Fractyl Health Q2 2025 Earnings Report

Fractyl Health EPS Results

• Actual EPS: -$0.53
• Consensus EPS: -$0.37
• Beat/Miss: Missed by -$0.16
• One Year Ago EPS: N/A

Fractyl Health Revenue Results

• Actual Revenue: N/A
• Expected Revenue: N/A
• Beat/Miss: N/A
• YoY Revenue Growth: N/A

Fractyl Health Announcement Details

• Quarter: Q2 2025
• Date: 8/12/2025
• Time: After Market Closes
• Conference Call Date: Tuesday, August 12, 2025
• Conference Call Time: 4:30PM ET

Fractyl Health (NASDAQ:GUTS), a metabolic therapeutics company, develops therapies for the treatment of type 2 diabetes (T2D) and obesity. The company develops Revita DMR System (Revita), an outpatient procedural therapy designed to durably modify duodenal dysfunction, a pathologic consequence of a high fat and high sugar diet, which can initiate T2D and obesity in humans. It also develops Rejuva, a novel adeno-associated virus delivered pancreatic gene therapy platform that is designed to enable long-term remission of T2D and obesity by durably altering metabolic hormone function in the pancreatic islet cells of patients. Fractyl Health, Inc. was formerly known as Fractyl Laboratories Inc. and changed its name to Fractyl Health, Inc. on June 09, 2021. The company was incorporated in 2010 and is headquartered in Burlington, Massachusetts.

Fractyl Health Q2 2025 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: We raised $23 million in an underwritten public offering (with warrants up to $69 million), extending our cash runway through key upcoming clinical milestones.
• Positive Sentiment: We reduced cash burn from $25.4 million in Q1 to $19.8 million in Q2, reflecting disciplined cost management and strategic reprioritization.
• Positive Sentiment: New real-world registry data from Germany show our Revita therapy delivers up to two years of sustained weight maintenance with greater potency at two years than at one.
• Positive Sentiment: Enrollment is complete for the pivotal REMAIN-One study, with three-month randomized data due next month and six-month pivotal readout in 2026 aiming to show at least 50% less weight regain than GLP-1 cessation alone.
• Neutral Sentiment: Our Rejuva program has completed preclinical work, manufacturing is nearly finished, and the Phase 1/2 trial design is agreed, targeting first patient dosing and preliminary data in 2026.

Presentation

[Operator]

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

[Brian Luque, Head - IR & Corporate Development at Fractyl Health]

Thank you. This afternoon, we issued a press release that outlines the topics we plan to discuss today. This release is available at www.frackle.com under the investors tab. Joining us on the call today are doctor Harith Rajagopalan, Chief Executive Officer and Lisa Davidson, Chief Financial Officer. During this call, we make forward looking statements, involve risks and uncertainties that may cause actual results to differ materially from our forward looking statements.

[Brian Luque, Head - IR & Corporate Development at Fractyl Health]

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 Hari.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Thank you, Brian. Good afternoon, everyone. Fracil is tackling the next major crisis in metabolic care, weight regain after GLP-one discontinuation. Tens of millions of people are struggling with their weight and will start a GLP one with the hope of achieving lasting weight loss. But most will stop the drug within a year.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Nearly all will regain weight. This rebound problem is a massive unmet need because most patients cannot stay on drug therapy for weight loss for the rest of their lives. And when they stop drug therapy, not only does their weight come back, but so too does their profound hunger and all of the metabolic complications associated with obesity, including type two diabetes. Frontal Health may be the first company with a scalable solution to this problem, because our therapies target the root cause of disease for the very first time. Since our last earnings call, we have strengthened our balance sheet, further sharpened our strategic focus, and delivered on critical milestones.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

