Greetings. Welcome to Fractyl Health's one-year REMAIN-1 midpoint cohort data call. At this time, all attendees are in a listen-only mode, and a question and answer session will follow the formal presentation. As a reminder, this call is being recorded, and a replay will be made available on the Fractyl Health website following the conclusion of the event. I'd now like to turn the call over to Brian Luque, Head of Investor Relations and Corporate Development at Fractyl Health. Please go ahead, Brian.
Thank you. Welcome, everybody. This morning, we issued a press release that outlines the topics we plan to discuss today. The press release is available at www.fractyl.com under the Investors tab. Presenting today will be Dr. Harith Rajagopalan, Co-Founder and CEO of Fractyl Health, with Dr. Adarsh Thaker from UCLA joining to share his perspectives after the formal presentation. 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 31st, 2025, and our quarterly report on Form 10-Q, filed on May 12th, 2026, 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 these statements, even if subsequent events cause our views to change. It is now my pleasure to pass the call over to Harith.
Good morning, everyone. Thank you for joining us today. We are thrilled to present strong one-year data from the randomized REMAIN-1 midpoint cohort, demonstrating meaningful and durable weight maintenance with Revita one full year after the discontinuation of GLP-1 medicines. The key result is that patients treated with Revita maintained up to 84% of their GLP-1 induced weight loss at one year, compared to only 46% in the sham arm among patients who received complete duodenal ablations. This addresses the most significant unmet need in obesity today, durable weight maintenance after stopping GLP-1 therapy. The data show something many people believed was not possible, that durable drug-free weight maintenance can be achieved with a single outpatient endoscopic procedure.
We are also pleased to have with us today Dr. Adarsh Thaker, the co-lead of the UCLA Bariatric Endoscopy Program and a principal investigator of the REMAIN-1 study, who will share his perspectives on the data and his expectations for the upcoming pivotal trial results. We believe these positive results significantly strengthen the probability of success of our ongoing pivotal trial. We look forward to reporting top-line six-month data from our landmark REMAIN-1 study early in the fourth quarter of 2026, followed by potential FDA De Novo submission later the same quarter. With positive one-year randomized data in hand and major catalysts approaching, we believe now is a particularly compelling time for investors to engage with our story. We have very strong conviction in Revita based on four key pillars shown here. First, the clinical signal is real. Second, our pivotal study is built to win.
Third, there is a clear path to commercial value. Fourth, we are funded through definitive data later this year. For those new to our story, Revita is an endoscopic procedure that targets the duodenal mucosa or the first 25 cm of the small intestine just beyond the stomach. This short segment plays a critical role in metabolic regulation. Chronic exposure to high-fat, high-sugar diets cause long-term changes to the duodenal mucosa that impair normal nutrient sensing and contribute to metabolic dysfunction. Revita is designed to ablate this damaged tissue and allow the regeneration of healthier duodenal mucosa, offering a potential new way to restore normal metabolic regulation. Revita is like LASIK for obesity. It targets the underlying cause of disease with a single outpatient procedure rather than relying on chronic medication.
This approach is particularly valuable in the post GLP-1 setting, where millions of patients are looking to maintain their weight loss without staying on therapy long term. The REMAIN-1 midpoint cohort is our randomized, sham-controlled proof of concept study in post GLP-1 weight maintenance. The study was not formally powered for statistical significance. Our goal was to generate descriptive data to better understand the treatment effect exactly as a phase II informs a phase III and help inform the design of our pivotal trial. We enrolled patients with obesity with a BMI between 30 and 45 who were GLP-1 naive and did not have type 2 diabetes. Patients were started on tirzepatide to achieve at least 15% total body weight loss. GLP-1 therapy was discontinued in these participants, they were randomized two to one to either Revita or sham.
