Summary of Fractyl Health FY Conference Call (December 03, 2025) Company Overview - **Company**: Fractyl Health (NasdaqGM:GUTS) - **Focus**: Development of Revita, a treatment targeting obesity and type 2 diabetes through an outpatient endoscopic procedure Key Industry Insights - **Obesity and GLP-1 Drugs**: There are approximately 10 million people using GLP-1 medications for weight loss, with an estimated 6 million expected to stop treatment this year, leading to significant weight regain risks for many patients [1][2] - **Market Opportunity**: The potential market for Revita includes nearly 1 million patients annually who are already undergoing endoscopies for other reasons, making it easier to integrate the Revita procedure into existing healthcare practices [8] Core Findings from Clinical Studies - **Reveal-1 Study**: - Patients who lost an average of 24% body weight (over 50 pounds) on GLP-1s and then underwent Revita maintained a weight regain of only 1.5% over six months, compared to an expected regain of over 10% [4][5] - The study demonstrated that 40% of patients continued to lose weight after the procedure, indicating a stable weight maintenance profile [14] - Hemoglobin A1c levels remained stable, with only a 0.04% change, suggesting effective glucose control alongside weight maintenance [15][16] - **Remain-1 Study**: - In a pilot study with 45 subjects, those who received Revita lost an average of 2 kg after stopping tirzepatide, while the sham group regained approximately 8 kg, highlighting a significant treatment difference of about 10 kg [21] - The pivotal Remain-1 study, which includes 315 patients, is expected to provide further data in the second half of 2026, with a focus on post-GLP-1 weight maintenance [24][23] Important Data Points - **Endoscopy Statistics**: Approximately 20 million endoscopies are performed annually in the U.S., with 800,000 of those being patients on GLP-1s [7] - **Patient Cohorts**: Fractyl is studying three patient cohorts: Reveal-1 (open-label), Remain Midpoint (pilot randomized), and Remain pivotal [13][20] - **FDA Designation**: The company has received Breakthrough Device Designation from the FDA, which may expedite the approval process for Revita [25] Additional Considerations - **Market Expectations**: A 50% reduction in weight regain is considered a significant win for the market, with stability in weight maintenance being a critical factor for patient outcomes [30][32] - **Clinical Consistency**: The data from both Reveal-1 and Remain-1 studies show a consistent signal of stability in weight maintenance, which is crucial for the therapeutic potential of Revita [33] This summary encapsulates the key points discussed during the Fractyl Health FY Conference Call, highlighting the company's innovative approach to addressing obesity and the promising clinical data supporting its treatment.

Core Insights - Fractyl Health, Inc. announced positive results from the REVEAL-1 Cohort, showing that participants who lost 24% of total body weight on GLP-1 drugs maintained stable weight and glycemic control six months after a single Revita treatment [1][3][6] - Revita demonstrated a mean weight change of 1.5% after six months, significantly lower than the ~10% weight regain observed in third-party studies following GLP-1 withdrawal [1][6] - The company anticipates key clinical data releases in 2026, including the REMAIN-1 Midpoint Cohort data in January and potential PMA filing in H2 2026 [1][13] Company Overview - Fractyl Health focuses on innovative treatments for obesity and type 2 diabetes, aiming to transform metabolic disease management from chronic symptomatic treatment to durable, disease-modifying therapies [11] - The company has a robust intellectual property portfolio with 35 granted U.S. patents and approximately 45 pending applications [11] - Revita, the company's lead product, is designed to remodel the duodenal lining to reverse damage caused by unhealthy diets, and has received FDA Breakthrough Device designation for weight maintenance after GLP-1 drug discontinuation [12] Study Details - The REVEAL-1 Cohort included 22 participants who had lost at least 15% of their body weight on GLP-1 medications and chose to discontinue therapy [9][10] - Participants maintained stable weight and minimal change in HbA1c levels after the Revita procedure, indicating potential for long-term metabolic health [6][8] - The study reported excellent tolerability, with no serious adverse events and mild, transient treatment-emergent adverse events in 36% of participants [6][8] Future Outlook - Fractyl Health is preparing for multiple clinical readouts in 2026, including 1-year data from the REVEAL-1 Cohort and the REMAIN-1 Pivotal Cohort [13] - The company is experiencing rapid clinical enrollment in its pivotal studies, reflecting a strong demand for non-drug alternatives in obesity treatment [8]