This focused execution sets us up for a transformational second half of the year. Last week, we strengthened our financial position through a $23,000,000 underwritten public offering of common stock with accompanying warrants that could provide up to a total of $69,000,000 in proceeds. This financing was led by leading health care investors, including Nantahala Capital, Adar One Capital Management, Second Line Capital, six eighty three, and SilverArc, investors who understand the significance of our upcoming catalysts and chose to scale their investments alongside them. With this capital structure in place, we positioned ourselves to fully capture the value of our clinical and strategic progress in the months ahead. With the proceeds from this primary capital raise, we expect to extend our cash runway through important remain one midpoint cohort milestones with next month's three month randomized data readout, as well as the six month randomized data from this cohort in the 2026.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

We sharpened our strategic focus by reducing our burn rate from twenty five point four million in q1 to nineteen point eight million in q2, as we wound down our spend on non critical programs, following the strategic reprioritization earlier in the year. Going forward, we will continue to see reduced cash burn be a key area of focus with disciplined cash management through the remain one pivotal study milestones ahead. We have also delivered on key milestones across our Revita and Rejuva programs during this time. Revita is emerging as a foundational therapy to reset the body's metabolic set point in obesity and type two diabetes. Last week, we reported new data from our German real world registry study that reinforced Revita's durability, showing up to two years of benefit in weight maintenance and blood sugar control following a single treatment.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

What is impressive about the new data from Germany is not only the duration of effective up to two years, but also the potency of the therapy over that period of time, with even greater improvements in body weight at two years than at one year. What this implies is that Revita can deliver real world results that could get even better over time as the body accommodates to a more physiologic and healthy relationship with food. These long term outcomes are consistent with prior Revita clinical studies and solidify its potential as a real world non pharmacologic solution for sustained metabolic results with a broad set of potential indications in obesity and metabolic disease. Our near term focus is solving weight regain after GLP one discontinuation, a challenge that is now recognized by patients, physicians, and payers alike. In June, we shared positive three month open label data from the REVEAL one cohort.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Patients who stopped tirzepatide and received a single Revita procedure demonstrated weight stability at three months with nearly half losing even more weight after stopping the drug. This is the first human clinical evidence that Revita may stabilize weight after stopping GLP-1s. Enrollment of our REMAIN one pivotal study is complete, and randomizations are on track. We continue to see a favorable safety profile and strong procedural consistency across sites, important indicators for study success and potential commercial scale. Next month, we expect to report three month randomized data from the REMAIN one midpoint cohort.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

These are people with obesity but without type two diabetes who have lost 15% of their total body weight with tirzepatide before randomization to Revita or Sham. This will be the first blinded controlled dataset assessing whether Revita can preserve GLP-one induced weight loss and metabolic benefit. The goal of the REMAIN-one midpoint cohort will be to establish an early efficacy signal for Ruvita in a rigorous sham controlled study ahead of our pivotal cohort for which top line data are expected in the second half of next year. We believe this randomized midpoint data in September will be a key proof point for the therapy, and we are optimistic for a positive outcome. For the REMAIN one midpoint cohort readout, including the three month readout next month, success means showing clear separation between Revita and sham on weight regain over time.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

More specifically, we are aiming to show that Revita performs at least 50% better than what one would expect from tirzepatide withdrawal alone. Based on surmount four data from Eli Lilly, patients who discontinued tirzepatide typically regain five to 6% of their body weight by three months. If Revita treated patients show only 3% weight regain or less at the same time point, that would not only be statistically significant, it would also be a highly meaningful result for patients, for physicians, and for payers. To put this in context, we shared three month data from our open label revealed one study in June, where the median weight regain was less than a half a percentage point or just one pound of weight change compared to the five to 6% body weight or 10 to 15 pounds of weight regain typically seen by this time point when patients stop tirzepatide. That early signal of weight loss maintenance was incredibly encouraging, and we believe it bodes very well and sets a strong precedent heading into the next month randomized readout from REMAIN one.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Success with REMAIN one could position Ruvita as the LASIK for obesity, a straightforward one time intervention that targets a root cause of disease and offers a potential for a lasting alternative to chronic disease management. This is not just theoretical. Our recent field visits to clinical trial sites and multiple advisory boards have confirmed three key themes. First, GI physicians are incredibly excited about Ruvita and believe it can be a valuable tool in their armamentarium as they increasingly move into treating obesity and metabolic disease. Second, based on the rapidity of enrollment in remain one, and the enthusiasm they see from patients, GI physicians anticipate significant procedure volumes upon potential FDA approval.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

