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]

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. 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]

Summary of Fractyl Health's REMAIN1 Midpoint Cohort Data Call Company Overview - **Company**: Fractyl Health (NasdaqGM: GUTS) - **Industry**: Obesity treatment and metabolic disease management Key Points and Arguments 1. **Milestone Presentation**: Fractyl Health presented the first prospective randomized double-blind control data from the REMAIN1 midpoint cohort, demonstrating that Revita prevented weight regain three months after discontinuation of GLP-1 drugs [5][6] 2. **Therapeutic Category**: The results indicate a new potential therapeutic category in obesity post-GLP-1 weight maintenance, positioning Fractyl to lead in this area [5][6] 3. **Future Milestones**: The company anticipates four weight maintenance data readouts in the next year, with pivotal data and potential PMA filing expected in the second half of 2026 [5][18] 4. **Cash Flow**: Fractyl expects to have sufficient cash to fund operations into early 2027 [5] 5. **Revita's Mechanism**: Revita targets duodenal dysfunction as a root cause of obesity, aiming to restore normal signaling and create a durable metabolic reset [6][15] 6. **Clinical Efficacy**: In the REMAIN1 midpoint cohort, Revita patients lost 2.5% more body weight compared to sham patients, who regained 10% of their weight, resulting in a clinically significant treatment difference of 12.5% [9][14] 7. **Safety Profile**: Revita demonstrated an excellent safety and tolerability profile, with no serious device-related adverse events reported [10][15] 8. **Patient Demographics**: The study included 45 adults with obesity, mirroring the real-world GLP-1 population, with an average BMI of 37.1 kg/m² [13] 9. **Weight Loss Maintenance**: Revita patients lost an additional 2 kg after stopping tirzepatide, while sham patients regained 8 kg, highlighting Revita's effectiveness in maintaining weight loss [14][15] 10. **Market Demand**: There is significant demand for a durable alternative to GLP-1 drugs, with many patients eager to find solutions for weight maintenance after stopping medications [19][20] Additional Important Content 1. **Regulatory Designation**: Revita received FDA Breakthrough Device designation for post-GLP-1 weight maintenance, emphasizing its potential in a hard-to-treat patient population [7][10] 2. **Commercial Strategy**: If approved, Revita could fit seamlessly into existing endoscopy practices, with a sales model targeting hospitals and endoscopy centers [20][21] 3. **Payer Interest**: Early feedback from health plans indicates interest in a sustainable solution for long-term weight maintenance, which Revita could provide [20] 4. **Clinical Trial Design**: The REMAIN-1 program was designed to replicate pivotal cohort protocols, ensuring consistency in patient selection and treatment [10][18] 5. **Future Data Expectations**: Upcoming data releases include six-month results from the midpoint cohort and open-label data from the REVEAL-1 cohort, which will further validate Revita's efficacy [22][36] This summary encapsulates the critical insights from Fractyl Health's recent conference call, highlighting the company's innovative approach to obesity treatment and the promising data surrounding its product, Revita.

Core Insights - Fractyl Health, Inc. announced significant results from the REMAIN-1 Midpoint Cohort, indicating that Revita may be the first therapy to maintain weight loss after discontinuation of GLP-1 drugs, with Revita-treated patients losing an additional 2.5% total body weight compared to a 10% regain in sham-treated patients, achieving statistical significance (p=0.014) [2][3][8] Study Design and Results - The REMAIN-1 Midpoint Cohort involved 45 participants who had lost at least 15% of their body weight with tirzepatide, randomized to receive either Revita or a sham procedure after stopping the drug [4] - The study met its primary efficacy endpoint at 3 months, showing Revita's effectiveness in promoting further weight loss while ensuring excellent safety and tolerability, with no serious adverse events reported [8][10] Future Milestones - The ongoing REMAIN-1 Midpoint Cohort is expected to provide 6-month data in Q1 2026, while the Pivotal Cohort aims to complete randomization in early 2026, with topline primary endpoint data and potential PMA filing anticipated in H2 2026 [11]

Revita Program - The durable weight maintenance market represents an untapped opportunity of approximately $175 billion[7] - 85% of patients regain weight after stopping GLP-1 drugs, highlighting a significant unmet clinical and economic need[10] - The REMAIN-1 Pivotal Cohort is on track to complete randomization in early 2026, with potential PMA filing in H2 2026[10] - In the REMAIN-1 Midpoint Cohort study, Revita patients experienced a further 2.5% weight loss after stopping GLP-1s, compared to a 10% weight regain in sham-treated patients (p=0.014) at 3 months[54] Rejuva Program - The company submitted the first CTA module in the EU for RJVA-001, with anticipated preliminary data in 2026[10] - Rejuva aims for a cost of goods (COGs) of less than $10,000 per patient, targeting a price benchmark of approximately $10,000 per year based on ICER pricing[92] - Preclinical data showed that Rejuva's RJVA-001 demonstrated glucose-lowering activity and improved weight compared to daily semaglutide in a db/db murine model[101] - In a DIO mouse model, RJVA-001 prototype showed sustained weight loss while preserving lean mass, outperforming semaglutide[104] Intellectual Property - The company has a robust intellectual property estate with 100+ patents issued globally, including 33 U S patents, and 70+ pending patent applications as of June 2025[135]

