Core Insights - Fractyl Health, Inc. has completed randomization in the REMAIN-1 Pivotal Cohort, with topline 6-month data expected in early Q4 2026, and received favorable FDA feedback on its De Novo classification request, with submission anticipated in late Q4 2026 [1][2][10] Clinical Developments - New post-hoc analyses from the REMAIN-1 Midpoint Cohort show a statistically significant ablation-length (dose)-dependent treatment effect on post-GLP-1 weight maintenance at 6 months, reinforcing confidence in the REMAIN-1 Pivotal Cohort design [2][4][5] - Patients with greater GLP-1-induced weight loss prior to randomization exhibited larger sham-adjusted treatment effects at 6 months, with effect size increasing over time [1][3][5] Financial Performance - For Q4 2025, Fractyl reported a net loss of $43.7 million, compared to $25.0 million for the same period in 2024, primarily due to a non-cash accounting change in fair value related to warrant liabilities [19][31] - Research and development expenses were $16.5 million for Q4 2025, down from $20.3 million in Q4 2024, attributed to strategic reprioritization [19][29] - As of December 31, 2025, the company had approximately $81.5 million in cash and cash equivalents, which is expected to fund operations into early 2027 [19][28] Regulatory Strategy - The FDA has acknowledged the safety profile of the Revita DMR System as consistent with a Class II device classification, with final determinations pending a complete safety dataset review [10][17] - The company is advancing toward multiple anticipated clinical and regulatory milestones, including pivotal readout and potential U.S. regulatory submission [9][10] Market Context - Approximately 30 million patients are projected to be on GLP-1s by 2035, with many facing discontinuation and significant weight regain, highlighting the potential market for Fractyl's procedural therapy for post-GLP-1 weight maintenance [3][4]

Financial Data and Key Metrics Changes - Revenue for the year ended December 31, 2025, was $22 million, a decrease of approximately 14% from $25.7 million in 2024 [18] - Gross profit increased to $8.4 million or 38.2% of revenue compared to $8.2 million or 32% of revenue in 2024 [20] - Operating loss narrowed by 33% to $19.7 million in 2025 compared to $29.3 million in 2024 [22] - Net loss narrowed by 31% to $19.9 million in 2025 compared to $28.9 million in 2024 [22] - Operating cash usage reduced by 23% to $16.8 million in 2025 compared to $21.7 million in 2024 [23] Business Line Data and Key Metrics Changes - Revenue from ReWalk Personal Exoskeleton was relatively flat at $8.5 million in 2025 compared to $8.9 million in 2024, with units sold increasing by 22% year-over-year [18] - Revenue from MyoCycle FES bike declined by 50% to $600,000, reflecting a strategic focus on core products [19] - Revenue from AlterG products and services was $12.9 million, a decline of 18% from 2024, primarily due to lower international sales [19] Market Data and Key Metrics Changes - ReWalk achieved reimbursement coverage with three largest Medicare Advantage insurers in the U.S., representing over 16 million covered lives [13] - International distribution for ReWalk expanded, with Germany as the primary test market [13] Company Strategy and Development Direction - The company is executing a strategy to build a diversified biomedical innovation company with multiple technology platforms [3] - A strategic transaction with Oramed is expected to strengthen the financial foundation and support growth initiatives [4] - The acquisition of technology from Skelable aims to enhance the upper extremity rehabilitation market [6][9] Management's Comments on Operating Environment and Future Outlook - Management expressed cautious optimism about growth in the core med tech business and improvements in operating expenses driving the company toward positive cash flow [16] - The company is focused on expanding reimbursement coverage and building a stronger payer engagement capability [11] Other Important Information - The company will not provide guidance at this time due to significant transformations and pending transactions [15] - The strategic agreement with Oramed is expected to close soon, providing additional capital support [23] Q&A Session Summary Question: How does the Oramed POD technology align with the company's commercial infrastructure? - Management indicated that the integration of Oramed's technology will drive synergies across med tech and biotech, enhancing the company's decentralized approach to commercialization [27] Question: What is the timeline for the upper extremity robotic assistance product? - Management stated that the product could be 510(k) exempt and expects to complete the necessary studies within 18-24 months [31][32] Question: How does the company plan to address competition in the upper extremity market? - Management acknowledged the presence of competitors but emphasized the unique approach and simplicity of their product [36] Question: Can the company quantify the backlog entering 2026? - Management noted that while the pipeline is growing, specific numbers are not available at this time, but there is a focus on the 22% growth in units year-over-year [51]

Core Insights - Fractyl Health, Inc. has completed participant randomization in its REMAIN-1 Pivotal Cohort study, which evaluates the effectiveness of Revita for weight maintenance after discontinuation of GLP-1 therapy [1][2][3] - The topline 6-month results from this study are expected to be reported in early Q4 2026, with a potential FDA marketing application submission anticipated in late Q4 2026 [1][7] - The company has reiterated its cash runway guidance, indicating sufficient funds to support operations through early 2027, beyond the pivotal data readout [1][5] Study Design and Objectives - The REMAIN-1 Pivotal Cohort is a randomized, double-blind, sham-controlled study involving adults with obesity (BMI ≥30 kg/m and ≤45 kg/m) who have lost at least 15% of their total body weight on tirzepatide [3] - Participants are randomized in a 2:1 ratio to receive either Revita or a sham procedure, with co-primary endpoints focusing on weight regain at 6 months and the proportion of participants maintaining a ≥5% weight loss at 12 months [3] Clinical and Regulatory Milestones - Fractyl Health is on track for several key clinical and regulatory milestones in 2026, including FDA feedback on the De Novo pathway for Revita expected in Q2 2026 [5][7] - The company plans to report 1-year data from the REVEAL-1 Cohort and the REMAIN-1 Midpoint Cohort randomized data in Q2 and Q3 2026, respectively [7] Product Information - Revita is designed to remodel the duodenal lining through a minimally invasive endoscopic procedure, aiming to restore nutrient sensing and signaling disrupted by chronic metabolic diseases [8] - The product has received FDA Breakthrough Device designation for weight maintenance in individuals who discontinue GLP-1 therapies and is currently for investigational use only in the U.S. [8]

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 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]

Table of Contents Registration No. 333-276046 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 AMENDMENT NO. 1 to Index to Financial Statements FORM S-1 REGISTRATION STATEMENT UNDER As filed with the Securities and Exchange Commission on January 29, 2024. THE SECURITIES ACT OF 1933 FRACTYL HEALTH, INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) Delaware 3841 27-3553477 (Primary Standard Industrial Classificatio ...

Table of Contents Index to Financial Statements As filed with the Securities and Exchange Commission on December 14, 2023. Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 FRACTYL HEALTH, INC. Harith Rajagopalan, M.D., Ph.D. Chief Executive Officer Fractyl Health, Inc. 17 Hartwell Avenue Lexington, MA 02421 (781) 902-8800 (Name, address, including zip code, and telephone number, including area code, ...