Duvakitug

- 第3668期 - 扫码直达本期11文 01 · 由人和协同创作，仅供参考 02 · 识别二维码，直达本期所有内容 03 · 文末添加小秘书，提交纠错信息 本文要点 IF: 39.1 Efficacy and safety of duvakitug in patients with Crohn's disease (RELIEVE UCCD): a phase 2b, randomised, placebo-controlled trial Vipul Jairath Jaroslaw Kierkus, George Aaron Duvall, Silvio Danese, Bruce E Sands, Bogdan Ratiu-Duma, Rajendra Singh, Phillip Levine, Hadas Barkay, Nicholas Gross, Ken Abrams, Walter Reinisch Vipul Jairath Article|2026-07-16 10.1016/S2468-1253(26)00119-6 靶点与设计 针对克罗恩病中肿瘤坏死因子样细胞因子1A（TL1A）经死亡受体3（DR3）放大炎症与纤维化、且抗TL1A疗法缺乏安慰剂对照数据的问题，开展随机、双盲、安慰剂对照Ⅱb期试验，评估特异性阻断TL1A-DR3信号的duvakitug。 总体疗效 duvakitug在中重度活动性克罗恩病中显示优于安慰剂的第14周内镜应答证据，支持TL1A作为治疗靶点，并提示该药具有诱导治疗潜力。 主要终点 以克罗恩病简易内镜评分（SES-CD）较基线降低≥50%定义内镜应答，450 mg组、900 mg组和安慰剂组应答率分别为26%、48%和13%，两剂量组优于安慰剂的后验概率分别为0.94和＞0.99。 多维获益 两剂量组在克罗恩病活动指数临床应答、患者报告结局和粪钙卫蛋白下降方面均呈数值改善，其中900 mg组的改善幅度总体更大。 安全性 不良事件发生率在450 mg组、900 mg组和安慰剂组分别为67%、43%和48%，严重不良事件分别为13%、2%和11%，未观察到新的安全信号，治疗诱导抗药抗体发生率较低。 人群表现 既往接受先进疗法与未接受先进疗法的亚组中，duvakitug组内镜应答比例均高于安慰剂，900 mg组疗效在不同既往治疗背景下总体保持。 核心关键词 duvakitug克罗恩病2b期临床试验内镜应答TL1A-DR3通路贝叶斯分析SES-CD 科普解读 在克罗恩病的治疗领域，一个长期未能破解的困境是：即便现有的生物制剂和JAK抑制剂等先进疗法不断涌现，仍有高达80%的患者无法达到临床缓解。反复发作的肠道炎症会逐渐导致纤维狭窄，约半数患者最终面临肠梗阻等严重并发症，而寻找一种既能有效控制炎症、又具备良好耐受性的新机制药物，始终是临床的迫切需求。这一局面如今迎来了一个重要的转折点。 Lancet Gastroenterology & Hepatology 近日发表的一项IIb期临床研究（RELIEVE UCCD），首次为抗TL1A单克隆抗体Duvakitug在克罗恩病中的疗效提供了安慰剂对照证据。该研究由韦仕敦大学医院的Vipul Jairath等团队领衔，结果显示，在为期14周的诱导治疗后，Duvakitug显著提升了中重度活动性克罗恩病患者的内镜应答率，且未发现新的安全性信号。 精准阻断炎症放大器 TL1A（TNF样细胞因子1A）是近年来炎症性肠病研究中备受关注的靶点。它像一个炎症信号的放大器，通过与功能性受体DR3结合，不仅能够加剧免疫反应，还被认为在肠道纤维化的进程中扮演了关键角色。Duvakitug作为一种人源化IgG1单克隆抗体，其设计特点在于优先阻断TL1A-DR3信号通路，而非与中和性的诱骗受体DcR3结合，从而更有针对性地抑制下游的炎症与纤维化级联反应。 为了验证这一机制在临床上的实际效果，RELIEVE UCCD研究采用了创新的篮式试验设计，在同一个主方案下，同时评估了Duvakitug对克罗恩病和溃疡性结肠炎两种适应症的疗效，这在炎性肠病领域尚属罕见的操作。 关键数据：内镜改善的量化证据 这项多中心、随机、双盲、安慰剂对照试验纳入了138名对至少一种常规或先进疗法应答不佳、失应答或不耐受的中重度活动性克罗恩病患者。研究人员将受试者随机分配至Duvakitug 450mg组、Duvakitug 900mg组（每两周一次皮下注射）或安慰剂组。 研究采用了贝叶斯统计方法，其预设的疗效判定标准为：在后验概率上，Duvakitug治疗组的应答率优于安慰剂组的概率需达到0.90或以上。第14周时的内镜应答（定义为SES-CD评分较基线降低至少50%）结果如下： - 安慰剂组的内镜应答率为13%。 - Duvakitug 450mg组的应答率提升至26%，后验应答率差值为13个百分点，优于安慰剂的后验概率为0.94。 - Duvakitug 900mg组的应答率则攀升至48%，后验应答率差值高达33个百分点，其优于安慰剂的后验概率超过0.99。 毫无疑问，900mg剂量组的数据同时满足了统计上的显著性和临床意义上的显著改善。这组数据的价值在于，它直接回应了该领域对于“黏膜愈合”这一核心治疗目标的追求。 贯穿始终的疗效趋势 除了主要终点，Duvakitug在多个次要终点上也展现出一致的获益趋势。无论是基于CDAI评分的临床应答和缓解，还是基于患者自报结局（PRO2）的症状改善，抑或是基于更精细的MM-SES-CD评分的内镜应答，Duvakitug治疗组均优于安慰剂组。 此外，观察到粪便钙卫蛋白和高敏C反应蛋白等炎症生物标志物也有所下降。研究团队发现，在既往接受过先进疗法且应答困难的难治性亚组中，900mg剂量组依然保持了与整体人群相似的疗效，而安慰剂效应在该亚组中则极为微弱。 安全性特征与未来展望 在安全性方面，Duvakitug表现出与安慰剂相当的安全性特征，未出现非预期的安全信号。450mg组、900mg组和安慰剂组的治疗期间不良事件发生率分别为67%、43%和48%。最常见的不良事件为鼻咽炎和头痛。严重不良事件在450mg组中发生率为13%，其中一例出现过敏反应，但停药后经对症处理迅速缓解。900mg组的严重不良事件发生率仅为2%，低于安慰剂组的11%。值得注意的是，研究中抗药抗体的产生率极低，约为5%，且未检测到中和抗体，提示其免疫原性风险较低。 综合来看，RELIEVE UCCD研究的数据为TL1A这一靶点提供了强有力的临床验证，表明Duvakitug有望成为一种对所有克罗恩病患者——无论其既往治疗经历如何——均具潜力的新型诱导治疗选择。当然，研究团队也明确指出，该试验并非为探究药物对肠道纤维化的影响而设计，这一重要方向仍有待更长治疗周期的后续研究来揭示。目前，针对Duvakitug的III期临床试验已经启动，该药物能否在更大规模的人群中延续其疗效，并为克罗恩病治疗格局带来真正变革，值得期待。 图片摘要 图片由AI生成，可能有错，请谨慎辨别。 