GUTS

Good afternoon, and welcome to Fractyl Health First Quarter 2026 Financial Results and Business Update Call. As a reminder, this conference call is being recorded. At this time, all participants are listen only mode. There will be a Q&A session following management's prepared remarks. I'll now turn the call over to Brian Luque, Head of Investor Relations and Corporate Development at Fractyl. Brian, you may now begin.

Thank you. This afternoon we issued a press release that outlines the topics we plan to discuss today. This release is available at www.fractyl.com under the Investors tab. Joining us on the call today are Dr. Harith Rajagopalan, Chief Executive Officer, and Lara Smith Weber, Chief Financial Officer. During this call, we make forward-looking statements which involve risks and uncertainties that may cause our actual results to differ materially from those expressed or implied by forward-looking statements. A discussion of these risks and uncertainties is included in our filing with the SEC from time to time, including the section titled Risk Factors in our annual report on Form 10-K for the year ended December 31, 2025, and our quarterly report on Form 10-Q filed today, which I encourage you to review.

Any forward-looking statements on the call are subject to substantial risks and uncertainties, speak only as of the call's original date. We undertake no obligation to update or revise any of the statements, even if subsequent events cause our views to change. It is now my pleasure to pass the call over to Harith.

Thank you, Brian. Good afternoon, everyone. Tens of millions of Americans are now on GLP-1 therapy. Over 1 million people are discontinuing GLP-1s each month in the U.S. What happens next is increasingly well-characterized. Weight regain of roughly 10% of total body weight in the first six months and 15% total body weight by 12 months. Every one of those patients stopping a GLP-1 faces a moment with no durable off-ramp, no alternative to either resuming chronic pharmacotherapy or accepting the risk of the return of the weight they've worked so hard to lose. The more weight lost on GLP-1s, the greater the risk of rapid weight and metabolic rebound upon discontinuation. Revita is being built for that moment. On our Q4 earnings call in March, we made four commitments to this audience.

First, we said that the signal is real, and we understand with greater clarity how Revita works and in whom it works best. Second, we said that the pivotal trial is fully randomized, built to succeed, and executing on plan. Third, we said the path from clinical data to commercial value is clear and that we are actively building it. Fourth, we said that we have the financial runway to reach pivotal data without a planned capital raise and that we intend to hold that line. Q1 2026 was a quarter of execution, and today I want to reaffirm these four commitments and give you a clear accounting on each of them. Let me take them each in turn. First, the clinical signal is real. The medical community sees it and appreciates its potential.

In March, we shared two findings from our REMAIN-1 midpoint cohort study that formed the clinical foundation for the pivotal study. A larger treatment effect in participants with higher run-in GLP-1 induced weight loss and a statistically significant dose-dependent treatment effect tied to duodenal ablation length, the right dose in the right patients. In early May, we presented the REMAIN-1 midpoint cohort six-month data at Digestive Disease Week, or DDW, which is the largest international meeting in gastroenterology, hepatology, and endoscopy. DDW is jointly sponsored by four major medical societies and showcases more than 6,000 abstracts on the latest advances in GI research, medicine, and technology. Ahead of this year's meeting, the DDW program committee selected the REMAIN-1 midpoint cohort for its press program, one of only four studies featured from those 6,000+ accepted abstracts.

This was the first time the dose response analysis and patient selection findings were presented in a peer-reviewed setting to a broad and expert clinical audience. During the meeting, we convened a clinical advisory board with leading gastroenterologists and metabolic medicine physicians from across the country, and the discussions confirmed their alignment on the mechanism, the procedural rationale, and our pivotal study design. Beyond the science, these are the clinicians who, in our view, are best positioned to lead a center of excellence model in bariatric and metabolic endoscopy, pending potential FDA approval of Revita. We already have a strong network of champion physicians who have been part of our clinical trial program over the years, and we are cultivating even more relationships now in parallel with the pivotal study.

The enthusiasm among the physician community for a new therapeutic option in metabolic endoscopy, and in particular for a solution for post GLP-1 weight rebound, is real, palpable, and growing. When management tells you the clinical signal is real, that is our conviction. When the clinical community at the world's largest GI meeting chooses your study for more than 6,000 abstracts as one of the four most newsworthy and engages with the data on its scientific merits, that is external validation. When we begin lining up the clinical leaders who would deliver this therapy if and when it reaches the market, that is preparation. We have all three: conviction, scientific validation, and clinical champions.

