Fractyl Health, Inc.

Randomized 6-month data from the REMAIN-1 Midpoint Cohort expected in late January 2026 Topline 6-month data from the REMAIN-1 Pivotal Cohort and potential PMA submission expected in H2 2026 Approximately $85.6 million in cash and cash equivalents on hand, supporting execution across planned 2026 milestones Received gross proceeds of $23.0 million from exercises of Tranche A warrants from August 2025 financing, with cash runway into early 2027 Jan. 05, 2026 -- Fractyl Health, Inc. (Nasdaq: GUTS) (the Company or Fractyl), a metabolic therapeutics company focused on pattern-breaking approaches that treat root causes of obesity and type 2 diabetes (T2D), today outlined its strategic outlook for 2026, highlighting anticipated clinical and regulatory milestones across its Revita® and Rejuva® programs. “As we enter 2026, we believe Fractyl is positioned for a definitional year, and our focus is on disciplined execution with an accelerating cadence of clinical and regulatory milestones and progress,” said Harith Rajagopalan, M.D., Ph.D., Co-Founder and Chief Executive Officer of Fractyl Health. “We are rapidly advancing Revita as an outpatient endoscopic therapy designed to address a root cause of obesity. This year, we expect to deliver pivotal data and potential PMA filing in what we see as the single biggest problem in obesity today: post-GLP-1 weight maintenance. With millions of patients expected to start and then stop taking a GLP-1 this year, we believe weight loss maintenance is the new unmet need in obesity care, and is clearly what patients, prescribers, payers, and the broader health economic community are looking for.” In 2026, the Company plans to advance Revita through a series of important clinical and regulatory milestones, building on continued progress across the REVEAL-1, REMAIN-1 Midpoint, and REMAIN-1 Pivotal Cohorts as the program moves through pivotal validation in post-GLP-1 weight maintenance. In parallel, Fractyl is aligning clinical development with regulatory strategy and real-world implementation considerations for Revita as the Company advances through a registrational year. Late January 2026: 6-month randomized data from the REMAIN-1 Midpoint Cohort Early 2026: Complete randomizations for the REMAIN-1 Pivotal Cohort Q2 2026: 1-year REVEAL-1 Cohort data Q3 2026: 1-year REMAIN-1 Midpoint Cohort data H2 2026: Topline 6-month randomized data from the REMAIN-1 Pivotal Cohort H2 2026: Potential Revita PMA filing in post-GLP-1 weight maintenance Fractyl plans to continue advancing its Rejuva gene therapy platform toward clinical validation in 2026, with progress expected toward first-in-human (FIH) evaluation of its lead program, RJVA-001, in patients with inadequately controlled T2D, subject to regulatory authorization. In H2 2025, Fractyl completed Clinical Trial Applications (CTA) for a RJVA-001 FIH study in EU and Australia, setting the stage for expected dosing of first patients and preliminary data in 2026. Q2 2026: Regulatory feedback on CTA for RJVA-001 H2 2026: First-in-human dosing of RJVA-001, subject to CTA authorization, and preliminary data As of December 31, 2025, Fractyl had approximately $81.5 million, in preliminary unaudited cash and cash equivalents. In connection with exercises of Tranche A warrants from Fractyl’s August 2025 financing, an additional $4.1 million of proceeds were received on January 2, 2026, resulting in a balance of $85.6 million in cash and cash equivalents as of such date. Fractyl’s current cash and cash equivalents are expected to fund its operations through early 2027 and support execution across planned 2026 clinical and regulatory milestones. Fractyl Health is a metabolic therapeutics company focused on pioneering new approaches to the treatment of metabolic diseases, including obesity and T2D. Despite advances in treatment over the last 50 years, obesity and T2D continue to be rapidly growing drivers of morbidity and mortality in the 21st century. Fractyl’s goal is to transform metabolic disease treatment from chronic symptomatic management to durable disease-modifying therapies that target the organ-level root causes of disease. The Company has a robust and growing IP portfolio, with 35 granted U.S. patents and approximately 45 pending U.S. applications, along with numerous foreign issued patents and pending applications. Fractyl is based in Burlington, MA. Fractyl Health’s lead product candidate, Revita, is based on the company’s insights surrounding the potential role of the gut in obesity. Revita is designed to remodel the duodenal lining via hydrothermal ablation (i.e. duodenal mucosal resurfacing) to reverse damage to intestinal nutrient sensing and signaling mechanisms caused by chronic high-fat and high-sugar diets that are a root cause of metabolic disease. In the U.S., Revita is for investigational use only under U.S. law. Revita has U.S. FDA Breakthrough Device designation in weight maintenance for people with obesity who discontinue GLP-1 based drugs. A pivotal study of Revita in patients with obesity after discontinuation of GLP-1 based drugs, called REMAIN-1, was initiated in the third quarter of 2024 and has completed enrollment. Fractyl Health’s Rejuva platform focuses on developing next-generation adeno-associated virus (AAV)-based, locally delivered gene therapies for the treatment of obesity and T2D. The Rejuva platform is in preclinical development and has not yet been evaluated by regulatory agencies for investigational or commercial use. Rejuva leverages advanced delivery systems and proprietary screening methods to identify and develop metabolically active gene therapy candidates targeting the pancreas. The program aims to transform the management of metabolic diseases by offering novel, disease-modifying therapies that address the underlying root causes of disease. The Company has submitted the first Clinical Trial Application (CTA) module for RJVA-001 in T2D to regulators, and if the CTA is authorized, the Company expects to dose the first patients with RJVA-001 and report preliminary data in H2 2026. RJVA-002, the Company’s second candidate from the Rejuva platform, is a dual GIP/GLP-1 gene therapy for obesity that has demonstrated approximately 30% weight loss in preclinical studies after a single administration, underscoring its potential to deliver durable, well-tolerated metabolic benefits from a one-time intervention. The content above comes from the network. if any infringement, please contact us to modify.