Core Insights - Fractyl Health, Inc. announced positive results from the REVEAL-1 Cohort, indicating that participants who lost 24% of total body weight on GLP-1 drugs maintained stable weight and glycemic control for 6 months after a single Revita treatment [1][3][5] - Revita shows potential as a first-in-class therapy for weight maintenance post-GLP-1 therapy, with minimal weight change of 1.5% observed [1][5][7] Study Results - Participants in the REVEAL-1 Cohort lost an average of 24% of total body weight (>50 lbs.) on GLP-1 drugs before receiving Revita treatment [5][9] - After the Revita procedure, participants maintained stable weight with a mean total body weight change of 1.5% ± 1.3% at 6 months [5][9] - Glycemic control was also sustained, with minimal change in HbA1c levels (0.04% ± 0.08%) compared to a ~0.4% increase seen in other studies post-GLP-1 withdrawal [5][9] Safety and Efficacy - The study included 22 participants, with safety data available for all and efficacy data for 17 [5][9] - No serious adverse events were reported, and 36% of participants experienced mild, transient adverse events consistent with prior Revita experiences [5][7] - The average ablation length during the procedure was approximately 16 cm, aligning with previous real-world experiences [5][7] Future Developments - Upcoming clinical data from the REMAIN-1 Midpoint Cohort is expected in January 2026, with additional pivotal data anticipated in H2 2026 [1][12] - Revita has received FDA Breakthrough Device designation for post-GLP-1 weight maintenance, highlighting its potential as a scalable, non-drug alternative for obesity treatment [7][11] Company Overview - Fractyl Health focuses on innovative treatments for metabolic diseases, including obesity and type 2 diabetes, aiming to transform treatment from chronic management to disease-modifying therapies [10][11] - The company has a robust intellectual property portfolio with 35 granted U.S. patents and approximately 45 pending applications [10]

Core Insights - Fractyl Health, Inc. is focused on innovative treatments for obesity and type 2 diabetes (T2D), aiming to address the root causes of these metabolic diseases rather than just managing symptoms [2][3] - The company will participate in the 8th Annual Evercore Healthcare Conference, highlighting its commitment to engaging with investors and stakeholders [1][2] Company Overview - Fractyl Health is based in Burlington, Massachusetts, and specializes in metabolic therapeutics [2] - The company has developed a significant intellectual property portfolio, including 33 granted U.S. patents and approximately 45 pending U.S. applications, along with various foreign patents [2] Industry Context - Obesity and T2D are increasingly recognized as major health challenges in the 21st century, contributing to rising morbidity and mortality rates [2] - The company aims to shift the treatment paradigm from chronic management to durable, disease-modifying therapies that target the organ-level causes of metabolic diseases [2]

Financial Data and Key Metrics Changes - For Q3 2025, research and development expenses decreased to $17.5 million from $19.0 million in Q3 2024, primarily due to reduced spending on the Revitalize One study and lower stock-based compensation [17] - Selling, general, and administrative expenses increased to $5.2 million from $4.8 million in the same period last year, reflecting one-time costs associated with the issuance of warrants [17] - The company reported a net loss of $45.6 million, compared to a net loss of $23.2 million in Q3 2024, largely driven by a $23.5 million non-cash accounting change in the fair value of warrants [17] - As of September 30, 2025, cash and cash equivalents stood at approximately $77.7 million, bolstered by $83 million from recent underwritten offerings, extending the cash runway into early 2027 [18] Business Line Data and Key Metrics Changes - Revita, the company's endoscopic procedural therapy, demonstrated significant clinical results, with treated patients losing an additional 2.5% of total body weight while sham group patients regained about 10% after discontinuing tirzepatide [6][8] - Enrollment in the Remain One pivotal cohort was completed in Q2 2025, with over 60% of patients randomized as of October 31, 2025, ahead of schedule [7] Market Data and Key Metrics Changes - The company anticipates nearly 1 million annual procedures at peak adoption for Revita, translating to a substantial revenue opportunity [13] - Revita's unit economics are expected to create strong incentives for adoption at clinical sites, with gross margins comparable to or better than other advanced endoscopic interventions [13] Company Strategy and Development Direction - The company is focused on advancing clinical programs and regulatory milestones, with a clear path for multiple catalysts expected within the next 12 months, including pivotal data and potential PMA submission [19] - Revita is positioned as a transformative therapy for obesity, particularly in post-GLP-1 weight maintenance, complementing existing chronic drug therapies [9][11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming clinical and regulatory milestones, emphasizing the strong data supporting Revita and the growing market need for effective obesity treatments [4][19] - The company is optimistic about the potential for Revita to significantly reduce weight regain rates, which is a critical challenge for patients discontinuing GLP-1 therapies [9][22] Other Important Information - The company has established a ready-to-activate commercial model with experienced physicians at major clinical centers across the U.S. [12] - Revita's durable activity is expected to provide economic advantages by potentially reducing the need for ongoing drug therapy and associated health risks [11] Q&A Session Summary Question: What are the expectations for the six-month updates for Reveal One and Remain One Midpoint? - Management expects the six-month Reveal dataset to show consistency in results, with a goal of less than 5% weight regain, which would be a compelling outcome [21][23] Question: Can you clarify the German registry data regarding weight loss maintenance? - The average weight loss at one year was 8%, and at two years was 8.9%, indicating no waning of effect [26][27] Question: What are the manufacturing needs for Revita? - The company is confident in its current manufacturing capabilities to support clinical studies and is preparing for scale [41]