Point number two, the pivotal is executing on plan. Not only does the clinical community appreciate that the Revita clinical signal is real and growing, the REMAIN-1 pivotal cohort completed randomizations in February with more than 300 participants across more than 30 sites across the United States. It's the largest sham-controlled GI endoscopy pivotal trial ever conducted. Every operational metric that predicts pivotal success continues to track favorably. Let's turn to the analytical framework for the pivotal cohort. We have two pre-specified co-primary endpoints. The first measures the percent total body weight regain at six months in Revita participants versus sham after the discontinuation of tirzepatide. This is the endpoint that anchors our early Q4 readout. As I noted earlier, the published trajectory in patients who discontinued GLP-1 therapy is to expect roughly 10% total body weight regain by six months.

Against that benchmark, a meaningful statistically significant reduction in regain in the Revita arm versus sham, particularly in participants with longer ablation lengths or higher run-in weight loss, is what we believe a successful readout looks like. The second co-primary endpoint is a responder rate at 52 weeks, defined as a percentage of Revita-treated participants who maintain at least 5% total body weight loss from pre-tirzepatide levels through one year. Together, these endpoints test both the magnitude and the durability of the Revita treatment effect. Alongside the co-primaries, we will also evaluate the high run-in weight loss patient selection and dose response as key secondary endpoints that emerged from the midpoint cohort data analysis. Participant retention in the pivotal study continues to exceed well over 90%. Medication resumption rates remain below our modeled assumptions.

The blinded adverse event profile remains consistently reassuring and in line with what we've seen in our prior studies. The study is running as planned. We remain on track as well to deliver top-line six-month primary endpoint data in early Q4 2026. The countdown to last patient six-month visit in Q3 is clear and well-defined. On regulatory progress, we previously reported in March favorable FDA feedback on our De Novo classification request, confirming our review that Revita's safety profile is consistent with a moderate risk rather than a high-risk device classification. I'm pleased to reaffirm that we are on track for FDA submission in late Q4 2026 with our six-month pivotal data in-hand. Number three, we are actively building the commercial path. The underlying commercial opportunity has only continued to accelerate since we last spoke to you.

In early April, FDA approved Foundayo, the first once-daily oral GLP-1 for chronic weight management. This is a meaningful development in its own right and a concrete accelerator of the population that will eventually face post GLP-1 weight regain. While the advent of oral GLP-1s provides more options for patients, early data suggests that patients are not titrating their oral GLP-1s or refilling them at the expected rates, indicating that the need for a durable alternative will likely still be very large, even though the number of GLP-1 initiators only continues to grow. These market dynamics are favorable for Revita's position in the market. On the payer side, public programs are moving to expand low-cost access to GLP-1 therapies for Medicare and Medicaid beneficiaries. The specific policy mechanics for GLP-1 coverage are still being worked out, but the underlying direction is unmistakable.

Seniors, a population with among the highest obesity prevalence and among the highest risk of GLP-1 discontinuation, will have meaningfully expanded access to these therapies over the next 18 months. That matters for Revita for a simple reason. Every additional patient who starts a GLP-1 is another patient who will eventually face the question of what to do when that drug is discontinued. As public payers take on more of the cost of chronic GLP-1 therapy, the economic case for a durable, long time alternative gets sharper. Remember, approximately 1 million patients per month are discontinuing GLP-1s and needing a safe and effective off-ramp. The problem of post GLP-1 weight rebound turns a chronic heterogeneous disease like obesity into an acute problem that mandates an acute solution. Today, the only options are to continue chronic pharmacotherapy or accept the risk of rebound. Revita is being built to be the third answer at that moment of decision.

One additional development from the past few weeks deserves special mention as well. In late April, CMS and FDA jointly announced the RAPID coverage pathway designed to align Medicare national coverage with FDA market authorization for eligible breakthrough devices. Under RAPID, CMS issues a proposed national coverage determination on the same day a device receives FDA authorization, with full national coverage and payment potentially in place within approximately two months. We believe Revita may be well-positioned to benefit from this pathway. Revita holds FDA breakthrough device designation in both weight maintenance after GLP-1 discontinuation and Type 2 diabetes. Our REMAIN-1 pivotal study is an FDA-approved IDE trial measuring clinically meaningful outcomes that we believe are relevant to both FDA review and Medicare coverage. We have a track record of CMS collaboration.