The primary efficacy endpoints were the perent total body weight change from post GLP-1 nadir between Revita and sham at three and six months. Today, we are presenting the 12-month data, with patients and investigators remaining blinded to their treatment allocation throughout the full year. 41 of 45 randomized patients completed the full 52 weeks of follow-up. All discontinuations were due to patient withdrawal of consent, importantly, there was no reinitiation of GLP-1 therapy after randomization. Today's safety and efficacy analyses include all available data. When we presented the six-month results from this midpoint cohort earlier this year, we highlighted two key observations that directly informed our pre-specified pivotal statistical analysis plan. First, we observed a clear dose response. Patients who received more complete duodenal ablation maintained significantly more weight at six months.
Based on this finding, we defined the per-protocol population in our pivotal study as those who received a complete ablation of more than 14 cm. Second, we saw that patients who lost more weight on GLP-1 therapy were at higher risk of more regain after discontinuation. In the midpoint cohort, the separation between Revita and sham was therefore greater in patients with higher GLP-1 induced weight loss. Based on this, our pivotal statistical analysis plan includes run-in weight loss as a key covariate in the primary analysis. We applied this exact same methodology to today's 12-month analysis to give investors as much read-through as possible to the potential results of the pivotal study. We are presenting data today across four analysis populations. The full mITT population includes all randomized and treated patients consistent with the primary analysis in our pivotal study.
We are also showing data in a high run-in population, a complete ablation population, and an optimized population that combines both high run-in weight loss and complete ablation. We believe this optimized population best represents Revita's ultimate clinical profile. Turning to the efficacy results at one year, Revita clearly reduced weight regain with the benefit becoming more pronounced when an adequate dose of ablation was delivered. In the full mITT population, Revita reduced weight regain by approximately 40% versus sham, and this increased to over 60% reduction in regain in patients who received complete ablations. The sham arm regained approximately 13% from nadir or 54% of their GLP-1 weight loss at one year, which is consistent with, but slightly lower than, the roughly 60% regain that is reported in SURMOUNT-4 and other post GLP-1 meta-analyses. This similarity provides an important external validation for this study's findings.
Looking at the complete ablation population over the full year analyzed in the MMRM that we will be using in the pivotal statistical analysis plan, patients first underwent a GLP-1 titration phase, losing a substantial amount of weight. After discontinuing GLP-1, they were randomized. At one year, Revita patients retained 81% of their weight loss while sham patients retained less than half. This large treatment effect appears durable throughout the one-year follow-up period. Importantly, the median ablation length in our ongoing pivotal trial is 16 cm, meaning that a majority of patients in the pivotal are expected to have received complete ablations. Turning now to the optimized population, the right dose in the right patient. In this group, Revita patients regained only 16% of their GLP-1 weight loss at one year, compared to 54% in the sham arm. This represents over a 70% reduction in weight regain versus sham.
The pivotal cohort had a mean GLP-1 induced weight loss of over 18% during the run-in period, which suggests that a majority of pivotal participants will be well-represented from this high run-in weight loss population. Let's put this in practical terms. A patient starts at 220 pounds, loses 44 pounds on tirzepatide, weighs 176 pounds at the time of randomization. They would regain 23 pounds on sham over a year, but only eight pounds with Revita, meaning they would maintain 36 pounds of their GLP-1 weight loss one year later. Turning to safety, Revita continued to demonstrate a favorable safety profile through one year. There were no new device-related treatment emergent adverse events between six and 12 months, no device-related serious adverse events in the entire study. We saw no excess frequency of any treatment emergent adverse events with Revita at all.
There were only four incidents of TEAEs in total. Intriguingly, there were no new diagnoses of type 2 diabetes in the Revita arm, but there was one diagnosis of type 2 diabetes in the sham arm. These four mild treatment emergent adverse events occurred in two patients. Let's zoom in on them. Abdominal discomfort, sore throat, nausea, dry mouth, all resolved within two days with no further device-related adverse events at any point in the study. This is an incredibly mild periprocedural profile, especially when compared to the GLP-1 medicines that represent the only treatment alternative for these patients. We believe it supports a potentially very broad outpatient utilization for a large population. With one-year data presented, let's now turn to our ongoing REMAIN-1 pivotal study. This trial has the same design, patient population, and enrollment criteria to the midpoint cohort you just saw.
