Selonsertib in NASH: phase 2 Design Randomisation * 2:2:1:1:1 Open-label W24 Selonsertib 6 mg 18-70 years Liver biopsy within 3 months with NASH + stage 2 or 3 fibrosis or NAS ** ≥ 5 with a score ≥ 1 for each 3 components + ≥ 3 components of metabolic syndrome ALT ≤ 5 x ULN Fibroscan ≥ 7 kPa Selonsertib 18 mg N = 72 Selonsertib 6 mg + simtuzumab 125 mg Assessment Selonsertib 18 mg + simtuzumab 125 mg ** NAS (NAFLD Activity Score): steatosis (0 to 3), lobular inflammation (0 to 3), ballooning (0 to 2) Simtuzumab 125 mg * Randomisation was stratified by diabetes mellitus (yes or no) Selonsertib (PO): selective inhibitor of ASK1 (apoptosis signal-regulating kinase 1) Simtuzumab (SC): humanized monoclonal antibody directed against lysyl oxidase-like molecule 2 Assessment at W24 Paired pre- and post-treatment liver biopsies, magnetic resonance elastography, MRI-estimated proton density fat fraction, quantitative collagen content, and non invasive markers of liver injury Selonsertib - Phase 2 Loomba R, Hepatology 2018;67:549-59

Selonsertib in NASH: phase 2 Baseline characteristics SEL 18 mg + SIM N = 32 SEL 6 mg + SIM N = 30 SIM N = 10 Median age, years 55 54 57 Female, % 69 73 60 Diabetes mellitus, % 66 80 Non invasive measures (median) MRI-PDFF (proton density fat fraction), % MRE, kPa FibroScan kPa 18 3.7 10.4 17 11.0 16 3.4 13.5 Liver histology, % NASH CRN fibrosis stage 3 NAS 6-8 Steatosis grade 2-3 Lobular inflammation grade 3 Hepatocyte ballooning grade 2 66 69 41 66 81 67 80 30 77 90 60 50 20 50 90 Hepatic collagen content, % 3.8 4.3 3.5 Selonsertib - Phase 2 Loomba R, Hepatology 2018;67:549-59

Selonsertib in NASH: phase 2 Fibrosis change at W24 Worse No change Improved ( ≥ 1 stage of fibrosis [NASH CRN]) 20 40 60 80 100 Selonsertib 18 mg + simtuzumab N = 30 Selonsertib 6 mg + simtuzumab N = 27 Simtuzumab N = 10 7 % 50 % 43 % 30 % 56 % 15 % 40 % 20 % % Selonsertib - Phase 2 Loomba R, Hepatology 2018;67:549-59

Selonsertib in NASH: phase 2 Changes in histology and imaging at W24 SEL 18 mg + SIM N = 32 SEL 6 mg + SIM N = 30 SIM N = 10 Histology Improvement in fibrosis, % Progression to cirrhosis, % Median change in hepatic collagen content NAS ≥ 1 point reduction ≥ 2 points reduction ≥ 1 point reduction in steatosis ≥ 1 point reduction in lobular inflammation ≥ 1 point reduction in ballooning 43 3 - 8.7 52 23 32 32 16 30 7 - 8.2 41 19 30 22 33 20 20 2.1 60 20 20 20 30 Imaging MRDI-PDFF Median % change ≥ 30% reduction MRE ≥ 15% reduction Fibroscan, median change in kPa - 4.55 26% 1.79 15% 0.2 - 6.67 13% - 0.09 32% - 0.80 - 12.72 10% 2.06 - 0.50 Selonsertib - Phase 2 Loomba R, Hepatology 2018;67:549-59