And third, GLP one prescribers know that most of their patients do not want to be on these drugs for the rest of their lives, either because of side effects, costs, or concerns about long term drug therapy. And with these insights in mind, we are building the foundation for commercial scale. In June, we announced a nonbinding letter of intent with Bariendo, a nationwide endoscopic obesity care platform to prepare for potential adoption of Revita pending FDA approval. This collaboration could help create a ready made distribution channel across high volume ambulatory and hospital endoscopy centers. The collaboration will focus on precommercial preparation, including workflow design, provider education, health economic analysis, and the development of referral pathways.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

As we pioneer new therapeutic areas in metabolic medicine, we are also establishing a leadership position that is built to last. In June, we were granted two new US patents reinforcing our foundational innovations in duodenal mucosal resurfacing. Today, our portfolio includes over 100 granted patents throughout the world, including 32 granted US patents and nearly 40 pending applications, making Fractal the clear innovation leader in gut targeted metabolic therapy. Let me now turn to Rejuva. With Rejuva, we believe we've created a truly breakthrough therapy, the first potentially one and done smart GLP one platform designed to program pancreatic beta cells to secrete GLP one in response to nutrients, potentially delivering durable physiologic metabolic control at far lower circulating GLP one levels than required by injectable therapies.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Rejuva one has completed preclinical efficacy, toxicity, and biodistribution studies. CMC manufacturing is progressing well and nearly complete. We reached agreement with regulators on the design of the Rejuva one phase onetwo clinical study. It will be an open label multicenter study that will evaluate the safety, tolerability, and preliminary efficacy of Rejuva one in adults with inadequately controlled type two diabetes despite multiple glucose lowering agents. In May, we submitted the first module of our clinical trial application.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Pending regulatory clearance, we expect to dose first patients and report preliminary data in 2026. Rejuva one could redefine the risk benefit profile of long term GLP one therapy and open the door to a durable, potentially curative solution for chronic metabolic disease. We believe that the future of metabolic care lies in durability, in physiologic design, and in root cause solutions that work in the real world. With Revita, we aim to be the LASIK for obesity. With Rejuva, we are reprogramming the pancreas itself for life.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Our execution is tight, our focus is clear, and our opportunity is substantial. Lisa will now walk through the financials.

[Lisa Davidson, CFO & Treasurer at Fractyl Health]

Thank you, Harith. In the 2025, we continue to invest in the execution of our clinical strategy across both the Revita and Rejuva programs. R and D expense for the quarter was $21,200,000 compared to $16,800,000 in the 2024, reflecting the continued advancement of the REMAIN one clinical study and the Rejuva program, including personnel related costs. SG and A expense was $4,900,000 compared to $6,200,000 in the same quarter last year. The reduction is primarily due to the lower stock based compensation.

[Lisa Davidson, CFO & Treasurer at Fractyl Health]

