Fractyl Health, Inc. · NASDAQ:GUTS
Fractyl Health — Corporate Update (September 2025)
20 slides from Fractyl Health's corporate update, Sep 26, 2025
Slide 1: Positive Randomized Data from REMAIN-1 Midpoint Cohort Study
Positive Randomized Data from REMAIN-1 Midpoint Cohort StudyRevita®: Unlocking Durable Weight Maintenance After GLP-1 Discontinuation September 26, 2025Revita is for Investigational Use Only in the US Under Federal Law Positive Randomized Data from REMAIN-1 Midpoint Cohort StudyRevita®: Unlocking Du
Slide 2: Legal Disclaimer
2 Legal DisclaimerThe study database has not been locked as this is an ongoing study, and the data are subject to further cleaning and validation.Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 199
Slide 3: Targeting Duodenal Mucosa for a Durable Metabolic Reset
3Hypothesis: Endoscopic duodenal ablation designed to provide:Safe, well-tolerated, straightforward procedureHighly effective metabolic disease modificationDurable weight and metabolic impact designed to last for yearsEvidence: Revita clinical experience has already shown:Sustained improvements in w
Slide 4: GLP-1s drive weight loss but can't deliver long-term results alone
4Majority of patients discontinue GLP-1s within 1 year2: Weight and metabolic rebound occur rapidly upon discontinuation1First symptoms are profound hunger and food noise, usually occurring within weeks of treatment discontinuationRevita is the first and only FDA Breakthrough Device targeting this g
Slide 5: Key Takeaways
5 Key TakeawaysClear evidence of Revita activity: At 3 months, Revita patients experienced 2.5% further weight loss after stopping GLP-1s, vs 10% weight regain in sham-treated patients (p=0.014)Excellent safety and tolerability through 3 months: No Revita-related SAEs or Grade II+ AEs observed, cons
Slide 6: REMAIN-1 Pivotal Program Overview
6 1. These forward-looking statements are based on management’s current estimates and expectations. Refer to the latest disclosures filed with the SEC for a discussion regarding Risk Factors to these and other estimates and expectations. BMI=body mass index, GLP-1=glucagon-like peptide-1, PMA=premar
Slide 7: REVEAL-1: Encouraging Weight Maintenance at 3 Months
7 1. Aronne et al. JAMA. 2024;331(1):38–48. doi:10.1001/jama.2023.24945. 2. Wilding et al. Diabetes Obes Metab.2022 Aug;24(8):1553-1564. 3. Fractyl Health press release dated June 23, 2025. GLP-1Rx weight loss from months -12 to 0 are illustrative based on average weight loss and time on medication
Slide 8: REMAIN-1 Midpoint Cohort Study in Weight Maintenance
8 REMAIN-1 Midpoint Cohort Study in Weight MaintenanceFirst randomized sham-controlled study in post-GLP-1 weight maintenance1. These forward-looking statements are based on management’s current estimates and expectations. Refer to the latest disclosures filed with the SEC for a discussion regarding
Slide 9: REMAIN-1 Midpoint Cohort Patient Disposition
9 REMAIN-1 Midpoint Cohort Patient Disposition Strong study execution, high retention, scalable procedure Tirzepatide run-in and dose-escalation period was approximately 16-26 weeks. Sham procedure consisted of placing the Revita catheter into the duodenum for a minimum of 30 minutes with no manipul
Slide 10: Balanced, Representative Study Population Supports Generalizability of Results
10 Balanced, Representative Study Population Supports Generalizability of Results1. Fractyl Health REVEAL-1 data disclosure https://ir.fractyl.com/static-files/8110e855-b50a-4333-b551-678d5e854663. 2. Fractyl Health data on file. *Patients with a diagnosis of pre-diabetes in their medical history. *
Slide 11: Both Arms Achieved 18% Weight Loss on Tirzepatide Prior to Randomization
11Both Arms Achieved 18% Weight Loss on Tirzepatide Priorto RandomizationTirzepatide run-in and dose-escalation period was approximately 16-26 weeks. Sham procedure consisted of placing the Revita catheter into the duodenum for a minimum of 30 minutes with no manipulations of thedevice or activation
Slide 12: Clear Evidence of Revita Activity
127 58 08 59 09 50 1 3Least-squares mean (LS mean) estimates were derived from a mixed model for repeated measures (MMRM), with treatment, visit, and treatment×visit interaction as fixed effects, andbaseline weight and as a covariate. LS means are presented at the overall mean baseline to standardiz
Slide 13: Percent Total Body Weight Change by Month
50-2.5 ± 2.7% 12.5% Treatment Difference at 3 Months (95% CI, -18.4 to -2.1%) [GRAPHIC APPEARS HERE]-50 1 3Time (Months)[GRAPHIC APPEARS HERE]Least-squares mean (LS mean) estimates were derived from a mixed model for repeated measures (MMRM), with treatment, visit, and treatment×visit interaction as
Slide 14: Treatment-Emergent Adverse Events
No treatment-emergent serious Table 3: Treatment-Emergent Adverse EventsRevita(n=29) Sham(n=16) Total(N=45) adverse events related to device orprocedure• *1 SAE (cholecystitis) > 60 days post- randomization—unrelated todevice or procedure• 4 mild procedure-related events(Grade I) in Revita, 0 in Sha
Slide 15: REMAIN-1 Pivotal Cohort Study Design
Patient population• Adults with obesity (BMI 30-45 kg/m2)• GLP-1 naïve; no T2D• N=~ 315 Co-primary endpoints• % TBW regain: Revita vs sham at 6 months; and• Responder rate: % participants who maintain weight loss at 12 months Study design• Randomized (2:1 Revita vs Sham), double-blind, sham- control
Slide 16: Observed 3-Month Treatment Effect Supports Potential Success in 6-Month Pivotal Endpoint
16 Observed 3-Month Treatment Effect Supports Potential Success in 6-Month Pivotal Cohort Primary Endpoint-505101520250136 Total Body Weight Change from Baseline (%) Time (Months) Sham arm expected to continue weight gain Revita arm expected to maintain weightIllustrative12.5% difference at 3 months
Slide 17: REMAIN-1 Enrollment
450400350 First site [GRAPHIC APPEARS HERE][GRAPHIC APPEARS HERE][GRAPHIC APPEARS HERE][GRAPHIC APPEARS HERE]REMAIN-1 EnrollmentMidpoint Cohort enrolled REMAIN-1 Pivotal Cohort fully enrolled[GRAPHIC APPEARS HERE]3 months ahead of scheduleHigh site and patient enthusiasmpoints to unmet need 300 acti
Slide 18: GI endoscopists participating in clinical studies
GI endoscopists focused on obesity and metabolic disease therapies are currently participating in clinical studies An estimated800k will get an endoscopy [GRAPHIC APPEARS HERE]Potential candidates for Revita procedure[GRAPHIC APPEARS HERE]18
Slide 19: Midpoint Cohort achieved its goal
19 Midpoint Cohort achieved its goal: Clear evidence of Revita’s activity Highly encouraging safety and tolerability profileBuilds confidence in powering assumptions for pivotalMomentum and acceleration into next steps1:Midpoint Cohort: Anticipate 6-month results from these 45 subjects in Q1 2026Piv
Slide 20: Significant Clinical Milestones for Revita Over the Next 12 Months
20 Significant Clinical Milestones for Revita in Weight Maintenance Over the Next 12 Months1. These forward-looking statements are based on management’s current estimates and expectations. Refer to the latest disclosures filed with the SEC for a discussion regarding Risk Factors to these and other e