Our prior Revita IDE studies in Type 2 diabetes received Medicare coverage of routine costs and study-related expenses. RAPID builds on that foundation. The pathway is still early in implementation, and we are continuing to work through the specifics with our reimbursement experts. Our initial read is that RAPID materially de-risks and potentially accelerates the commercialization reimbursement timeline for Revita should we reach the market. Beyond RAPID, our broader reimbursement infrastructure continues to advance on schedule. We remain on track to file a Category III CPT code application this summer with a code that would be expected to be effective in the summer of 2027. Transitional passthrough payment from CMS continues to provide a clear, positive pathway to a favorable contribution margin for hospitals should Revita reach the market.

One lesson we are learning from physicians at DDW is that this transitional passthrough payment mechanism has been successfully used in GI endoscopy by centers across the country, presenting a compelling option for Revita centers of excellence to be able to secure payment soon after launch. To our knowledge, Revita remains the only potential procedural therapy in development for post GLP-1 weight maintenance. Certainly, it's the only potential post GLP-1 weight maintenance option with pivotal trial data expected within six months. Turning briefly to Rejuva, our smart GLP-1 gene therapy platform targeting long-term metabolic remission from a single dose. We recently received authorization from EU regulatory authorities in the Netherlands to initiate the phase I/II first in human study of the RJVA-001 drug candidate, the first clinical candidate from our Rejuva platform.

With this authorization, we believe RJVA-001 is the first AAV-based gene therapy candidate to enter clinical development for Type 2 diabetes, and Fractyl now advances Rejuva to a clinical stage, just as Revita is potentially poised to exit clinical stage and graduate to commercial stage over the coming quarters. RJVA-001 is a one-time beta cell-targeted gene therapy designed to enable nutrient-responsive physiologic GLP-1 expression within the pancreas, potentially avoiding the high circulating drug levels that contribute to side effects seen with systemic GLP-1 therapy. The therapy is delivered via a minimally invasive endoscopic ultrasound-guided infusion directly into the pancreas, and this authorization reflects years of rigorous translational work, deep engagement with regulators, and a disciplined tissue-targeted approach to local AAV gene therapy that we believe differentiates RJVA-001.

We also plan to conduct the study at other sites in Europe and in Australia, where a clinical trial application has also been submitted. Regulatory feedback for Australia is expected in the third quarter of this year. Pending site activation, we expect to dose the first patient with RJVA-001 and report preliminary data in the second half of 2026. As a deliberate part of our capital allocation strategy, Rejuva clinical development is funded within our existing cash runway into early 2027, beyond the anticipated REMAIN-1 pivotal data readout, and there is no change to our capital plans.

Before I turn to Lara, I want to spend a moment on what the next several months look like. Three Revita data readouts lie ahead between now and year-end. The first two will provide specific incremental signals about what the pivotal cohort is likely to show, and the third is the pivotal data itself. Before I walk through each, let me be specific about what a good result looks like because we get that question often. The published literature predicts that patients who have lost approximately 20% total body weight on GLP-1s and then stop that medicine regain approximately 15% of their total body weight within a year. Against that benchmark, we would view roughly a 50% reduction in weight regain or 7.5% or less as a strong 12-month result in these studies for patients, clinicians, regulators, payers, and investors alike.

Based on the dose response and patient selection findings we have already described, we would expect the signal to be even stronger in participants with higher run-in weight loss and longer ablation lengths. The pilot sham control data provide visibility into the right dose and the right patients, and the upcoming clinical milestones offer the opportunity to bear that thesis out. Investors have also asked whether we intend to present these upcoming data sets through the same dose response and run-in weight loss lenses we used at Q4 earnings. The answer is yes. The biology has not changed, and neither has our view of how to interpret the data.

