LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1 Design Randomisation* 1 : 1 Open label W12 W24 Randomisation 1 : 1 DCV 30 mg qd + SMV 150 mg qd N = 76 > 18 years Chronic HCV infection Genotype 1 Treatment naïve or prior null response to PEG-IFN + RBV HCV RNA ≥ 100,000 IU/ml Compensated cirrhosis ** allowed No HBV or HIV coinfection Stop GT 1b DCV 30 mg + SMV 150 mg qd + RBV N = 71 Continue GT 1a N = 21 DCV 30 mg qd + SMV 150 mg qd + RBV * Randomisation was stratified on cirrhosis (yes or no) and prior treatment (naïve or null response) ** Biopsy or Fibroscan ≥ 14.6 kPa RBV (bid dosing): 1000 mg/d (< 75 kg) or 1200 mg/d (≥ 75 kg) Objective SVR12 (HCV RNA < 25 IU/ml), by mITT, with 80% CI, by cohort based on HCV genotype 1 subtype and prior treatment experience SVR12 was also reported by treatment regimen (with or without RBV) and treatment duration (12 or 24 weeks) for the genotype 1b cohort LEAGUE-1 Zeuzem S, J Hepatol 2016; 64:292-300

LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1 ARV-trial.com LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1 Baseline characteristics and patient disposition Genotype 1b Genotype 1a Treatment-naïve Null responder DCV + SMV N = 53 DCV + SMV + RBV N = 51 N = 23 N = 20 + RBV N = 21 * Median age, years 54 53 56 59 52 Female 59% 51% 48% 55% 33% Race : white 91% 92% 100% 85% 95% HCV RNA log10 IU/ml, mean 6.2 6.4 6.3 Metavir : F0-F2 / F3 / F4, % 70 / 19 / 11 77 / 10 / 14 39 / 22 / 39 60 / 20 / 20 43 / 29 / 29 IL28B CC 30% 26% 4% 5% 14% Resistance-associated polymorphisms NS5A NS3 14% 17% 22% 18% 33% 33% 20% 25% Discontinuation, N Lack of efficacy Adverse event Other 7 4 2 1 8 5 2 1 6 4 2 1 0 0 13 11 * Treatment-naïve, N = 12 ; null responder to prior PEG-IFN + RBV, N = 9 LEAGUE-1 Zeuzem S, J Hepatol 2016; 64:292-300 2

LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1 ARV-trial.com LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1 SVR12 (HCV RNA < 25 IU/ml) in genotype 1b 25 50 100 75 84.9 % 74.5 Treatment-naïve 80.8 88.7 85.3 N 53 51 47 4 6 14 16 73.9 78.6 85.1 93.8 44 7 All Cirrhosis 83.3 DCV + SMV + RBV DCV + SMV Null-responder 12W of therapy 24W of No cirrhosis 95 88.9 82.6 55.6 9 57.8 69.6 23 20 Of the 29 failures, there were 15 virologic breakthrough and 5 relapses LEAGUE-1 Zeuzem S, J Hepatol 2016; 64:292-300 3

LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1 Outcome in genotype 1a SVR12 in treatment-naïve patients: 66.7% All prior null responders with genotype 1a were offered the addition of PEG-IFN for 24 weeks after the initial 5 patients experienced virologic breakthrough. They were considered SVR12 non responders Resistance analysis in genotype 1b At baseline, NS5A polymorphisms at L28, R30, L31, or Y93 were detected in 29/136 (21.3%) available sequences; SVR12 in 16/29 (55.2%) compared with 97/107 (90.7%) patients without these polymorphisms Baseline NS3 polymorphisms at V36, T54, Q80, or S122 were detected in 30/138 genotype 1b–infected patients with available sequences ; SVR12 in 24/30 (80.0%) versus 89/108 (81.5%) patients without these polymorphisms LEAGUE-1 Zeuzem S, J Hepatol 2016; 64:292-300

LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1 ARV-trial.com LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1 Adverse events and grade 3-4 laboratory abnormalities, N (%) DCV + SMV N = 76 DCV + SMV + RBV N = 92 Serious adverse event 9.2% 4.3% Adverse event leading to discontinuation 2 (2.6%) 2 (2.2%) Death 1 (1.3%) Adverse event in ≥ 10% of patients Asthenia 55% 54% Headache 43% Nausea 35% 40% Pruritus 31% 34% Fatigue 25% Nasopharyngitis Dyspnea 28% 27% Hemoglobin < 9 g/dl Neutrophils < 750/mm3 1 Lymphocytes < 500/mm3 ALT > 5 x ULN / AST > 5 x ULN 0 / 0 1 / 1 Total bilirubin > 2.5 x ULN 3 14 Lipase > 3 x ULN LEAGUE-1 Zeuzem S, J Hepatol 2016; 64:292-300 5

LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1 ARV-trial.com LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1 Summary With all-oral, IFN-free treatment of DCV + SMV, with or without RBV In genotype 1b, treatment for 12 or 24 weeks achieved combined SVR12 rates of 84.9% (DCV + SMV) and 74.5% (DCV + SMV + RBV) in treatment naïve patients and 69.6% (DCV + SMV) and 95.0% (DCV + SMV + RBV) in prior null responders SVR12 rates were higher in patients without NS5A polymorphisms at baseline In genotype 1a, DCV + SMV + RBV for 24 weeks achieved SVR12 of 66.7% in treatment-naïve patients. Null responders required intensification with PEG-IFN The DCV dose of 30 mg in combination with SMV provided lower than expected DCV exposure, however no relation with SVR12 DCV + SMV was well tolerated with or without RBV The standard 60mg dose of DCV will be utilized in all future studies involving DCV and SMV DCV + SMV + RBV is not recommended for the treatment of genotype 1a Other available options for HCV genotype 1b infection have surpassed this regimen in terms of efficacy LEAGUE-1 Zeuzem S, J Hepatol 2016; 64:292-300 6