Fractyl Health, Inc.

Good afternoon, and welcome to Fractal's Health Third Quarter 2025 Financial Results and Business Updates Call. As a reminder, this conference call is pre-recorded. At this time, all participants are listen-only mode. There will be a Q&A session following management repair remarks. I'll now turn the call over to Brian Luque, Head of Investor 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 Harith.

Thank you, Brian. Good afternoon, everyone. This quarter marked a major inflection point for Fractal. we delivered the first randomized double-blind sham-controlled data showing that a single Revita procedure can sustain weight loss after GLP-1 drug discontinuation. We believe Revita addresses one of the most urgent challenges in obesity, which is how to maintain success once therapy stops. We also strengthened our balance sheet to support our upcoming clinical and regulatory milestones into early 2027. And we continue to advance our clinical programs ahead of schedule setting the stage for a series of important catalysts in weight maintenance over the next several quarters. Across every front, clinical, regulatory, and financial, we are building momentum toward what I believe will be the most exciting and definitional 12 months in our company's history. The science is working, the data are strong, and the opportunity ahead of us has never been clearer. Let's start with Revita. Revita is our endoscopic procedural therapy designed to remodel the duodenal lining by a hydrothermal ablation to address a root cause of metabolic disease. Revita resets the gut's metabolic control system, the duodenum, which is a key site of nutrient sensing and signaling in the gut and is hardwired to the brain through a key gut-brain connection that controls body weight and blood sugar. Decades of high-fat and high-sugar diet can damage this duodenal lining, disrupt gut-brain signaling, and drive hunger and insulin resistance. Revita is designed to remove this damaged tissue and allow a healthy new lining to regrow, restoring normal gut-brain signaling and metabolic balance. It's like LASIK for obesity. Since enrolling the first patients in our Remain Weight Maintenance Program in August of 2024, the last five quarters have been a period of incredible clinical operational execution and momentum. In September, we reported three-month data from the Remain One midpoint cohort. Ravida-treated patients lost an additional 2.5% of total body weight, while patients in the sham group regained about 10%, a statistically significant and clinically meaningful separation after the discontinuation of terzapatide. The procedure was well tolerated with no related serious adverse events. These results not only materially de-risk the pivotal readout ahead, they also represent a true turning point in metabolic medicine. If Revita continues to sustain weight loss at 6 and 12 months, in line with the durability we have seen across prior clinical studies involving hundreds of patients with Revita, we believe we will have a transformative new treatment option in obesity. Enrollment in our Remain 1 pivotal cohort was completed in Q2, and randomizations in that cohort are progressing ahead of schedule. As of October 31st, we have randomized over 60% of the pivotal cohort patients, and we are on track to complete randomization of the full 315 participants early next year. This pivotal study has advanced ahead of plan from the outset. and we are executing it with the focus and precision that this opportunity deserves. Looking ahead, we expect a rich set of value-creating catalysts in the coming quarters. Six-month data from the Reveal 1 open-label cohort this quarter, six-month randomized data from the Remain 1 midpoint cohort in the first quarter of 2026, and top-line pivotal data and potential PMA submission in the second half of 2026. Based on prior Eli Lilly studies, patients who stopped GLP-1 therapy typically regain about 10% of their body weight by six months. We believe that Revita can be a highly successful therapy if it cuts the rate of weight regain in half, so roughly less than a five percentage point weight regain at six months, which would represent a clinically meaningful and substantial benefit for patients and a strong validation of Revita's potential. We believe Revita is defining a new therapeutic category in obesity, post-GLP-1 weight maintenance, a category that complements, not competes, with chronic drug therapy and provides the off-ramp that patients and physicians have been waiting for. Millions of Americans are expected to discontinue GLP-1 therapy over the next year. Every one of them will face the challenge of keeping the weight off. Revita is built for that moment. Durability is central to Revita's value and a huge advantage compared to chronic pharmacology. And we continue to see encouraging real-world durability outcomes in Revita clinical studies, including