Fractyl Health, Inc. · NASDAQ:GUTS
Fractyl Health — DDW 2026
18 slides from Fractyl Health's conference presentation, May 2026
Slide 1: Endoscopic Duodenal Mucosal Resurfacing for Post-GLP-1 Weight Maintenance
Endoscopic Duodenal Mucosal Resurfacing for Post-GLP-1 Weight Maintenance: 6-Month Randomized, Sham-Controlled Results from the REMAIN-1 Midpoint Cohort Study Shelby Sullivan, MD, FASGE, FACG and DABOM Director of Bariatric and Metabolic Program Professor of Medicine Geisel School of Medicine, Dartm
Slide 2: Disclosures
Disclosures • Research Support / Grants Last 24 Months • Allurion Technologies (ended), Fractyl Health, Viking Therapeutics • Consulting / Employment Last 24 Months • Allurion Technologies (ended), Fractyl Health (ended), Biolinq, Olympus, Steris, Harbor Labs 2
Slide 3: Post-GLP-1 Weight Rebound: The New Unmet Need in Obesity Care
Post-GLP-1 Weight Rebound: The New Unmet Need in Obesity Care Percent change in body weight (week 0-88) Overall mean baseline body weight = 107.3 kg ~40% U.S. adults currently living with obesity 1 Tirzepatide lead-in Placebo Tirzepatide Change in Body Weight, % ~22% U.S. adults with obesity have tr
Slide 4: Duodenal Mucosal Resurfacing Leads to Sustained Weight Loss
Duodenal Mucosal Resurfacing Leads to Sustained Weight Loss Pooled Data from 5 Clinical Demographic/Characteristic N=118 Male, n(%) 88 (75%) Age, years 58 (8) Diabetes Duration, years 10 (5) A1c, % 8.2 (0.7) Body Weight, kg 93 (14) White K. Duodenal mucosal resurfacing durably maintains weight loss
Slide 5: Duodenal Dysfunction Occurs in Patient with Obesity and Metabolic Disease
Duodenal Dysfunction Occurs in Patient with Obesity and Metabolic Disease ➢ Increased enterocyte mass1 ➢ Increase in carbohydrate uptake ➢ Increased protein levels of glucose and fructose transporters2 ➢ Altered nutrient absorption in human enteroids3,4 ➢ Potential alterations in gut permeability5 ➢
Slide 6: Duodenal dysfunction as a therapeutic target in obesity and metabolic disease
Duodenal dysfunction as a therapeutic target in obesity and metabolic disease Nutrient signals from the Diet-induced mucosal changes lead Regenerated mucosa has potential duodenum travel via the to increased nutrient uptake and to restore signaling and metabolic vagus nerve to regulate impaired gut-
Slide 7: Revita Duodenal Mucosal Resurfacing Procedure
Revita Duodenal Mucosal Resurfacing Procedure Targeted mucosal ablation designed to durably reset abnormal weight and metabolic setpoint1-4 Images 7 Revita designed to achieve targeted mucosal ablation without damaging deeper structures via > > > circumferential submucosal saline lift followed by hy
Slide 8: REMAIN-1 midpoint cohort study in weight maintenance
REMAIN-1 midpoint cohort study in weight maintenance Pilot randomized study designed to inform effect size and powering of pivotal study Patient population Efficacy endpoints Study design Sample size • Adults with obesity • % TBW change from baseline • TZP administration to achieve • n=45 (BMI 30-45
Slide 9: REMAIN-1 midpoint cohort patient disposition
REMAIN-1 midpoint cohort patient disposition High retention rate through 6 months of follow-up Patient disposition • 44/45 participants (98%) completed 6- Screened month follow-up N=46 • Efficacy analysis includes all participants Enrolled TZP run-in N=46 who followed protocol-specified diet and exe
Slide 10: Balanced, Representative Study Population Supports Generalizability of Results
Balanced, Representative Study Population Supports Generalizability of Results Revita Sham Total Demographic/Characteristic (n=29) (n=16) (N=45) • Reflects broad US GLP-1 obesity population and REMAIN-1 Pivotal Age, yrs, mean (SD) 44 (14) 40 (11) 43 (13) Cohort (BMI ~ 37 kg/m2; 80% Sex, no. (%) fema
Slide 11: REMAIN-1 midpoint cohort: Revita reduced post-TZP weight regain at 6 months
REMAIN-1 midpoint cohort: Revita reduced post-TZP weight regain at 6 months 6-Month Body Weight Change3 12 Total Body Weight Change from BL Expected Regain1,2 10 (LS Mean % ± SEM) 8 7.5% p=0.07 6 4.5% 4 2 0 Sham Revita n=16 n=24 Change from baseline through 6 months analyzed using a mixed model for
Slide 12: Dose-Response: Ablation length correlates with weight maintenance treatment effect
Dose-Response: Ablation length correlates with weight maintenance treatment effect 6-Month Body Weight Change2 12 Ablation length inversely associated with weight regain 10 Dose-response: Significant correlation 8.8% between ablation length and weight 8 7.3% maintenance treatment effect (p=0.048 per
Slide 13: Dose-Response: Ablation length correlates with weight maintenance treatment effect
Dose-Response: Ablation length correlates with weight maintenance treatment effect 6-Month Body Weight Change2 12 Ablation length inversely associated with weight regain These findings inform 10 standardized ablation length of 8 16 cm adopted for Pivotal 6 Cohort 4 2 0 Sham Revita Revita Control < 1
Slide 14: High GLP-1 responders showed sustained and growing treatment effect over time
High GLP-1 responders showed sustained and growing treatment effect over time1 In participants who were high GLP-1 High GLP-1 Responders1 Change in Body Weight Over Time responders >18%1, Revita showed early 16 Sham (n = 7) Total Body Weight Change From BL and sustained separation vs sham Revita (n
Slide 15: Cardiometabolic and craving signals consistent with Revita's proposed duodenal mechanism of action
Cardiometabolic and craving signals consistent with Revita’s proposed duodenal mechanism of action LS Mean change from BL (SEM)1 Revita Sham Cardiometabolic Parameter (n = 29) (n = 16) p-value • Secondary endpoints consistent with Revita’s Triglycerides, mg/dL 8.2 (10.2) 35.6 (14.9) 0.04 proposed me
Slide 16: Favorable safety and tolerability through 6 months
Favorable safety and tolerability through 6 months • No Treatment-Emergent Serious AEs Treatment-Emergent Adverse Events (TEAEs) Revita (n = 29) Sham (n = 16) Total (N = 45) definitely or probably related to device or Patients experiencing any TEAE 8 (28) 2 (13) 10 (22) procedure n, (%) of subjects
Slide 17: REMAIN-1 pivotal study in weight maintenance
REMAIN-1 pivotal study in weight maintenance Pivotal Cohort fully randomized; 6-mo topline pivotal data anticipated in early Q4 2026 Patient population Co-primary endpoints Study design Anticipated milestones1 • Adults with obesity • % TBW regain: • TZP administration to achieve Complete randomizati
Slide 18: Conclusions
Conclusions • REMAIN-1 Midpoint is the first randomized, double-blind, sham-controlled study of a procedural intervention for post-GLP-1 weight maintenance • Endoscopic duodenal mucosal resurfacing (Revita DMR) was safe and well-tolerated through 6 months, with no definite or probabe device- or proc