Financial Performance - For the nine months ended September 30, 2025 and 2024, the company incurred net losses of $97.2 million and $43.7 million, respectively, with an accumulated deficit of $512.5 million as of September 30, 2025[130]. - The net loss for the three months ended September 30, 2025, was $45.6 million, a 96.8% increase from a loss of $23.2 million in 2024[166]. - Net loss for the nine months ended September 30, 2025, was $97.2 million, an increase of $53.5 million or 122.4% from a loss of $43.7 million in 2024[175]. - The company reported a net loss of $97.2 million for the nine months ended September 30, 2025, adjusted for non-cash expenses of $28.4 million[212]. - The company may face substantial doubt about its ability to continue as a going concern for at least one year after the issuance of its financial statements due to liquidity concerns[202]. Revenue and Expenses - Revenue for the nine months ended September 30, 2025, was $0, a decrease of $90,000 or 100.0% compared to $90,000 in 2024[175]. - Cost of goods sold for the same period was $0, down from $50,000, representing a 100.0% decrease[175]. - Research and development expenses totaled $17.5 million for the three months ended September 30, 2025, a decrease of 8.1% compared to $19.0 million in 2024[166]. - Research and development expenses increased by $7.9 million, or 15.6%, to $58.0 million compared to $50.2 million in 2024, driven by advancements in Revita and Rejuva programs[177]. - Selling, general and administrative expenses increased by $0.4 million, or 9.2%, during the three months ended September 30, 2025, primarily due to professional service fees[171]. - Selling, general and administrative expenses decreased by $2.7 million, or 14.8%, to $15.5 million, primarily due to a $3.7 million decrease in stock-based compensation[181]. - Other expense, net, was $22.9 million for the three months ended September 30, 2025, primarily due to a $21.2 million loss from the change in fair value of warrant liabilities[172]. - Other net expense was $23.7 million for the nine months ended September 30, 2025, compared to other income of $24.6 million in 2024, reflecting a change of $48.3 million or 196.3%[182]. Cash Flow and Financing - The net cash used in operating activities for the nine months ended September 30, 2025, was $68.992 million, compared to $48.487 million for the same period in 2024[211]. - Cash provided by financing activities for the nine months ended September 30, 2025, was $79.739 million, primarily from common stock issuances, while for the same period in 2024, it was $101.159 million[215][216]. - The company received approximately $20.7 million in net proceeds from the August 2025 Offering, which included the issuance of 19,047,619 shares of common stock[196]. - The September 2025 Offering generated approximately $56.0 million in net proceeds from the sale of 60,000,000 shares at $1.00 per share[199]. - The company expects to seek additional funds through equity or debt financings, collaborations, or licensing transactions to support its operations[203]. - The company expects to incur substantial operating losses and negative cash flows for the foreseeable future, necessitating additional funding to achieve business objectives[200]. Clinical Trials and Research - The Revita DMR System has received reimbursement authorization in Germany and a CE mark in Europe, with a limited commercial pilot initiated in Düsseldorf, Germany[121]. - The REMAIN-1 Midpoint Cohort (n=45) demonstrated a statistically significant 2.5% further weight loss with Revita after GLP-1 discontinuation, compared to a 10% weight regain in sham-treated patients (n=16) with a p-value of 0.014[136]. - The REMAIN-1 Pivotal Cohort has completed enrollment of 315 participants, with randomization of 194 participants as of October 31, 2025, and no serious adverse effects reported[139]. - The first Clinical Trial Application module for RJVA-001 has been submitted, with preliminary data expected in 2026[128]. - RJVA-002 showed a robust, dose-dependent reduction in body weight in preclinical studies, with mid- and high-dose cohorts losing a mean of 18% (p<0.01) and 29% (p<0.0001) of body weight, respectively[144]. - The company anticipates presenting 6-month data for the REVEAL-1 Cohort in Q4 2025 and 1-year data in Q2 2026[135]. - The company expects to complete randomization for the REMAIN-1 Pivotal Cohort in early 2026, with 6-month topline primary endpoint data anticipated in the second half of 2026[140]. Weight Loss Outcomes - After a single Revita procedure, participants achieved a mean total body weight loss of 8.0%, decreasing from 102 kg to 94 kg at 3 months, sustained at 94 kg for 1 year[152]. - Mean HbA1c decreased by 1.0% at 3 months, from 8.8% at baseline to 7.7%, and this improvement was maintained at 7.9% throughout 1 year post-procedure[152]. - Among 30 participants, 28 lost weight, with 20 experiencing at least a 5% reduction and 12 achieving 10% or more[152]. - For 14 participants followed for 2 years, mean weight loss was 7.9% at 1 year, from 104 kg to 95 kg, maintained at 94 kg after 2 years[155]. - The Germany Real-World Registry study initiated in 2023 included participants with a mean age of 60 years, mean weight of 102 kg (225 lbs), and mean HbA1c of 8.8% despite treatment with up to three glucose-lowering agents[151]. Patent and Market Risks - The company has built a patent portfolio that includes 33 issued U.S. patents and approximately 45 pending U.S. applications as of September 30, 2025[149]. - The company is exposed to various market risks, including interest rate risk and credit risk, which could impact its financial condition[224]. - Future contractual commitments for leases as of September 30, 2025, totaled $53.8 million, with $52.8 million related to operating leases[218]. - The company may need to implement cost reduction strategies if it is unable to obtain additional financing[203].

