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]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________________ to ___________________ Commission File Number: 001-41942 Fractyl Health, Inc. (Exact Name of Registrant as Specified in its Charter) (State o ...

Exhibit 99.1 Fractyl Health Announces Second Quarter 2025 Financial Results and Business Updates Randomized 3-month REMAIN-1 Midpoint Cohort data expected in September 2025 Positive 3-month REVEAL-1 Cohort data showed single Revita ® procedure sustained weight loss after GLP-1 discontinuation; incremental 6-month open-label data expected in Q4 2025 Top-line REMAIN-1 Pivotal Cohort 6-month data and PMA filing expected in H2 2026 Recent Highlights and Upcoming Milestones Revita ® The Company is evaluating Rev ...

BURLINGTON, Mass., Aug. 06, 2025 (GLOBE NEWSWIRE) -- Fractyl Health, Inc. (Nasdaq: GUTS) (the “Company” or “Fractyl”), a metabolic therapeutics company focused on pattern breaking approaches that treat root causes of obesity and type 2 diabetes (T2D), today announced it will report financial results for the second quarter 2025 and provide business updates on Tuesday, August 12, 2025, at 4:30 p.m. ET. The Company also announced that Harith Rajagopalan, M.D., Ph.D., Co-Founder and Chief Executive Officer of F ...

BURLINGTON, Mass., Aug. 06, 2025 (GLOBE NEWSWIRE) -- Fractyl Health, Inc. (Nasdaq: GUTS) (the “Company” or “Fractyl”), a metabolic therapeutics company pioneering pattern-breaking approaches that treat root causes of obesity and type 2 diabetes (“T2D”), today announced the pricing of its underwritten public offering of 19,047,619 shares of common stock and accompanying Tranche A and Tranche B warrants, for gross proceeds of $20 million before deducting underwriting discounts, commissions, and offering expen ...

Core Viewpoint - Fractyl Health, Inc. is planning to conduct an underwritten public offering of its common stock and pre-funded warrants to raise capital for its pipeline programs and general corporate purposes [1][2]. Group 1: Offering Details - The company intends to sell shares of its common stock and pre-funded warrants, with each pre-funded warrant priced slightly lower than the common stock price [1]. - Fractyl expects to grant underwriters a 30-day option to purchase up to an additional 15% of the offered shares at the public offering price [1]. - The offering is subject to market conditions, and there is no assurance regarding its completion or the final terms [1]. Group 2: Use of Proceeds - The net proceeds from the offering will be used to support the Revita and Rejuva pipeline programs, along with working capital and other general corporate purposes [2]. Group 3: Company Overview - Fractyl Health focuses on innovative treatments for metabolic diseases, particularly obesity and type 2 diabetes, aiming to shift from chronic management to disease-modifying therapies [5]. - The company holds a robust intellectual property portfolio, including 32 granted U.S. patents and approximately 40 pending applications [5]. - Fractyl is headquartered in Burlington, Massachusetts, and aims to redefine metabolic disease treatment [5].

Core Insights - Fractyl Health, Inc. (NASDAQ: GUTS) is currently positioned with a classic biotech setup, indicating potential for growth and investment opportunities [1] - The company faces a near-term catalyst and has a floor level valuation, suggesting that the current market prices may not fully reflect its intrinsic value [1] - There is an asymmetric risk-reward profile, which indicates that the potential upside may outweigh the risks involved [1] - Investor anxiety is evident due to the company's need for a capital raise within the year, which could impact market perception and stock performance [1]

Core Insights - Fractyl Health's Rejuva platform shows promise as a one-time, durable therapy for obesity and type 2 diabetes (T2D), demonstrating a favorable toxicity profile in preclinical studies [1][2][4] - The mechanism of action for Rejuva is distinct from systemic GLP-1 receptor agonists, allowing for nutrient-responsive secretion that activates only under metabolic stress [2][3] - Preliminary clinical data for RJVA-001, the first clinical candidate from the Rejuva platform, is expected in 2026, pending regulatory authorization [5][11] Key Findings - A single dose of Rejuva in a study with mice resulted in a 20% reduction in body weight and a 38% decrease in blood glucose levels by day 21, effects maintained despite continued high-fat diet exposure [7] - Rejuva-treated lean animals showed no weight gain or hyperglycemia when switched to a high-fat diet, maintaining baseline body weight and showing an 8% reduction in blood glucose [7] - The treatment was well-tolerated with no signs of toxicity or excessive weight loss in healthy animals, reinforcing the self-limiting nature of Rejuva's mechanism [7] Momentum Toward the Clinic - Fractyl Health has completed key in vivo studies for RJVA-001 and anticipates dosing the first patients in 2026, aiming for a first-in-class gene therapy that reprograms the pancreas for natural metabolic control [5][11] Scientific Validation - The study was conducted by a team from Fractyl Health and the University of Michigan, including experts in metabolic diseases, highlighting the scientific momentum behind Rejuva's approach [6][8]

Core Insights - Fractyl Health, Inc. has strengthened its intellectual property portfolio with the issuance of two new U.S. patents, enhancing its leadership in metabolic innovation and duodenal resurfacing technologies [1][2][3] Intellectual Property Developments - The company has built a robust patent portfolio since 2011, now comprising 31 granted U.S. patents and approximately 40 pending U.S. applications, along with numerous foreign patents [2][5] - The newly issued patents focus on electrical energy ablation systems for treating tissue, specifically targeting duodenal mucosa with thermal and non-thermal energy applications [3][4] Product and Clinical Development - Fractyl's lead product candidate, Revita, aims to remodel the duodenal lining to reverse damage caused by high-fat and high-sugar diets, which are root causes of metabolic diseases [6][7] - Revita has received U.S. FDA Breakthrough Device designation for weight maintenance in patients who discontinue GLP-1-based drugs [6][7] - The company is preparing for three key data readouts from its pivotal study of Revita, with significant milestones expected in June 2025, Q3 2025, and the second half of 2026 [4][5]