iStock, klenger A push to reshore some drug production and progress in advanced manufacturing technologies have been prominent trends this year, industry leaders say. In 2025, the question of where medicines are made went mainstream. Once largely discussed in business terms within pharma companies, the question gained traction as the Trump administration, citing national security and sovereignty, unleashed a barrage of actions to pressure drugmakers to reshore production. Leaders working in different parts of the production process independently called out the supply chain conversation as the trend that defined pharma manufacturing in 2025. Brian Doty, vice president of R&D and programs at the nonprofit API Innovation Center (APIIC), told BioSpace via email that the “growing urgency around reshoring critical generic medicines” was a key shift in 2025. Doty pointed to President Donald Trump’s executive orders—including a call to bolster a stockpile of active pharmaceutical ingredients (APIs), purchasing from domestic manufacturers where possible—and a Senate Special Committee on Aging hearing that spotlighted U.S. companies making essential generic medications domestically. Heavily prescribed generic drugs that rely on foreign APIs were a particular focus of these actions, Doty said. The APIIC leader attributed the development to “a growing recognition of our nation’s overreliance on foreign suppliers as a national health security risk.” John Murphy, CEO of the Association for Accessible Medicines (AAM), an industry group for makers of generics and biosimilars, made a similar point. He told BioSpace that the realization the U.S. needs to prioritize manufacturing was his top trend of 2025. The acknowledgment has emerged in lockstep with rising understanding that the U.S. has medicine supply vulnerabilities because “we don’t make much here,” Murphy said. “We lead the world in generic drug shortages because of our problematic reimbursement system for medicines,” he added. “We have very little capacity to manufacture API and [key starting materials] here in the United States, and so we are wholly reliant on a number of trading partners.” Manufacturing Trump’s Push To Shore Up Pharma Supply Chain With US API Welcomed but Questioned While trade groups hail the executive order as a national health security opportunity, analysts warn that production costs could go up in the near term. September 2, 2025 · 4 min read · Nick Paul Taylor Read more The U.S. has little capacity because it has let its generic and biosimilar manufacturing base “atrophy,” Murphy said. The tariff debate brought on by the Trump administration has sparked wider awareness of the situation, he said, and the resulting conversation was “very illuminating” for the healthcare sector. Doty believes the message has reached healthcare systems, industry and government. “It has been encouraging to see how quickly stakeholders have recognized the value of modernizing U.S.