It is being conducted by the same investigators using the same protocol. What this means is that the pivotal study is essentially a larger, well-powered version of the exact same experiment you just saw. Same patients, same doctors, same protocol. This significantly de-risks the pivotal results for us. Because of the strong similarity between the two studies, the midpoint cohort provides valuable read-through to the ongoing pivotal. Based on the data we've just shown you, both co-primary endpoints in the pivotal study are powered at over 95%. Let's take the first co-primary. It is a percent of total body weight regain in Revita versus sham at six months. The table shows illustrative sham six-month regain in the mITT population versus what Revita regain needs to be in order to be able to win statistically.
Hold that up against what we observed in the midpoint cohort in the mITT population, you will see the results clear comfortably. Let's take the second co-primary endpoint, the responder rate. The FDA-mandated pre-specified performance goal is a single-arm result of at least 50% of patients maintaining at least 5% of their total body weight loss at 12 months. In the midpoint cohort, this figure was 73% in the mITT population and over 90% in the complete ablation cohort. In summary, we saw substantial weight loss maintenance with up to 84% of on-drug weight loss retained one year off GLP-1 when an adequate dose of ablation is used, versus only 46% in the sham arm. Given the absence of any dose-limiting toxicity observed, we see room for even further profile optimization in the future as we continue to develop our technology.
The periprocedural AE profile supports what we believe to be a very broad potential outpatient endoscopic use. All of this translates to a well-powered pivotal with top-line data expected in early Q4 2026 and a potential De Novo regulatory filing later next quarter. With that, I'd like to turn the microphone over to Dr. Adarsh Thaker. 12 days ago, he became associate professor of medicine at the David Geffen School of Medicine at UCLA, and he's also the co-lead of their UCLA Bariatric Endoscopy Program. He's also a clinical advisor to us and a REMAIN-1 investigator. Dr. Thaker?
Thank you, Harith, for the introduction. It's good to be here this morning to review this data. As you mentioned, I'm a gastroenterologist. I've been involved in the type 2 diabetes trials. Now I'm involved in the weight maintenance program for the Revita DMR procedure. As you mentioned, I have a busy practice treating patients with obesity and metabolic syndrome with endoscopic therapies. When I saw these data, I have to say that I'm highly enthusiastic about the results. I think particularly compared to the data before, we continue to see clinically significant separation between the two groups. The separation is meaningful and appears to be sustained.
I think that one of the worries that I had. I think it was shared by others, was that perhaps there was no plateau in the earlier data, and maybe performing the DMR procedure is not actually giving us true separation, but just delaying the inevitable with the weight gain and shifting it downstream. I think as we start to see the curves get to their 1-year mark and beyond, we are starting to see hints of a plateau, even with the small numbers in this pilot study. From my standpoint, I think with the numbers presented here, the benchmarks for my own clinical practice, for my partners to accept it in clinical practice, and most importantly for patient acceptance, I think those benchmarks have clearly been surpassed.
There's a lot of different ways to present these numbers. I think about how I would describe it to a gastroenterologist or even a patient who are considering incorporating or undergoing these procedures respectively, and I think that slide where Harith showed how much weight regain in the 220-pound patient. The way I would say is that if you do this procedure, you get to keep an extra 15 pounds off compared to just stopping the GLP-1 agent. I think that's a meaningful and powerful message. That is not easy to do. I think that framing it that way with simplicity, I think again, will gain a lot of acceptance in the field and by patients. I want to highlight that I think that the dose optimization information is quite important.