相关文章推荐 01 IF: 14.1 Advanced Science江苏省人民医院张红杰团队：克罗恩病肠道狭窄背后，特定巨噬细胞成关键推手 02 IF: 17.5 Experimental and Molecular Medicine破解克罗恩病炎症密码，新型CD8+ T细胞成关键推手 03 IF: 15.6 Science Translational MedicineScience子刊：驯化而非消灭，新型噬菌体疗法为炎症性肠病带来新曙光 04 IF: 10.3 Journal of Crohn's and Colitis肠道炎症与膳食乳化剂联手，加速克罗恩病相关大肠杆菌向高致病性演化 05 IF: 15.3 Gut MicrobesFlaPro算法解码肠道鞭毛组，揭示克罗恩病免疫激活机制 扫码查看相关文章 识别右侧二维码进入详情页可点击访问 AI解读仅供参考 本期11文目录 01 IF: 10.4 Food Chemistry 上海六院贾伟团队：建立两千样本数字风味库，AI实现白酒品质客观量化 02 IF: 24.6 Gut GUT：修复肠道屏障，IBD临床试验迎来首个国际共识 03 IF: 39.1 Lancet Gastroenterology & Hepatology Lancet子刊：贝叶斯设计助力新药开发，肠炎靶向治疗再添利器 04 IF: 39.1 Lancet Gastroenterology & Hepatology Lancet子刊：阻断TL1A通路，克罗恩病迎来新型靶向单抗 05 IF: 11.4 NPJ Biofilms and Microbiomes 荟萃分析揭示心衰患者肠道代谢物TMAO的异常蓄积 06 IF: 15.3 Gut Microbes 城市化如何重塑人类肠道？真菌与寄生虫的消长 07 IF: 10.8 Genome Medicine 肠道激素新开关！一株人源共生菌挑战GLP-1替代路径 08 IF: 39.1 Lancet Gastroenterology & Hepatology Lancet子刊：从肠道微生态到中枢敏化，解析IBS致病全景（综述） 09 IF: 16.4 Science Immunology Science子刊：黏膜疫苗设计新启示，组织微环境决定B细胞命运 10 IF: 29.7 Gastroenterology 为何有些dMMR大肠癌能响应免疫治疗？解析关键分子机制 11 IF: 39.1 Lancet Gastroenterology & Hepatology Lancet子刊：林奇综合征肠镜监测，当前AI工具增量价值有限 扫码直达本期11文 识别右侧二维码直达本期所有内容 欢迎加入"热心肠菌群"微信群 01 · 扫描添加热心肠小秘书微信 02 · 发送您的姓名、单位和职务 03 · 审核通过后将发出进群邀请

Structure-free AI platform delivers picomolar leads while cutting wet-lab validation to 20-50 samples per round The number that matters to a partner is not how many molecules our model can score, it is how many they have to make” — Dr. Lurong Pan, Founder and CEO of Ainnocence SAN FRANCISCO , CA, UNITED STATES, July 20, 2026 / EINPresswire.com / -- Ainnocence Inc., an AI-driven pharmaceutical & material IP-generating platform company, today reported performance results from 75 completed protein design programs and announced that it is seeking licensing and partnering agreements for 28 antibody, bispecific and ADC programs that have generated positive preclinical data across oncology, immunology and metabolic indications. Across 58 affinity maturation campaigns, Ainnocence's SentinusAI ® platform succeeded in 53, a 91.4% program success rate, with only five campaigns failing to produce an improved binder. On novel targets attempted with no structural information and no prior binder, 9 of 17 de novo campaigns (53%) yielded validated hits. Performance without structure Unlike 3D structure-dependent approaches, SentinusAI ® predicts binding directly from sequence, removing the requirement for a resolved co-crystal or predicted complex. That design choice underpins both the platform's throughput and its economics: Ainnocence reports a roughly 10,000-fold reduction in computational cost relative to conventional 3D modeling workflows, a computation cycle of one to two weeks per round, and capacity to run more than 100 programs concurrently. The practical effect is on the wet lab. Because each round is narrowed to 20–50 designs before synthesis, partners test tens of molecules rather than thousands: De novo design: 7.5% positive rate on round-1 zero-shot prediction, rising to 30% on round-2 reinforcement-learning iteration Affinity maturation: 21.5% positive rate on round-1 zero-shot prediction, rising to 43.8% on round-2 iteration Affinity gains from tens- to thousands-fold over