Fractyl Health, Inc.

BURLINGTON, Mass., July 22, 2026 (GLOBE NEWSWIRE) -- Fractyl Health, Inc. (Nasdaq: GUTS) (the Company or Fractyl), a clinical-stage metabolic therapeutics company focused on pioneering novel approaches to treat obesity and type 2 diabetes (T2D), today announced that Harith Rajagopalan, M.D., Ph.D., Co-Founder and Chief Executive Officer of the Company, will be participating in the following upcoming investor conferences: BTIG Virtual Biotechnology Conference Format: One-on-one meetings Dates: July 28 – 29, 2026 Needham & Company MedTech & Diagnostics 1x1 Conference Format: One-on-one meetings Dates: August 10 – 11, 2026 Canaccord Genuity 46th Annual Growth Conference Format: Fireside chat and one-on-one meetings Date: August 12, 2026 Time: 8:30 AM ET ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); A live webcast of the conference call can be accessed in the “Events” section of Fractyl Health’s website at The webcast will be archived and available for replay for 90 days following the live event. About Fractyl Health Fractyl Health is a clinical-stage metabolic therapeutics company advancing two differentiated candidates designed to target the root causes of obesity and T2D: Revita, a procedural therapy in pivotal development for post-GLP-1 weight maintenance, and Rejuva, an AAV-based gene therapy platform with its lead candidate RJVA-001 entering first-in-human clinical studies. Fractyl’s goal is to advance metabolic disease treatment from chronic management toward prevention and reversal of disease. Fractyl is headquartered in Burlington, Massachusetts. Contact Brian Luque, Head of Investor Relations and Corporate Development IR@fractyl.com, 951.206.1200

Up to 84% of GLP-1 induced weight loss retained with Revita® versus 46% with sham at one year in patients receiving complete duodenal ablations Next anticipated Revita® milestones are topline six-month randomized data from the REMAIN-1 Pivotal Cohort in early Q4 2026 and a potential FDA De Novo marketing application submission in late Q4 2026 Company to host investor webcast today at 8:00 a.m. ET BURLINGTON, Mass., July 15, 2026 (GLOBE NEWSWIRE) -- Fractyl Health, Inc. (Nasdaq: GUTS) (the Company or Fractyl), a clinical-stage metabolic therapeutics company focused on pioneering novel approaches to treat obesity and type 2 diabetes (T2D), today announced positive one-year results from its REMAIN-1 Midpoint Cohort (“Midpoint Cohort”). The new results reinforce the potential of the Revita DMR System (Revita) to be the first durable procedural therapy for post-GLP-1 weight maintenance. Key Findings: Dose-dependent durability confirmed at one year: In the full modified intention-to-treat (mITT) population (N=45), a single Revita procedure reduced weight regain by approximately 40% versus sham at one year (least-squares mean weight regain of 7.8% versus 13.0% of body weight; n=29 versus 16 for Revita versus sham). Participants who received complete duodenal ablation (>14 cm) maintained approximately 81% of GLP-1-induced weight loss at one year, compared with 48% in sham participants (least-squares mean weight regain of 4.8% versus 13.0% of body weight; n=17 versus 16 for Revita versus sham), reflecting a reduction in weight regain of over 60% versus sham. This is consistent with earlier findings that more complete duodenal ablation drives greater treatment effect. Greatest benefit in patients