Revita targets a root cause of obesity and type 2 diabetes in the gut with a less than one-hour outpatient endoscopic treatment. We are in a pivotal study now for the single biggest problem in obesity today, which is post-GLP-1 weight rebound. If there are 10 million people on GLP-1s this year, there will be 6 million who will stop taking their GLP-1, and the vast majority of them will be at risk of regaining substantial weight in less than one year. We're aiming to try to solve that problem. We have three different patient cohorts. We just presented data yesterday on one of them. The single biggest thing that we are looking for is whether our intervention can prevent people from regaining weight after stopping GLP-1s, even if they've already lost a substantial amount of weight on those medicines.
We think that if they can, it's going to be incredibly compelling for patients, for payers, and for the broader health economic community.
Got it. So Fractyl has three important catalysts reading out in the next seven months or so that'll further help de-risk the REMAIN-1 pivotal cohort, which is expected in the second half of 2026. But just focusing on the REVEAL-1 open-label study, recently presented six months' data, maybe talk about that, kind of how that helps de-risk the pivotal study for this program.
Sure, so as Mike said, we have got three patient cohorts. The REVEAL-1 open-label cohort are people who have already lost at least 15% body weight on either semaglutide or tirzepatide. They need to or want to stop taking the GLP-1 for whatever reason, and then when they stop taking the medicine, we then perform our Revita intervention. We follow them out over time. Yesterday, we presented the first six-month data in post-GLP-1 weight maintenance with Revita from this REVEAL-1 open-label cohort. What we showed is that patients who had lost, on average, 24% of their body weight, which is over 50 pounds, most of them on tirzepatide, stopped their medicine, underwent Revita, and then maintained almost all of that body weight loss through six months.
The exact number that we quoted in 17 patients at six months is a regain of only 1.5% of total body weight compared to the expected 10%+ body weight that they should have regained by that time. And so what we're talking about is something that is really beginning to elaborate a very compelling clinical profile for patients who can't or won't stay on GLP-1 drugs for the rest of their lives. And that data matters because it's our first six-month look at the effects of Revita in this clinical setting. And six months matters because that's also the same time point as our pivotal trial. So in September, we presented three-month prospective randomized double-blinded sham-controlled data on Revita's effects versus a sham in the post-GLP-1 setting. Those results were incredibly encouraging. And today, we are now building on that with six-month open-label data.
We will soon, in January, have six-month randomized data from 45 patients. And later in 2026, we'll have our full pivotal data. It's an exciting set of catalysts coming. I think the lineup of catalysts will afford the opportunity to really totally de-risk Revita's opportunity in post-GLP-1 weight maintenance.
So I want to sort of break that down, Harith, sort of step by step. Folks in the audience listening in for the first time might say, "Oh my God, this is like a procedure in a GLP setting. That sounds too difficult. Why would anyone do it?" So maybe could you start by reminding us, is this like an endoscopy procedure? And how many endoscopies are already happening outside of your procedure among GLP users, for example?
Yeah. So this is an upper endoscopy. About 70% of people above the age of 45 in the United States have undergone an endoscopy already in their lives. So this is something that is very, very routinely performed each year in the U.S. And there are 20 million endoscopies performed annually in the U.S. each year for other reasons. Of those 20 million endoscopies, we estimate that 800,000 of those 20 million are people who are currently on a GLP-1 for weight loss and are otherwise already undergoing an endoscopy.
What our market research suggests is if presented with the opportunity to perform the Revita procedure while they're getting an endoscopy anyway for other reasons, a large fraction of patients would choose to undergo Revita, which means that we have the ability to access nearly a million potential patients annually without them doing anything differently than what they are otherwise already doing. It actually takes less work than going to the pharmacy to pick up a GLP-1 medicine itself.
Okay, great. Mike, you want to pick up on that? Should we start with the REVEAL-1 data update from this week first?
Yeah, we'd love to.
