Fractyl Health, Inc. · NASDAQ:GUTS
Fractyl Health — Diabetes Technology Meeting 2019
23 slides from Fractyl Health's conference presentation, Nov 16, 2019
Slide 1: Duodenal Mucosal Resurfacing (DMR) for the Treatment of Type 2 Diabetes
Duodenal Mucosal Resurfacing (DMR) for the Treatment of Type 2 Diabetes Juan Carlos Lopez-Talavera, MD, PhD Chief Medical Officer Fractyl Laboratories Inc Lexington, MA, USA Diabetes Technology Meeting Session 11: Live Demonstrations November 16, 2019
Slide 2: Insulin resistance and hyperinsulinemia underlie metabolic diseases
Insulin resistance and hyperinsulinemia underlie metabolic diseases Westernized diet Metabolic diseases1-3 Lifestyle Insulin resistance • T2D • NAFLD/NASH • PCOS Genes Current pharmacotherapies for T2D do not adequately address pathophysiologic defects underlying insulin resistance.4-6 Novel, diseas
Slide 3: The duodenum is a key metabolic signaling center and critical regulator of metabolic homeostasis
The duodenum is a key metabolic signaling center and critical regulator of metabolic homeostasis1 Pouch Duodenal bypass surgery (eg, RYGB) reverses metabolic disease (T2D2,3, NAFLD/NASH4, PCOS5,6) independent of Duodenum (bypassed) weight loss7 Stomach Jejunum (bypassed) Normal Hyperplastic Altered
Slide 4: Revita DMR: A novel, minimally invasive, outpatient, endoscopic procedure
Revita DMR®: A novel, minimally invasive, outpatient, endoscopic procedure • Submucosal lift and hydrothermal ablation of hyperplastic duodenal mucosa to promote epithelial regrowth and restore insulin sensitivity in patients with T2D1,2 1. Rajagopalan et al. Diabetes Care. 2016;39:2254–2261; 2. Hai
Slide 5: Revita DMR: Fractyl-sponsored studies
Revita DMR®: Fractyl-sponsored studies First in REVITA-1 REVITA-2 US Pilot Human (FIH) • Completed • Completed • Active – Follow up • Active (enrolling) (enrollment complete) • N = 57 • N = 46 • N=5 • N = 31 open-label cases; • Single center (Chile) • Multicenter (EU) N = 108 randomized-sham • Multi
Slide 6: REVITA-1: An open-label, prospective, multicenter study in suboptimally controlled T2D
REVITA-1: An open-label, prospective, multicenter study in patients with suboptimally controlled T2D on ≥ 1 OAD Endoscopic evaluation and DMR procedure Screening Safety and efficacy results through 12 months1 Long-term safety and efficacy through 24 months2 Med HbA1c 7.5% – 10%, 24 ≤ BMI ≤ 40, run-i
Slide 7: REVITA-1: DMR is feasible, safe, and effective using OAD medication (HbA1c)
REVITA-1: DMR is feasible, safe, and effective in patients with suboptimally controlled T2D using OAD medication 10 • Sustained significant improvements in HbA1c (p < 0.01) despite net medication ± SEM) 9 reductions HbA1c, % (Mean * * 8 % * * * 7 6 ks as g ks ks ks s 4 M e th D lin B nin wR ee ee ee
Slide 8: REVITA-1: DMR is feasible, safe, and effective (FPG)
REVITA-1: DMR is feasible, safe, and effective in patients with suboptimally controlled T2D using OAD medication 220 • Sustained significant improvements in (Mean ± SEM) HbA1c (p < 0.01) despite net medication 200 reductions FPG (mg/dL) • Substantial and clinically significant 180 * improvement in F
Slide 9: REVITA-1: HOMA-IR
REVITA-1: DMR is feasible, safe, and effective in patients with suboptimally controlled T2D using OAD medication • Sustained significant improvements in HbA1c (p < 0.01) despite net medication HOMA-IR (Mean ± SEM) reductions • Substantial and clinically significant improvement in HOMA-IR van Baar et
Slide 10: REVITA-1: Weight
REVITA-1: DMR is feasible, safe, and effective in patients with suboptimally controlled T2D using OAD medication • Sustained significant improvements in HbA1c (p < 0.01) despite net medication Weight, kg (Mean ± SEM) reductions • Substantial and clinically significant improvement in weight van Baar
Slide 11: REVITA-1: ALT
REVITA-1: DMR is feasible, safe, and effective in patients with suboptimally controlled T2D using OAD medication • Sustained significant improvements in HbA1c (p < 0.01) despite net medication ALT, U/L (Mean ± SEM) reductions • Substantial and clinically significant improvement in ALT van Baar et al
