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]

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].

Financial Data and Key Metrics Changes - In Q1 2025, the company reported a net loss of $23.7 million, compared to a net loss of $3.3 million in Q1 2024, largely due to fluctuations in the non-cash change in fair value of notes and warrants and increased operating expenses [20] - Research and development expenses increased to $19.4 million from $14.4 million in the same period last year, reflecting advancements in the REMAIN one study and the Rejuva program [19] - Cash and cash equivalents as of March 31, 2025, were approximately $42.1 million, expected to fund operations into Q4 2025 [20] Business Line Data and Key Metrics Changes - The REMAIN one pivotal cohort has completed full enrollment, evaluating Revita for durable weight maintenance after GLP-1 discontinuation, significantly ahead of schedule [8] - The REVEAL one cohort showed promising initial results, with participants experiencing only a 1.2% average weight regain after one month, compared to the typical 3% after GLP-1 cessation [10] Market Data and Key Metrics Changes - The company is focused on addressing the efficacy and durability gaps in obesity care, as evidenced by real-world studies showing GLP-1s do not deliver the expected weight loss [6][7] - Market research indicates strong patient interest in alternatives to chronic pharmacotherapy for obesity management, highlighting the potential for Revita [12] Company Strategy and Development Direction - The company aims to redefine obesity treatment by offering patient-friendly solutions for durable improvements in weight and metabolic control, particularly through the Revita and Rejuva platforms [5][13] - The Rejuva platform is designed to deliver a first-in-class GLP-1 based therapy for obesity and metabolic disease, focusing on safety, efficacy, and commercial viability [17][18] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming year, anticipating significant milestones including data from the REVEAL one cohort and the first CTA module submission for Rejuva [24] - The company is closely monitoring regulatory developments but does not foresee any immediate impacts on its submission processes [41][42] Other Important Information - The company has established a hub and spoke network across the U.S. for the Revita program, enhancing its commercial model and patient access [11] - The Rejuva platform has achieved regulatory alignment with European authorities for its first-in-human study design, with plans to submit the first CTA module soon [16] Q&A Session Summary Question: Clarification on REMAIN one midpoint analysis - Management confirmed that over 45 patients have achieved the required 15% weight loss, and they are confident in the Q3 dataset [29][30] Question: Upcoming REVEAL one update - The three-month data will include the majority of previously reported patients, with additional data expected from new enrollees [34] Question: Concerns regarding FDA shakeup - Management indicated no current concerns affecting regulatory interactions, with ongoing dialogue with the FDA proceeding normally [41][42] Question: Enrollment progress in REMAIN one - Enrollment was approximately three months ahead of schedule due to higher than expected demand at individual sites [48] Question: Sham procedure details - The sham procedure involves an upper endoscopy and catheter introduction, with strict protocols to maintain blinding [51]

Financial Data and Key Metrics Changes - In Q1 2025, the company reported a net loss of $23.7 million, compared to a net loss of $3.3 million in Q1 2024, largely due to fluctuations in the non-cash change in fair value of notes and warrants and increased operating expenses [18] - Research and development expenses increased to $19.4 million from $14.4 million in the same period last year, reflecting advancements in the REMAIN one study and the Rejuva program [17] - Cash and cash equivalents as of March 31, 2025, were approximately $42.1 million, which is expected to fund operations into Q4 2025 [18] Business Line Data and Key Metrics Changes - The REMAIN one pivotal cohort has completed full enrollment, evaluating Revita for durable weight maintenance after GLP-1 discontinuation, significantly ahead of schedule [7] - The REVEAL one cohort showed promising initial results, with participants experiencing only a 1.2% average weight regain after GLP-1 cessation, compared to the typical 3% [9] Market Data and Key Metrics Changes - The company is addressing a significant unmet need in obesity care, as real-world evidence indicates that GLP-1 drugs do not deliver the expected weight loss seen in clinical trials [5] - There is a clear demand for non-drug options to enhance efficacy in weight maintenance after discontinuation of GLP-1 therapy, as patients express a strong interest in alternatives like Revita [11] Company Strategy and Development Direction - The company aims to redefine obesity treatment by offering patient-friendly solutions for durable improvements in weight and metabolic control, focusing on scalable outpatient solutions [4] - The Rejuva platform is designed to deliver a best-in-class GLP-1 based therapy for obesity and metabolic disease, emphasizing potency, durability, and convenience [12] Management's Comments on Operating Environment and Future Outlook - Management anticipates 2025 to be a year of acceleration, with multiple data readouts and regulatory filings expected [4] - The company is confident in its ability to deliver key milestones, including pivotal data from the REMAIN one study and the first CTA module submission for Rejuva [21] Other Important Information - The company has developed a large-scale cGMP manufacturing process for Rejuva, which could significantly lower costs compared to current systemic gene therapy products [15] - Management does not foresee any material impact from current tariff policies on its business operations [19] Q&A Session Summary Question: Regarding the midpoint analysis of REMAIN one - Management confirmed that over 45 patients have achieved the required 15% total body weight loss and anticipates the dataset in Q3 [27][28] Question: Upcoming REVEAL one update - The three-month data will include the majority of previously reported patients, with additional data expected from new participants [31][33] Question: Concerns about FDA shakeup - Management stated that there are no current concerns affecting regulatory interactions, and preparations for the CTA are on track [40][41] Question: Enrollment progress in REMAIN one - Enrollment was approximately three months ahead of schedule, driven by higher than expected demand at individual sites [47] Question: Sham procedure details - The sham procedure involves an upper endoscopy and randomization, ensuring rigorous controls to limit placebo effects [50][52]