Okay, let's start there. But also, just, Harith, I feel like people can sort of start to get confused between the REVEAL-1 versus the REMAIN-1. So remind us, which trial is that? Is this the tirzepatide off therapy or not so that folks can just catch up on which one we're looking at?
Okay, so what we're about to talk about is the data that we just put out yesterday, which is open-label data from our REVEAL-1 study. These are patients who are on tirzepatide or semaglutide in the real world, had lost at least 15% body weight, and did not feel like they could continue on the medicine. So we stopped the medicine. They underwent the outpatient Revita procedure under an hour endoscopic treatment. And we've been following them like a real-world registry in order to give ourselves some visibility into what Revita could look and feel like for people in the real world who are stopping GLP-1s.
Are patients in this REVEAL-1 open-label cohort adhering to a prescribed diet or not?
So all of the major manufacturers of GLP-1 drugs, in their obesity trials, have a fairly prescriptive diet and lifestyle program, 500 calorie a day deficit and three to four days a week of exercise. We're doing exactly the same thing.
What did we know on this data previously? So again, just so we're all level set, you took a bunch of patients. So tirzepatide, they were already on GLP-1. This is not the trial where you guys gave tirzepatide.
They were already on a GLP-1, and almost all but one of them was on tirzepatide.
Okay, so you have a REVEAL and you have a REMAIN trial. In REMAIN , you guys Fractyl paid for tirzepatide, and then they got off of it, and that's being evaluated, and then there's the REVEAL, which we're discussing right now, which they were already on a GLP, and then they're coming off of it.
Yeah, okay so there's three patient cohorts that we're following in post-GLP-1 weight maintenance. One of them is the REVEAL open-label cohort, which I just described. Another one is a pilot randomized sham-controlled trial, REMAIN Midpoint. That's a second cohort, and a third cohort is the REMAIN pivotal trial, and that's 315 patients, so let's still go through each of them systematically.
Yes, let's do that.
Okay. The REVEAL-1 open-label cohort, we presented data yesterday. Mike, what's your question?
Yeah, I know the top line just released, but at least as far as the three-month data goes, you had presented individual patient data kind of showing if patients continue to lose weight versus the one-month data. Will we be getting that granular level detail with the six-month data at a certain point?
In June, we presented data from 13 patients at three months post-GLP-1 open-label. And what we showed is that patients regained about half a percentage point of weight on average in those 13 subjects at three months. And slightly less than half of them lost further weight even after stopping their GLP-1. I mean, think about that. That's a pretty profound observation that someone could have already lost 50 pounds on a GLP-1, stopped taking the GLP-1, and yet have nearly 50-50 odds that you're going to continue to lose weight. But that was only 13 patients, and it was only open-label data, and it was only three months. So today, we provide an update on that cohort. We have a slightly larger N, and we have longer-term follow-up. We have 17 patients at six months.
It's still open-label, but what we see is very consistent treatment effect out to six months. The results at one and three months are highly predictive of the results at six months in the population. About roughly 40% of them have lost weight at six months compared to their last dose of tirzepatide, and that's still an incredibly compelling statistic. We also presented new data on what happens to their hemoglobin A1c. You see, when people's weight rebounds when they stop taking the GLP-1, that's not the only thing that rebounds. Their metabolic parameters also worsen. People who stop taking a GLP-1, even if they're not diabetic, on average may gain about a 0.4% change in their HbA1c by six months. We saw one-tenth of that, a 0.04% change in their HbA1c, effectively totally stable.
So what that shows is now not just is weight stable, but also glucose control is stable through six months in people who are stopping tirzepatide. It speaks to not only the effect for potential to keep the weight off, but also to have broader cardiometabolic protection sustained. The last point I'll make is a trajectory from one to three to six months looks really flat, very, very encouraging. If you want to draw a line and say, "Where do I think this is going to go at over a 12-month or a 24-month period?" It's highly encouraging. This is not the first clinical study we're running. We have run clinical studies in type 2 diabetes in the past. We have shown over and over again two years of durable results in both weight and blood sugar control in a type 2 diabetes population.