As we went through the study, we had our own learning curve, we had our own safety tolerance. As we saw, the safety data is really, really good. The training wheels and the kid gloves or gentle hands that we were using early on in our learning curve experience came off, and we were able to be more aggressive. For that reason, I'm hoping that these data represent a floor and not a ceiling in terms of how effective the treatment can be to maintaining the weight loss. I'm looking forward to the pivotal numbers. The safety data is in line with my own observations of what patients have been experiencing after undergoing the procedure.
Looking forward, as we await the pivotal results from the larger cohort, I think it's important to reflect on that there's often a difference between what we as providers want to see in terms of data and what patients actually want. Particularly in a world where upcoming GLP-1 agents are revealing ever-increasing weight loss numbers. Patients don't need a grand slam. They don't need perfect separation in terms of how much weight regain they might have between this and just doing nothing, stopping cold turkey. Patients just need a boost. Even some separation, I think, will be good enough to get widespread buy-in and certainly keep me immediately busy from even just my own patients in my own practice. Even a 5%-10% weight loss compared to the original baseline is linked to very meaningful health benefits.
That's often what we counsel patients with things like fatty liver, diabetes. They don't have to get 30% weight loss, even 5%-10% will help them. I think if I can say to a patient that doing a Revita DMR procedure is more likely than not going to keep most of your weight off after you stop this GLP-1 medication, that'll be enough to get buy-in. The reason for that is that the safety data is so good and the stakes are so low. The procedure really is more of a timing inconvenience. You have to spend half a day, take off of work, and find a ride home after undergoing anesthesia, but why not do this? It's very well tolerated. It's a straightforward procedure. We're only going to get better and more efficient at it.
Really for, again, the time commitment and having to go under anesthesia for a little while, the patients are being freed from a pharmacologic agent. I'll finish with kind of just an anecdote where we were in the REMAIN-1 study, for one reason or another, our startup and activation was towards the back end and we were told that we only had a couple of weeks to fill our entire study cohort if we wanted to participate. My obesity medicine partner went to work, and just from her own clinic, within one week, we found 25 patients and filled our entire quota of participants. That was without even leaving or advertising or talking to other people. It was just from her own clinic, and that's how quickly we filled the study.
Now you could say, okay, maybe it was the free tirzepatide that they're getting, and that was the reason that patients wanted this. I was in the REVITALIZE-1 trial for type 2 diabetes, back then we had minimal to no data, very little safety data. Even then, patients, when they heard about the possibility of coming off of medications, the buy-in was very high. I've never had a single patient, even when I had very little data to back up my claims on what this could do, never had a single patient refuse to consent for the procedure. I think the patient drive is strong. I think that, again, we don't need to see grand slam numbers for myself and other gastroenterologists who do bariatric and metabolic endoscopy procedures to immediately be overwhelmed with patient demand after this procedure.
I'm hopeful, and I look forward to seeing the overall cohort data. I'll turn it back to Harith.
Thank you, Adarsh. In closing, we see a clear near-term path to a potential launch. Later this quarter, we're going to have an investor day to walk through our review on the substantial commercial opportunity ahead of us. You'll remember earlier this quarter, we hired Mike Zumdahl as our SVP of Market Access and Commercial Strategy. He's going to walk you through our strategy to tackle this exciting new market development opportunity in front of us. In early Q4, we will present pivotal top-line six-month data. In late Q4, we anticipate our potential FDA De Novo submission. With that, I'll pause. Dr. Thaker and I would both be happy to open the floor for questions.
Great. Thank you. Yes, at this time, we'll be conducting a question and answer session with our speakers. Please hold for a brief moment while we poll for questions. Our first question comes from Michael DiFiore at Evercore. Please go ahead, Michael.
Great. Thanks so much for taking my question, and congrats on the great data. Two questions from me. For the pivotal trial, how will dropouts be handled statistically? Separately, can you remind us of the dietary modifications in the pivotal trial and how they will be monitored and enforced throughout the study? Thank you.