Selonsertib in NASH: phase 2 Factors associated with fibrosis improvement 1 2 3 4 5 6 7 8 7.52 2.50 1.45 1.20 2.66 1.44 1.25 1.12 1.15 - 49.4 1.49 - 4.18 1.13 - 1.86 1.01 - 1.43 0.90 - 7.85 1.01 - 2.04 1.04 - 1.52 1.00 - 1.25 0.04 < 0.001 < 0.01 0.08 0.02 NAS, improved/no change vs worse Hepatic collagen, per 1% decrease Alpha-SMA, per 1% decrease Fibroscan, per 1-kPa decrease MRE, per 1-kPa decrease GGT, per 10 U/L decrease Cytokeratin-18 M30, per 100 U/L decrease Cytokeratin-18 M65, per 100 U/L decrease Histology Imaging Laboratory Odds ratio (adjusted for baseline values) 95% CI p SMA: smooth muscle actin ; MRE: magnetic resonance elastography Changes in body weight, MRI-PDFF and grades of steatosis and ballooning were not associated with fibrosis improvement Selonsertib - Phase 2 Loomba R, Hepatology 2018;67:549-59

Selonsertib in NASH: phase 2 % changes in MRE and MRI-PDFF at W24 MRE stiffness MRI-PDFF -50 100 p = 0.17 50 Non responder N = 36 Responder N = 18 Median 150 p = 0.01 -100 -50 50 100 Non responder N = 47 Responder N = 18 Fibrosis response:  ≥ 1 stage of fibrosis [NASH CRN] Steatosis response:  ≥ 1 grade of steatosis Selonsertib - Phase 2 Loomba R, Hepatology 2018;67:549-59

Selonsertib in NASH: phase 2 Changes in serum and metabolic biomarkers at W24 SEL 18 mg + SIM N = 32 SEL 6 mg + SIM N = 30 SIM N = 10 Enhanced liver fibrosis test 0.02 - 0.07 - 0.13 FibroSure/FibroTest - 0.01 0.01 AST, U/L - 8 - 6 - 3 ALT, U/l - 5 - 4 Gamma-glutamyl-transferase, U/L - 7 - 2 Triglycerides, mg/dL - 21 12 - 30 Total cholesterol, mg/dL - 10 - 13 High-density lipoprotein, mg/dL 1 2 Low-density lipoprotein, mg/dL - 25 HOMA-IR 0.98 2.17 - 0.22 Hb A1c, % - 0.2 0.2 Cytokeratin-18 fractions M30, U/L M65, U/L -110 - 222 - 34 - 162 - 89 - 185 Selonsertib - Phase 2 Loomba R, Hepatology 2018;67:549-59

Selonsertib in NASH: phase 2 Adverse events and laboratory abnormalities, % SEL 18 mg ± SIM N = 32 SEL 6 mg ± SIM N = 30 SIM N = 10 Grade 3-4 adverse event 9 13 10 Serious adverse event 7 Discontinuation for adverse event 6 3 Most common adverse events Headache Nausea Sinusistis Nasopharyngitis Upper abdominal pain Fatigue 28 19 13 16 Grade 3-4 laboratory abnormalities Alkaline phosphatase > 5 x ULN ALT > 5 x ULN AST > 5 x ULN Gamma-glutamyltransferase > 5 x ULN Serum glucose > 250 mg/dL GFR < 30 mL/min Triglycerides > 500 mg/dL 17 0 0 3 0 0 40 20 Selonsertib - Phase 2 Loomba R, Hepatology 2018;67:549-59

Selonsertib in NASH: phase 2 Summary In this phase 2 exploratory trial, selonsertib appeared to improve liver fibrosis in a substantial proportion of patients with NASH and stage 2 or 3 fibrosis This suggests that selonsertib has the potential to help address an important unmet medical need for an effective antifibrotic therapy for patients with NASH and advanced fibrosis Rationale for phase 3 studies of selonsertib in patients with NASH and bridging fibrosis (STELLAR-3) and compensated cirrhosis (STELLAR-4) Selonsertib - Phase 2 Loomba R, Hepatology 2018;67:549-59