Fractyl Health, Inc. Common Stock Status update

Good morning, and welcome to the Fractyl Health Commercial Strategy Day. At this time, all attendees are in a listen-only mode. A question and answer session will follow the formal presentations. As a reminder, this call is being recorded, and a replay will be available on the Fractyl Health website following the conclusion of the event. I will now turn the call over to Brian Luque, Head of Investor Relations and Corporate Development at Fractyl Health.

Please go ahead, Brian. Good morning, everyone, and thanks for joining us.

I am Brian Luque, Head of Investor Relations and Corporate Development at Fractyl Health. Today is our commercial investor day. Our purpose this morning is to walk you through how we intend to commercialize Revita, our investigational procedural therapy for post GLP-1 weight maintenance, assuming we are successful in our pivotal trial and in our regulatory submission. Before we begin, I will turn to the legal disclaimer.

During this presentation, we will be making forward-looking statements, including statements about the timing and results of the REMAIN-1 pivotal cohort, our regulatory strategy and the potential use of the De Novo pathway, coding, coverage, and payment, the timing and content of a potential commercial launch, our expected financial performance, the potential sales and estimated total addressable markets currently and in the future for our product candidates, the potential timeline for profitability following the launch of Revita, and our cash runway. These statements involve risks and uncertainties that may cause our actual results to differ materially.

A discussion of those risks is included in our filings with the SEC, including the Risk Factors section of our annual report on Form 10-K for the year ended December 31, 2025, filed on March 24, 2026, and our quarterly report on Form 10-Q for the quarter ended June 30, 2026, filed on August 10, 2026, which I encourage you to review. Forward-looking statements speak only as of today's date, and we undertake no obligation to update them. I want to be clear about two things at the outset. Revita is an investigational device. It is for investigational use only in the U.S. and a CE mark in the E.U. and the U.K. FDA pre-submission feedback is advisory and non-binding, and there is no assurance that the FDA will accept a De Novo marketing application or that Revita will receive marketing authorization.

The REMAIN-1 study database has not been locked, as this is an ongoing study, so the data are subject to further cleaning and validation. You will be hearing from four speakers this morning. Dr. Harith Rajagopalan, our co-founder and CEO, will start with the problem we are solving, the opportunity, and the evidence we have generated thus far. We are then delighted to be joined by Dr. Folahan Ayoola. Dr. Ayoola is a medical director of bariatric surgery at Texas Health. He will give you the view from inside a metabolic practice on the unmet need in post GLP-1 patients. Mike Zumdahl, our Senior Vice President of Market Access and Commercial Strategy, will then take you through our Center of Excellence strategy and our market access plan.

Mike joined us in June from Inari Medical where he built global reimbursement and health economic infrastructure for a breakthrough procedural therapy through its acquisition by Stryker last year for nearly $5 billion. Lara Smith Weber, our Chief Financial Officer, will close with the commercial model and the path to profitability. Following prepared remarks, we will be happy to take your questions. With that, it is my pleasure to hand it over to Harith.

Thank you, Brian. Good morning, everyone. In July, we shared one year randomized data from the REMAIN-1 midpoint cohort and why we have conviction in Revita for the large post GLP-1 weight maintenance opportunity. Today is a different conversation about the potential market opportunity for Revita in post GLP-1 weight maintenance. Six key points. The unsolved problem in obesity is now maintenance, not weight loss, and there is no approved off-ramp. We have randomized and open label data showing a durable signal with six-month top line from the 300-plus patient pivotal cohort expected in early Q4. That study is built to support a potential De Novo filing in latent Q4 on a Class 2 path. The commercial build is activation, not market creation. The payment work is already in motion, and we believe a focused Center of Excellence launch can reach profitability five to eight quarters after launch.

