Fractyl Health, Inc. · NASDAQ:GUTS
Fractyl Health — Technical Presentation (September 2024)
24 slides from Fractyl Health's technical presentation, September 2024
Slide 1: REVITA-1 study
REVITA-1 study Evaluation of the Duodenal Mucosal Resurfacing (DMR) for the Treatment of Type 2 Diabetes Trial Rationale and Design F. Holleman
Slide 2: Objective
Objective To demonstrate the efficacy and safety of the Fractyl Revita DMR procedure compared to a sham procedure for the treatment of type 2 diabetes
Slide 3: Objective
Objective To demonstrate the efficacy and safety of the Fractyl Revita DMR procedure compared to a sham procedure for the treatment of type 2 diabetes
Slide 4: Multicenter trial
Multicenter trial Single arm phase: • ≥ 25 patients DMR treatment • 3-month follow-up • Establish safety, feasibility, approximate effect size & SD
Slide 5: Multicenter trial
Multicenter trial Single arm phase: • ≥ 25 patients DMR treatment • 3-month follow-up • Establish safety, feasibility, approximate effect size & SD Randomization phase: • Up to 240 patients • Randomized 2:1 double blind to DMR or sham • At 3 months primary endpoint: Reduction in HbA1c • After 3 mont
Slide 6: Inclusion criteria
Inclusion criteria • Age 28-75 years • Type 2 diabetes ≤ 10 years • HbA1c 59-97 mmol/mol (7.5-11.0%) • BMI ≥ 24 and ≤ 40 kg/m2 • On at least 1 stable oral glucose lowering drug for at least 3 months
Slide 7: Exclusion criteria (1)
Exclusion criteria (1) • Insulin production failure – fasting C-peptide < 1ng/mL (333 pmol/l) • Current use of insulin or GLP-1 analogues • Hypoglycaemia unawareness or a history of severe hypoglycaemia • Known autoimmune disease • Previous GI surgery (that affects ability to treat duodenum) • Histo
Slide 8: Exclusion criteria (2)
Exclusion criteria (2) • Known active hepatitis or active liver disease • Symptomatic gallstones or kidney stones • History of coagulopathy or upper gastro-intestinal bleeding conditions • Specific medications • Persistent anaemia (Hb < 10 mg/dl) • eGFR or MDRD < 60 ml/min/1,73m^2 • Active systemic
Slide 9: Screening period
Screening period Visit 1: Screening: • Verification primary in- and exclusion criteria 4-week medication run-in: • Glucose concentration-independent insulin secretagogues (sulfonylureas and meglitinides) discontinued • Adding DPP-IV inhibitors optional (investigator’s discretion) • Other medication
Slide 10: Screening period
Screening period Visit 2: Baseline: • Medication / Compliance, • Glycaemia diary, DTSQs, • Blood analysis and urine analysis (MA)
Slide 11: Screening period
Screening period Visit 2: Baseline: • Medication / Compliance, • Glycaemia diary, DTSQs, • Blood analysis and urine analysis (MA) Additional exclusion criteria: • HbA1c < 7.5% (59) or > 11.0% (97) after run-in • Hyperglycaemic events o 3x FBG > 15 mmol/L (270 mg/dL) or NFBG > 20 mmol/L (360 mg/dL) o
Slide 12: Endoscopic Screening
Endoscopic Screening Visit 3: Endoscopic screening • Assessment of the esophagus, stomach, duodenum and associated structures
Slide 13: Endoscopic Screening
Endoscopic Screening Visit 3: Endoscopic screening • Assessment of the esophagus, stomach, duodenum and associated structures Additional exclusion criteria: • Active and uncontrolled GERD (≥ grade III esophagitis) • Abnormalities GI tract preventing access to duodenum • Abnormalities duodenum preclu
Slide 14: Endoscopic Treatment
Endoscopic Treatment Visit 3: Endoscopic treatment • Randomization: DMR or sham (2:1) • Followed by diet for 2 weeks • PPI 5weeks from procedure
Slide 15: Endoscopic Treatment
Endoscopic Treatment Visit 3: Endoscopic treatment • Randomization: DMR or sham (2:1) • Followed by diet for 2 weeks • PPI 5weeks from procedure 3-month follow-up phase: • Stable medication • Record hypo- and hyperglycaemic events in glycaemia diary
Slide 16: Follow-up
Follow-up Visit 4: Phone call (day 7) Visit 5 – 13: Office visits • 1, 3, 6, 9, 12, 18, 24, 30, 36 months • Anamnesis & physical exam • Blood analysis & urine analysis • Medication use • DTSQs (additional DTSQc at 3 months)
Slide 17: Follow-up
Follow-up Visit 6: Primary endpoint visit • 3 months • Unblinding DMR patients: • Follow up endoscopy and standard follow up • Medication regimen intensively managed (changes allowed) Sham patients: • DMR treatment and restart follow up from visit 4
Slide 18: Overview
Overview Exclusion criteria Blinding Unblinding Unblinded
Slide 19: Efficacy endpoints
Efficacy endpoints Primary (at 3 months): • Reduction HbA1c from baseline Secondary (at 3 months): • Achievement of ≥1% reduction in HbA1c • Reduction in FBG • Reaching a target HbA1c ≤ 7% • Weight loss (Kg and % EW) • DTSQ (s and c) Exploratory (up to 36 months)
Slide 20: Safety endpoints
Safety endpoints Primary (through 3 months post randomization): • Incidence rate SAEs • Incidence rate UADEs • Incidence rate hypoglycaemic events Secondary: • Incidence rate of all SAEs and UADEs • Device performance • Successful completion of submucosal expansion • Successful completion of ablatio
Slide 21: Questions?
Questions? ame
Slide 22: Background
Background Type 2 diabetes: Most prevalent and costly pandemic of our time GI tract largest endocrine organ Bariatric surgery and GI Dynamics Endobarrier: Anti-diabetic effect In duodenum cellular and hormonal changes in type 2 diabetes Bypass duodenum: GLP-1 ↑ and GIP ↓
Slide 23: DMR procedure
DMR procedure DMR: Duodenal Mucosa Resurfacing Endoscopic outpatient treatment (sedation) Submucosal injection of saline Thermal mucosal ablation (3 segments of 3 cm) Alter the hormonal response to food intake similar to bariatric surgery and GI Dynamics Endobarrier
Slide 24: Clinical experience
Clinical experience 33 patients treated in Santiago, Chile Fasting glucose change (mg/dL) SF-36 Physical Mental Composite CompositeScore Score 60 54 50 1 52 53 54 52 HbA1c change (%) 3 8 9 52 49 50 108 16 12 47 6 <3 0 44 8 50 15 7 7 5 50 15 <3 40 8 49 -1 11 15 48 -50 12 30 12 53 46 46 >=3 >=3 46 -2
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