In Q2, we will see one-year data from the REVEAL-1 cohort, our open-label study. REVEAL-1 enrolled a population with broadly varied run-in GLP-1 exposure and significant weight loss, representative of the variation we would expect to see in a real-world GLP-1 discontinuer population. 12-month data from this cohort is our first look at how durable the Revita treatment effect is after a full year of GLP-1 therapy. It will not on its own settle the durability question, but it is a critical important first read on the shape of the curve. Remember that REVEAL-1 patients lost more than 20% total body weight on GLP-1 over more than a year on medicine, and we would expect a regain of about 15% at one year in those who discontinue. We look forward to seeing what the data from REVEAL-1 cohort teach us. The second major data catalyst is in Q3, 12-month randomized sham control data from the REMAIN-1 midpoint cohort.

This is the same cohort in which we shared our six-month randomized data, now with six additional months of follow-up under a blinded randomized sham-controlled design. At six months, we observed a compounding monotonically increasing separation between Revita and sham in the optimized patient population. If that trajectory continues, 12-month randomized data will potentially show a durable treatment effect in the same cohort over a period of time that regulatory guidance equates to durability of therapeutic effect. The third major data catalyst is the pivotal itself, with top-line six-month data expected in early Q4. By the time this readout arrives, investors will have seen two prior data points through 12 months that provide the opportunity to build conviction leading into the definitive pivotal readout. We believe this is a potentially rich and systematic catalyst setup up into the year-end and potential regulatory filing.

With 12-month data from the REVEAL-1 and the midpoint cohort and top line six-month data from the pivotal cohort, the entire clinical profile for Revita in post GLP-1 weight maintenance has the potential to be substantially clarified and defined by Q4 of this year. Layer on top of this clinical profile, the favorable feedback we've already received on our device classification, the breakthrough device designation in GLP-1 weight maintenance, the streamlined reimbursement pathway just announced by CMS, and the vocal support of clinical champions in GI endoscopy, we believe we are set up for an exciting upcoming set of quarters. Catalyst summary. In Q2, the DDW presentations are now complete. RJVA-001 CTA regulatory feedback has been received, we will soon see REVEAL-1 12-month open label data. Q3, REMAIN-1 midpoint cohort 12-month randomized sham control data.

Early Q4, top line six-month randomized data from the REMAIN-1 pivotal cohort. Late Q4, potential De Novo marketing application submission for Revita in post GLP-1 weight maintenance. In parallel, in H2, we expect to see first-in-human dosing of RJVA-001 and reporting of preliminary data subject to first site activation for Rejuva. Lara?

Thank you, Harith. Research and development expenses were $15.6 million for Q1 2026 compared to $19.4 million for the same period in 2025. The decrease was primarily related to reduced spending on our Revita and Rejuva programs, as well as lower personnel-related expenses. SG&A was stable, coming in at $5.2 million for Q1 2026 compared to $5.3 million for the same period in 2025. We reported net income of $9.2 million for Q1 2026 compared to a net loss of $23.7 million for the same period in 2025. The shift was driven by a $30.1 million non-cash accounting change in the fair value of our warrant liabilities, which does not reflect a change in our underlying operating performance.

Our total operating expenses for Q1 2026 were $3.9 million lower than the same period in 2025. Adjusted EBITDA was negative $18 million for Q1 2026, compared with negative $23 million in Q1 of 2025. The decrease was primarily due to a decrease in operating expenses. As of March 31, 2026, we had approximately $63.2 million in cash and cash equivalents. Q1 spend included certain one-off costs, primarily associated with completing REMAIN-1 pivotal cohort randomization and is not representative of our expected run rate for the remainder of the year. Based on current business plans, this cash position is expected to fund operations into early 2027 beyond anticipated REMAIN-1 pivotal data readout in early Q4 2026 and through a potential De Novo submission in late Q4 2026.

With that, I'll turn it back to Harith.

Thank you, Lara. Before we open Q&A, I want to reaffirm our capital posture without ambiguity. Our ATM facility remains closed. We do not plan to raise capital before we have pivotal data in-hand. Our runway extends into early 2027. This posture is a deliberate choice grounded in conviction. We believe the pivotal data will be successful, and we are operating within our existing capital envelope as a signal of management alignment with shareholders through the most consequential six months in this company's history. I want to acknowledge the patients in our pivotal study who trust us with their health and their commitment, the investigators and operators who have executed the trial with skill and rigor, our employees whose focus through a demanding stretch of clinical and operational work has been exceptional, and our shareholders, whose conviction in the science makes everything we are building possible.

