEED collaborates with Eli Lilly and Company and Eisai Co., Ltd., and is advancing its RBM39 degrader into clinical development. Learn more at seedtherapeutics.com . Investor Contact: IR@beyondspringpharma.com Media Contact: PR@beyondspringpharma.com Cautionary Note Regarding Forward-Looking Statements This press release includes forward-looking statements that are not historical facts. Words such as “will,” “expect,” “anticipate,” “plan,” “believe,” “design,” “may,” “future,” “estimate,” “predict,” “objective,” “goal,” or variations thereof and similar expressions are intended to identify such forward-looking statements. Forward-looking statements are based on BeyondSpring’s current knowledge, beliefs, and expectations regarding possible future events and are subject to risks, uncertainties, and assumptions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of a number of factors, including, but not limited to, difficulties raising the anticipated amount needed to finance the Company’s future operations on terms acceptable to the Company, if at all; unexpected results from preclinical studies or clinical trials; the risk that preclinical results may not be predictive of clinical results; delays in, or failure to obtain, regulatory approvals; results that do not meet the Company’s expectations regarding the safety, efficacy, clinical utility, or regulatory pathway of the Company’s product candidates; increased competition in the market; the Company’s ability to meet Nasdaq’s continued listing requirements; and other risks described in BeyondSpring’s most recent Form 10-K and subsequent filings with the U.S. Securities and Exchange Commission. All forward-looking statements made herein speak only as of the date of this release, and BeyondSpring undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law. Financial Tables to Follow BEYONDSPRING INC. CONDENSED CONSOLIDATED BALANCE SHEETS (Amounts in thousands of U.S. Dollars (“$”), except for number of shares and per share data) As of December 31, 2025 March 31, 2026 $ $ (Unaudited) Assets Current assets: Cash and cash equivalents 7,786 4,036 Short-term investments 4,775 3,827 Advances to suppliers 227 177 Prepaid expenses and other current assets 71 181 Current assets of discontinued operations 8,023 5,283 Total current assets 20,882 13,504 Noncurrent assets: Property and equipment, net 166 152 Operating right-of-use assets 305 240 Other noncurrent assets 224 126 Noncurrent assets of discontinued operations 4,356 4,384 Total noncurrent assets 5,051 4,902 Total assets 25,933 18,406 Liabilities and equity Current liabilities: Accounts payable 363 646 Accrued expenses 938 1,278 Current portion of operating lease liabilities 320 246 Other current liabilities 822 937 Current liabilities of discontinued operations 11,133 9,263 Total current liabilities 13,576 12,370 Noncurrent liabilities: Deferred revenue 28,600 28,994 Other noncurrent liabilities 3,981 4,239 Noncurrent liabilities of discontinued operations 3,766 3,157 Total noncurrent liabilities 36,347 36,390 Total liabilities 49,923 48,760 Shareholders ’ deficit Ordinary shares ($0.0001 par value; 500,000,000 shares authorized; 41,122,320 and 41,119,820 shares issued and outstanding as of December 31, 2025 and March 31, 2026) 4 4 Additional paid-in capital 375,664 375,739 Accumulated deficit (408,431 ) (410,590 ) Accumulated other comprehensive income 602 360 Total BeyondSpring Inc.’s shareholders’ deficit (32,161 ) (34,487 ) Noncontrolling interests 8,171 4,133 Total shareholders’ deficit (23,990 ) (30,354 ) Total liabilities and shareholders ’ deficit 25,933 18,406 BEYONDSPRING INC. CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) (Amounts in thousands of U.S. Dollars (“$”), except for number of shares and per share data) (Unaudited) Three months ended March 31, 2025 2026 $ $ Revenue - - Operating expenses Research and development (874 ) (1,076 ) General and administrative (1,736 ) (1,156 ) Loss from operations (2,610 ) (2,232 ) Foreign exchange gain, net 29 50 Interest income 17 8 Other income, net - 15 Loss before income tax (2,564 ) (2,159 ) Income tax expenses (20 ) (192 ) Net loss from continuing operations (2,584 ) (2,351 ) Discontinued operations Loss from discontinued operations (3,232 ) (4,323 ) Gain on sale of subsidiary interests 6,986 - Income tax expenses - - Net income (loss) from discontinued operations 3,754 (4,323 ) Net income (loss) 1,170 (6,674 ) Less: Net loss attributable to noncontrolling interests from continuing operations (75 ) (132 ) Less: Net loss attributable to noncontrolling interests from discontinued operations (3,232 ) (4,383 ) Net income (loss) attributable to BeyondSpring Inc. 4,477 (2,159 ) Earnings (loss) per share, basic and diluted Continuing operations (0.06 ) (0.05 ) Discontinued operations 0.17 - Basic and diluted earnings (loss) per share 0.11 (0.05 ) Weighted-average shares outstanding Basic and diluted 40,316,320 41,119,803 Other comprehensive loss, net of tax of nil: Foreign currency translation adjustment loss from continuing operations (151 ) (379 ) Foreign currency translation adjustment loss from discontinued operations (7 ) (47 ) Comprehensive income (loss) 1,012 (7,100 ) Less: Comprehensive loss attributable to noncontrolling interests from continuing operations (130 ) (269 ) Less: Comprehensive loss attributable to noncontrolling interests from discontinued operations (3,238 ) (4,430 ) Comprehensive income (loss) attributable to BeyondSpring Inc. 4,380 (2,401 )