Net loss for the quarter was $27,900,000 compared to $17,200,000 in Q2 twenty twenty four, largely due to changes in non cash fair value of notes and warrants and increased operating expenses. As of June 30, we had $22,300,000 in cash and cash equivalents. Based on our current operating plans and after considering the net proceeds from the underwritten public offering, we expect our current cash position to fund operations into 2026 through key upcoming data readouts from the REMAIN-one midpoint cohort. With that, I'll turn the call back over to Hari.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Thank you, Lisa. To wrap up, we believe Fractal is building what comes next in metabolic care. This is an exciting period of focus and execution for the business. We are entering our data rich, catalyst heavy stretch with momentum, focus, and capital in place. As a reminder, we have a rich set of clinical milestones ahead.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Next month, we expect randomized three month data post tirzepatide discontinuation in forty five patients randomized two to one to Revita versus Sham in the remain one midpoint cohort. In the fourth quarter, we expect incremental six month open label data from the REVEAL one cohort. In the 2026, we expect six month randomized data from the REMAIN one midpoint cohort. And the six month time point is significant because it aligns with the time point for the registrational REMAIN one pivotal study. In the 2026, we expect to see the first one year open label data from the reveal one cohort one year after stopping a GLP one undergoing a single treatment, and then following patients to see weight maintenance over time.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

And in the second half of twenty twenty six, we expect the six month top line primary endpoint data from the REMAIN one pivotal cohort. Also in the 2026, we anticipate submitting a pre market approval application or PMA with the FDA for Rubida in weight maintenance. With a stronger balance sheet to execute against these exciting milestones, sharper strategic focus, and these exciting upcoming catalysts, the near term future is bright for guts. With that, I'd like to thank the people who make this work possible. To our employees, thank you for your relentless drive and belief in our mission.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

To the physicians and investigators advancing our clinical programs with care and commitment, we are proud to partner with you. To the patients participating in our trials, thank you for your courage and your trust. And to our investors, thank you for your continued support and conviction. Operator, we are now ready to take questions.

[Operator]

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 11 on your telephone and wait for your name to be announced. To withdraw your question, please press 11 again. Please stand by while we compile the Q and A roster.

[Operator]

And our first question comes from the line of Jason Gerberry of Bank of America Securities. Your line is now open.

[Jason Gerberry, MD & Equity Research Analyst - Biotech & Pharma at Bank of America Merrill Lynch]

Hey, guys. Thanks for taking my questions. I guess just first on the midpoint update in September. Beyond, I guess, maintenance of preservation of the weight, any other data points that you guys plan to share that you just kind of flag in terms of what you think will be important in the update just beyond sort of the main efficacy measure? Will you plan to speak to any outliers in the dataset?

[Jason Gerberry, MD & Equity Research Analyst - Biotech & Pharma at Bank of America Merrill Lynch]

And then on Rejuva IND clearance, any status update in terms of what are the gating items there would be helpful. Thanks.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Thanks, Jason. Appreciate the question. So on the midpoint update, as a reminder, forty five patients randomized two to one to Ruvita versus Sham, three months post tirzepatide discontinuation. We expect that patients who stopped tirzepatide at three months should regain five to 6% of their body weight. If we can cut that in half, we think we've got a blockbuster therapy on our hands.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

It's important for us in the midpoint data update to be able to provide people visibility into the things that will really matter for the pivotal studies readout in h two twenty twenty six, and in particular, safety, tolerability, and the effectiveness of weight loss maintenance. I expect that we'll continue to see the excellent safety and tolerability signals that we've already been sharing in our REVEAL study and all of our prior clinical work, and enough information on the dispersion of the weight maintenance effect in order for people to be able to get a critical appraisal of how things are shaping up for the pivotal study of three fifteen randomized patients, which is also already underway. And I think that should answer your question on outliers, it's going to be important for us to understand what we need to understand to believe that the pivotal will be successful. There are additional things that we're looking at in this REMAIN one midpoint cohort. Many of them don't occur at three months, but actually occur at six months.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

And so, as an example, there are DEXA scans that are built into the study, but they occur at baseline six and twelve months, but not at three months. There's additional laboratory measures that we're also going to be looking at as well, but you can expect to see more information on those in the months ahead. May not but the most important thing for right now, safety, tolerability, and effectiveness with enough visibility to understand how the overall population is behaving in a manner to look ahead to the pivotal. With respect to Rejuva IND, there's been tremendous progress behind the scenes. I know we just talked about like how filed our CTA module.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

The bottom line is that we are weeks away from seeing the lot release of our GMP product. All of the assays look like they have gone well, and all of our other testing has gone well as well. We're wrapping up our reports, and we will update you in due course. But we remain committed to the timelines that we've pre we publicly shared, which is first preliminary data in 2026. Thank you, Jason.