with greatest need: In an optimized population of participants who received complete duodenal ablation (>14 cm) and had higher GLP-1 run-in weight loss (≥17.5%), Revita maintained approximately 84% of GLP-1-induced weight loss at one year versus 46% with sham (least-squares mean weight regain of 4.1% versus 13.5% of body weight; n=10 versus 8 for Revita versus sham). These results are consistent with the view that patients at greatest need may derive the greatest benefit from Revita due to their higher propensity for weight regain after GLP-1 discontinuation. Weight-maintenance responder rate: The second co-primary endpoint of the Pivotal Cohort, assessed against a U.S. Food and Drug Administration (FDA) mandated pre-specified performance goal of >50%, measures the proportion of Revita patients maintaining at least 5% total body weight loss relative to their pre-tirzepatide weight at one year. As a reference point for the Pivotal Cohort, this responder rate was 73% in the Midpoint Cohort mITT population, rising to 91% in those with complete duodenal ablation (>14 cm). Excellent tolerability: No device- or procedure-related serious adverse events occurred. No new device-related treatment-emergent adverse events (TEAEs) were observed between six and 12 months. Overall TEAE rates were comparable between arms through one year (24% Revita versus 25% sham), reflecting a generally mild peri-procedural adverse event pro supports potentially broad outpatient use for Revita. One new diagnosis of type 2 diabetes occurred in the sham arm versus none with Revita. Figure 1: Change in body weight in (i) Complete Ablation population: > 14 cm duodenal ablation, no run-in weight loss restriction (Sham n=16, Revita n=17) and (ii) Optimized population: complete ablation (> 14 cm) and run-in weight loss ≥ 17.5% (Sham n=8, Revita n=10). Y-axis: LS-mean % total body-weight change from baseline; MMRM, compound-symmetry covariance, estimated at 20% run-in weight loss; error bars ± SE; n contributing shown per visit below axis. Retention = % of run-in weight loss maintained at 12 months. Exploratory REMAIN-1 Midpoint Cohort subgroup; not powered for formal inference. Abbreviations: MMRM, mixed-model repeated measures; LS-mean, least-squares mean; SE, standard error. “The success of GLP-1 medicines has created a new unsolved problem: what happens when patients stop. Most do stop eventually, whether because of cost, side effects, or simply not wanting to inject a drug for the rest of their lives. When they stop, the weight most often comes back,” said Harith Rajagopalan, M.D., Ph.D., Co-Founder and Chief Executive Officer of Fractyl. “Today's results are the first randomized, sham-controlled evidence that a single Revita procedure can keep most of the weight off for a full year after GLP-1 is stopped, without the need for ongoing medication. We eagerly anticipate an early Q4 2026 topline readout from the REMAIN-1 Pivotal Cohort with deep conviction that Revita may represent the first procedural entrant into the post-GLP-1 weight maintenance category.” Webcast Fractyl Health will host a webcast today, July 15, 2026, at 8:00 a.m. Eastern Time. The live webcast can be accessed by clicking this link . This webcast can also be found in the “Events” section of Fractyl’s website at ir.fractyl.com. The webcast will be archived and available for replay for at least 30 days after the event. About REMAIN-1 