Core Insights - Fractyl Health, Inc. has appointed Christopher Thompson, M.D. and Ian Sheffield as Independent Directors to strengthen its Board of Directors as it advances its product candidates Revita and Rejuva [1][2][5] Company Overview - Fractyl Health is a metabolic therapeutics company focused on innovative treatments for obesity and type 2 diabetes (T2D), aiming to transform disease management from symptomatic to disease-modifying therapies [6] - The company has a robust intellectual property portfolio with 33 granted U.S. patents and approximately 40 pending U.S. applications [6] Product Development - Revita is designed to remodel the duodenal lining to reverse damage caused by high-fat and high-sugar diets, and it has received U.S. FDA Breakthrough Device designation for weight maintenance in patients who discontinue GLP-1 based drugs [7] - The pivotal study REMAIN-1 for Revita has been initiated and completed enrollment [7] - The Rejuva platform focuses on developing AAV-based gene therapies for obesity and T2D, with the first Clinical Trial Application submitted for RJVA-001 [8] Leadership Appointments - Christopher Thompson, M.D. brings extensive experience in bariatric endoscopy and has co-founded several start-ups in endoscopic technology, which aligns with Fractyl's upcoming clinical milestones [2][3] - Ian Sheffield has a 20-year track record in healthcare investing and operations, which will aid Fractyl in navigating late-stage development and strategic partnerships [3][5] Strategic Importance - The appointments of Thompson and Sheffield are seen as timely as the company prepares for key milestones and aims to capture significant clinical and economic opportunities in metabolic care [5]

Summary of Fractyl Health (GUTS) FY Conference Call - August 13, 2025 Company Overview - Fractyl Health is focused on developing therapies for obesity and metabolic diseases, aiming for durable, long-lasting effects after a single therapeutic intervention [1][3] - The company is addressing the urgent need for post-GLP-1 weight maintenance solutions, as many patients experience weight regain after stopping GLP-1 medications [2][8] Core Strategies 1. **Revita**: A medical device-enabled therapeutic procedure targeting the duodenum to address obesity and diabetes by correcting the body's weight set point [2][4] - The procedure is designed to have long-lasting effects, potentially allowing patients to maintain weight loss after discontinuing GLP-1s [2][8] - Revita is currently in late clinical stages, with over 400 patients treated in clinical studies [6][7] 2. **Rejuva**: A gene therapy platform aimed at providing a one-time treatment for type 2 diabetes and obesity, with a focus on durability and safety [39][40] - REJUVA001 targets type 2 diabetes, while REJUVA002 is aimed at the obesity market [41] Market Dynamics - An estimated 10 million people are expected to receive GLP-1 prescriptions this year, with over half likely to stop within a year, and 85% of those regaining most or all of the weight lost [2][30] - The market is in need of solutions for the 5 million Americans expected to stop GLP-1 treatments annually, as they face hunger and weight regain without effective alternatives [8][16] Revita Mechanism and Efficacy - Revita targets the mucosa of the small intestine, specifically the duodenum, to reset the body's weight thermostat, allowing for sustained weight loss and improved blood sugar levels [5][12] - The procedure is minimally invasive, performed in under an hour, with immediate effects observed within four weeks and sustained results for two years or more [6][7] - Initial open-label data showed patients maintaining weight after stopping GLP-1s, contrary to expected weight regain [28][29] Clinical Trials and Future Expectations - The pivotal study, REMAIN one, involves patients losing 15% body weight on tirzepatide before randomization to either Revita or a sham treatment [18][19] - Interim updates from the study are expected, with the first randomized data set to be released in September [22][30] - The company anticipates filing for approval by the end of next year if clinical data supports efficacy [23] Economic Considerations - Revita is positioned to align the interests of patients, healthcare providers, and payers, with a pricing model that offers a cost offset to GLP-1s [30][32] - The procedure is expected to be priced between $5,000 to $8,000, with over 80% gross margins [32][33] Competitive Landscape - The company believes that small molecules, such as those being developed by competitors, will not adequately address the long-term needs of patients who wish to avoid lifelong medication dependency [34][35] Conclusion - Fractyl Health is poised to address significant gaps in the obesity and metabolic disease treatment landscape with its innovative Revita and Rejuva platforms, focusing on durable solutions that reduce dependency on ongoing medications [39][40]