Let me start with the problem. There are roughly 29 million people in the U.S. on a GLP-1 for weight loss today. These drugs work. They have changed what patients and physicians believe is possible. But look at the curve on the right. This is Lilly's SURMOUNT-4 study of tirzepatide discontinuation. Patients lost about 20% of their body weight during the lead-in. Those switched to placebo went straight back up and were still gaining at one year. That pattern has been consistently seen across studies, with almost all weight regained by around 18 months. Because patients regain fat faster than muscle they lost, body composition worsens on the way back up. To a patient, the consequences are severe. Not only weight regained, but also metabolic rebound and the psychological turmoil of having lost the weight and then gained it all back.

Roughly 85% of patients regained the weight they lost. There is no FDA-approved therapy for post GLP-1 weight maintenance. As newer drugs become more potent and more accessible, we believe that gap will only widen. It is estimated that over 1 million patients discontinue a GLP-1 each month in the U.S. The pattern is consistent. Initiation, weight loss, then discontinuation driven by costs, side effects, or access, and then rapid regain, with two-thirds of the lost weight back within a year of stopping. This is a systemic pattern, not individual failure, and it is the single largest unaddressed problem in obesity care today. Let's consider a typical GLP-1 patient. She lost nearly 50 pounds on a GLP-1, but her weight loss has plateaued, and she wants to recover the energy to sit on the ground and play with her grandchild.

She asks her physician, "Do I have to stay on this forever? Will the weight come back?" Unfortunately, today the answer is yes. There is no durable non-drug off-ramp. Revita is a single one-time outpatient endoscopic procedure that ablates the duodenal mucosa like LASIK for obesity. The duodenum is where nutrient sensing goes wrong after chronic high-fat, high-sugar diets, and Revita is designed to ablate that damaged tissue and allow healthier mucosa to regenerate. Revita holds FDA breakthrough device designation for weight maintenance in patients discontinuing GLP-1 therapy. It is designed to complement lifestyle changes and pharmacology, not replace them, and it is protected by a robust IP portfolio covering thermal and non-thermal ablation approaches.

The catheter is placed through the mouth over a guide wire while the patient is asleep, and the length of the duodenum is treated by a repeated sequence of circumferential saline lift and then precisely controlled hydrothermal ablation at each lift site along more than 14 centimeters of postpapillary duodenum. There are a few aspects of this procedure that make it a potentially scalable option for a broad population and attractive to physicians. First, the procedure uses skills an advanced endoscopist already has. Second, and critically for patient acceptance, it does not alter the patient's structural anatomy. Nothing is resected, implanted, or sutured, no restriction is created, and patients go home the same day. Third, it does not close the door on any other option, from diets to drugs to other procedures.

Our clinical program is a stepwise validation run under a single IDE built to support a potential De Novo submission late in Q4 of this year. Three cohorts. REVEAL-1 is our open-label real-world cohort. One-year data came in Q2. The midpoint cohort is our randomized, double-blinded, sham-controlled pilot of 45 patients with a tirzepatide run-in, randomized 2 to 1. We reported one-year data in July. The pivotal cohort is the same design, the same population, and the same investigators at over 300 patients. Here's what those first two cohorts have shown. REVEAL-1 open-label real-world data set, 22 patients enrolled who had already lost at least 15% total body weight on a GLP-1 and wanted to come off. At one year after a single Revita procedure, participants retained approximately 78% of the total body weight loss achieved on their GLP-1. That is open-label, real-world data.

But what does it look like in a randomized setting? In the midpoint cohort at one year, up to 84% of GLP-1-induced weight loss was retained with Revita, versus 46% with sham in patients who received complete duodenal ablations. The pivotal cohort is the box on the right. Topline six-month data early in Q4 expected. Topline one-year data in the first quarter of 2027. As an illustrative example from the midpoint cohort, a participant spent five months on a GLP-1 and lost 44 pounds. Then the drug was stopped. One year later, with no GLP-1, a sham patient is back up at 199 pounds on average, regaining 23 pounds, holding on to less than half of what she lost. The Revita patient is at 184 pounds. She has regained only eight pounds. These are mean results in the complete ablation population.