Core Insights - Fractyl Health is advancing its metabolic therapeutics, particularly focusing on maintaining weight loss after discontinuation of GLP-1 therapy, with promising early clinical data from its Revita treatment [3][7][15] - The company anticipates significant milestones in 2025, including data updates from various cohorts and the submission of its first Clinical Trial Application for its Rejuva gene therapy platform [2][4][16] Company Updates - Fractyl Health reported first quarter 2025 financial results, highlighting rapid clinical and operational momentum [2] - The company has completed enrollment for the REMAIN-1 Pivotal Cohort ahead of schedule, with 6-month primary endpoint data expected in the second half of 2026 [9] - The REVEAL-1 Cohort has shown encouraging results, with an average weight regain of only 1.2% after GLP-1 discontinuation, compared to the typical 3% [7][8] Clinical Trials and Data - The REVEAL-1 Cohort is designed to provide real-world insights on Revita's performance after GLP-1 therapy cessation, with early data expected in June 2025 [5][7] - The REMAIN-1 Midpoint Cohort, which includes 45 participants, aims to assess Revita's efficacy in maintaining weight loss post-GLP-1 therapy, with initial efficacy analysis planned after 12 weeks of follow-up [6][8] - The Rejuva gene therapy platform is progressing towards first-in-human studies, with the first CTA module submission for RJVA-001 expected in June 2025 [10][16] Financial Performance - For Q1 2025, Fractyl reported a net loss of $23.7 million, an increase from $3.3 million in Q1 2024, primarily due to higher operating expenses [11][23] - Research and development expenses for the quarter were $19.4 million, up from $14.4 million in the same period last year, reflecting ongoing advancements in clinical programs [11][23] - As of March 31, 2025, the company had approximately $42.1 million in cash and cash equivalents, which is expected to fund operations into Q4 2025 [11][20]

Core Insights - Fractyl Health is addressing the critical need for weight maintenance solutions post-GLP-1 therapy, with strong demand from patients and physicians for its REMAIN-1 study [2][4] - The company plans to submit the first Clinical Trial Application (CTA) module for RJVA-001 in type 2 diabetes in H1 2025, with preliminary data expected in 2026 if authorized [7][20] - 2025 is anticipated to be a pivotal year for Fractyl, with multiple key clinical milestones ahead [3] Company Developments - Fractyl Health reported significant progress in the REMAIN-1 pivotal study, enrolling over 189 patients across 13 clinical sites within six months [4] - The company has paused investment in its Revita programs for type 2 diabetes to focus exclusively on weight maintenance through the REMAIN-1 study [10] - The Revita product candidate aims to remodel the duodenal lining to reverse damage caused by high-fat and high-sugar diets, and has received U.S. FDA Breakthrough Device designation for weight maintenance [18] Financial Performance - For Q4 2024, Fractyl reported a net loss of $25.0 million, compared to a net loss of $19.2 million in Q4 2023, attributed to increased operating expenses [14] - Research and development expenses rose to $20.3 million in Q4 2024 from $10.1 million in Q4 2023, primarily due to advancements in the REMAIN-1 study [12] - As of December 31, 2024, the company had approximately $67.5 million in cash and cash equivalents, sufficient to fund operations through key clinical milestones into 2026 [15]