Duvakitug

点击上方“蓝字”关注我们！ 本文来源于药闻社； 如果喜欢，欢迎在文末处点个“赞”和“推荐”，感谢您的支持！ 中国创新药的价值还是要靠BD来验证 如果说过去十年自身免疫疾病的关键词是TNF-α、IL-23、JAK，那么未来五到十年，炎症性肠病（IBD）的关键词很可能是TL1A。 这个全名为TNF-like ligand 1A、又称TNFSF15的靶点，正在从一个免疫学里的“炎症调节因子”，变成跨国药企争抢的黄金资产。默沙东108亿美元买下Prometheus，罗氏71亿美元买下Telavant，赛诺菲/梯瓦推进duvakitug，艾伯维连续下注中国TL1A资产，背后指向同一个判断：IBD治疗还远没有被满足，TL1A可能是继TNF-α之后最有机会诞生新药王的通路。 Bernstein近期预计，抗TL1A药物到2040年市场规模可能达到660亿美元。这个数字足够解释，为什么MNC愿意在尚未商业化的临床资产上提前下注。 直面炎症和纤维化两大痛点 TL1A成IBD最热靶点？ IBD主要包括溃疡性结肠炎（UC）和克罗恩病（CD）。这是一个长期、反复、难治的慢病市场。现有药物不少：TNF-α抑制剂、整合素抗体、IL-12/23、IL-23、JAK、S1P调节剂陆续登场，但临床痛点依旧清晰：不是所有患者都有应答，即使应答也可能逐渐失效；更关键的是，克罗恩病中的肠道纤维化、狭窄等结构性损伤，现有抗炎药很难真正解决。 TL1A的吸引力就在这里。 它不是单纯压低一个炎症因子，而更像是免疫炎症反应里的“放大器”。TL1A通过DR3等受体参与T细胞活化、炎症因子释放，也被认为与肠道纤维化过程相关。因此，抗TL1A的潜在价值不只是改善症状，而是有机会同时打到炎症和纤维化两个环节。 这也是它和传统TNF-α抑制剂相比更诱人的地方：TNF-α已经成就了修美乐这样的超级药王，但IBD治疗仍然存在大量应答不足患者。TL1A如果能在临床中证明更深的黏膜愈合、更好的内镜改善，以及对纤维化进展的干预能力，它就不只是“又一个自免靶点”，而可能成为IBD治疗范式的升级。 默沙东、罗氏等MNC百亿美元抢疯了 TL1A的全球竞争，已经不是早期概念验证，而是进入后期临床和商业化预演阶段。第一梯队的玩家几乎都是大药企，背后的共同逻辑是：谁先拿到高质量后期资产，谁就有机会在IBD下一轮迭代中占住入口。 图表一：海外TL1A主要并购与合作 目前看，默沙东最有可能先冲线。它用108亿美元买下Prometheus，本质是在Keytruda专利悬崖前寻找下一个大单品。Tulisokibart若率先拿出III期阳性数据，将定义TL1A赛道的监管和商业标准。 但Bernstein更看好罗氏成为长期赢家。原因在于罗氏通过Telavant拿到afimkibart后，既有成熟的免疫管线开发能力，也有全球商业化经验。对IBD这种需要长期用药、医生教育和支付准入的慢病市场来说，数据重要，商业化体系同样重要。 赛诺菲/梯瓦的duvakitug则更像第三极。其IIb数据显示，在UC和CD中均有较强缓解信号。如果后续能在给药便利性、维持治疗和安全性上形成差异，也有机会占据重要份额。 这一轮竞争的关键不只是“谁有效”，而是三个问题：谁能证明深度缓解，谁能降低给药负担，谁能通过生物标志物找到最适合的患者。 中国玩家以双抗后发制人 中国药企并没有错过TL1A。 和PD-1、ADC早期路径类似，国内企业最初多以单抗跟进为主，但很快进入双抗、多抗、长效化和License-out阶段。相比海外MNC，中国公司的机会不在于抢第一个上市，而在于用分子设计、成本效率和临床推进速度，做出差异化资产。 图表二：国内TL1A管线布局 国内企业的竞争重点已经很清楚：单抗不是终局。 TL1A单抗的商业空间大，但海外三大玩家已经强势占位。后来者如果只是做一个相似单抗，很难在全球市场获得高估值。真正有想象力的方向是双抗和多抗，例如TL1A/IL-23、TL1A/LIGHT、TL1A/IL-12/23等组合。这些设计试图解决一个核心问题：IBD不是单一通路疾病，单靶点抑制可能不够深，联合通路可能带来更高的黏膜愈合率和更稳定的长期缓解。 但双抗并不天然更好。它也带来更复杂的剂量、安全性、药代和适应症选择问题。谁能在疗效增强和安全窗口之间找到平衡，谁才可能真正跑出来。 对中国创新药来说，TL1A的机会有三层。 第一层，是跟随全球验证，把国内IBD市场做起来。中国IBD患者基数正在扩大，诊断率提升，生物制剂渗透率仍有空间。 第二层，是通过双抗、多抗做差异化，避开海外单抗巨头的正面火力。 第三层，是继续License-out。FG-M701和SIM0709已经证明，只要靶点足够热、设计足够新、数据足够早期可读，中国资产仍然能被MNC买单。 TL1A之所以热，不是因为它又讲了一个新靶点故事，而是它站在三个确定性之上：IBD仍有巨大未满足需求，MNC急需寻找下一代免疫重磅药，中国创新药正在从跟随走向差异化输出。 660亿美元市场能否兑现，最终要看III期数据。但资本和产业已经提前投票。TL1A的战争才刚刚开始，第一批赢家可能属于默沙东和罗氏；下一批变量，或许会来自中国双抗。 —END— 因为公众号平台更改了推送规则，如果不想错过药闻社的文章，记得读完点个“赞”，这样每次新文章推送才会第一时间出现在你的订阅列表里。 文章推荐 跨越“药械耦合”地狱难度  博瑞医药完成吸入制剂平台跃迁？吸入一哥正大天晴的十字路口吸入制剂全球攻防重构  中国药企欲凭体系化竞争逆袭？新兴战略产业之后 中国Biotech重启齐鲁制药惊蛰前告别“军令状”  传统仿制药巨头如何改命？蚂蚁阿福，能撬开大厂逢医疗健康必死局吗？体检这门生意，为什么只做了一半？