Sure. Michael, dropouts are handled in the MMRM analysis that we've pre-specified as missing at random, and MMRM handles them through its own modeling. We will have some sensitivity analyses as well, but that's the primary analysis. Dietary modifications in the pivotal are exactly like what we have done here. You will note that there were some patients who were better about following it than others. None of the data was excluded from this analysis, and we are confident that we have done a good job of centralizing an appropriate moderate diet and lifestyle program through centralized blinded dieticians who are overseeing the work of individual site-level dieticians at every clinical trial site. It's literally the same diet and exercise program that all of the GLP-1 studies have also run, 500 kcal calorie deficit plus some exercise recommendation each week.
Great. Thanks so much.
Thanks.
Yes. Thanks for the questions, Michael. Our next question comes from Whitney Ijem at Canaccord Genuity. Please go ahead, Whitney.
Hey, guys. Congrats on this update. A question for Dr. Thaker, I guess. What are you currently offering patients who come to you for an endoscopy-based procedure, obesity patients who come to you for an endoscopy-based procedure? Can you maybe compare and contrast how these data compare to those options?
Sure, Whitney. Right now, the primary procedures we perform are endoscopic sleeve gastroplasty. It would be a suturing-based procedure where we're reducing the size of the stomach through the mouth, and we use that as an alternative to patients who may undergo surgical sleeve gastrectomy but don't want to have the incisions or the aggressiveness or changes in surgery. Followed by that, it's actually revisions of patients who had actually already had bariatric surgery and need tightening because their anatomy has become dilated. With the primary ESG, I'll talk mostly about that one, but typically quote patients as having between 14%-17% total body weight loss at one year. That's the average. Real-world numbers vary significantly based on diet and exercise programs and settings. That looks to be around the number.
I think it's a slightly different procedure because we are doing that primarily for weight loss. It's something that I'm certainly interested in looking at to see if that can be used as an off-ramp for GLP-1. I don't think that the physiology alteration is as good as what we're doing here in the duodenum. In the duodenum, we're not changing the anatomy. We're trying to restore a normal, healthy gut tissue physiology. I see no reason why you couldn't do this in combination with the ESG, either at the same time or in tandem, and really see if we could start to meet surgery-level numbers by doing everything endoscopically.
Got it. Really helpful. Just one quick follow-up for the company. I think in the previous randomized cohort data, you talked about the P value with an understanding that this is a small N and read through to the pivotal. Unless I missed it, can you remind, what did you see as a P value here? Just kind of curious how that compares to the last update and read-throughs to the pivotal. Thanks.
We have not powered the study for formal statistical inference. You can look at the standard error bars, and you can see that there's clear separation. There is no question that what we are seeing is going to be highly statistically significant if it continues in the pivotal trial.
Great. Thanks so much.
Thanks for the questions, Whitney. Our next question comes from Chase Knickerbocker at Craig-Hallum. Please go ahead, Chase.
Good morning. Thanks for taking the questions. Maybe just two for Dr. Thaker to start. Would greatly appreciate your thoughts as far as what the level of efficacy that needs to be seen in the pivotal for, however you want to define it, but substantial adoption of Revita in your practice, ultimately, if approved. Is that bar, however you want to define it, whether that's retention of weight loss or absolute weight loss from GLP-1 baseline. Just your thoughts there would, I think, be really helpful to contextualize this for us.
Yeah, I think the second point that you made is the easier way. How am I going to describe this to my partners, to referring physicians, or to patients, which is from the original start, before the GLP-1, how much weight can we keep off if we did a one-two punch of GLP-1 and then DMR to get the patient off of it? I think that even 5% weight loss maintained, compared to the original baseline, would be a win. 10% would be great, and that would meet a lot of the other endoscopic procedures I do and have meaningful health benefits. I believe that's one of the secondary study endpoints, where if we can keep more than 5% total body weight loss from the original baseline after a DMR treatment, to me, that would be enough to offer this to patients.