We're just beginning to elaborate that profile and seeing a lot of consistency in the post-GLP-1 setting.
So Harith, just for everyone to follow up, in diabetes setting, you guys did your procedure. For two years, weight was more or less flat.
Down by 9%.
Initially come down at 6.
And then flat, exactly.
Number one. Number two, in obesity setting, you took a cohort of about 30 patients, which is the one we're discussing right now. They were already on a GLP, came off, they just got the procedure, and up to six months out, they're up only 1%, 1.5% or so.
That's right.
And that takes us to the study that folks really do care about, where in your own trial, tirzepatide was given, randomized withdrawal. So you now have a case control. So it's not just versus natural history. In that trial, the third one, which is key, at month three, eight kilos weight gain versus minus two.
This is the REMAIN-1 midpoint cohort.
Yeah. So we have a pilot study running called the REMAIN-1 midpoint. We have a pivotal study also running. The REMAIN-1 midpoint is 45 subjects. We gave them tirzepatide. We paid for it. We got them to at least 15% total body weight loss in an open-label run-in. And once they got to 15% total body weight loss, we then discontinued the tirzepatide. And then we randomized them in a two-to-one treatment allocation to either Revita or a sham. It's a true double-blind because the patients were not randomized until the catheter was inserted into the body when they were already under propofol. And the GI physician performing the procedure never saw them after they woke up. There's a whole new care team that started to take care of them afterwards who were also blinded to the treatment allocation.
So in 45 patients in the REMAIN-1 midpoint, at three months, we presented back in September, the sham arm regained eight kilograms, roughly. You can correct my exact numbers. The Revita arm actually lost two kilograms from their last weigh-in on tirzepatide. That was like a 10-kilogram difference, like a 12% treatment difference in total body weight change, a profound result because no one really has shown data. Just take the sham arm for a second. No one's really shown data on what happens in the people who really respond to GLP-1s in terms of their weight regain at one, three, six months. What we've seen is some randomized withdrawal data from large populations, but what we showed is that the people who actually respond to GLP-1s, who really lose 15% body weight, actually regain weight very, very rapidly. They regain 10% body weight within three months.
We're talking 20 lbs of regain after stopping tirzepatide.
Are you tracking DEXA and muscle in this?
In our pivotal study, the 315-patient pivotal study, the third study that we're talking about, it's designed exactly like this midpoint that I just described to you. It's also a prospective randomized double-blind study. It's in 315 patients, randomized two to one. We will also have DEXA scans at six months in those patients.
Using the same sites and even same physicians, right?
Same physicians, same sites, same protocol, same inclusion/exclusion criteria. So we have essentially two identical studies running in parallel. One of them is 45 subjects, and we've reported three-month data in September, and we just guided to six-month data coming in January. And then we have the 315-patient pivotal, identical other than in number, which has a six-month primary endpoint date. We'll see that data in the second half of 2026 because that study is fully enrolled already.
Sorry, which one is that?
The pivotal REMAIN study, yeah. That one will have six-month data in early second half of 2026, and we will file for approval with the FDA.
In obesity setting.
In the post-GLP-1 obesity setting next year.
So this filing will be still with the device division?
This is with the device division with the indication of post-GLP-1 weight maintenance. We have alignment with the FDA on our clinical trial and endpoints. We've fully enrolled the study. We're nearly complete with randomizations. Safety has been excellent so far, and we have Breakthrough Device Designation from the FDA for this indication.
And Harith, remind us, yeah, exactly what I was going to get to. So the Breakthrough Device Designation, how does that accelerate your review process when you do make that filing?
On average these days, breakthrough devices that have positive pivotal data are getting approved without a panel or AdC om, and it's taking about nine months on average. That's the most recent statistic that I found.