Operator, we're ready to take questions.

Thank you. At this time, we'll conduct a question and answer session. As a reminder to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Whitney Ijem of Canaccord Genuity. The line is now open.

Hey, guys. Thanks for taking our question. This is Angela on for Whitney. maybe a question to start on Rejuva. Can you just walk us through how you're thinking about enrollment timelines, the target product profile, what should we expect to see from the preliminary data set in the second half of the year?

Sure. Subject to site activation, there is a several week run-in period for first patients. Just remember, this is a three-by-three study design, first patients will be treated at an initial dose. We'll evaluate safety, feasibility, and initial PK/PD from those three individuals before we consider escalating to the next dosing regime. What you would expect is that each patient will be treated, and then there will be a short period of time in between each individual patient is dosed within each cohort. What the initial thing that we're obviously looking for, and the clear early signal pertains to the safety and the feasibility of the delivery, and that is an answer that we should be able to see within the first one-two weeks of patients being dosed.

We don't expect to really see preliminary PK and PD signals until roughly eight weeks afterwards when the GLP-1 level expression levels should be reaching their target levels, and then the effect on glucose and insulin-related physiology will be discernible. We'll give you an update after those first patients are enrolled on both initial safety and feasibility, and then you'll get a sense for what we expect to see from an efficacy standpoint.

Great. Thank you.

Thanks.

Thank you. One moment for our next question. Our next question comes from the line of Umer Raffat of Evercore. Your line is now open.

Hi, guys. This is Michael DiFiore in for Umer Raffat. Thanks so much for taking my question, and congrats on all the progress. A few quick ones from me. The first one regarding De Novo submission, Harith. My question is an all-comer pivotal success required for De Novo submission, or could a dose response or subgroup data influence the regulatory package there? Separately, any updates in the German commercial use, any insights gained from that? I know it's kinda been a while since that's been going on. Last question is, Yeah, I'll just leave it there. Thank you.

Sure. The De Novo pathway has a different clinical threshold than a PMA. Though I think we feel like we are highly confident in the pivotal trial success under any metric, I don't think that we have anything to worry about there. De Novo, because it's deemed moderate risk, has, you know, and because the FDA thinks about benefit/risk ratio, the De Novo seeks a reasonable assurance of safety and effectiveness, which is often translated to interpret as the totality of clinical evidence rather than any one single P value. I do think that there is flexibility there. I don't think we're going to need it.

With respect to German commercial use, we are continuing to follow patients, and we have patients who are. As you know, we reported two-year data last year to continuing to follow patients up to five years. We will have an update for you in the coming quarters once a reasonable number of patients have hit three years, which hasn't quite happened yet. That's the next major update to come. We're not giving guidance on exactly when that will be, but you can reasonably expect it to be coming in the coming quarters.

Great. Thank you.

Yeah. We're excited about what that can show about the durability of effect, obviously, and round out the clinical picture of what the real-world use looks like for Revita.

Thank you. One moment for our next question. Our next question comes from the line of Jason Gerberry of Bank of America Securities. Your line is now open.

Hey, guys. This is Chi Fong for Jason. Thanks for taking our question. Maybe just piggyback on the De Novo marketing application submission. Would you expect to file to include the one-year REVEAL-1 cohort data and the one-year REMAIN-1 midpoint cohort data in the submission package? To what extent those one-year data, while not in the pivotal cohort, to what extent those one-year data can support the totality of the data in terms of the De Novo marketing application? Thanks so much.

We'll be submitting all of the data to the FDA, and totality of data means totality of data. We've been working on Revita and establishing the science now for the better part of a decade. We have hundreds of patients that we've treated across a range of different clinical venues, clinical trial sites, and patient populations. We do intend to file on the REVEAL-1 data and the REMAIN-1 midpoint cohort data in order to contribute to the totality of that evidence. I believe that the FDA, based on prior experience with De Novo, will consider the totality of available evidence when making their marketing authorization decision in the De Novo pathway. I think that that provides us all of the reassurance and confidence that we are well on our way. The pivotal trial is built to succeed.

We have favorable feedback from the FDA. I think all signs are pointing green for us.

Okay. Great. Thanks.

Thanks.