Weight Maintenance Program REMAIN-1 is Fractyl Health’s pivotal program evaluating Revita for weight maintenance in adults with obesity following discontinuation of GLP-1 therapy. The Midpoint Cohort (N=45) is a randomized, double-blind, sham-controlled study in adults who achieved at least 15% total body weight loss on tirzepatide; after discontinuing the drug, participants were randomized 2:1 to a single Revita procedure or a sham endoscopic procedure and followed for one year. The Midpoint Cohort is not powered for formal statistical significance; results are descriptive and are intended to characterize the treatment effect and inform the Pivotal Cohort design and execution. Results in the Midpoint Cohort at one year are evaluated per the pre-specified statistical analysis plan defined for the pivotal study, with GLP-1 weight loss fitted as a covariate on treatment effects, calculated as least-square means at the 20% reference. Both a Complete Ablation cohort (defined as >14cm of duodenal ablation) and an Optimized responder population (with > 14 cm duodenal ablation and ≥17.5% run-in weight loss) are pre-specified key secondary endpoints in the pivotal study. The Pivotal Cohort is fully randomized and well powered at the expected effect size to clear both co-primary endpoints in the modified intention-to-treat (mITT) population: (i) weight regain at six months (Revita versus sham) and (ii) a responder rate defined as the proportion of participants maintaining at least 5% total body weight loss relative to their pre-tirzepatide weight at one year. Topline six-month randomized data from the Pivotal Cohort are anticipated in early Q4 2026. About Revita Revita is Fractyl Health’s lead product candidate, designed to remodel the duodenal lining via a one-time, minimally invasive endoscopic procedure intended to restore healthy nutrient sensing and signaling disrupted by chronic metabolic disease. Revita has received Breakthrough Device designation from the FDA for weight maintenance in people with obesity who discontinue GLP-1 therapies. Revita is for investigational use only in the United States and is CE marked in the European Union and United Kingdom. About Fractyl Health Fractyl Health is a clinical-stage metabolic therapeutics company advancing two differentiated candidates designed to target the root causes of obesity and T2D: Revita, a procedural therapy in pivotal development for post-GLP-1 weight maintenance, and Rejuva, an AAV-based gene therapy platform with its lead candidate RJVA-001 entering first-in-human clinical studies. Fractyl’s goal is to advance metabolic disease treatment from chronic management toward prevention and reversal of disease. Fractyl is headquartered in Burlington, Massachusetts. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact are forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, without limitation, statements regarding: the promise and potential impact of our clinical trial data and product candidates, including Revita’s potential for maintaining weight loss after GLP-1 based therapy discontinuation and stabilizing cardiometabolic parameters; the translatability of results and scalability of technique related to Revita; the design, initiation, timing and results of clinical enrollment and any clinical studies or readouts, including readouts from the REMAIN-1 Midpoint Cohort and the REMAIN-1 Pivotal Cohort; the potential