Slide 12: REVITA-1: DMR is feasible, safe, and effective using OAD medication
REVITA-1: DMR is feasible, safe, and effective in patients with suboptimally controlled T2D using OAD medication • Sustained significant improvements in HbA1c (p < 0.01) despite net medication reductions ALT, U/L (Mean ± SEM) • Substantial and clinically significant improvement in glycemia parameter
Slide 13: REVITA-1: Safety, no UADEs or unanticipated SAEs
REVITA-1: DMR is feasible, safe, and effective in patients with suboptimally controlled T2D using OAD medication • Sustained significant improvements in HbA1c (p < 0.01) despite net medication reductions ALT, U/L (Mean ± SEM) • Substantial and clinically significant improvement in glycemia parameter
Slide 14: REVITA-1: Improved patient treatment satisfaction
REVITA-1: DMR is feasible, safe, and effective in patients with suboptimally controlled T2D using OAD medication • Sustained significant improvements in HbA1c (p < 0.01) despite net medication reductions ALT, U/L (Mean ± SEM) • Substantial and clinically significant improvement in glycemia parameter
Slide 15: A single DMR procedure results in durable glycemic improvements through 24 months
REVITA-1: A single DMR procedure results in durable glycemic improvements through 24 months in T2D patients No device- or procedure-related AEs or UADEs between 12 and 24 months post-DMR Durability of HbA1c reduction HbA1c reduction through 24 months Patients with decrease in HbA1c: 84.8% 68.8% 76.7
Slide 16: A single DMR procedure results in durable hepatic improvements through 24 months
REVITA-1: A single DMR procedure results in durable hepatic improvements through 24 months in T2D patients Durability of ALT Reduction Patients with decrease in ALT: 67.6% 78.8% 71.4% 71.4% 0 • Persistent reductions in ALT in treatment Mean (SEM) reduction in ALT responders suggest: -5 • Sustained a
Slide 17: REVITA-2: First sham-controlled study of DMR
REVITA-2: First sham-controlled study of DMR in patients with suboptimally controlled T2D Bergman et al. oral presentation at AASLD; 11 Nov 2019; Boston, MA. AESI = adverse event of special interest; BG = blood glucose; DMR = duodenal mucosal resurfacing; Med = medication; MRI-PDFF = magnetic resona
Slide 18: REVITA-2: DMR positively impacts glucose metabolism
REVITA-2: DMR positively impacts glucose metabolism More clinically significant A B Change in HbA1c from C reductions in HbA1c in patients HbA1c < 7% at 24 weeks baseline to 24 weeks with baseline FPG ≥ 180 mg/dL DMR Sham DMR Sham 0 0 30 n = 33 n = 19 HbA1c < 7% at 24 weeks, % n = 19 26.3 from basel
Slide 19: REVITA-2: DMR significantly improves liver fat content
REVITA-2: DMR significantly improves liver fat content A B Responder analysis: >30% reduction in Change in liver MRI-PDFF in patients with >5% liver MRI-PDFF at baseline (mITT) relative liver MRI-PDFF from baseline to week 12 (mITT) DMR Sham 100 0 Median absolute change from n = 30 n = 27 baseline a
Slide 20: REVITA-2: DMR significantly improves liver fat content (FPG ≥ 180 mg/dL)
REVITA-2: DMR significantly improves liver fat content Change in liver MRI-PDFF in patients with FPG ≥ 180 mg/dL at baseline (mITT) DMR Sham Change in hepatic transaminases from baseline at 12 weeks Liver MRI-PDFF absolute change 0 from baseline to 12 weeks, % n = 14 n = 14 DMR Sham –2 Parameter N =
Slide 21: REVITA-2: Favorable safety profile 24 weeks post-DMR
REVITA-2: Favorable safety profile 24 weeks post-DMR (mITT Population*) DMR Sham (N = 39) (N = 36) Summary of device-/procedure-related • No device-/procedure-related SAEs or SAE, n (%) 0 0 UADEs reported through 24 weeks UADE, n (%) 0 0 AESI, n (%) 13 (33.3) 10 (27.0) • No clinical or laboratory si
Slide 22: Conclusions
Conclusions • DMR is a novel, intestinal-targeted therapy for T2D • REVITA-1 demonstrated durable glycemic and hepatic improvements through 2 years1 • REVITA-2 (first sham-controlled study): A single DMR procedure safely elicits favorable metabolic effects with improvements in glycemic and hepatic p
Slide 23: FRACTYL
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