Got it. And just one last thing because I think it's very relevant to the broader conversation. In your REVEAL trial, sorry, in your REVEAL trial where patients were on a GLP, came to your study, it's basically flat. It's up 1%, but it's basically flat. But in the REMAIN study where you gave tirzepatide, you showed further weight loss.
They actually lost further weight.
So why the difference between the two? Or is there a calorie restriction difference between the two trials?
There's no discernible difference. It's the same sites performing the same procedures, the same physicians caring for them. There are some small differences between the two cohorts. The open-label cohort, as I mentioned, they lost 24% of their body weight. These are like tirzepatide super responders. Whereas in the randomized trial, we took them to at least 15% body weight loss, not all the way to full 24% plateaued body weight loss. That is one difference. In the REMAIN study, they're on GLP-1 just until they get to that 15%. So on average between 16 and 26 weeks. In the open-label study, they were on GLP-1 in their lives for anywhere between five months and five years, as it turns out, before they entered into the trial. So there is some heterogeneity to the REVEAL cohort because it's a real-world cohort.
It reflects what's happening in the real world. REMAIN is much more homogeneous.
Fantastic. Fantastic. Sorry, Mike, if I may just, what update are we expecting now on the REMAIN study? Because I think that's where investors are most intrigued.
Investors are super intrigued because we saw really exciting three-month data in the randomized sham-controlled trial in 45 patients. Clear evidence of activity, no safety, tox burden whatsoever.
So there's six-month data coming in February or January?
Six-month data coming in January from those same 45 patients, and that's, we think, is going to be like a fantastic bridge to the pivotal data coming later in the year because it's also prospective randomized sham-controlled. It's also six months to six months. It's only difference is the end.
So Harith, we saw, like I keep going back to, in REVEAL, there was slight gain. In REMAIN , there's further decline after. So if it just normalizes back to the mean, some folks might interpret as, "Oh, there's a regain happening," even though it may just be that at month three, it just went down and came right back up.
I think we just got to think about noise, right? Obesity is noisy in general. Any one patient with these small n's can skew it up or down in a small way. What I would hope that people take away is stability. Consistent stability of body weight loss hovering around very little regain to no regain at all. Even if there's further loss, that would be like extraordinary, but the market only needs a 50% reduction in weight regain for this to be a compelling therapeutic option, so if they would have regained 10% body weight by six months, if Revita patients only regained 5%, that's a huge win for the market. Though we are elaborating new science with a new indication for the first time, it's very exciting to see, like we don't even know what the sham arm was going to do when we started this.
All we really need to do is to curb weight regain for patients to have a really exciting new option.
So, the key is what you're saying is forget about the month three kind of went down. As long as broadly it stays stable, that's the ultimate thing where we should sort of hold our expectations to.
50% reduction in regain is a huge win from the market.
And if it's stable, that's.
Even better.
Even better.
Yeah.
What I'm trying to avoid is someone might say, "Oh, month three was down minus two. Now it's like plus one." So it sounds like this is going to start to gain back. So people don't want to make a slope on their own.
Right. Well, I think that people are going to do, like I get questions about each individual patient, like Mike was just asking me. Like this is a heterogeneous disease and weight bounces around. So if you look at the totality of hundreds of patients that we've treated and followed them at one, three, six months, what we see is a very consistent signal of stability where one, three, six months is very, very predictive of 12- and 24-month results. And so small nuances of like whether it's down 0.2 or down one or relative to up 1.5 does not matter to the market at all. This is a brand new indication. It is a breakthrough. It is a very, very large market need.
What I'm now telling you is from either the REVEAL-1 or the REMAIN-1 midpoint, both populations. What we've seen is roughly, you know, a substantial fraction are losing weight. Some are gaining a little bit of weight, but on average, there's a lot of stability. That's what I'm seeing.
Got it. Well, unfortunately, we're at time. Harith, this has been very informative. Thank you so much for spending time with us.
Thank you. Appreciate it.