ARREST Study: Phase 2b of Aramchol in NASH Design 57 sites 11 countries 247 patients 13 weeks follow-up Diabetic or pre-diabetic NAS ≥ 4 MRS > 5.5% 52 weeks Randomization 1:2:2 Placebo N = 48 Aramchol 400 mg Aramchol 600 mg Baseline End of treatment MR spectroscopy MR spectroscopy Liver biopsy Liver biopsy Aramchol: stearoyl-CoA desaturase receptor modulator Endpoints Primary: absolute change in liver triglycerides Secondary: decrease in fibrosis ≥ 1, NASH resolution Aramchol-phase 2 Ratziu V, AASLD 2018, Abs. LB5 1
Relative reduction > 30% > 5% absolute reduction from baseline ARREST Study: Phase 2b of Aramchol in NASH Reduction in liver fat Relative reduction > 30% > 5% absolute reduction from baseline 10 20 30 35 5 15 25 30% relative change % Aramchol 600 vs placebo, p = 0.0279 OR = 2.77 (95% CI : 1.12 - 6.89) 50 40 30 20 10 Placebo (N = 41) Aramchol 400 (N = 90) Aramchol 600 (N = 83) 36.7% 47.0% 24.4% % Placebo Absolute change from baseline vs placebo: 400 mg: -3.32% ; p = 0.0450 600 mg: -3.09% ; p = 0.0655 Aramchol 400 mg Aramchol 600 mg Aramchol-phase 2 Ratziu V, AASLD 2018, Abs. LB5 2
ARREST Study: Phase 2b of Aramchol in NASH ALT normalization (%) 5 10 15 20 -5 -10 -15 -20 -25 W24 W40 W52 Aramchol 400 vs placebo ; p = 0.0002 Aramchol 600 vs placebo ; p < 0.0001 ALT statistically significant, drops pretty modest over a year Placebo Aramchol 400 mg Aramchol 600 mg 13.3 21.9 29 Effect similar for AST Statistically significant reductions in GGT and Alkaline phosphatase in both groups vs placebo Aramchol 600 mg Placebo Aramchol 400 mg Aramchol-phase 2 Ratziu V, AASLD 2018, Abs. LB5 3
NASH resolution without worsening of fibrosis, % ARREST Study: Phase 2b of Aramchol in NASH NASH resolution without worsening of fibrosis, % % Placebo (N = 40) Aramchol 400 (N = 80) Aramchol 600 (N = 78) 5% 7.5% 16.7% Aramchol 600 vs placebo ; p = 0.0514 OR = 4.74 (95% CI : 0.99 - 22.7) 15% Average placebo response (previous Studies): FLINT, PIVENS, GENFIT, LEAN In subgroups of F2/3, NAS > 4 ; Abnormal AST/AST, BMI > 30 ; HbA1C > 6,4% : NASH resolution was noted in a larger proportion of patients in the 600 mg aramchol group vs placebo Aramchol-phase 2 Ratziu V, AASLD 2018, Abs. LB5 4
ARREST Study: Phase 2b of Aramchol in NASH Fibrosis improvement (> 1 stage) without worsening of NASH, % Progression to cirrhosis, % % % Placebo (N = 40) Aramchol 400 (N = 80) Aramchol 600 (N = 78) 17.5 21.3 29.5 p = 0.21 Placebo (N = 40) Aramchol 400 (N = 80) Aramchol 600 (N = 78) N = 6 N = 3 N = 1 F2/3, NAS > 4 ; Abnormal AST/AST, BMI > 30 ; HbA1C > 6.4%: fibrosis improvement was noted in a larger proportion of patients in the 600 mg aramchol group vs placebo Abnormal ALT/AST and BMI > 30: Significant difference between placebo and 600 mg aramchol Aramchol-phase 2 Ratziu V, AASLD 2018, Abs. LB5 5