in Germany. In our German real-world registry study, 30 patients have now reached one year of follow-up and 14 patients have reached two years of follow-up. The first 14 patients with two years of follow-up maintained an average total body weight loss of 9% and a 1.7% reduction in HbA1c in a patient population with advanced type 2 diabetes, despite a net reduction in medications. Three-month results were highly predictive of 6, 12, and 24-month results. These durable outcomes not only strengthen our confidence as we move toward a pivotal readout in Remain 1, but also underscore Revita's potential to deliver long-lasting benefit in real-world settings. By this time next year, we expect to have one-year open-label data in weight maintenance, top-line data from our Remain One pivotal cohort, and a larger sample of patients with two-year data and beyond from our German real-world registry study. Taking these clinical proof points together, we believe Revita will have a compelling and comprehensive clinical data package that will be ready for both regulatory filings and reimbursement discussions by the second half of next year. Revita's durable activity also drives its economic rationale by potentially reducing the need for ongoing drug therapy and reducing the risk of downstream adverse health outcomes it offers a multi-year health and cost advantage for payers who are seeking sustainable alternatives to chronic GLP-1 treatment. In light of this, we're encouraged by the recent announcement from the U.S. government on GLP-1 access in Medicare. Expanding access to these medicines is good for patients and it's good for the field. More patients starting GLP-1s, either as injectables or as orals, also means more patients who will eventually need an off-ramp when most inevitably discontinue treatment. Our clinical work and our relationships have also positioned us well for rapid activation once RUVIDA is approved. Many of the physicians participating in our clinical studies are experienced users of the procedure, committing to treating obesity and metabolic disease with their endoscopic skills, and they are based at leading centers across the country. Already active at major clinical centers from Miami to Seattle, from New England to Southern California, and together with partners like Barriendo, we have already established and have a ready-to-activate footprint at several of the highest volume endoscopy centers in the US. This enables, in our view, a targeted and efficient commercial model for us or our partners to access upon approval. Our market analysis confirms the size and strength of this opportunity. Because the procedure fits naturally into an existing endoscopy workflow, Revita could reach nearly 1 million annual procedures at peak adoption, translating to a sizable revenue opportunity. Importantly, Revita's unit economics create strong incentives for adoption at the clinical site level. We expect gross margins for participating centers to be comparable to or better than other advanced endoscopic interventions, creating meaningful financial alignment between clinical and commercial stakeholders. Taking a step back, what we are talking about is potentially the first scalable therapy that addresses a root cause of obesity and type 2 diabetes and can change the trajectory of both diseases. If Ravida is successful in post-GLP-1 weight maintenance, a hard-to-treat and high unmet need patient segment, we believe it can be effective across a spectrum of metabolic disease, not only for maintenance, but also as frontline, not only as a standalone therapy, but also in combination with weight loss medications. Turning to Rejuva now, our smart GLP-1 platform, we continue to make exciting progress. Earlier this month, we presented new preclinical data from Rejuva 002, our candidate for obesity, which showed nearly 30% body weight loss after a single dose in a translational obesity model with no observed adverse effects. Rejuva-001, our lead candidate in type 2 diabetes, is designed to reprogram pancreatic islet cells to secrete GLP-1 in response to glucose, with the goal of restoring physiologic hormone regulation and achieving long-term metabolic remission. We have now completed our preclinical CMC and lot release for our Rejuva 001 drug product. And with all preclinical milestones now checked off, we remain on track to dose the first patients and report preliminary data in 2026. Between Revita and Rejuva, complementary endoscopic approaches designed to reset the gut and reprogram the pancreas, we are building a platform that can fundamentally change how metabolic diseases are treated. Our differentiation is our strength. Our product candidates are designed to do what the majority of patients need, but current therapies cannot deliver. Durable, physiologic, and designed to work with the body, not against it. Now let me hand it to Lisa to discuss our financials.