Financial Data and Key Metrics Changes - The net loss for Q2 2025 was $27.9 million, compared to $17.2 million in Q2 2024, primarily due to changes in non-cash fair value of notes and warrants and increased operating expenses [20] - R&D expenses for the quarter were $21.2 million, up from $16.8 million in the same quarter last year, reflecting continued advancement in clinical studies [19] - SG&A expenses decreased to $4.9 million from $6.2 million in the same quarter last year, mainly due to lower stock-based compensation [19] Business Line Data and Key Metrics Changes - The Revita program is emerging as a foundational therapy for resetting the body's metabolic set point in obesity and type 2 diabetes, with new data showing up to two years of benefit in weight maintenance and blood sugar control following a single treatment [7][8] - The Rejuva program has completed preclinical efficacy, toxicity, and biodistribution studies, with plans for a phase one/two clinical study to evaluate safety and preliminary efficacy in adults with inadequately controlled type 2 diabetes [16][17] Market Data and Key Metrics Changes - The company is addressing the significant unmet need for weight regain after GLP-1 discontinuation, with a focus on patients who have lost weight through GLP-1 therapy but struggle to maintain it after stopping [4][5] - Insights from key stakeholders indicate a shift in patient and prescriber attitudes, with a growing desire for alternatives to long-term GLP-1 therapy [36] Company Strategy and Development Direction - The company has strengthened its financial position through a $23 million public offering, which could provide up to $69 million in total proceeds, positioning it to capture the value of clinical and strategic progress [6] - A nonbinding letter of intent with Bariendo aims to prepare for potential adoption of Revita pending FDA approval, focusing on pre-commercial preparation and distribution channels [13] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about upcoming data readouts and the potential for Revita to serve as a long-term solution for weight maintenance after GLP-1 therapy [10][22] - The company anticipates a transformational second half of the year, with multiple clinical milestones ahead, including randomized data from the REMAIN one midpoint cohort [21][22] Other Important Information - The company has been granted two new US patents, reinforcing its position as an innovation leader in gut-targeted metabolic therapy, with over 100 granted patents worldwide [14] - The company aims to redefine the risk-benefit profile of long-term GLP-1 therapy with Rejuva, potentially offering a durable solution for chronic metabolic disease [17] Q&A Session Summary Question: What additional data points will be shared in the midpoint update? - Management indicated that the update will focus on safety, tolerability, and effectiveness of weight loss maintenance, with visibility into the overall population's behavior [27][28] Question: What is the status of Rejuva IND clearance? - Management reported significant progress and expects to see the lot release of the GMP product soon, with preliminary data anticipated in 2026 [30] Question: What trends are observed in the GLP-1 market? - There is a growing desire among patients to stop long-term GLP-1 therapy, highlighting the need for better real-world outcomes, which bodes well for Revita and Rejuva [36] Question: How does GLP-1 therapy impact observed outcomes? - Management believes that the contribution from GLP-1 to weight loss in patients is minimal, as consistent signals of weight loss have been observed across various studies [42] Question: Will patients in the REMAIN one cohort be tracked longer for durability? - Management confirmed that patients will be followed for a year, with incremental data updates expected over time [48][49] Question: What are the expectations for DEXA scans in the REVEAL trial? - DEXA scans will not be included in the open-label REVEAL study, and historical comparators for body composition upon tirzepatide discontinuation are lacking [70]

Core Insights - Fractyl Health, Inc. is advancing its Revita and Rejuva platforms aimed at treating obesity and type 2 diabetes (T2D) through innovative approaches [2][3][18] - The company recently completed a $23 million underwritten public offering to extend its cash runway for upcoming clinical milestones [2][18] - Positive early data from the REVEAL-1 Cohort indicates that Revita can help maintain weight loss after discontinuation of GLP-1 drugs [7][20] Financial Performance - For Q2 2025, Fractyl reported a net loss of $27.9 million, compared to a net loss of $17.2 million in Q2 2024, largely due to increased operating expenses [16][27] - Research and development expenses were $21.2 million for the quarter, up from $16.8 million in the same period last year, reflecting ongoing clinical study advancements [16][27] - As of June 30, 2025, the company had approximately $22.3 million in cash and cash equivalents, which is expected to fund operations into 2026 [16][27] Clinical Developments - The REMAIN-1 pivotal study includes three cohorts: REVEAL-1, REMAIN-1 Midpoint, and REMAIN-1 Pivotal, with the latter expected to report 6-month data in H2 2026 [4][9][13] - The REVEAL-1 Cohort showed that 12 out of 13 participants maintained or reduced weight after a single Revita procedure following GLP-1 discontinuation [7][8] - The REMAIN-1 Midpoint Cohort is designed to assess Revita's efficacy in maintaining weight loss after GLP-1 discontinuation, with initial data expected in September 2025 [8][12] Strategic Initiatives - Fractyl has entered a non-binding Letter of Intent with Bariendo Inc. to explore collaboration for Revita as a post-GLP-1 weight maintenance intervention [18] - The company has been issued two new U.S. patents that enhance its duodenal mucosal resurfacing platform, strengthening its intellectual property portfolio [18] - The Rejuva platform is progressing towards clinical trials, with the first-in-human study expected to begin in 2026 [11][14]