[Jason Gerberry, MD & Equity Research Analyst - Biotech & Pharma at Bank of America Merrill Lynch]

Thanks.

[Operator]

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

[Rohit Bhasin, Biotech Equity Research at Morgan Stanley]

Yeah. Hi. This is Rohit on for Mike. Thanks for taking our questions. As the GLP-one market evolves, can you share any new learnings or trends that you're seeing that stand out for the outlook of Revita and Rejuva? Thanks.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Yeah, certainly. Thank you for the question. It's a broad question, and one could take that in a lot of different ways. Let me just talk about my personal experience in conversation with key stakeholders and how they feel about it.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Two years ago, the question that patients were asking their doctors is how do I get access to these medicines? And today when I go and talk to prescribers, the single biggest question that they are telling me that they're hearing is when can I stop taking this medicine? What is amazing to me is how rapidly people have completely routinized the assumption that they can lose weight on the GLP one and are now asking what is next. And what I'm equally surprised about is how willingly the prescribers recognize that patients do not want to be on GLP-one drugs for the rest of their lives. I think that bodes incredibly well for both Revita and Rejuva, but for different reasons.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

When I other thing that I'm noticing is that the the general perception of the GLP one category is that they are excellent drugs, but the weaknesses are becoming more clearly apparent in the real world in a manner that would not be visible from phase three studies. You may know that in our last call, we talked about data from Cleveland Clinic showing that the real world effectiveness of semaglutide and tirzepatide in Cleveland Clinic patients is substantially worse than how they looked in clinical trials. I will tell you that I've now visited other clinical trial sites who read that paper, have done their own analysis, and are confirming exactly that same finding. And all of these, I think, speak to the value that we can bring because that because the limitations that the drugs have on real world effectiveness do not affect our disease modifying approach. So I'll stop there.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Otherwise, I could keep going. But I think the two key messages are the desire for patients to stop and a need for better real world outcomes. Thanks. Thank you.

[Operator]

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

[John Pancari, Senior MD & Senior Research Analyst at Evercore ISI]

Hello, guys.

[John Pancari, Senior MD & Senior Research Analyst at Evercore ISI]

This is JP in view of Michael. Congrats on the quarter and thanks for taking our questions. The first one, among the nine patients in the two year follow-up in Germany, three remain on the GLP-one therapy throughout. Could you please help us understand the relative contribution of GLP-one to the observed outcomes? And are there any notable differences in weight loss or glycemic control between the ones who stay in GLP-one or not?

[John Pancari, Senior MD & Senior Research Analyst at Evercore ISI]

And the second question also regarding the process. Given the natural weight variability, can you walk us through your way measurement protocols like timing, repeatability, calibration and how you account for day to day fluctuations? I mean, it's well known that weight can vary a lot during the day, so that's why we want to understand a little bit more about the protocol. Thank you.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Sure. Absolutely. So nine patients in Germany, three of them were on a GLP-one. They were on a GLP-one when they entered the study. They've been on a GLP-one for two years.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

We do not believe that there is a contribution from the GLP-one to the weight loss seen in the patients in Germany, because when you exclude those patients, you look at the others, there's also a consistent signal of weight loss and the profile of weight, a single treatment, early effects and sustained results has been true across our clinical work for patients who are on any other background medical therapy. And so therefore, we believe that this is sort of an important point to make because of the evolving GLP-one landscape and its utilization, but we do not think it affects our interpretation. With respect to weight variability, I'm going assume that the conversation we're talking about here is around the REMAIN pivotal study and we have been very focused on all of the potential sources of variability in the trial. Measuring weight is one of them and we have explicit quality control protocols like other companies do that are running obesity studies where the scale that the sites are using must be appropriately calibrated on a regular basis that this is accounted for and that the manner in which the weight is being measured in patients is also consistent.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Nonetheless, we all know that there is some weight variability from people from time to time. I know it when I step on the scale every morning myself And so therefore, I think that we can do what we can to control it, but human beings are what they are.