the parent molecule, with leads reaching picomolar potency Picomolar leads across formats Delivered programs span Fabs, scFvs, mAbs, bispecifics and ADC-enabling binders. Of the campaigns with quantified KD readouts, 28 reached sub-nanomolar affinity and seven reached 100 pM or better. Leading results include an IL-15×IL-21 bispecific at approximately 0.09 pM on the IL-21 arm, a TNFα-OX40L bispecific at 8.6 pM, an anti-C1q program at 1-20 pM and a TL1A×p40 bispecific at 23 pM. An anti-VEGF scFv-IgG measured 27.8-34.6 pM by SPR, outperforming the bevacizumab reference run in the same experiment. Twenty-eight programs available for licensing Ainnocence's internal pipeline comprises 37 programs, of which 28 have produced positive data and are now available for licensing or partnering, individually or as a portfolio. Highlights include a TL1A×p40 bispecific (KD 0.16 nM; benchmark duvakitug, Phase 3), an anti-IL-36R Fab with 13 of 21 matured variants binding below the 1 pM detection limit (benchmark spesolimab-class HB-0034), an anti-TROP2 ADC lead at 0.37-0.43 nM with confirmed internalization (benchmark Trodelvy) and an anti-B7-H3 program at approximately 0.56 nM (benchmark ifinatamab deruxtecan, Phase 2). Seven ADC-ready internalizing oncology targets have been validated by FACS and internalization assay and leads have expressed at titers up to approximately 440 mg/L at greater than 99% SEC purity. “The number that matters to a partner is not how many molecules our model can score, it is how many they have to make,” said Dr.Lurong Pan, PhD, Founder and CEO of Ainnocence. “Twenty to fifty designs per round, one to two weeks of compute and a 91.4% program success rate across 58 maturation campaigns is a different operating model for antibody discovery. And because we never depended on a resolved structure, the targets other platforms set aside are the ones we take on.” Collaborate with Ainnocence Ainnocence is seeking licensing and partnering relationships to advance the pipeline through affinity finalization, ADC conjugation, in vivo efficacy and clinical development. Additional non-confidential and confidential materials are available on request. About Ainnocence Inc. Founded in 2021 and headquartered in California, Ainnocence is a next-generation biotechnology company transforming drug discovery and synthetic biology through AI-based, sequence-first engineering. The company’s self-evolving platform evaluates up to 10 billion molecules spanning proteins, antibodies, small molecules, nucleic acids, and chemical formulations within hours to weeks, enabling rapid, multi-objective design across therapeutic, biological, and chemical systems. By reducing R&D timelines and costs while increasing success rates, Ainnocence empowers industry and academic partners to pursue complex biological innovation with greater precision and control. Lurong Pan, PhD Ainnocence +1 205-249-7424 service@ainnocence.com Visit us on social media: LinkedIn YouTube X Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. 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