Fractyl Health, Inc. (GUTS) Q3 FY2025 Earnings Call Transcript & Summary

Good afternoon, and welcome to Fractyl Health Third Quarter 2025 Financial Results and Business Update Call. As a reminder, this conference call is being recorded [Operator Instructions]. 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 Lisa Davidson, Chief Financial Officer. During this call, we'll make forward-looking statements which involve risks and uncertainties that may cause actual results to differ materially from our forward-looking statements. We provide a comprehensive list of risk factors in our SEC filings, including the 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, and we undertake no obligation to update or revise any of the statements, even if subsequent events cause the company's views to change. It is now my pleasure to pass the call over to Harith.

Thank you, Brian. Good afternoon, everyone. This quarter marked a major inflection point for Fractyl. We delivered the first randomized, double-blind, sham-controlled data showing that a single Revita procedure can sustain weight loss after GLP-1 drug discontinuation. We believe Revita addresses one of the most urgent challenges in obesity, which is how to maintain success once therapy stops. We also strengthened our balance sheet to support our upcoming clinical and regulatory milestones into early 2027, and we continue to advance our clinical programs ahead of schedule, setting the stage for a series of important catalysts on weight maintenance over the next several quarters. Across every front, clinical, regulatory and financial, we are building momentum toward what I believe will be the most exciting and definitional 12 months in our company's history. The science is working, the data are strong and the opportunity ahead of us has never been clearer. Let's start with Revita. Revita is our endoscopic procedural therapy designed to remodel the duodenal lining via hydrothermal ablation to address a root cause of metabolic disease. Revita resets the gut's metabolic control system, the duodenum, which is a key site of nutrient sensing and signaling in the gut and is hardwired to the brain through a key gut-brain connection that controls body weight and blood sugar. Decades of high fat and high sugar diet can damage this duodenal lining, disrupt gut-brain signaling and drive hunger and insulin resistance. Revita is designed to remove this damaged tissue and allow a healthy new lining to regrow, restoring normal gut-brain signaling and metabolic balance. It's like LASIK for obesity. Since enrolling the first patients in our REMAIN weight-maintenance program in August of 2024, the last 5 quarters have been a period of incredible clinical operational execution and momentum. In September, we reported 3-month data from the REMAIN-1 Midpoint Cohort. Revita-treated patients lost an additional 2.5% of total body weight, while patients in the sham group regained about 10%, a statistically significant and clinically meaningful separation after the discontinuation of tirzepatide. The procedure was well tolerated with no related serious adverse events. These results not only materially derisk the pivotal readout ahead, they also represent a true turning point in metabolic medicine. If Revita continues to sustain weight loss at 6 and 12 months, in line with the durability we have seen across prior clinical studies involving hundreds of patients with Revita, we believe we will have a transformative new treatment option in obesity. Enrollment in our REMAIN-1 pivotal cohort was completed in Q2 and randomizations in that cohort are progressing ahead of schedule. As of October 31, we have randomized over 60% of the pivotal cohort patients, and we are on track to complete randomization of the full 315 participants early next year. This pivotal study has advanced ahead of plan from the outset, and we are executing it with the focus and precision that this opportunity deserves. Looking ahead, we expect a rich set of value-creating catalysts in the coming quarters, 6-month data from the REVEAL 1 open-label cohort this quarter, 6-month randomized data from the REMAIN-1 Midpoint Cohort in the first quarter of 2026 and top line pivotal data and potential PMA submission in the second half of 2026. Based on prior Eli Lilly studies, patients who stop GLP-1 therapy typically regain about 10% of their body weight by 6 months. We believe that Revita can be a highly successful therapy if it cuts the rate of weight regain in half, so roughly less than a 5 percentage point weight regain at 6 months, which would represent a clinically meaningful and substantial benefit for patients and a strong validation of Revita's potential. We believe Revita is defining a new therapeutic category in obesity post GLP-1 weight maintenance, a category that complements, not competes with chronic drug therapy and provides the off-ramp that patients and physicians have been waiting for. Millions of Americans are expected to discontinue GLP-1 therapy over the next year. Every one of them will face the challenge of keeping the weight off. Revita is built