launch or commercialization of any of our product candidates or products; our regulatory strategy, including potential use and benefits of the De Novo pathway (FDA pre-submission feedback is advisory and non-binding, and there is no assurance that FDA will accept a De Novo marketing application submission or that Revita will receive marketing authorization); the potential treatment population or benefits for any of our product candidates or products; our strategic and product development objectives and goals; and the timing of any of the foregoing. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the risks that are discussed more fully in our filings with the Securities and Exchange Commission (the SEC), including the “Risk Factors” section of our Annual Report on Form 10-K for the year ended December 31, 2025, filed with the SEC on March 24, 2026, and other documents we subsequently or furnish to the SEC, including our Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, filed with the SEC on May 12, 2026. These forward-looking statements are based on management’s current estimates and expectations. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. Contact Brian Luque, Head of Investor Relations and Corporate Development IR@fractyl.com, 951.206.1200 A photo accompanying this announcement is available at

打一针,然后接下来两个多月,你的肌肉细胞开始自己生产减肥药。 费城Wistar研究所今年6月刚发表的一篇论文,写的正是这件事，而且这两天在X上被反复转发。种子帖配的信息图一目了然:一支注射器,一束肌肉纤维,旁边写着"UP TO 70 DAYS""10× longer"。 评论区很快吵起来了。有人兴奋,觉得每周挨一针的日子可能要到头;也有人当场泼冷水:小鼠身上管用的减肥药,到人身上翻车的例子太多了。每周一针,停药就打回原形 先弄清楚这项研究到底在回应什么麻烦。 GLP-1(胰高血糖素样肽-1)和GIP(葡萄糖依赖性促胰岛素多肽),是肠道进食后分泌的两种激素,统称肠促胰岛素(incretin)。它们让胰腺在血糖升高时多分泌胰岛素、让胃排空变慢、让大脑觉得吃饱了。司美格鲁肽(semaglutide,也就是Ozempic和Wegovy里的活性成分)、替尔泊肽(tirzepatide,Mounjaro/Zepbound),靠的都是模拟这两种激素。 麻烦在于,天然GLP-1在血液里只能撑2分钟左右,GIP也就4到5分钟,很快被一种叫DPP-IV的酶切断失活。药厂做的都是"抗降解版本",可即便加了脂肪酸链延长半衰期,大多数产品还是得每周挨一针,少数做成每日口服。 停药会发生什么,已经是被反复验证过的现实:体重和血糖往回走,医学界管这个叫"代谢回力镖"。停药的理由五花八门，恶心、价格、供应链、生育计划、达到目标体重后想歇一歇，反弹却总是如约而至。 Wistar团队想动的,正是给药方式本身这层麻烦:能不能打一针,让身体自己连续造药,把"终身每周一针"变成一次偶发的事件? ▲ @SciTechera 2026年7月9日发布的提醒帖:约24赞、5转发、7收藏、1.3k浏览。信息图把"70天""10×"两个数字摆在了最显眼的位置。打一针,身体自己造了70天的药 这项研究由Wistar研究所Ebony N. Gary领衔,资深作者是David B. Weiner，他执掌Wistar疫苗与免疫治疗中心多年,是合成核酸疗法领域的资深人物。论文6月19日在线发表于Cell Press旗下的Trends in Biotechnology,开放获取。 官方新闻稿里,Gary这样描述团队的目标: "What we're trying to do here is simple: We want to deliver a drug once and have it work for a really long time." 「我们想做的事情其实很简单:打一针药,让它管用很长很长时间。」 具体怎么做到?团队设计了一种环状质粒DNA,里面装着抗降解、抗切割的GLP-1和GIP类似物基因序列,还把它们和抗体的Fc片段融合在一起，Fc片段能借助FcRn循环通路,把这些小分子在血液里的存活时间大幅拉长。这类构建被命名为pLincretins(plasmid-encoded long-acting incretins,质粒编码长效肠促胰岛素)。 质粒注射进小鼠肌肉后,团队用电穿孔(electroporation)，极短的电脉冲,在细胞膜上打出可逆的微孔,帮质粒挤进细胞核。核里的DNA被转录、翻译成蛋白,再分泌进血液,肌肉就这样被临时改造成了一座药物工厂。 新闻稿反复强调一条边界:这套质粒不碰染色体本身,只负责递送一份临时的生产说明书。它会随着细胞分裂被稀释、被酶降解，读完就作废,不会写进你的染色体,也不会遗传给下一代。 结果是,饮食诱导肥胖(DIO)的糖尿病小鼠,单次注射pLincretins后,团队检测到肠促胰岛素蛋白持续表达长达约70天,体重、摄食量和血糖都随之持续改善。头对头对比里,司美格鲁肽组一旦停药就开始回涨体重,DNA组在观察期结束时仍然维持着改善，新闻稿把这个时间差,总结成"约10倍于Ozempic/Wegovy类药物"的时长。 ▲ Wistar研究所2026年6月26日官方新闻稿,标题写明了"single-dose DNA method"与"10 times as long as...Ozempic and Wegovy"。 团队没有止步于分别表达GLP-1或GIP,又用AI结构建模(借助AlphaFold一类工具)加合成共有序列,设计出pSynCretin，一个能同时激动GLP-1受体和GIP受体的分子,概念上对标替尔泊肽这种双受体激动剂,只是这次由DNA在体内现场生产。论文称单剂pSynCretin同样在小鼠身上驱动了明显减重。兴奋归兴奋,论文自己先泼了盆冷水 科普账号的标题起得格外抓人,论文正文的语气却谨慎得多。开篇专门有一段"Technology readiness"(技术就绪度),按行业通用的TRL分级给自己打分: 更宽泛的肌肉电穿孔DNA生物药平台，已经在人体完成过两株抗体的表达试验,接近TRL 6(相关临床环境中的技术演示);这次的肠促胰岛素具体实现，只有TRL 4,即候选分子优化、非GLP规范下的体内药效证明。 