[John Pancari, Senior MD & Senior Research Analyst at Evercore ISI]

Thank you very much. Thanks.

[Operator]

Thank you. One moment for our next question. Our next question comes from the line of Whitney Ijem of Canaccord Genuity. Your line is now open.

[Whitney Ijem, MD & Senior Biotechnology Analyst at Canaccord Genuity Inc]

Hey, guys. Just a quick follow-up thinking about durability. For the REMAIN-one midpoint cohort, will you continue to track those patients and then present updates at like nine months, twelve months beyond that? How should we be thinking about that as like an early signal for durability ahead of the larger cohort follow-up?

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

So thanks, Whitney. If you go to our corporate deck on page four, you'll see our upcoming catalysts. And I'm happy to say that on the REVEAL one cohort, this is the open label cohort where we've already shared three month data back in June. We'll share six month data in Q4, and then one year open label data in 2026. For the remain midpoint cohort, we are currently projecting three month data in September, which next month, and then randomized six month data early in Q1.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

We have not gone out into additional data points, but all of these patients will be followed for a year, you can reasonably expect that you will get incremental data updates over time. And all of that now helps by the time we see our six month primary endpoint data from the pivotal cohort, there will be an ample body of six twelve month data to look at from REVEAL one and the midpoint cohort in order to help inform the regulatory but also the commercial value proposition of Ruvita and weight maintenance.

[Whitney Ijem, MD & Senior Biotechnology Analyst at Canaccord Genuity Inc]

Got it. Okay. And then I guess just I was curious about longer term then, like, either the midpoint or the pivotal cohort be tracked longer than that, such that over time, post approval, let's say, whatever, you could present updates on eighteen and twenty four months durability, or is that not something we should expect from these studies?

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Well, we're excited about the two year durability we're seeing in Germany and the two year durability we've seen from our prior RUVITA-one study and the durability we've seen in our pooled analysis and all of our types of diabetes studies. We think it's a major advantage of the therapy, and our intention will be to follow these patients longer and report those data as they emerge.

[Whitney Ijem, MD & Senior Biotechnology Analyst at Canaccord Genuity Inc]

Okay. Perfect. That's helpful. And then on the point of the DEXA scans that you mentioned that will be coming at the six month time point, can you talk about any expectations there, either pre clinically or just mechanistically? Like how should we be thinking about the potential of Revita to sort of differentiate in that regard?

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

There is a preclinical study that I just reviewed that showed that the muscle that the weight loss in duodenal bypass has is principally a fat mass loss rather than a muscle mass loss. That is the only preclinical work that I've seen. It's not ours. So I think that one way to think about this is what is the way regain phenotype looking like in those who are stopping tirzepatide? And what will the weight what will the body composition difference be in individuals with Ruvita assuming that they're able to maintain that body weight loss?

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

I have been unable to find maybe you can tell me differently any evidence of what happens in tirzepatide withdrawal or semaglutide withdrawal in the DEXA scans of those patients who have stopped taking those medicines. We know that those trials had DEXA scans, but I don't know what they showed after the drug was stopped. Now we'll get an answer, and I'm excited to see what it has to show.

[Whitney Ijem, MD & Senior Biotechnology Analyst at Canaccord Genuity Inc]

Got it. Likewise. Yeah. Okay. Perfect. Super helpful. Thanks very much.

[Operator]

Thank you. One moment for our next question. And our next question comes from the line of Jeffrey Cohen of Ladenburg. Your line is now open.