for that moment. Durability is central to Revita's value, and a huge advantage compared to chronic pharmacology, and we continue to see encouraging real-world durability outcomes in Revita clinical studies, including in Germany. In our German real-world registry study, 30 patients have now reached 1 year of follow-up and 14 patients have reached 2 years of follow-up. The first 14 patients with 2 years of follow-up maintained an average total body weight loss of 9% and a 1.7% reduction in HbA1c in a patient population with advanced type 2 diabetes, despite a net reduction in medications. Three-month results were highly predictive of 6-, 12- and 24-month results. These durable outcomes not only strengthen our confidence as we move toward a pivotal readout in REMAIN-1, but also underscore Revita's potential to deliver long-lasting benefit in real-world settings. By this time next year, we expect to have 1-year open-label data in weight maintenance, top line data from our REMAIN-1 pivotal cohort and a larger sample of patients with 2-year data and beyond from our German real-world registry study. Taking these clinical proof points together, we believe Revita will have a compelling and comprehensive clinical data package that will be ready for both regulatory filings and reimbursement discussions by the second half of next year. Revita's durable activity also drives its economic rationale by potentially reducing the need for ongoing drug therapy and reducing the risk of downstream adverse health outcomes, it offers a multiyear health and cost advantage for payers who are seeking sustainable alternatives to chronic GLP-1 treatment. In light of this, we are encouraged by the recent announcement from the U.S. government on GLP-1 access in Medicare. Expanding access to these medicines is good for patients, and it's good for the field. More patients starting GLP-1s, either as injectables or as orals also means more patients who will eventually need an off-ramp when most, inevitably, discontinue treatment. Our clinical work and our relationships have also positioned us well for rapid activation once Revita is approved. Many of the physicians participating in our clinical studies are experienced users of the procedure, committing to treating obesity and metabolic disease with their endoscopic skills, and they are based at leading centers across the country, already active at major clinical centers from Miami to Seattle, from New England to Southern California and together with partners like Bariendo, we have already established and have a ready-to-activate footprint at several of the highest volume endoscopy centers in the U.S. This enables, in our view, a targeted and efficient commercial model for us or our partners to access upon approval. Our market analysis confirms the size and strength of this opportunity. Because the procedure fits naturally into an existing endoscopy workflow, Revita could reach nearly 1 million annual procedures at peak adoption, translating to a sizable revenue opportunity. Importantly, Revita's unit economics create strong incentives for adoption at the clinical site level. We expect gross margins for participating centers to be comparable to or better than other advanced endoscopic interventions, creating meaningful financial alignment between clinical and commercial stakeholders. Taking a step back, what we are talking about is potentially the first scalable therapy that addresses the root cause of obesity and type 2 diabetes and can change the trajectory of both diseases. If Revita is successful in post GLP-1 weight maintenance, a hard-to-treat and high unmet need patient segment, we believe it can be effective across the spectrum of metabolic disease, not only for maintenance, but also as frontline; not only as a stand-alone therapy, but also in combination with weight loss medications. Turning to Rejuva now, our Smart GLP-1 platform, we continue to make exciting progress. Earlier this month, we presented new preclinical data from RJVA-002, our candidate for obesity, which showed nearly 30% body weight loss after a single dose in a translational obesity model with no observed adverse effects. RJVA-001, our lead candidate in type 2 diabetes is designed to reprogram pancreatic islet cells to secrete GLP-1 in response to glucose with the goal of restoring physiologic hormone regulation and achieving long-term metabolic remission. We have now completed our preclinical CMC and lot release for our RJVA-001 drug product. And with all preclinical milestones now checked off, we remain on track to dose the first patients and report preliminary data in 2026. Between Revita and Rejuva, complementary endoscopic approaches designed to reset the gut and reprogram the pancreas, we are building a platform that can fundamentally change how metabolic diseases are treated. Our differentiation is our strength. Our product candidates are designed to do what the majority of patients need, but current therapies cannot deliver; durable, physiologic and designed to work with the body, not against it. Now let me hand it to Lisa to discuss our financials.

