Fractyl Health, Inc.

Good afternoon, and welcome to Fractal Health's first quarter 2025 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 question and answer session following management prepared remarks. I'll now turn the call over to Brian Luque, head of investment relations and corporate development at Fractal. Brian, you may now begin.

Thank you. This afternoon, we issued a press release that outlines the topics we plan to discuss today. This release is available at www.fractal.com under the Investors tab. Joining us on the call today are Dr. Harith Rajagopalan, Chief Executive Officer, and Lisa Davidson, Chief Financial Officer. During this call, we make forward-looking statements which involve risks and uncertainties that may cause actual results to differ materially from our forward-looking statements. We provide a comprehensive list of risk factors in our SEC filings, including the quarterly report on Form 10-Q filed today, which I encourage you to review. Any forward-looking statements on the call are subject to substantial risks and uncertainties, speak only as of the call's original date, and we undertake no obligation to update or revise any of the statements, even if subsequent events cause the company's views to change. It is now my pleasure to pass the call over to Harish.

Thank you, Brian. Good afternoon, everyone. Thank you for joining us today. With multiple data readouts from Reveal 1 and Remain 1, key commercial insights in weight maintenance, and a regulatory filing in Rejuva 001 expected over the course of the next two quarters, 2025 is poised to be a year of acceleration for Fractal. When we went public in early 2024, we did so with a bold ambition. to redefine the treatment of obesity by offering patient-friendly solutions for durable improvements in weight and metabolic control. Since then, GLP-1 drugs have accelerated a revolution in obesity care and have proven to be amazing medicines. But real-world evidence is beginning to show that there's still room for improvement to meet the needs of patients struggling with obesity today. A recent study published by researchers at the Cleveland Clinic in JAMA suggests that GLP-1s do not deliver nearly as much weight loss in the real world as they did in their clinical trials. 377 semaglutide-treated patients with obesity lost only 5.9% of their body weight in one year, representing only about one-third of the body weight loss seen in semaglutide clinical trials, even when accounting for persistent medical coverage. In addition to this efficacy gap, these drugs also have a durability gap. Today, most patients stop GLP-1 treatment in less than one year and only a minority resume GLP-1s in the year after discontinuation. So, there's a clear need for non-drug options to drive greater efficacy in the real world and to offer an alternative when patients need to stop medical therapy. At Fractal, we are focused on solving that problem. We are pioneering scalable outpatient solutions aimed at delivering durable metabolic resets for patients, building a new category of care based on existing patient flow into GI endoscopy, and initially targeting the critical need for weight maintenance after discontinuing GLP-1 drugs. Regardless of short-term market dynamics, by nearly every operational measure, we have made extraordinary advances. positioning Fractal at the forefront of this emerging and substantial clinical and market opportunity. Today, we are excited to share significant progress on that front. I will start with a major milestone. We have completed full enrollment of the Remain One pivotal cohort, which is evaluating Revita for durable weight maintenance after GLP-1 discontinuation. We filed with the FDA just in March of last year to initiate that study, received an IDE in April, obtained breakthrough device designation in July, initiated enrollment in August, and have now completed enrollment only nine months later and significantly ahead of schedule. This rapid enrollment reflects not only the significant unmet need felt by both patients and physicians for an off-ramp for GLP-1 drugs, but also clearly demonstrates product market fit for Revita in weight maintenance. Now that the study is fully enrolled and the last patients are initiating trisepatite therapy, Based on our observed time to achieve 15% total body weight loss, we anticipate completing randomization of these 315 participants to Revita versus Sham in the first half of 2026 and anticipate reporting pivotal six-month primary endpoint data in the second half of 2026. Remember, we believe only a single pivotal study is required for approval for Revita in weight maintenance. The Remain One midpoint cohort completed enrollment in Q4 2024, and we are confident in our ability to deliver the first blinded, controlled data from these 45 participants with three months of follow-up in Q3 2025, a major catalyst that we believe will help validate Revita's potential for these patients in need. Now, turning to the Reveal One cohort, in April, we shared encouraging initial results. Fifteen participants who had lost weight on GLP-1 drugs discontinued their GLP-1, underwent Revita, and entered structured diet and lifestyle support. For the participants who had one-month follow-up data at that time, average weight regain was just 1.2% compared to the approximately 3% typically seen after GLP-1 cessation. Two participants with three-month