-based pharmaceutical manufacturing,” he said. Murphy and Doty are each now working to turn recognition into action. That process remains a work in progress as 2025 draws to a close. “Our nation’s overdependence on foreign API supply for some of the most commonly prescribed generic drugs persists, and few backup options are available when disruptions occur,” Doty said. Advanced Therapy Sector Seeks Scale Doty sees continuous flow and other advanced manufacturing technologies as part of the answer to the question of how to reshore API production. In the cell and gene therapy field, companies turned to advanced manufacturing technologies in 2025 to answer the question of how to improve scalability and reduce production costs. Fabian Gerlinghaus, Cellares’ co-founder and CEO, told BioSpace via email that “the defining challenge of 2025 was the industry’s realization that scaling complex, labor-intensive manufacturing workflows across fragile supply chains is no longer commercially viable.” Multiple cell and gene therapies have struggled commercially, in part because of a reliance on expensive, poorly scalable manufacturing processes. David Dismuke, chief technical officer at Forge Biologics, shared an upbeat assessment of work to tackle the challenge, telling BioSpace via email that 2025 was “a turning point where several long-anticipated manufacturing improvements finally translated into measurable performance gains.” Dismuke named yield-boosting additives known as enhancers, improved media for cell growth and improved plasmid designs as innovations that have boosted productivity. Gene therapy Cracking the Commercial Code for Cell and Gene Therapies From innovation in manufacturing to more-flexible regulation and better communication with payers, much needs to happen to make CGTs commercially viable. But it is possible, experts agreed at a recent panel. August 5, 2025 · 9 min read · Jef Akst Read more “These advancements matter because they expand the kinds of programs gene therapy developers can target. As manufacturing performance improves, developers can pursue programs for larger populations and more prevalent diseases that were previously out of reach,” Dismuke said. “We are already seeing this shift among some of our own clients, such as Fractyl Health, which is developing an AAV-based gene therapy aimed at metabolic diseases like obesity and type 2 diabetes.” Regulators appear to support the changes. Gerlinghaus said the most unexpected development in 2025 was “the speed and clarity with which U.S. regulators embraced advanced manufacturing.” In the year the Advanced Manufacturing Technologies (AMT) program began to take shape, Gerlinghaus said the pace of action “was significantly faster than anticipated” and showed the FDA is serious about supporting change. The AMT is a new designation aimed at streamlining the regulatory process for early adopters of new technologies. Just how far the advanced therapy field has come became clear in May when news emerged that a nine-month-old boy with an ultrarare disease had received a CRISPR treatment made just for him. John Maslowski, president and CEO of Forge, told BioSpace via email that the Baby KJ case showed “something fundamentally new: the ability to build a therapy even when there was no roadmap.” To Maslowski, the story showed “rapid design, rapid manufacturing and rapid regulatory coordination for an individual patient is possible.” The significance of the case could extend beyond KJ, he said, as it demonstrates the emergence of “a new way to think about platforms and manufacturing systems that can flex to meet the needs of any patient.” “Urgency around pharmaceutical resilience has grown significantly,” Doty said. “The coming year will be about putting those solutions into action across the industry.” Manufacturing FDA’s Manufacturing Designation Could Derisk Mid-Development Manufacturing Changes The status could support staged transitions to new manufacturing processes, potentially mitigating some risks of high-stakes switches. December 9, 2025 · 4 min read · Nick Paul Taylor Read more