[Jeffrey Cohen, MD & Director - Equity Research at Ladenburg Thalmann & Co. Inc]

Hey, good afternoon. Thanks for taking our questions. I wanted to expand upon the last question. Could you hypothesize a bit how the last discussion reflects upon BMIs as far as treatment groups, BMI's prior to tirzepatide, or BMI's after treatment of tirzepatide.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Sure, I mean, I think we there's a there's a study called Surround four from Eli Lilly that I think may speak to this best. These are individuals who had obesity but not type two diabetes. They were given tirzepatide for a period of thirty six weeks, and then they were randomized to either discontinuation of the tirzepatide or ongoing treatment with tirzepatide for an additional year. Individuals who had lost body weight on tirzepatide during the open label run-in phase over that first thirty six week period of time lost a little bit over 20% of their body weight. But by one month and this is true for percent total body weight.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

It's also true for BMI. By one month, they had regained about 3% of their body weight. By three months, they had regained five to 6% of their body weight. By six months, they had regained nine to 10% of their body weight. And by one year, they had regained, I I wanna say, about 12% of their body weight, 11 to 12% of their body weight.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

And so what is true for percent total body weight is also true for BMI. And so what you can see is that these patients are losing really significant amounts of body weight. And what when you tie that back to the DEXA scan, the general perception in the field is that these people are regaining mostly fat mass and not muscle mass so that the BMI regain or the weight regain may be actually underestimating the metabolic problem caused by the weight loss and then the regain. And that's what we're hoping to be able to show we can do something about with Ruvita and weight maintenance.

[Jeffrey Cohen, MD & Director - Equity Research at Ladenburg Thalmann & Co. Inc]

Got it and then one more if I could. As far as treatment goes, what have you found to be duration time of any information you could provide on patients and their preferences and also any variations within the energy delivered and the duration of energy delivered as well as the length of the duodenum.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Sure, okay, so well, there's like four questions in there, Jeff. Number one is, I'll start with the end. Okay. Length of ablations. In the REMAIN one study, we are ablating an average of sixteen centimeters length of the duodenum or eight ablations of two centimeters each.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

That is slightly better than the average that we were seeing in REVEAL one, which was an average of seven and a half or ablations per patient or 15. And definitely much better than what we had done in prior studies. This is important and relevant for two reasons. First, it's relevant because we are not seeing any signal of safety or tolerability with higher lengths of ablation. And yet, we have also seen dose dependent effects in our earlier clinical work.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

And so we will be analyzing the, you know, in a post hoc way, the length of ablation versus the magnitude of effect in order to further substantiate the efficacy that we've already feel like we've established with the dose response in our earlier work. And the absence of any safety and tolerability suggests that we are continuing to optimize the clinical profile here without causing any harm to patients, which is highly encouraging for us with respect to the magnitude and durability of the efficacy that can be achieved. Average procedure time as people are ablating a longer length of the duodenum is still about an hour or less. And we have we're very pleased by the observation that as we go through the various clinical trial sites and the new physicians who are performing the procedure, we are seeing excellent clinical results and excellent quality and length of duodenal ablation, even with new users as they are getting up to speed on the technology, which strengthens our sense for the ease of the learning curve. Now, the last point that I would make is that we're not changing the actual ablation energy delivered or the time of the energy that that ablation is delivered.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

So the only thing that we are making is to the length of the duodenum that's ablated and with respect to patient preference, a lot of people asked us whether they were whether the rapid enrollment that we saw in REMAIN was and was simply because people were getting free tirzepatide in order to be able to enter the study. And what I there's two things that argue that patients are really excited about Ruvita. The first one is that patients were choosing the Revita weight maintenance trial over other weight loss drug therapy trials being run concurrently at clinical trial sites that had both. Second one is we have lost very few patients post tirzepatide prior to endoscopic randomization to either Revita or Sham. The vast majority of the patients in this trial have continued all the way through, and both of those are very encouraging empirical evidence for patient preference. Hope I got all those questions answered.