If it's more than 10% from total body weight baseline, then I think that it'll be very popular and an easy sell.
Got it. Then maybe just second, as you've had greater experience with Revita, done more procedures, maybe just talk to us about how your kind of comfortability going longer with the ablation length has progressed, then also the time to complete the procedure, how that's developed and how the level of complexity here compares to some of the other things that you do in your practice.
Yeah, certainly. This is really the first time anyone's bothered to go after the duodenum like this, even though we've known that it's a key regulator for the metabolism. One of the reasons that duodenum is it's thin-walled, and it has a rich blood supply, we've always been afraid of complications. The other major complication we were afraid of is pancreatitis. Early on, particularly in the diabetes studies and for providers who had picked up the device for the first time for this study, we were being very careful and trying to not overdo it. As a result, we ended up, I think, in many ways, underdoing it. That's why you're seeing not every patient achieving this dose optimization, the optimized dose length. Which roughly, to me, it translates into seven ablations. Can you do more than seven?
As I got more comfortable and the way that I would teach it to now to someone who is picking it up for the first time, I would say that the duodenum can take it turns out. The data, again, my own experience, has shown that we don't need to be so careful. While before we were obsessing over avoiding overlapping treatment areas, avoiding going too far, avoiding starting too close to the beginning of the duodenum, now we can be more aggressive without sacrificing safety. We can start pushing the bar, I think that's a learning curve that I had to go through that just with simple training and coaching, other providers won't need to. I think that we can get that into their hands much more quickly to make sure we meet that benchmark of seven ablations or more.
How complicated is this?
At the moment, there was a little bit of a procedure and a technical learning curve of driving the catheter, et cetera. There's a lot of work being done to democratize this procedure, really to make it as easy and as quick as a screening colonoscopy. When you think about how many people, I think the number needed to treat for a screening colonoscopy is like 450. The reality is that most patients that we're doing screening colonoscopy are not being helped by that procedure. Whereas I think with this, we're going to see a lot more meaningful benefit on an individual level.
I envision a world where you can do this in line with or even at the same time as a screening colonoscopy one day, and I think that's the goal, to make this an under 30-minute procedure that can be done by any gastroenterologist who wants to. We're working hard to make that happen.
Very helpful, Doctor. Thank you.
Thanks for the questions, Chase. Our next question comes from Qi Fang at Bank of America. Please go ahead, Qi.
Hey, guys. This is Qi in for Jason. Thanks for taking our questions. The first one that I have here is, I want to revisit slide number 15 from the corporate presentation where you provide some nice sensitivity analysis on what Revita need to hit in the pivotal cohort data for it to be statistically significant. Curious your thoughts about the base case assumption of 11.6% weight regain from the sham arm in six months. If I recall correctly, the six-month data from the midpoint cohort, the sham arm regained 7.5%. If you can talk about the differential assumption there, that would be great. In the event that the sham arm did perform more similar to the midpoint six-month data, say 7.5% weight regain, what would Revita need to hit to still hit statistic? Would the 5.1% still be sufficient or not? That would be my first question.
Great question. Bottom line is that the 5.1% and the 11.6% that we're showing here are measured in exactly the same way as the pivotal statistical analysis will be conducted. That explains the difference between the number that we reported back in January and the number that we are reporting now, because we're taking run and weight loss as a treatment interaction term, as we laid out on one of the earlier slides. I think you can see that the Revita regain needed to win is the delta versus the illustrative regain in the mITT population is roughly two and a half percentage points. That is the number that we would need in order to feel comfortable, regardless of the methodology used.
Got it. My second question is that, under the De Novo pathway, do you think that the one-year midpoint data that you have today, coupled with the six-month pivotal data in 4 Q, could be sufficient for approval consideration? Or do you think that even in the De Novo pathway, would the FDA still require the one-year data from the pivotal cohort for registrational purposes?