Thank you, Harith. Turning now to our financial results for the third quarter of 2025. For the quarter ended September 30, research and development expenses were $17.5 million compared to $19.0 million for the same period in 2024. The decrease was primarily due to reduced spending on the REVITALIZE-1 study and lower stock-based compensation expense, partially offset by continued investment in the REMAIN-1 pivotal study and Rejuva program. Selling, general and administrative expenses were $5.2 million compared to $4.8 million in the third quarter of last year. The year-over-year increase primarily reflected onetime costs associated with the issuance of warrants in connection with our August underwritten public offering. We reported a net loss of $45.6 million compared to $23.2 million in the same period of 2024. The variance was largely driven by a $23.5 million non-cash accounting change in the fair value of warrants and does not reflect a change in our underlying operating performance. As of September 30, 2025, we had approximately $77.7 million in cash and cash equivalents. With the proceeds from our recent $83 million in underwritten offerings, we expect our cash runway to extend into early 2027. funding key milestones, including 6-month randomized data from the REMAIN-1 Midpoint Cohort, top line pivotal data and our potential PMA submission. Overall, we remain in a strong financial position, well capitalized to advance our strategic and clinical priorities in the quarters ahead. Back to you, Harith.

Thank you, Lisa. As we look ahead, the path for Fractyl Health is clear and compelling. Within the next 12 months, we expect multiple catalysts that will transform the company. REVEAL 1, 6-month data in Q4, REMAIN-1 midpoint 6-month data in Q1, REVEAL 1 1-year data in Q2, top line pivotal data and potential PMA submission of our PMA to the FDA, both in H2 2026, all funded by a strong balance sheet that extends into early 2027. Each of these milestones moves us closer to delivering a first-in-class, durable, non-drug solution for obesity and type 2 diabetes. With those catalysts ahead, our growing body of data, expanding clinical footprint and strengthened balance sheet, we are entering 2026 with confidence, clarity and purpose. I am incredibly proud of how far we have come, and I'm more excited than ever about where we are headed. With that, I would like to thank the people who make this work possible. To our employees, thank you for your relentless drive and belief in our mission. To the physicians and investigators advancing our clinical programs with care and commitment, we are proud to partner with you. And to the patients participating in our trials, thank you for your courage and your trust. To our investors, thank you for your continued support and conviction. Together, we are building what comes next in metabolic medicine. Operator, we are now ready to take questions.

[Operator Instructions] And our first question comes from the line of Jason Gerberry of Bank of America Securities.

This is Chi on for Jason. I guess, Harith, could you just walk us through what you are looking for with the 6-month update for REVEAL-1 in 4Q and also the 6-month update for REMAIN-1 midpoint in 1Q as you think about -- looking at Revita profile as it pertains to, say, durability of benefit?

Sure, Chi. Thanks for the question. The 6-month REVEAL data set coming up later this quarter will be our first look at patients 6 months after stopping a GLP-1-based therapy and then undergoing Revita procedure. We have hundreds of patients' worth of experience in type 2 diabetes with Revita as a primary therapy, all of which have shown that 1- and 3-month results are excellent predictors of durability at 6, 12 and 24 months. And so, our hope would be to see a similar consistency of results between 3 months and 6 months. Based on SURMOUNT-4's tirzepatide data where tirzepatide was withdrawn, patients typically regained about 10% of their body weight within 6 months after discontinuing treatment. So, looking at REVEAL and REMAIN upcoming 6-month data, if Revita patients are able to regain less than half of that body weight or less than 5% total, that would be a very compelling outcome and a very strong signal heading into the pivotal trial. Remember that 6 months is important because it is also the timing of the pivotal trial's primary endpoint. And so, because of the fact that our REVEAL open-label data at 3 months translated to the main randomized data at 3 months, we're very hopeful and optimistic that the 6-month data from REVEAL and the REMAIN midpoint will translate very directly to positive read-through for the full pivotal study, whose data are expected next year.

Yes. That sounds great. If I may squeeze one in. It looks like the pivotal cohort for REMAIN-1 is randomizing ahead of schedule. It looks like you're expecting randomization to complete in early 2026. And as we think about the primary analysis being 6 months, should we expect potentially a readout early part of second half 2026?

Yes, that is a very reasonable expectation, Chi. We are heading towards completing randomizations early in '26. The last patient visit, we expect early, as very early in the latter half of the year. And so, we feel very confident based on where we sit today in the timing of our pivotal top line readout and PMA submission, both in the back half of '26. And I will also say that while we've -- as I mentioned, we've completed randomization in over 60% of the patients as of end of October, we are randomizing every single day, every single workday, and we have good line of sight to the completion of randomizations early in '26.

Our next question comes from the line of Umer Raffat of Evercore.

This is Michael DiFiore in for Umer. Congrats on the continued progress. A few for me. On Revita, just would like some clarity on the German registry data, where you said that patients have maintained an average total body weight loss of around 9%. My question is, in the 14 patients that have reached 2 years of follow-up, what was their average weight loss at 1 versus 2 years? I just kind of want to get a sense of, if efficacy has waned at all in this specific subset of patients? And then I have a follow-up.