Financial Performance - Fractyl Health reported a net loss of $45.6 million for Q3 2025, compared to a net loss of $23.2 million in Q3 2024, primarily due to a $23.5 million non-cash accounting change[13]. - The company reported no revenue for the three months ended September 30, 2025, compared to $14,000 for the same period in 2024[24]. - The net loss for the three months ended September 30, 2025, was $45,603,000, significantly higher than the loss of $23,173,000 for the same period in 2024[24]. - Total operating expenses for the nine months ended September 30, 2025, were $73,532,000, an increase from $68,361,000 in the same period of 2024[24]. - Research and development expenses for the three months ended September 30, 2025, were $17,457,000, compared to $19,004,000 for the same period in 2024[24]. - The company's total liabilities increased to $117,450,000 as of September 30, 2025, from $79,653,000 as of December 31, 2024[22]. - Cash and cash equivalents increased to $77,657,000 as of September 30, 2025, up from $67,464,000 as of December 31, 2024[22]. - The company reported a working capital of $61,021,000 as of September 30, 2025, compared to $51,988,000 as of December 31, 2024[22]. - The company continues to incur significant net losses and expects this trend to continue for the foreseeable future[19]. Research and Development - Research and Development expenses for Q3 2025 were $17.5 million, down from $19.0 million in Q3 2024[13]. - Fractyl's RJVA-002 gene therapy candidate for obesity demonstrated approximately 30% weight loss in preclinical studies after a single administration[13]. - Positive 3-month data from the REMAIN-1 Midpoint Cohort showed Revita-treated patients lost an additional 2.5% of total body weight after stopping tirzepatide, while sham-treated patients regained 10% (p=0.014)[9]. - The REMAIN-1 Pivotal Cohort is fully enrolled with over 60% of the 315 planned participants randomized as of October 31, 2025[9]. - Fractyl expects to report 6-month data from the REVEAL-1 Cohort in Q4 2025 and 1-year data in Q2 2026[5]. - The company anticipates reporting 6-month primary endpoint data from the REMAIN-1 Pivotal Cohort in H2 2026 and potentially filing a PMA application with the FDA in H2 2026[9]. Funding and Cash Position - The company completed $83 million in underwritten offerings, extending its cash runway into early 2027[2]. - Fractyl's cash position as of September 30, 2025, was approximately $77.7 million, expected to fund operations into early 2027[13]. Regulatory and Operational Risks - The company relies on third parties for conducting certain aspects of its preclinical and clinical studies, which may introduce additional risks[19]. - The regulatory approval process for the company's product candidates is lengthy and unpredictable, impacting the timeline for potential commercialization[19]. - The company aims to transform metabolic disease treatment from chronic management to durable disease-modifying therapies[15].

