Alector, Inc.

iStock, dickcraft Disappointing results for iluzanebart come shortly after Vigil Neuroscience struck a buy-out deal with Sanofi, but analysts say the outcome is unsurprising and shouldn’t affect the deal. Two weeks after agreeing to be bought out by Sanofi, Vigil Neuroscience’s monoclonal antibody iluzanebart failed a Phase II study for a rare brain disorder and its development is being discontinued. While noting good safety, tolerability and pharmacokinetics, Vigil said that iluzanebart showed “no beneficial effects on biomarker or clinical efficacy endpoints” in the Phase II IGNITE trial and concurrent natural history study called ILLUMINATE. Vigil had been pursuing accelerated approval for the antibody but hadn’t provided an update from the FDA in some time. In a note to investors Wednesday morning, William Blair analysts said they were “not surprised” by the results, given that in buying Vigil, Sanofi did not get iluzanebart along with the rest of the company. Instead, the drug will go back to Amgen, the drug’s original licensor. Vigil launched back in 2020 with Amgen’s backing and ex-Amgen assets in its pipeline. “We are disappointed on the IGNITE miss given early promising signals,” the William Blair analysts wrote, pointing to earlier testing results that showed pharmacological activity, but also noted that they’d had questions on bioavailability and reproducibility of the trial’s results. The results shouldn’t affect the deal with Sanofi, according to the analysts. Iluzanebart, a monoclonal antibody TREM2 agonist, was being developed by Vigil for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare, progressive brain disease that can lead to personality changes, loss of muscle function, and develop into dementia. “While this is not the data outcome we hoped to see for our iluzanebart program and our patients . . . we believe our efforts and the data collected from the IGNITE clinical trial and ILLUMINATE natural history study have increased awareness and provided a deeper understanding of ALSP,” Vigil President and CEO Ivana Magovčević-Liebisch said in a statement announcing the results. Sanofi agreed to buy Vigil in late May for about $470 million, with the hopes of bulking up its neuroscience pipeline. Central to the deal was Vigil’s other TREM2 agonist, VG-3927, aimed at neurodegenerative diseases such as Alzheimer’s. Iluzanebart’s failure is another ding for a TREM2 space that has already seen a recent high-pro Last November, Alector’s TREM2 antibody failed its own Phase II study for Alzheimer’s disease, triggering layoffs. In 2017, AbbVie paid $200 million for the global option to develop and commercialize the antibody.

正文共2000字 2图预计阅读时间5分钟在2025年5月22日，全球医药巨头赛诺菲（Sanofi）宣布了一项重要决定：以每股8美元现金的价格，总额约4.7亿美元收购Vigil Neuroscience。这一价格显著高于Vigil Neuroscience目前1.15亿美元的市值，溢价高达246%。这次收购的核心在于VG-3927，一种针对骨髓细胞表达触发受体2（TREM2）的口服小分子激动剂，用于治疗包括阿尔茨海默病（AD）在内的神经退行性疾病。该药物预计将在今年下半年进入II期临床试验。图片来源：sanofi官网在TREM2靶点中突破重围为何赛诺菲愿意溢价246%收购一家AD新药公司呢？让我们先了解一下它的核心产品吧。口服小分子TREM2激动剂VG-3927旨在增强小胶质细胞对聚集淀粉样蛋白和tau的保护性反应，同时不增加炎症反应。基于其激动剂和正变构调节剂（PAM）的新型作用模式，可能会放大VG-3927在病灶部位的作用，从而强烈调节小胶质细胞并可能增强神经保护。由于VG-3927不与sTREM2结合，与抗体TREM2激动剂相比，该疗法可最大限度地提高受体活化和小胶质细胞功能，这可能会增加其进入AD病灶的机会。此外，VG-3927没有Fc结构域，该结构域与免疫系统中与淀粉样蛋白相关成像异常（ARIA）风险增加相关的元素有关。图片来源：Vigil Neuroscience披露资料在今年年初，Vigil Neuroscience公布了VG-3927用于阿尔茨海默病的一期临床试验结果。 VG-3927在患者脑脊液中实现了高达约50%的游离TREM2（sTREM2）显著剂量依赖性降低，且显示出高脑外显率、可耐受的安全性。这意味着，VG-3927作为全球首款用于AD治疗、目前临床进展最快的口服小分子TREM2激动剂，证明了TREM2这条通路用于治疗AD的可行性。值得一提的是，考虑到其他竞争对手如武田与Denali共同开发的单抗NL919、艾伯维与Alector共同开发的单克隆抗体AL002等TREM2靶向药物相继折戟的背景下，VG-3927的积极数据显得尤为突出，对CNS领域的研究者有着借鉴与鼓舞的作用。此外，VG-3927还是TREM2赛道中唯三治疗CNS适应症的临床阶段项目，并取得了积极的临床数据（其余两款为诺华自主研发的单抗VHB937、安进原研、已授权给Vigil的单抗VGL101），这或许也是赛诺菲砸下重金的关键原因。更何况VG-3927还有一个亮点，是以上管线中唯一一款口服小分子TREM2激动剂，可实现每日1次给药。口服剂型将成为AD研发next level近年来，随着Aduhelm、Leqembi以及Donanemab等药物的相继获批，AD药物的研发进入了快速发展阶段。然而，这些新批准的药物在商业化过程中面临着一系列挑战，特别是与输液相关的基础设施需求。例如，Leqembi需要每月两次给药，并且患者必须在专科中心接受输液治疗。目前，在研的AD药物中，上市的口服剂型相对较少。首款FDA批准的口服AD药物是2014年的美金刚/多奈哌齐复方制剂，而直到2024年第二款药物Zunveyl才获得批准。2025年1月8日，康哲宣布获得了Zunveyl在亚洲（除日本）、澳大利亚和新西兰的独家权益，协议总金额达到4000万美元。这一动态表明，尽管存在挑战，但口服AD药物因其便利性和潜在的市场吸引力，正逐渐成为研发的next level。VG-3927在此领域的领先优势获得了赛诺菲的青睐。结语：综上所述，赛诺菲对Vigil Neuroscience的收购标志着其在神经病学领域的关键战略布局，成功将具有潜力的阿尔茨海默病口服小分子药物VG-3927纳入麾下。凭借其独特的作用机制、积极的临床数据以及口服剂型所带来的优势，此次收购有望为赛诺菲开辟新的增长点，并为全球阿尔茨海默病患者提供新的治疗希望。随着VG-3927二期临床试验的推进，其能否实现创新突破并改变AD治疗格局，值得行业持续关注。参考资料：1.https://www.vigilneuro.com/trem22.https://www.sanofi.cn/zh3.https://www.biospace.com/deals/sanofi-buys-vigil-for-470m-upfront-reigniting-a-battered-alzheimers-target4.其他公开资料图片来源：豆包AI突破的力量：这家跨国药企如何用4年成为中国医药创新 “造氧机”？2025-05-26中国创新药出海排行榜（征求意见稿）2025-05-25超越·盈领｜2025诺和诺德首届肥胖症论坛璀璨落幕，擘画肥胖管理新篇章2025-05-24版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn点击这里，查看更多精彩！