Spyre Therapeutics has unveiled Phase II data for a second ulcerative colitis (UC) candidate in its pipeline, this time an extended half-life anti-TL1A antibody. On Monday, the company said SPY002 met its primary endpoint in the SKYLINE study.The 12-week induction readout comes about two months after it reported positive results for the anti-α4β7 antibody SPY001, a potential challenger to Takeda's Entyvio (vedolizumab), which shares the same mechanism of action.SKYLINE is a two-part induction and maintenance platform trial of both SPY001 and SPY002 as well as SPY003, which targets IL-23, in patients with moderately-to-severely active UC. The study also tests pairwise combinations of the three.'Indication-leading' responseDeanna Nguyen, SVP of clinical development and study lead for SKYLINE, said SPY002 produced an "indication-leading" reduction of 10.7 points in Robarts Histopathology Index (RHI) score from baseline, as well as "meaningful clinical remission and endoscopic outcomes in line with the anti-TL1A class and among the highest across therapeutic classes."On the latter two measures, both secondary endpoints, clinical remission by modified Mayo Score was 33% with SPY002, while endoscopic improvement was 42%. The study enrolled a relatively challenging population, with 35% of participants previously exposed to advanced therapies, the company noted.SPY001 had achieved a significant 9.2-point reduction on RHI at 12 weeks, clinical remission of 40% and endoscopic improvement of 51%."Together with its target Q3-6M subcutaneous maintenance profile, [Monday's] data…reinforce our thesis that optimised monotherapy components are the foundation for potentially best-in-class combinations," Nguyen said.Spyre said SPY002 had a safety profile consistent with the TL1A class. There were 20 patients with treatment-emergent adverse events during the induction treatment period, though only two had serious adverse events (SAEs), and neither were deemed related to the drug. One of the SAEs was due to an exacerbation of UC, and another occurred in a patient with pre-existing heart failure whose condition worsened.TL1A landscape in UCMerck & Co.'s anti-TL1A mAb tulisokibart (MK-7240), already in Phase III for both UC and Crohn's disease, is among a handful of other contenders vying to be the first drug in the class to win approval for inflammatory bowel disease.Sanofi and Teva recently posted long-term extension data for their partnered anti-TL1A candidate duvakitug, showing that 47% and 58% of UC patients taking the low and high doses, respectively, achieved clinical remission after 44 weeks (see – Physician Views Results: Mixed sentiments from gastroenterologists temper Sanofi's best-in-class aims for duvakitug in IBD and KOL Views Q&A: Teva, Sanofi's anti-TL1A will compete in IBD but Spyre eyeing bigger prize).Roche's afimkibart (RG6631), acquired through its $7.1-billion purchase of Telavant, is currently in Phase III studies for an induction regimen, as well as both induction and maintenance, in UC (Ametrine-1 and Ametrine-2) and Crohn's (SIBERITE-1 and SIBERITE-2).