2025年12月GLP-1领域重大进展全盘梳理 ——口服三靶点、非GLP-1减重、停药反弹解决方案同时推进 Ascletis（歌礼制药）、Ventyx Biosciences、Fractyl Health 近期分别在肥胖与代谢疾病领域公布重要进展。 同时，诺和诺德启动大规模结构调整，WHO 首次发布 GLP-1 治疗肥胖的全球临床指南。 这意味着：GLP-1 赛道正从“单靶点减重”迈入“多靶点 + 长期管理 + 非药物干预”的新阶段。 Ascletis：首款口服三靶点激动剂进入临床准备阶段 Ascletis 已正式选定 ASC37 作为其首个口服 GLP-1R / GIPR / GCGR 三靶点多肽激动剂 的核心临床候选药物。 关键药代数据 口服生物利用度：4.2%相比现有产品：比口服司美格鲁肽高 约9倍比替尔泊肽高 约30倍比瑞他鲁肽（Retatrutide）高 约60倍整体药物暴露量：比口服瑞他鲁肽高 约57倍 需要说明的是：这里的数据来源于非人灵长类动物实验，属于进入人体临床前的“最高级别动物验证阶段”。 技术平台与作用强度 该药采用歌礼自研的口服递送技术平台，核心作用是让原本只能注射的多肽类药物，能够经口服进入体内并被有效吸收。 同时结合 AI 辅助药物设计系统进行分子结构优化。 在体外实验中，其受体激活强度最高可达瑞他鲁肽的 5 倍。 半衰期与给药频率 半衰期约 56 小时理论上可支持：每日一次口服或更低频给药方案 临床时间表 预计 2026 年第二季度（Q2 2026）提交 IND正式进入全球 口服多靶点减肥药竞争赛道 核心意义：如果 ASC37 在后续人体临床中验证安全有效，它将成为少数真正具备产业竞争力的 “口服三靶点减重药” 候选物，有望对诺和诺德、礼来形成实质性技术挑战。 Ventyx：从炎症疾病跨界进入肥胖与心代谢领域 Ventyx 并未直接布局 GLP-1 激动剂，而是选择从“炎症机制干预代谢病”入手，走出一条差异化路线。 临床与专家团队扩充 新任命：Mark McKenna：战略顾问Peter Libby 教授（哈佛医学院）：临床顾问其核心药物 VTX2735（复发性心包炎）正在将 II 期临床扩展至英国、欧盟、加拿大使用 每日一次口服剂型 肥胖+心代谢新靶点：NLRP3 抑制剂 药物：VTX3232机制特点：可穿透中枢神经系统（CNS-penetrant）靶向 NLRP3 炎性小体通路最新进展：已在 肥胖合并心代谢风险人群中完成 II 期临床初步结果显示具有潜力更多肥胖管线数据预计 2026 年 Q1 公布 一句话总结 Ventyx：不是卷 GLP-1，而是试图通过“抗炎”这条底层机制，切入减重与心代谢赛道。 Fractyl：首次在“GLP-1停药后体重反弹”问题上取得突破 Fractyl 公布其 REVEAL-1 研究 6 个月随访数据，直接瞄准当前 GLP-1 治疗中的最大现实难题之一： 一旦停药，体重几乎必然反弹。 该研究评估的问题是： 在曾使用 GLP-1 成功减重 ≥15% 的人群中，停药后联合一次 Revita® 十二指肠重塑术，是否可以显著降低反弹？ 关键结果 停用 GLP-1 六个月后：平均体重仅回升 1.5%对比既往研究：传统人群停药后通常 反弹约 10% 甚至更高血糖控制同步保持稳定 Revita® 技术定位 一种 非药物、内镜介入式治疗作用靶点：十二指肠黏膜重塑目标机制：重新调节 “肠—胰—脑” 代谢轴 后续关键节点 REMAIN-1 随机对照临床试验预计 2026 年公布结果PMA（上市前许可）目标同样设定在 2026 年 核心意义：这是目前极少数专门用于解决“GLP-1 停药反弹”问题的临床技术路线。 如果后续随机对照试验证实有效，Revita 可能成为 GLP-1 长期管理体系中的关键补充。 Hoth Therapeutics：GDNF系列代谢疗法处于人体前阶段 Hoth 正在推进基于 GDNF（胶质细胞源性神经营养因子） 的全新代谢治疗平台。 在研管线包括：HT-001：肥胖HT-KIT：脂肪肝HT-ALZ：代谢紊乱当前状态：正在 亚特兰大 VA 医疗中心进行临床前研究计划：2026 年启动早期人体临床 这标志着 Hoth 正由传统免疫/皮肤管线，正式转向代谢疾病新赛道。 Novo Nordisk：在“裁员”与“加码投资”之间双线调整 在新任 CEO Maziar Mike Doustdar 领导下，诺和诺德启动大规模结构调整。 裁员约 9000 人多个研发项目被削减或合并战略重心进一步集中至：下一代生物大分子药物肥胖与心代谢疾病 与此同时，竞争环境持续白热化。 礼来不断扩大 GLP-1 产品矩阵辉瑞通过 Metsera 重新切入肥胖赛道 即便在重组期，诺和诺德依然明确表态：肥胖与心代谢仍是最高优先级投资方向。 WHO 首次发布 GLP-1 治疗肥胖的全球临床指南 世界卫生组织（WHO）在 2025 年首次正式发布 GLP-1 类药物用于肥胖治疗的全球指导意见。 推荐对象 成人BMI ≥30在 饮食 + 运动 基础上，作为长期药物治疗手段 推荐药物 司美格鲁肽（Semaglutide）替尔泊肽（Tirzepatide）利拉鲁肽（Liraglutide） 同时发出重要警告 到 2030 年：可能有超过 10% 的合规患者因价格和产能问题无法获得药物全球将面临：药物可及性不平等医保支付压力持续上升 最后一眼看懂行业趋势 口服三靶点激动剂：进入实质性竞争阶段（Ascletis）非 GLP-1 抗炎减重通路：开始跑临床（Ventyx）停药反弹问题：首次出现可重复的非药物解决方案（Fractyl）全球政策层面：WHO 已正式为 GLP-1 在肥胖领域“定调”产业层面：诺和诺德、礼来、辉瑞进入减重赛道“军备竞赛” 数据来源： 1歌礼制药（2025）宣布，歌礼选择其首个口服GLP-1R/GIPR/GCGR三肽激动剂ASC37进行临床开发新闻稿。2亚太生物制药资讯网 (2025) 报道：歌礼制药将首个用于治疗肥胖症的口服三重激动剂 ASC37 推进至临床开发阶段。3Fractyl Health。（2025）产品线概览，包括 REMAIN-1 试验。4世界卫生组织（世卫组织）。（2025）世卫组织发布关于使用GLP-1类药物治疗肥胖症的全球指南。5cardiovascular-risk-factors/ Fractyl Health。（2025）Fractyl Health 公布了为期 6 个月的 REVEAL-1 开放标签研究的积极结果，该研究显示，单次 Revita 手术后，患者在接受 GLP-1 治疗后体重能够持续维持。6Ventyx Biosciences。（2025）Ventyx Biosciences宣布其VTX3232在肥胖和心血管风险因素患者中进行的II期研究取得积极的初步结果。