Sure. The answer is, there's absolutely no waning of effect between 1 year and 2 years. In fact, I believe that there is a slightly greater weight loss at 2 years than 1 year. The numbers I have in front of me are 8% weight loss at 1 year and 8.9% weight loss at 2 years. I want to put this in context, if I may. These are patients with advanced type 2 diabetes. Their BMI was 32. They are mostly men. That means these are the people who are hardest in whom to achieve weight loss. And what that 9% means is that you are achieving very significant and clinically meaningful and sustained weight loss maintenance in a population of individuals and whom it is very, very hard to get any weight loss at all. In addition, the large improvements in hemoglobin A1c in these patients actually tends to translate to harder to achieve weight loss as well. So, all of this was seen in the context of a substantial reduction in hemoglobin A1c and a significant net reduction in medication utilization. In fact, I suspected, Mike, that you were going to ask me a question about GLP-1 use and not. And what I will tell you is, there is less medication utilization at 2 years than there is at the -- in the start of the study. And if you sensor out the small number of patients who are on more medicines, the treatment effect is unchanged in the overall cohort. And so, we feel very, very confident about what this means for Revita's clinical profile. Both from a potency and from a durability standpoint, we think this translates directly to what you might expect to see in how REMAIN will perform in terms of both of those dimensions. And we think that payers will really care that Revita can do something reliably in the real world, which we know is a major problem in the obesity landscape today, where real-world results with most of the modern pharmacology is woefully underperforming relative to what Phase III showed because of treatment discontinuation, under titration and other factors that limit the effect of these medicines in the real world.

Excellent. Very, very helpful. And just a follow-up on RJVA-002 for obesity. Just curious at this point if you're able to disclose the relative GLP versus GIP receptor potency and affinities. And also, what would be the average circulating active GLP levels in mice? So, would it be greater than the 10 to 20 picomolar levels that have been seen with RJVA-001?

So, with respect to the relative GIP versus GLP ratios, this is something that we have actively optimized and have data on, but we have not shared publicly. But we do know that certain ratios work better than others. Happy to disclose that. We haven't yet compiled the GLP-1 circulating levels, but it's a wonderful opportunity for me to pivot to talking about the GLP-1 levels with RJVA-001, which is soon to enter the clinic. We were just coming out of Obesity Week and having a number of interesting conversations with obesity experts, and we have a fascinating and incredibly compelling aspect to RJVA-001 in that we have drug-like efficacy with 1/10 the circulating GLP-1 levels that are normally seen with these medicines, which implies we can achieve the efficacy and potency of these medicines and in some cases, exceed it, but are expecting far less in terms of tolerability issues because it's acting through more endogenous means locally in the gut rather than hitting the brain CNS receptors, which is where tolerability issues arise with current pharmacology.

Our next question comes from the line of Mike Ulz of Morgan Stanley.

Maybe just a follow-up on the Revita durability question for the German registry. It looks like out to 2 years, you're seeing a nice durable effect there. But just curious what the variability is among the patients and how tight that is?

It's remarkably consistent, I've got to say, Mike. I will follow up on -- some more detail on that, but you can just tell from the error bars in the graph that is in our updated corporate deck that the vast majority of patients who lose weight at 3 months maintain that body weight loss all the way through 1 year. And the error bars are not really getting wider over time, which tells us that there is a remarkable consistency to the weight loss maintenance here. It's very encouraging for us, as a signal. And let's just say, we are continuing to follow these patients. So, we have a nice sample of patients at 1 year and 2 years. And if you roll the clock forward, we're excited about the ongoing demonstration of durability entering into 2026 as we continue to follow these patients.

Great. That's helpful. And then, maybe just a follow-up on Rejuva and assuming you get the CPA cleared and you start the study next year, you mentioned potential for some preliminary data. Maybe just talk a little bit about what might be included in that preliminary data.

Well, we're focusing, first and foremost, on feasibility, safety and preliminary PK and PD profiles. And so, I think that as we enter into the new year, once the CTA is approved and we have crystal clarity on when the first patients will be dosed, be happy to answer that question for you.

Our next question comes from the line of Whitney Ijem of Canaccord Genuity.

This is Angela on for Whitney. Congrats on all the progress. Just a quick one from us. Can you remind us, are there diet and lifestyle measures taken for patients after they receive the Revita procedure in the studies? Are they getting counseling? Or are they following a program?

