Slide 1: Phase 2 Dose Ranging, Randomized, Double-blind, Placebo-Controlled Study of EDP-305 in NASH
A Phase 2 Dose From Ranging, Randomized, Chemistry Double-blind and to Cures Placebo-Controlled Study of EDP-305 in Subjects With Non-Alcoholic Steatohepatitis (NASH) Vlad Ratziu, Mary Rinella, Brent Neuschwander-Tetri, Eric Lawitz, Douglas Denham, Zeid Kayali, Aasim Sheikh, Kris Kowdley, Taddese De
Slide 2: Disclosures
Disclosures • V Ratziu, M Rinella, B Tetri : consultancy for Enanta The Digital ILC 2020- August 28th © Enanta Pharmaceuticals, Inc. 2 ENANTA Pharmaceuticals 2
Slide 3: EDP-305: A Novel, Potent FXR Agonist
EDP-305 A Novel, Potent FXR Agonist • NASH is considered the fastest-growing cause of cirrhosis, hepatocellular carcinoma and indication for liver transplantation • EDP-305 is a potent, non-bile acid FXR receptor agonist - Improvement in hepatocyte ballooning and overall NAFLD Activity Score (NAS) i
Slide 4: ARGON-1 Study Design
ARGON-1 Study Design Screening Blinded treatment phase Follow-up Up to 28 days 12 weeks 4 weeks Placebo (QD) Randomization Safety 2:2:1 EDP-305 1mg (QD) Follow-up EDP-305 2.5mg (QD) D1 D3 W2 W4 W8 W12 • The primary objectives of the study were as follows: - To evaluate change in ALT levels at Week 1
Slide 5: Key Eligibility Criteria
Key Eligibility Criteria Key Inclusion Criteria Key Exclusion Criteria • Histologic evidence of NASH with • Evidence of other chronic disease fibrosis on a historical liver biopsy within 24 months of screening, and • Any histology or clinical evidence elevated ALT 1 at screening of cirrhosis OR • Hb
Slide 6: Demographic and Baseline Characteristics
Demographic and Baseline Characteristics ITT Population Placebo EDP-305 1 mg EDP-305 2.5 mg Characteristics N=24 N=55 N=53 Age (years), mean (SD) 50.8 (10.5) 51.5 (12.0) 52.3 (11.8) Female, n (%) 11 (45.8%) 29 (52.7%) 29 (54.7%) White, n (%) 17 (70.8%) 42 (76.4%) 47 (88.7%) Hispanic/Latino, n (%) 11
Slide 7: ALT (U/L) Change - ITT Population
ALT (U/L) Change at Week 12 - ITT Population · Primary Endpoint Was Met in the 2.5mg Arm · Numerically Higher Reduction with 1mg Compared to Placebo SE: standard error The Digital ILC 2020- August 28th © Enanta Pharmaceuticals, Inc. 7 ENANTA Pharmaceuticals 7
Slide 8: MRI-PDFF Absolute Change From Baseline
MRI-PDFF Absolute Change From Baseline at Week 12 ITT Population Key Secondary Endpoint Was Met in the 2.5mg Arm SE: standard error The Digital ILC 2020- August 28th © Enanta Pharmaceuticals, Inc. 8 ENANTA Pharmaceuticals 8
Slide 9: Proportion of Subjects with Relative Change From Baseline in Liver Fat
Proportion of Subjects with Relative Change From Baseline (Absolute and Percent) in Liver Fat Reduction (%) at Week 12 ITT Population The Digital ILC 2020- August 28th © Enanta Pharmaceuticals, Inc. 9 ENANTA Pharmaceuticals 9
Slide 10: Mean Change in ALT by MRI-PDFF Response
Mean Change in ALT by MRI-PDFF Response at Week 12 ITT Population The Digital ILC 2020- August 28th ENANTA Pharmaceuticals 10 10 © Enanta Pharmaceuticals, Inc.
Slide 11: Response in Markers of Liver Injury and Target Engagement (ALP)
Response in Markers of Liver Injury and Target Engagement (ALP) ITT Population SE: standard error The Digital ILC 2020- August 28th ENANTA Pharmaceuticals 11 11 © Enanta Pharmaceuticals, Inc.
Slide 12: Percentage Change in C4 and FGF19
Percentage Change in C4 and FGF19 (Pre-dose) at Week 12 - ITT Population SE: standard error The Digital ILC 2020- August 28th ENANTA Pharmaceuticals 12 12 © Enanta Pharmaceuticals, Inc.
Slide 13: Most Frequent Treatment-Emergent Adverse Events
Most Frequent Treatment-Emergent Adverse Events Events Occurring in ≥ 5% of Subjects in Any Treatment Arm Safety Population Placebo EDP-305 1mg EDP-305 2.5mg N (%) N=24 N=55 N=53 Pruritus generalized 1 ( 4.2%) 5 ( 9.1%) 25 (47.2%) Rash 0 1 ( 1.8%) 4a ( 7.5%) Pruritus c 1 ( 4.2%) 0 3b ( 5.7%) Nausea
Slide 14: Lipid Values (mg/dL) Over Time
Lipid Values (mg/dL) Over Time ITT Population SE: standard error The Digital ILC 2020- August 28th ENANTA Pharmaceuticals 14 14 © Enanta Pharmaceuticals, Inc.
Slide 15: Summary of ARGON-1 Study Efficacy
Summary of ARGON-1 Study Efficacy Primary (ALT change) and key secondary (MRI-PDFF) endpoints were met at Week 12 • EDP-305 2.5mg achieved statistically significant ALT change - Mean reduction of ~28 U/L vs. 15 U/L in Placebo group (p<0.05) - Numerically higher reduction with 1mg (~22 U/L) vs. Place
Slide 16: Summary of ARGON-1 Study Safety and Tolerability
Summary of ARGON-1 Study Safety and Tolerability • EDP-305 regimens were generally safe in patients with NASH for up to 12 weeks with the majority of TEAEs being mild to moderate - The most common (≥5%) TEAEs included pruritus, GI related symptoms (nausea, vomiting, diarrhea), headache and dizziness
Slide 17: Acknowledgments
Acknowledgments We extend our thanks to the subjects who participated in this study, the Investigators and the site personnel for their conduct of the study Pavel Hamet, Naresh Aggarwal, Giada Sebastiani, Victor DeLedinghen, Francois Habersetzer, Jorn Schattenberg, Edward Gane, Michael Allison, Guru