follow-up showed persistent weight loss through that follow-up period as well. In June, we expect to present an incremental update with three-month data from the REVEAL-1 cohort, providing what we believe is critical early validation of Revita's potential. When patients stopped her Zepatide, one would expect them to regain about 6% body weight by three months. So we will compare REVEAL-1 cohort results to that historical comparator. As you recall, for Revita, we have built a hub-and-spoke network across the United States. with referring clinics called spokes sending patients to leading GI endoscopists at hub centers from Los Angeles to New Hampshire and Seattle to Miami. Looking ahead to potential approval and commercial launch, this broad and rapid enrollment in the Remain One study highlights the efficiency, scalability, and throughput of our commercial model. We anticipate that these centers and others like them will form the foundation of our first commercial wave And we are energized by these early indicators of Ravida's market potential and the relationships that we have been building with physicians across the United States. As part of our commercial planning, we conducted in-depth market research with patients and other key stakeholders as well. And the findings were clear. Patients are highly motivated to find an off-ramp to GLP-1 therapy. The patient living with obesity does not want to stay on chronic pharmacotherapy to manage their condition for the rest of their life. patients uniformly expressed strong interest in Ravida. So what you can see is that we made a lot of progress in a short time with Ravida in weight maintenance and seeing our acceleration into an exciting and important new area of medicine called weight maintenance, where we are breaking ground in a substantial therapeutic category that has emerged because of the success that GLP-1s have with weight loss, but where they fall short with weight maintenance. Now turning to Rejuva, our pancreatic gene therapy platform that is designed to reprogram the pancreas itself to deliver durable metabolic control from within. We are building what we believe will be the best-in-class GLP-1-based therapy for obesity and metabolic disease. Potency, durability, tolerability, and convenience. Rejuva is designed to deliver smart, nutrient-responsive GLP-1 expression in the pancreas. enabling natural metabolic regulation without the burden of chronic injections, adherence challenges, or escalating costs. We believe Rejuva sets a new standard for how to leverage the known therapeutic benefits of nutrient-stimulated hormones for long-term control of metabolic disease. It was only in January of last year that we nominated Rejuva 001 as our first clinical candidate and demonstrated that our one-time, Pancreas-targeted SMART GLP-1 gene therapy outperforms semaglutide in preclinical models of diabetes and obesity. Importantly, Rejuva doesn't just drive more weight loss, it seems to deliver better quality of weight loss compared to semaglutide. Rejuva preserves lean mass while reducing fat mass, addressing one of the major challenges seen with high-dose GLP-1 therapy. By December, we demonstrated the precision of local pancreatic delivery in a large animal model, achieving strong, durable GLP-1 expression with a single low dose and no safety signals observed. We also completed key in vivo CTA enabling studies for Rejuva 001 by the end of the year. Momentum continued into the first quarter of 2025 as we achieved regulatory alignment with European authorities on our planned first in human study design. This positions us for an exciting series of milestones ahead. This weekend at ASG CT, we look forward to sharing new exciting data on Rejuva 001 safety, efficacy, and potential tolerability based on our preclinical CTA enabling studies. And then in June, we plan to submit our first CTA module to regulators with additional filings following shortly thereafter. Pending regulatory authorization, We expect to dose our first patients with Rejuva 001 and to report preliminary data in 2026. If successful, Rejuva could totally redefine the treatment paradigm for diabetes and obesity, delivering a first-in-class, programmable, and durable therapy at scale. Working with the leading CDMO in AAD manufacturing, we've developed a large-scale CGMP manufacturing process to support the size of the projected patient population that could be served by our Rejuva platform. We have completed AAD production runs in 500-liter bioreactors, demonstrating a strong foundation for scalable manufacturing with the potential for significant expansion even from where we are now. What this means is that we see a pathway to drive COGS several orders of magnitude lower than current systemic gene therapy products. We believe this could be a huge win for patients, and enable a cost structure designed for the broadest possible access to our therapies. We believe that for AAV-based therapies to succeed, they must be safe, effective, and commercially viable. And this is precisely why we're so excited about the Rejuva platform. With Revita and Rejuva both advancing rapidly, we're entering a catalyst-rich period of acceleration and key proof points in the months ahead for Fractal, and we look forward to delivering transformative data within the next several months to you. With that, I'll turn the call over to Lisa for a financial update.