[Jeffrey Cohen, MD & Director - Equity Research at Ladenburg Thalmann & Co. Inc]

Super. Yeah, thanks for taking them all. I appreciate it.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Yeah.

[Operator]

Thank you. One moment for our next question. And our next question comes from the line of William Wood of B. Riley Securities. Your line is now open.

[William Wood, Biotech Equity Research Analyst at B.Riley Securities]

Thanks for taking our questions and congrats on a very nice quarter. Just to clarify a couple sort of building on what a couple other people asked, specifically for the REVEAL one, I know you sort of touched on this in regards to REMAIN. It looks like you've now treated 22 patients on REVEAL one. When you report the six month data, should we expect that all patients to have completed the six months? Or is this going to be more of a subpopulation, say, 13 patients that priorly treated the three month cut?

[William Wood, Biotech Equity Research Analyst at B.Riley Securities]

And with that six month, you mentioned that we should get more data specifically DEXA and this is where you were referencing REMAIN. But I was curious if we'll be also getting DEXA in the REVEAL trial, which could sort of tease out if there is a weight regain demonstrated, what that gain is composed of. So just sort of understanding that and then I have a quick, very quick follow-up.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Yeah, the majority of the patients in the 22 that we're mentioning were treated early enough to be able to be followed and report six month data in Q4. And I think it's generally in the better interest to be able to provide more data on more patients if possible. So you can expect that in the fourth quarter data. We do not have DEXA scans in the open label cohort. We don't have anything to compare it to.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

And while we also REVEAL one is an open label study and we are tracking weight, we at least have the historical comparator of weight regain from tirzepatide withdrawal from surmount four. But as I alluded to earlier, we don't have similar data on what happens to body composition upon tirzepatide discontinuation. So I don't have any historical comparator there. So you're gonna have to wait for the randomized data for us to be able to understand what the DEXA show and how to interpret them.

[William Wood, Biotech Equity Research Analyst at B.Riley Securities]

Got it. And then just to quickly verify, OWN, you noted at least in the PR that you expect to dose the first patients for REJUVA-one and then report preliminary data in 2026. Is that we should expect first dose and data in 2026 as in both occurring in 2026 or is it the first dose could actually occur in third quarter, fourth quarter this year and then data in '26?

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Yeah, as stated, expecting first doses and preliminary data both in '26.

[William Wood, Biotech Equity Research Analyst at B.Riley Securities]

Got it. Appreciate that. And thanks for the color. I'll hop back in the queue.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Thank you.

[Operator]

Thank you. I'll now turn the call back to Doctor. Raja Gopalan for closing remarks.

[Harith Rajagopalan, Co-Founder, CEO & Director at Fractyl Health]

Well, you all for joining the call today. It's, as I said, an exciting period with a data rich catalyst heavy set of quarters ahead. And our team is incredibly excited by the therapies that we're developing and the prospects for the patients in front of us. And we look forward to continuing to share our updates on our progress with all of you, and thanks very much.

[Operator]

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

Participants

Executives

• Brian Luque, Head - IR & Corporate Development
• Harith Rajagopalan, Co-Founder, CEO & Director
• Lisa Davidson, CFO & Treasurer

Analysts

• Jason Gerberry, MD & Equity Research Analyst - Biotech & Pharma at Bank of America Merrill Lynch
• Rohit Bhasin, Biotech Equity Research at Morgan Stanley
• John Pancari, Senior MD & Senior Research Analyst at Evercore ISI
• Whitney Ijem, MD & Senior Biotechnology Analyst at Canaccord Genuity Inc
• Jeffrey Cohen, MD & Director - Equity Research at Ladenburg Thalmann & Co. Inc
• William Wood, Biotech Equity Research Analyst at B.Riley Securities