A Study of Efruxifermin in Non-Cirrhotic Subjects With Histologically Confirmed Nonalcoholic Steatohepatitis (NASH)

Proportions of subjects in EFX vs placebo groups with improvement in liver fibrosis, defined as ≥ 1 stage NASH Clinical Research Network [CRN] fibrosis score (score ranges from 0 to 4, increasing with fibrosis severity), and no worsening of steatohepatitis (no increase in NASH Activity Score [NAS], which ranges from 0 to 8 and is the sum of scores of steatosis, lobular inflammation, and hepatocyte ballooning), at Week 24

Proportions of subjects in EFX vs baseline groups who achieve improvement in liver fibrosis (decrease of ≥ 1 stage in NASH CRN fibrosis score) and no worsening of steatohepatitis (no increase in NAS for ballooning, inflammation, or steatosis) at Week 96

Proportions of subjects in EFX vs placebo groups who achieve resolution of steatohepatitis (defined as a NAS of 0-1 for inflammation, 0 for ballooning, and any value for steatosis) and no worsening of liver fibrosis (determined by the NASH CRN criteria)

Proportion of subjects in EFX vs placebo groups who achieve improvement in liver fibrosis (decrease ≥ 1 stage in NASH CRN fibrosis score)

Change from baseline in hepatic fat fraction, measured by magnetic resonance imaging proton-density fat fraction (MRI-PDFF):

Week 24 and Week 96 MRI-PDFF Analysis Set

Change from baseline of lipoproteins (triglycerides, Non-HDL-C, HDL-C and LDL-C) in EFX vs placebo groups

Change from baseline in hemoglobin A1c (glycated hemoglobin, HbA1c) in EFX vs placebo groups

Change from baseline in C-peptide in EFX vs placebo groups

Change from baseline in adiponectin in EFX vs placebo groups

Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in EFX vs placebo groups

The Homeostatic Model Assessment of Insulin Resistance, HOMA-IR, is a calculated index that estimates insulin resistance based on fasting glucose and insulin levels. Higher values indicate greater insulin resistance.

< 1.0: Normal insulin sensitivity 1.0-1.9: Mild insulin resistance 2.0-2.9: Moderate insulin resistance > 2.9: Severe insulin resistance

Change from Baseline in Enhanced Liver Fibrosis (ELF) Score in EFX vs placebo groups

The Enhanced Liver Fibrosis (ELF) score is a non-invasive blood test that assesses the risk of liver fibrosis and its progression.

Lower risk (<9.8): Suggests a lower risk of advanced liver fibrosis. Mid risk (9.8-11.2): Indicates a moderate risk of disease progression. Higher risk (≥11.3): Suggests a higher risk of developing cirrhosis or liver-related events

Change from Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) in EFX vs placebo groups

Change from Baseline in Collagen III Neo-Peptide (C3M) in EFX vs placebo groups

Change from Baseline in NIS4 score in EFX vs placebo groups

NIS4 scores range from 0 to 1 and are calculated by combining the results of four individual biomarker assays [miR34a-5p, α2-macroglobulin (A2M), YKL-40 and HbA1c] each of which contributes to the test's ability to detect liver inflammation and/or fibrosis.

>0.63: Higher risk of NASH or advanced fibrosis 0.37-0.63: Moderate risk, and additional testing may be considered <0.36: Lower risk of of NASH or advanced fibrosis

Change from baseline in body weight (kg) in EFX vs placebo groups

Change from Baseline in Liver Stiffness Evaluated by FibroScan in EFX vs placebo groups at Week 24 and Week 96:

Full Analysis Set