Vigil Neuroscience was preparing to launch a phase 2 trial in the third quarter when it accepted the takeover offer from Sanofi.\n Sanofi’s 11 months watching over Vigil Neuroscience have led to a $470 million buyout. With the biotech into the final year of its cash runway, Sanofi has swept in to secure a small molecule that could challenge Novartis for the Alzheimer’s disease market. The French pharma invested $40 million in Vigil in June 2024 in a deal that gave Sanofi an exclusive right of first negotiation to license the biotech’s small molecule TREM2 agonist. Sanofi’s investment extended Vigil’s runway into 2026, but the biotech continued to burn through cash, culminating in the company warning investors of a substantial doubt about its ability to keep going for another year.This morning, Sanofi ended Vigil’s money worries by agreeing to buy the biotech for $8 a share upfront. Vigil traded at $2.31 a share when the market closed Wednesday, giving the company a market cap of $108 million. In addition to the upfront fee, Sanofi has agreed to pay $2 a share upon the first commercial sale of VG-3927. VG-3927 is Vigil’s small molecule TREM2 agonist. Studies suggest TREM2, a receptor expressed primarily on microglia in the brain, is involved in the development of Alzheimer’s. People with rare TREM2 variants are more likely to develop the neurodegenerative disease and researchers have shown the receptor has a role in the clearance of toxic substances and abnormal proteins. Yet, efforts to treat Alzheimer’s by targeting TREM2 have floundered. A phase 2 study of AbbVie and Alector’s TREM2-activating antibody flopped in November. Takeda and Denali Therapeutics axed a rival antibody in 2023 after seeing phase 1 data.The setbacks left Novartis flying the flag for TREM2-targeting antibodies, with its VHB937 candidate set to enter (PDF) phase 2 development in Alzheimer’s in the second half of the year. As rivals fell away, Vigil continued to advance a small molecule that could be free from some of the problems that have held antibodies back. Vigil has argued its small molecule maximizes receptor activation and microglial function because it does not bind soluble TREM2. The molecule’s lack of a domain that engages the immune system could nullify the risk of amyloid-related imaging abnormalities associated with TREM2 antibodies. If Vigil is right, the features will translate into greater neuroprotection and a better safety profile.Responsibility for showing if the hypothesis holds up in the clinic will fall on Sanofi. Vigil was preparing to launch a phase 2 trial in the third quarter when it accepted the takeover offer. Sanofi confirmed a phase 2 trial is next on the to-do list. While the Big Pharma is taking VG-3927 forward, the drugmaker isn’t buying Vigil’s other candidate, iluzanebart. The TREM2-targeting antibody, which is also called VGL101, is in phase 2 development in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Final data from the trial, dubbed Ignite, are due soon. William Blair analysts said they would be surprised if Vigil\'s board would have signed off on the Sanofi deal if the Ignite data had been “clearly promising.”“We believe this [deal] is a good outcome for shareholders in the current funding environment, especially if the Ignite data is mixed or not clear in demonstrating proof of concept in ALSP,” the analysts said in a May 22 note.