There are diet and lifestyle measures. They start when patients enroll in the trial even before they begin taking tirzepatide in the open-label run-in phase, and they continue all the way through end of study. So, there is no change to the diet and lifestyle per se at the time of Revita. It's an ongoing standardized diet and lifestyle recommendation. And those who are providing that recommendation are blinded to treatment allocation.

Got it. Are you able to disclose what those measures are?

Yes, we modeled it after very much what a semaglutide and tirzepatide Phase III studies used, which is a 500-kilocalorie net calorie deficit every day and 30 to 40 minutes of exercise 3 to 4 times a week, roughly.

Our next question comes from the line of Jeffrey Cohen of Ladenburg.

Just 2 questions from us. I guess, firstly, Harith, could you talk about -- let's go back to the German study. Were those patients type 1s or type 2s? And what percent were on pumping versus MDI?

Those patients were type 2 diabetics, Jeff, and most of them were on non-insulin medications. They were on an average of between 1 and 3 medications. Only a small number were on insulin. But what we are seeing is consistent data, independent of the background medication. The single biggest determinant of effect for Revita, both on weight and on blood sugar is whatever their baseline weight and blood sugar was rather than their background medicines.

Okay. That's helpful. And then secondly here, I know we talked about it earlier, but could you talk about CPT codes and how the payers are thinking about the procedure? I know there's been some changes on some codes, particularly in ablation and argon plasma.

Sure. We -- there are no CPT codes today for the Revita procedure, and we are actively working with reimbursement and market access experts on developing a road map towards establishing CPT coding ahead of approval in the United States. We will have more to share on the specifics of our reimbursement strategy when next we -- at our next earnings call.

Our next question comes from the line of Joe Pantginis of H.C. Wainwright.

I promise I won't be typing during your answers. So first, with regard to the comments that you made, obviously, from Lilly historical data and the patients regaining about 10% of their weight over 6 months, I just want to get some clarity or even a reminder that following the midpoint 3-month data, how these patients in the sham group fared based on the recovery of the Lilly data, the comparison.

Well, as you know, and I appreciate the question, Joe, in our Midpoint Cohort, patients who had lost 18% of body weight while on tirzepatide regained 10% of that body weight in the sham arm by 3 months. I told you that tirzepatide data from Lilly suggests 10% weight regain by 6 months. So, we saw a little bit more of that in the Midpoint Cohort than what Lilly showed. A couple of points. We're generating new data here because what we have done is we've taken tirzepatide. We are choosing only patients who have achieved at least 15% body weight loss, and we're choosing those patients who get there quickly. Both the size and the speed of weight loss are thought to also correlate with the size and speed of weight regain. So, one of the cruel aspects of starting and stopping GLP-1s is that the more effective and rapidly the drug works, the more vicious the rebound will be. As the drugs get better, as you go from tirzepatide to even whatever comes next, and you start hearing about drugs achieving greater and greater weight loss, you can immediately interpret that, that is likely to mean that the rebound of weight regain will be that much more violent and severe. We would expect in our Midpoint Cohort and in our pivotal cohort, a more or less linear rate of weight regain over the 3- to 6- to 12-month period of time. And we ourselves are incredibly interested to see what that weight regain picture will look like at 6 and 12 months. But the best data we have, as I said, is 10% regain at 6 months from Lilly's own data.

Really appreciate you highlighting that as part of the process. And then, sticking with Revita and my last question is, how would you sort of define your needs nearer term and intermediate term with regard to manufacturing needs and expansion?

Well, in the near term, we feel very good about our ability to support the clinical study, and we are now turning our attention with the excellent data that we just shared to ensuring that we have adequate manufacturing to be ready for scale. We have a -- just as a reminder for people, we do all final assembly and testing of our Revita catheter in our facility. And we have ample capacity to support our anticipated volumes for the coming years. But I should also say that we have subassemblies of our catheter that are currently manufactured by Tier 1 contract manufacturers who could assume larger and larger responsibilities in order to help us make sure that we meet the demand in the market. And may I just parenthetically add how wonderful it is to get a manufacturing question because that is a true sign of progress and success, and thank you for that.

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

Well, thank you very much. Thanks, everyone, for joining us this afternoon. Fractyl has exciting days ahead, lots of key catalysts coming in the coming quarters, 6-month REVEAL data, 6-month Midpoint Cohort data, 1-year data from weight maintenance in REVEAL, pivotal data; all coming within the next 12 months. We look forward to sharing updates on our progress and thank you, again.

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