换句话说,平台本身已经在人身上跑通,肠促胰岛素这个具体应用,才刚从小鼠身上拿到第一批说得过去的数据。下一步要做的,是IND前的毒理和生物分布研究、长期药代动力学和免疫原性数据、大动物代谢试验,之后才轮得到人体临床方案设计。 ▲ Trends in Biotechnology论文页面,"Technology readiness"段落把平台的TRL6和肠促胰岛素应用的TRL4分成了泾渭分明的两条线,这是判断这项研究离临床还有多远的关键依据。72周人体数据,才是这个故事的底气 如果只有70天的小鼠数据,这篇论文大概率会被归进又一批"预临床减肥新闻"。让它显得可信的,是同一个团队早几个月交出的另一份成绩单。 2025年10月,Wistar联合宾大、Inovio Pharmaceuticals、阿斯利康等机构,在Nature Medicine发表了DMAb(DNA-encoded monoclonal antibody,DNA编码单克隆抗体)的首次人体试验结果:同样是肌肉注射加电穿孔,这次装载的是两株新冠中和抗体的基因指令。健康受试者体内,抗体表达持续检测到72周,所有可评估参与者体内都测到了抗体,浓度峰值达到1.61微克/毫升，接近部分已获批生物药的水平,而且没有观察到抗药抗体(ADA)。 Weiner在当时的新闻稿里说: "While FIH studies require cautious interpretation, and rigorous validation, the long-term expression of biologic antibodies with demonstrated fidelity and functionality in all volunteers without induction of anti-drug antibodies represents an important development for the biologics field." 「首次人体试验的结果需要谨慎解读、严格验证,但所有志愿者体内长期表达的生物抗体都保持了准确的功能,还没有诱发抗药抗体，这对整个生物药领域是重要的进展。」 ▲ 2025年10月21日的DMAb人体首例试验新闻稿,72周的抗体表达数据,是把"肌肉造药"从假设推到现实的关键一步。 有了这72周垫底,Gary团队的逻辑顺理成章:同一套递送系统,已经证明能让人体肌肉持续生产复杂的抗体蛋白,这次把载荷换成经过Fc融合改造的肠促胰岛素,只是往同一个方向多走了一步。Gary本人的说法更坦率: "The really amazing part of this research is that once we have this toolkit, we can think about making novel proteins that didn't exist before…" 「这项研究真正让人兴奋的地方在于,一旦拥有这套工具,我们就可以着手制造那些世界上原本不存在的全新蛋白质……」 一台可靠的打印机造好了,能换的墨盒,理论上远不止减肥药一种。X评论区,吵的是另一件事 高互动科技博主@kimmonismus把这项研究整理成长贴转发,标题相当挑衅: "Forget GLP-1 drugs like Ozempic and Wegovy... The whole game is to be changed." 「忘掉Ozempic、Wegovy这类GLP-1药物吧……整个赛道可能要被改写。」 这条帖子拿下339赞、2.2万浏览,是这次讨论的主战场。可认真翻评论区就会发现,大多数较真的回复,聊的其实是数据之外的东西。 ▲ @kimmonismus 2026年6月30日发布的摘要帖:339赞、2.2万浏览,评论区聚集了这次讨论里最多的专业质疑。 科普博主@just_askkim的回复算是给出了一个平衡的判断:研究是真的,70天数据是真的,平台在人身上验证过其他蛋白也是加分项;但"忘掉Ozempic"说得太早，小鼠身上有效、人身上翻车的减肥药太多了。真正让他在意的,是停药权的问题:司美格鲁肽不舒服可以停,一针管几个月的DNA表达,没法说停就停。 @vedichi_的回复把这层担忧说得更利落: "the catch: you lose the off switch... can't exactly titrate a plasmid." 「隐患在于:你丢掉了'关断开关'。质粒可没法精确滴定。」 ▲ @vedichi_ 的回复直指核心矛盾:眼下GLP-1讨论里,很大一部分是患者在食欲被压得太狠时往回调剂量，质粒做不到这一点。 也有更专业的追问。@bo_joust想知道pSynCretin这个双激动分子,是像替尔泊肽一样设计了特定的受体激活比例,还是把GLP-1和GIP两段序列简单叠在了一起,这个细节要等论文全文里的受体信号数据才能回答。@gurtej__gill_的态度更正面:如果人体试验真能走通,"临时质粒表达"这件事本身分量很重，它说明长效不等于永久改写。而@RobertDMellish的回复,给这场讨论泼了最后一盆水: "'in animal models' is Proxima Centauri away from meaningful. Feels close. It ain't." 「'动物模型'离真正有意义的结果,隔着比邻星那么远。感觉很近,其实没有。」 ▲ @RobertDMellish 的回复代表了评论区里最谨慎的一派声音:动物实验的乐观,历史上很少能原样搬到人身上。谁都想把身体变成GLP-1工厂 这个方向上,同时发力的团队远不止Wistar一个。 RenBio走的是几乎一样的技术路线:裸质粒加盐水溶液,肌肉电穿孔,不整合染色体。CNN去年11月的报道里,他们的小鼠最佳数据是约15%体重下降,并维持至少一年量级,团队还专门做了猴子实验,计划先把平台用在寨卡病毒抗体这类人体应用上练手。这条路线更偏向"减肥药维持期"的定位，一年一针甚至两年一针。 另一条路线走得更极端。Fractyl Health的Rejuva项目,用腺相关病毒(AAV)把GLP-1指令送进胰岛素分泌细胞,目标是一次注射,终身生效。小鼠数据能做到约20%减重,团队甚至称优于司美格鲁肽,但UCLA等专家提醒:病毒载体带来的改变很难逆转,一旦体内表达量随年龄或疾病状态失控,回头路不好走。Fractyl已经在欧洲递交了人体试验相关文件,目标是在2026年前后拿到人体数据。 两条路线的分野其实相当鲜明:一条是可以被身体慢慢清除的"软件更新"(Wistar、RenBio),另一条是长期驻留的"固件刷写"(Fractyl)。前者更容易被当作"长期但非终身"的疗法接受,后者的效果愿景更彻底,面对的安全与伦理审视也重得多。Wistar这次站的位置,恰好是可清除的技术路线,叠加已经跑通的72周人体先例,故事讲起来才显得步步为营。焊死的旋钮,才是真正的门槛 把所有信息摆在一起看,这项研究真正值得记住的,是它悄悄改写了"什么才算一次治疗"这件事的定义，"10倍"只是一个抓眼球的数字。 司美格鲁肽时代,默认患者是要终身反复注射蛋白药的人;肌肉造药模型默认的,是患者只需要接受一次"指令更新"。这个转变里,商业模式、医患关系、副作用管理的逻辑,都得跟着重新写一遍。 但评论区里最聪明的那批反对意见,戳中的其实是同一个点:每周一针虽然麻烦,却给了患者和医生一个能随时拧动的旋钮，不舒服就减量,效果好就维持。持续数月的体内自产,相当于把这个旋钮焊死了几个月。食欲被压得太狠怎么办?营养不良怎么办?电穿孔设备能不能像笔式注射器一样,在社区诊所铺开?这些问题,眼下都没有答案。 论文自己给出的TRL4定位很诚实，这更像是一款还在路上的候选技术:平台已经在人身上证明能造蛋白,代谢载荷刚刚才在小鼠身上证明了药效。从小鼠到人,历史上失败的减肥药案例远比成功的多。 真正决定这项技术能走多远的因素,大概率是有没有人先把可滴定的启动子、可诱导的表达开关这些工程问题解决掉，单纯把药效再拉长十天,解决不了旋钮的问题。旋钮什么时候能重新拧动,答案还得靠接下来的大动物实验和人体临床试验去回答。