Fractyl Health, Inc. · NASDAQ:GUTS
Fractyl Health — Technical Presentation (September 2024)
18 slides from Fractyl Health's technical presentation, September 2024
Slide 1: Endoscopic Duodenal Mucosal Resurfacing (DMR) Improves Glycemic and Hepatic Parameters in Type 2 Diabetes
Endoscopic Duodenal Mucosal Resurfacing (DMR) Improves Glycemic and Hepatic Parameters in Patients with Type 2 Diabetes: Data from a First-in-Human Study Manoel Galvao Neto, MD1, Harith Rajagopalan, MD, PhD2, Pablo Becerra, MD3, Patricia Rodriguez3, Paulina Vignolo, MD3, Jay Caplan, MBA2, Leonardo R
Slide 2: Disclosures
Disclosures Harith Rajagopalan, MD, PhD – Employee and shareholder: Fractyl Laboratories, Inc. – Fractyl Laboratories provided funding for this study 2
Slide 3: Background
Background Bariatric surgeries that prevent nutrient contact with the duodenum improve measures of metabolism in type 2 diabetes (T2D), including indicators of fatty liver disease Revita™ duodenal mucosal resurfacing (DMR) may offer similar metabolic benefit 3
Slide 4: Aim
Aim To assess procedural safety in patients with suboptimally controlled T2D – HbA1c > 7.5% on ≥ 1 anti-diabetic agent To evaluate the effect of Revita DMR on metabolic parameters 4
Slide 5: The Central Role of Insulin Resistance
The Central Role of Insulin Resistance Insulin Resistance ”Inadequate” Insulin Compensatory insulin response Type 2 Resistance Hyperinsulinemia Diabetes Syndrome Retinopathy CVD Fatty liver Nephropathy HTN PCOS Neuropathy Stroke End-Organ End-Organ End-Organ Microvascular Macrovascular Metabolic Dis
Slide 6: Revita DMR: Pathophysiologic Principle
Revita DMR: Pathophysiologic Principle Bypass of upper GI tract (surgery, sleeve) exerts potent effects on metabolism through insulin sensitizing pathways Nutrient re-exposure to the ‘Roux’ elicits return to hyperglycemia Abnormal hypertrophy of mucosa noted in diabetics’ upper GI tract Abnormal ent
Slide 7: Revita DMR Procedure
Revita DMR Procedure Minimally invasive upper endoscopic therapy using an innovative balloon catheter Targets duodenal mucosa between Ampulla of Vater and Ligament of Treitz Procedural Steps ‒ Size duodenum and lift sub-mucosal space with saline injection to create protective barrier ‒ Circumferenti
Slide 8: First-in-Human Study: Methods
First-in-Human Study: Methods Single center, single arm study performed in Santiago, Chile, in patients with suboptimally controlled T2D Thermal ablation performed on either a short (n=11; mean 3.4 cm) or long (n=28; mean: 9.3 cm) segment of duodenum Procedures performed by trained endoscopists with
Slide 9: Study Details
Study Details Patient characteristics Age, yrs (range) Value (N=44) 53.4 +/- 7.5 (38-65) Inclusion criteria Sex, n (%) – Age 28-75 Female 16 (36) – BMI 24-40 Male 28 (64) – HbA1c 7.5-12% Weight, kg 84.4 +/- 11.9 – Disease diagnosed <10 years Height, cm 165.3 +/- 8.4 – Fasting c-peptide >1 ng/ml – ≥
Slide 10: Study Enrollment
Study Patients enrolled between August 2013 Enrollment 44 and December 2014 5 patients excluded: • 4 did not receive DMR • 2 failed screening endoscopy • 1 tortuous anatomy • 1 anticipated prolonged anesthesia duration • 1 patient anti-GAD+ (treated & Treated patients followed for safety, not effica
Slide 11: Safety & Tolerability
Safety & Tolerability Procedure well tolerated with minimal GI symptoms No difficulty tolerating oral diet in the days after the procedure AEs generally mild in severity & tended to occur in immediate post- procedure period Most common AE was transient abdominal pain due to air insufflation/endotrac
Slide 12: Safety & Tolerability: Endoscopy Findings
Safety & Tolerability: Endoscopy Findings Follow up endoscopies at 1 & 3 months showed intact mucosa with unremarkable mucosal plicae, indicating full mucosal healing Pre-Procedure Duodenum Ablated Duodenum One-Month Follow Up Three-Month Follow Up 12
Slide 13: Efficacy
Efficacy DMR procedure elicited improvements in glycemia (meal challenge plasma glucose, HbA1c) - HbA1c reduction of 1.2% at 6 months in efficacy cohort (n=39) More robust glycemic effect observed among long segment cohort (n=28) - 2.5% reduction in baseline mean HbA1c at 3 months post- procedure vs
Slide 14: Overview: Changes in Metabolic Parameters in LS Cohort
Overview: Changes in Metabolic Parameters in LS Cohort Screening 1 Month 3 Month 6 Month Normal* HbA1c - % 9.6±1.4 7.9±1.1 7.1±0.9 8.2±1.6 4.0-6.0 Weight - kg 86±11 82±11 83±12 85±11 -- ALT - IU/L 40±23 32±17 27±14 27±12 ≤ 38 AST - IU/L 32±17 27±11 23±8 22±6 ≤ 40 *Normal range based on ranges report
Slide 15: DMR Improves Glycemic Measures: Long Segment Cohort (n=28)
DMR Improves Glycemic Measures: Long Segment Cohort (n=28) Average Change in HbA1c (%) 11 HbA1c reduction of 1.4% 10 at 6 months (p<0.001 for 9 change from screening) HbA1c (%) 14/28 patients had 8 reduction in concomitant 7 anti-diabetic medications ADA/ EASD target post-procedure 6 Scr 0 1 3 6 Mon
Slide 16: Hepatic Transaminase Changes by Tertile
Hepatic Transaminase Changes by Tertile Lowering of ALT and AST more pronounced in subjects with elevated pre-treatment levels ALT Tertiles AST Tertiles LS Cohort (n=28) LS Cohort (n=28) >44 (N=9) >32 (N=7) 26-44 (N=9) 60 24-32 (N=11) 60 <=24 (N=10) <=26 (N=10) 40 AST (IU/L) ALT (IU/L) 40 20 20 0 0
Slide 17: DMR Reduced ALT and AST in Patients with Radiological Evidence of NAFLD
DMR Reduced ALT and AST in Patients with Radiological Evidence of NAFLD Metabolic benefits seen in 22 patients with incidental finding of fatty liver on ultrasound ALT in LS Subjects with Fatty Liver AST in LS Subjects with Fatty Liver Fatty liver (N=22) 40 40 AST (IU/L) ALT (IU/L) 20 20 0 0 Scr 0 1
Slide 18: Conclusions
Conclusions DMR improves metabolic control in T2D patients, including a robust and sustained lowering of hepatic transaminase levels DMR offers the potential for a single-point intervention that improves both glycemia and fatty liver Further study in patients with fatty liver disease is warranted 18
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