Core Insights - Fractyl Health, Inc. reported positive results from the REMAIN-1 Midpoint Cohort, indicating that the Revita procedure can maintain weight loss after discontinuation of GLP-1 therapy, with 6-month data expected in Q1 2026 [1][11] - The company completed $83 million in underwritten offerings, which is anticipated to extend its cash runway through early 2027, supporting upcoming clinical and regulatory milestones [3][20] Company Updates - Fractyl Health is focused on innovative treatments for obesity and type 2 diabetes (T2D), with ongoing momentum in its Revita and Rejuva platforms [3][18] - The REMAIN weight maintenance program includes three cohorts: REVEAL-1, REMAIN-1 Midpoint, and REMAIN-1 Pivotal, aimed at evaluating Revita's effectiveness in sustaining weight loss [5][21] - The REMAIN-1 Midpoint Cohort showed that Revita-treated patients lost an additional 2.5% of total body weight after stopping tirzepatide, while sham-treated patients regained 10% [11] Financial Performance - For Q3 2025, Fractyl reported a net loss of $45.6 million, compared to $23.2 million in Q3 2024, primarily due to a non-cash accounting change related to warrants [20][27] - Research and development expenses were $17.5 million for Q3 2025, down from $19.0 million in the same period of 2024 [20][27] - As of September 30, 2025, the company had approximately $77.7 million in cash and cash equivalents, which is expected to fund operations into early 2027 [20][26] Upcoming Milestones - The company expects to report 6-month data from the REVEAL-1 Cohort in Q4 2025 and pivotal data from the REMAIN-1 Pivotal Cohort in H2 2026 [1][12] - Fractyl anticipates filing a Premarket Approval (PMA) application with the FDA in H2 2026 [12] Research and Development - The Rejuva platform is advancing gene therapies for T2D and obesity, with RJVA-002 showing promising preclinical results, including approximately 30% weight loss in a mouse model [10][13] - The company has submitted the first Clinical Trial Application (CTA) module for RJVA-001, with preliminary data expected in 2026 [22][13]

Core Insights - Fractyl Health, Inc. is set to report its financial results for Q3 2025 on November 12, 2025, at 4:30 p.m. ET [1] - The company focuses on innovative treatments for obesity and type 2 diabetes (T2D), aiming to address the root causes of these metabolic diseases [3] Company Overview - Fractyl Health is dedicated to developing new therapeutic approaches for metabolic diseases, particularly obesity and T2D, which are significant contributors to morbidity and mortality in the 21st century [3] - The company aims to shift the treatment paradigm from chronic symptomatic management to durable disease-modifying therapies that target organ-level causes [3] - Fractyl Health has a strong intellectual property portfolio, including 33 granted U.S. patents and around 40 pending U.S. applications, along with various foreign patents [3] - The company is headquartered in Burlington, Massachusetts [3]

Core Insights - Fractyl Health, Inc. announced promising preclinical data for RJVA-002, indicating a potential for significant weight loss in obesity treatment, achieving approximately 30% weight loss over five weeks in a mouse model, with no observed adverse effects [1][2][3] Company Overview - Fractyl Health is focused on innovative metabolic therapeutics aimed at addressing the root causes of obesity and type 2 diabetes (T2D) [9] - The company has a robust intellectual property portfolio with 33 granted U.S. patents and around 40 pending applications [9] Product Development - RJVA-002 is the second candidate from the Rejuva Smart GLP-1 platform, which aims to provide a durable treatment for obesity and T2D [1][7] - The Rejuva platform utilizes gene therapy to enable long-term remission of metabolic diseases by reprogramming pancreatic islet cells to produce metabolic hormones [7][10] - RJVA-001, the first candidate from the Rejuva platform, is expected to enter clinical trials in 2026 for T2D patients [7][10] Preclinical Study Results - In a diet-induced obesity mouse model, a single administration of RJVA-002 resulted in a mean weight loss of 18% and 29% for mid- and high-dose cohorts, respectively, by day 35 [3][2] - The weight loss trajectory for RJVA-002 has not yet plateaued, indicating potential for sustained effects [2][3] Future Directions - The company plans to present further results from ongoing studies at upcoming scientific congresses, which will include metabolic measurements [4] - Fractyl Health aims to transform the treatment paradigm for obesity and T2D from chronic disease management to durable remission [3][10]