RJVA-002 achieved ~30% weight loss at five weeks in a translational obesity model; weight loss not yet plateauedPreclinical results show that a single point-in-time treatment with RJVA-002 has the potential to achieve significant weight loss that can match or exceed best-in-class chronic drug therapy BURLINGTON, Mass., Oct. 07, 2025 (GLOBE NEWSWIRE) -- Fractyl Health, Inc. (Nasdaq: GUTS) (the Company), a metabolic therapeutics company focused on pattern-breaking approaches to treat the root causes of obesit ...

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]

Core Viewpoint - Fractyl Health, Inc. has announced a public offering of 19,047,619 shares of common stock, along with Tranche A and Tranche B warrants, aiming for gross proceeds of $20 million to support its metabolic disease treatment programs [1][5]. Offering Details - The shares are priced at $1.05 each, with each share sold together with one Tranche A warrant (2-year term) and one Tranche B warrant (5-year term) [2]. - The exercise price for both warrant tranches is set at $1.05 per share, and the warrants do not have variable priced resetting mechanisms or price-based anti-dilution features [2]. - The Tranche A warrants can be called by the company after the release of 3-month randomized midpoint clinical data from the ongoing REMAIN-1 study, contingent on certain conditions being met [3]. Additional Options - The underwriters have a 30-day option to purchase up to an additional 2,857,142 shares of common stock, along with associated warrants, at the public offering price [4]. Financial Projections - The company expects to receive approximately $20 million from this offering, with potential future proceeds of up to $40 million if the warrants are fully exercised for cash [5]. - The net proceeds will be utilized to support the Revita and Rejuva pipeline programs, as well as for working capital and other general corporate purposes [5]. Company Background - Fractyl is focused on innovative treatments for metabolic diseases, including obesity and type 2 diabetes, aiming to shift from chronic symptomatic management to durable disease-modifying therapies [9]. - The company holds a robust intellectual property portfolio, with 32 granted U.S. patents and around 40 pending U.S. applications, alongside numerous foreign patents [9].

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. announced positive 3-month data from the REVEAL-1 Cohort of its REMAIN-1 pivotal study, indicating that Revita may help individuals maintain or lose weight after discontinuing GLP-1 drugs, suggesting a potential for durable, drug-free weight maintenance [2][3][5] Group 1: Study Findings - In the REVEAL-1 Cohort, 12 of 13 participants either maintained or lost weight at 3 months, with 6 participants losing additional weight after stopping GLP-1 therapy and undergoing the Revita procedure [1][7] - The median weight change was stable at 0.46% (~1 pound), significantly lower than the expected 5-6% weight regain (10-15 pounds) after stopping GLP-1 therapy [1][7] - The Revita procedure demonstrated excellent tolerability, with treatment-emergent adverse effects being infrequent, mild, and transient [1][7][9] Group 2: Participant Profile - The REVEAL-1 Cohort included 22 participants, with 3-month follow-up data available for 13 individuals, averaging 49 years of age, and a gender distribution of 11 women and 2 men [4] - Participants had previously been treated with GLP-1 therapy for 5 months to 3 years, achieving a median total body weight loss of 20.9% while on therapy [4] Group 3: Future Expectations - Randomized Midpoint Cohort data is expected in Q3 2025, with pivotal cohort data anticipated in H2 2026, aimed at demonstrating Revita's potential for weight maintenance after GLP-1 discontinuation [2][9] - The company emphasizes the significant unmet need in obesity treatment, particularly the ability for patients to stop GLP-1 drugs without regaining weight [5][10] Group 4: Revita's Mechanism - Revita is designed to remodel the duodenal lining via hydrothermal ablation to reverse damage caused by chronic high-fat and high-sugar diets, addressing root causes of metabolic disease [11] - The product has received U.S. FDA Breakthrough Device designation for weight maintenance in individuals who discontinue GLP-1 based drugs [11]

Core Viewpoint - Fractyl Health is advancing a first-in-human study for RJVA-001, a gene therapy targeting pancreatic beta cells to treat inadequately controlled type 2 diabetes (T2D) and obesity, with preliminary data expected in 2026 pending regulatory approval [1][9]. Company Overview - Fractyl Health, based in Burlington, MA, focuses on innovative treatments for obesity and T2D, aiming to shift from chronic management to disease-modifying therapies [8]. - The company is pioneering the Rejuva platform, which develops next-generation adeno-associated virus (AAV)-based gene therapies targeting metabolic diseases [9]. Product Details - RJVA-001 is designed to express glucagon-like peptide-1 (GLP-1) locally in pancreatic beta cells, potentially reducing side effects associated with systemic GLP-1 therapies [1][2]. - The therapy utilizes a minimally invasive endoscopic ultrasound-guided infusion directly into the pancreas, allowing for nutrient-triggered secretion of GLP-1 [2][4]. Clinical Study Design - The upcoming Phase 1/2 study will be an open-label, multicenter trial assessing the safety, tolerability, and preliminary efficacy of RJVA-001 in adults aged 35-70 with T2D [4][6]. - Participants will be monitored for 12 months post-treatment, with a long-term follow-up study extending up to 5 years [5]. Study Objectives and Endpoints - Primary endpoints include safety and tolerability, while secondary endpoints focus on changes in HbA1c, fasting plasma glucose, and time-in-range metrics [7]. - Exploratory endpoints will assess beta-cell function, metabolic biomarkers, cardiovascular risk markers, and transgene expression [7]. Future Implications - If successful, RJVA-001 could redefine diabetes treatment from daily management to a potential one-time therapy, significantly impacting patient care [5]. - The company aims to develop a platform of therapies that offer superior durability, potency, and tolerability compared to conventional GLP-1 drugs [3].