I've never known the FDA to turn down the opportunity to see all of the data that's available. I expect that they're going to want to see the 12-month data as well.
Okay. My last question is for both the company and KOL. Based on the cumulative data you have seen today, do you have any thoughts on the proportion of patients who could be retreated with Revita, meaning treating multiple times? What would potentially be the retreatment interval could be or frequency? Thanks.
Darsh, do you want to talk about retreatment potential, then I'll talk about what we think about intervals?
Yeah, I think that it's a little bit of a different situation than, say, someone with diabetes. I think that let's say I had a patient that was suboptimally responding after one treatment. Really, I don't see any reason why I couldn't go back in there and retreat them. I'm aware of data that's being worked on in Europe to kind of help answer this question. Once they've healed up, which we believe happens within months, I personally don't really see a reason why we couldn't offer a retreatment. Maybe there were some spots that I missed or maybe it didn't stretch the right way or something like that.
To me, I would say it would be a little early to make any judgments before the six to 12-month mark, which is similar to what I tell patients who have an ESG procedure and are not losing the expected weight before we would do a retreatment. From a practical standpoint, I think, to me, the anesthesia is becoming the riskiest part of this procedure. If a patient can undergo the sedation safely and I could reach their duodenum with the catheter, I don't see any reason why I couldn't offer this to most patients that want it from a health standpoint or anatomic standpoint.
I'll just add that in our type 2 diabetes work, we've seen durability out to two years. We're encouraged by the plateauing of weight regain that we're beginning to see in this cohort. If you especially combine that with the 20 or so patients from the REVEAL open label cohort, we're seeing a very consistent pattern of separation versus the expected regain. Obviously, 18 and 24-month data are expected. 24-month data are expected next year, given the fact that we just filed with the FDA and gotten a protocol accepted that allows longer-term follow-up. I have no concerns about the patient acceptability of a retreatment frequency that's measured in 18 to 24 months or more. At the same time, I don't think that that's going to be necessary. In this cohort, 20% of patients actually lost further weight even after stopping their GLP-1 at one year.
In the REVEAL open label cohort, over 30% of patients lost further weight. I think that this is a therapy that could have very long-lasting effects, and retreatment seems to potentially be quite safe and achievable and acceptable to patients. We love the profile that is emerging.
Great. Thanks so much for the update, and we look forward to the 4Q pivotal update again. Thanks.
Thank you, Qi.
Yes, thanks for the questions, Qi. Our next question comes from Rohit Bhasin at Morgan Stanley. Please go ahead, Rohit.
Hi. Good morning. Thanks for taking my question. This is Rohit on for Mike. Are there any recent discussions with regulators? Can you also share any preliminary plans in place for commercialization? Thanks.
Okay. With respect to the De Novo pathway, no new information than what we already shared in our last earnings call, which I would refer you. We feel like we've gotten favorable feedback from the FDA on the De Novo pathway. Ultimate decisions will be made once they have a chance to review all the safety data with our submission. Given the safety profile you're seeing here, our blinded view into safety through DSMB interactions in the pivotal, we feel very confident that we are well on our way towards a De Novo pathway. With respect to commercial strategy, we have added some new slides on this in our investor deck, and we're really excited to walk you through that and some of the health economics work that we've been doing with Mike's leadership now. That we will walk through in more detail at our upcoming investor day.
More on that to come.
Thank you.
Thanks, Rohit. Our next question comes from Jeff Cohen at Ladenburg. Please go ahead, Jeff.
Hi. Thank you. This is Destiny on for Jeff Cohen. Congratulations on the strong data. I wanted to go back to the greatest benefit in patients with the greatest need. I'm wondering, do you feel as though that's the most clinically meaningful data point? One for Dr. Thaker. How do you see yourself integrating this into, I guess, you call it the workflow, when a patient comes in? Are you starting them on a GLP-1 and then waiting for them to say, "I think I'd like to stop taking this," or are you saying, "Here's the strategy that I've seen work, and here's probably what I would recommend for you"? If you could just share your thoughts on that would be super helpful. Thank you.