Thank you. One moment for our next question. Our next question comes from the line of Mike Ulz of Morgan Stanley. Your line is now open.

Good afternoon. Thanks for taking the question. Maybe just to follow up on the RJVA-001 study that you're getting underway here. Can you just comment on the first dose cohort? Should we think about that as an active dose, or is the way to think about it is maybe you started with a lower dose to check the box on safety before you start increasing the dose. Thanks.

Yeah. Mandatory requirement here is that the first dose should be an active dose, and patients should be able to benefit from it. That's absolutely our intent with the first dose. This is a first time of performing this route of administration for this disease. We are obviously going to want to ensure that we are cautious in our approach in putting patient safety first. We are optimistic in being able to see active signals once enough time has transpired after the administration.

Great. Thank you.

Thank you.

Thank you. One moment for our next question. Our next question comes from line of Jeffrey Cohen of Ladenburg Thalmann & Co. Your line is now open.

Hi, Harith and Lara. Thanks for taking our questions. Firstly, could you talk about DDW a little bit and your advisory board and maybe give us a sense of some of the questions, curiosities, pushback, feedback, et cetera, that you received from physicians and clinicians?

I love DDW. It's a great meeting for us. The physicians who attend are leaders in GI endoscopy. Many of them are building practices around metabolic and bariatric endoscopy and are leaders in the society as well as in clinical practice around the country. We have been sharing our REMAIN pivotal midpoint cohort data, our REVEAL open label data. We've been walking through our pivotal study and our commercialization plans and have gotten incredibly positive feedback from folks all over the United States, from L.A. to New Hampshire, from Seattle, Washington, to Miami, Florida.

One benefit we have is that the clinical infrastructure that we built to run our pivotal studies, the physician relationships that we've established, the training that we've done, all represent the baseline sort of commercial distribution infrastructure with champions who are familiar with the technology, who have enrolled the patients in the study, who have seen how they have done with their own eyes. Their enthusiasm gives us the fuel and fire to continue to proceed in a way that is as optimistic as we are.

Super. Thanks for that. Then as a follow-up, could you maybe talk about any net material adds or changes to the IP portfolio the past quarter, including both, potentially Rejuva as well? Thank you.

We continue to strengthen our IP portfolio. We had in Q1, adds to the strength and breadth of our Revita portfolio, and we've been continuing to focus Rejuva on establishing a strong IP landscape around the device, around the procedure, and how the device and procedure and the gene therapy product and how they all work together to ensure what we believe will be a safe and feasible administration of the gene therapy. I don't know if any new patents were issued in the first quarter off the top of my head, but I'm gonna find out, and then I will get you that answer. We do have a very strong and robust portfolio across both Revita and Rejuva. Thank you.

Super. Thanks for taking the questions.

Thank you. One moment for our next question. Our next question comes to line of Joe Pantginis of H.C. Wainwright. Your line is now open.

Hello, everyone. This is Lander on for Joe. Thanks for the updates, and thanks for taking our questions. For Rejuva, when should we expect regulatory feedback from additional European countries for the phase I/II trial? Also, can you provide some color on past, current, or future interactions with the FDA for the progress of Rejuva in the U.S.? Thank you.

We have all of the feedback we need in order to initiate the RJVA-001 study in Europe, and I think that's the most important point. We chose Netherlands because there is an excellent, very highly regarded, internationally recognized GI endoscopist who does clinical research in the area at Amsterdam University Medical Center, where we anticipate our first patients in Europe being treated or being enrolled, has a track record of conducting high-quality gene therapy studies. Our next guidance for you is that we expect feedback from regulatory authorities in Australia in Q3. That's what I would look to next.

With respect to the FDA, While we've had positive repetitive interactions with the regulators in Europe, we have not yet approached the FDA on this topic and don't have a guidance for you yet on when we will. Our plan is to secure early safety feasibility data in this first human study before discussing with the FDA.

Awesome. Very helpful. Thank you so much. Thank you.

Thank you.

Thank you. I'll now turn the call back to Dr. Rajagopalan for closing remarks.

Thank you everyone. We are executing. The science is working. We have three major clinical catalysts from REMAIN-1 program coming in the next six months with pivotal top-line data in early Q4. Thank you for the call.

This concludes today's conference call. Thank you for participating. You may now disconnect.