Dr. Thaker, why don't you go first, I will answer her question for me.
Yeah, that's a great question. I think that there's multiple patient journeys that I could foresee. I would have an immediate injection of patients who are already on a GLP-1 and are looking to stop it. In fact, I think most patients that are on it would say that they'd be looking to stop it. That would be the first group that would immediately make me and my colleagues busy doing these procedures. That's the first step. The second step would be getting the word out to endocrinologists and primary care providers that are either managing obesity or are already treating patients with GLP-1s.
I think what you said is a great idea, that, yeah, I would present the whole treatment journey as one, that it's a one-two punch that we can start tirzepatide or another agent, once they achieve their desired weight loss goals, we do the procedure as a one-two punch, and do it right away. I think that that is going to be very attractive, that they not only get the benefit from the therapy, but there's a clear off-ramp insight right up front. Again, we would immediately be overwhelmed with demand just from our own clinics and then from people who hear about this finite treatment option.
I'll talk about the patients with highest need. There's no question, the more weight you lose on a GLP-1, the more violent and uncomfortable that rebound is. Everybody understands that. The better the drugs become as we go from tirzepatide to retatrutide and other agents, the more potent they are, the faster they achieve weight loss, the greater the need for a safe and effective off-ramp that can prevent that weight regain from happening. Every physician understands that. Every patient is hearing that. That becomes the easiest, most accessible population in whom to advocate for a therapeutic option like this, because the alternative is the worst. At the same time, as long as doctors are able to do more than seven ablations in a setting or greater than 14 cm, I'm confident we can offer benefit to a large swath of patients.
Part of the greatest benefit, the effect size that we're talking about here is really about the, let's say, the clinical trial design requirements of a double-blinded sham-controlled study where effect size is going to dictate perception of the therapy. In the real world, I think that physicians are going to be able to offer this to a broad swath of patients on label.
Great. Thank you so much for taking our questions.
Thanks, Destiny. Our final question comes from Lander Egaña Gorroño . Please go ahead, Lander.
Hi. Good morning, everyone. This is Lander on for Joseph. Congrats on the data, thanks for taking our question. Maybe can you remind us what was the average ablation length in the complete midpoint cohort?
The average ablation length in the midpoint cohort was a little bit lower than what we have in the pivotal. It was roughly 16 cm in the midpoint cohort, it was over 16 cm, closer to 17 cm in the pivotal cohort. This is a reflection of new investigators climbing the four to five procedure learning curve, to getting them to a point where they were able to feel comfortable ablating a longer length, as Dr. Thaker already laid out.
Awesome. Thank you for that. Also, just curious, at the one-year time point, anything that can be highlighted from the clinical sites in terms of patients' adherence to diet and lifestyle requirements?
Dr. Thaker, do you want to talk about adherence to diet and lifestyle at your site?
Yeah. I followed this a little bit loosely because I was the unblinded investigator who did the procedure.
just chatting with my obesity medicine partner, I think we have, fortunately, a good retention rate at our site, and it seems like most patients are still, even though the ones that can figure out that they got the sham, I think they are still adherent. I wouldn't be able to speak on an individual level. At least dropout appears to be low, even though I think patients are starting to realize that there is a clear separation, even themselves. We'll see.
Also-
The other thing I would tell a patient is that though the diet and lifestyle is important, I'm hopeful that at the end of the day, because we are addressing the underlying physiology and not trying to change their lifestyle necessarily, I envision a day one day where we don't have to be so obsessed on that. Right now, when we're trying to perform best practices, we will continue to package it as a full program with the diet and lifestyle interventions.
Awesome. Thank you, and congrats again.
Thank you.
Thanks for the questions, Lander. This concludes our Q&A session and our event for today. We thank you for joining, and you may now disconnect.