1. SIRIUS Placebo LDV/SOF + placebo Randomisation* 1 : 1 Double-blind SIRIUS Study: LDV/SOF ± RBV for genotype 1 and cirrhosis with non response to prior PI therapy  Design W24W12 ≥ 18 years Chronic HCV infection Genotype 1 HCV RNA ≥ 10,000 IU/ml Failure to PEG-IFN + RBV and then to PI + PEG-IFN + RBV Cirrhosis** No HBV or HIV co-infection Bourlière M. Lancet Infect Dis 2015;15:397-404 * Randomisation stratified on genotype (1a or 1b) and response to previous treatment (HCV RNA < lower limit of quantification acheived or not achieved) N = 77 N = 78 ** Liver biopsy or Fibroscan > 12.5 kPa or Fibrotest® > 0.75 + APRI > 2 LDV/SOF + RBV –Co-formulated ledipasvir-sofosbuvir (LDV 90mg/SOF 400 mg) : 1 pill qd –RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg)  Objective –SVR 12 (HCV RNA < 25 IU/ml), with two sided 95% CI : difference of 15% between groups, 80% power

2. SIRIUS Study: LDV/SOF ± RBV for genotype 1 and cirrhosis with non response to prior PI therapy LDV/SOF + RBV 12W N = 77 LDV/SOF 24W N = 78 Mean age, years5657 Female25%28% Body mass index, mean27.926.3 HCV genotype : 1a / 1b62% / 36%64% / 35% IL28B CC genotype5%8% HCV RNA log 10 IU/ml, mean6.5 Previous PI regimen Telaprevir Boceprevir Telaprevir and boceprevir Simeprevir Faldaprevir 56% 39% 1% 3% 63% 35% 0 3% 0 HCV RNA < LLOQ on previous PI : Yes / No58 % / 42%55% / 45% Presence of NS5A RAVs at baseline, n (%)12 (16%)12 (15%) Discontinuation01 (adverse event) SIRIUS Baseline characteristics and patient disposition Bourlière M. Lancet Infect Dis 2015;15:397-404

3. SVR 12 (HCV RNA < 25 IU/ml), % (IC 95%) 25 50 100 75 % 97.4 (91-100) N 77 LDV/SOF + RBV 12W LDV/SOF 24W p=0.63 96.1 (89-99) LDV/SOF + RBV 12W LDV/SOF 24W HCV RNA < lower limit of quantification on previous therapy Yes No 95.7% 96.8% 100% 94.3% Baseline platelets < 100 x 10 9 /l83.3%100% Baseline albumin < 35 g/l92.9%100% Sex Male Female 94.8% 100% 96.4% 100% Genotype 1a 1b 97.9% 92.9% 98.0% 96.3% IL28B CC Non-CC 100% 95.9% 100% 97.2% SVR 12 by subgroup SIRIUS SIRIUS Study: LDV/SOF ± RBV for genotype 1 and cirrhosis with non response to prior PI therapy 0 Bourlière M. Lancet Infect Dis 2015;15:397-404

4. SIRIUS Study: LDV/SOF ± RBV for genotype 1 and cirrhosis with non response to prior PI therapy NS5A RAVs SexGenotypeIL28B Fibroscan (kPa) Previous PI < LLOQ achieved previously at baseline at relapse LDV/SOF + RBV 12W Patient 1M1bTTNATelaprevirYesNoneY93H Patient 2M1bCT29.5TelaprevirNoNoneY93H Patient 3M1aCT39.4TelaprevirYesNoneQ30R LDV/SOF 24W Patient 4M1aCT34.3BoceprevirNo M28T Q30R L31M L31V Q30H Q30R L31M L31V Patient 5M1bCT18.4BoceprevirNoY93H Characteristics of patients who relapsed SIRIUS Bourlière M. Lancet Infect Dis 2015;15:397-404

5. SIRIUS Study: LDV/SOF ± RBV for genotype 1 and cirrhosis with non response to prior PI therapy LDV/SOF + RBV, N = 78LDV/SOF, N = 77 W0-W12 (+ placebo) W12-24 (+ RBV) W0-W12W0-W24 Discontinuation for adverse event, N1000 Serious adverse event, N1338 Adverse event in > 15% in either group Asthenia31%38%36%45% Headache21%17%35%40% Pruritus18%14%5%9% Insomnia12%9%14%17% Fatigue4%6%17%19% Arthralgia6%08%16% Bronchitis1%5% 17% Hemoglobin < 10 g/dl, N2201 ALT > 5 x ULN / AST > 5 x ULN, N7 / 60 / 0 1 / 1 Adverse events Other adverse events occurring in 5-15% of patients : nausea, cough, diarrhea, irritability, myalgia, dry skin, back pain, sleep disorder, dyspnea SIRIUS Bourlière M. Lancet Infect Dis 2015;15:397-404

6. SIRIUS Study: LDV/SOF ± RBV for genotype 1 and cirrhosis with non response to prior PI therapy  Summary –In this randomised, phase II study, patients with HCV genotype 1 infection and compensated cirrhosis who had not previously achieved SVR with standard treatment achieved high SVR 12 rates (96-97%) after treatment with LDV/SOF + RBV for 12 weeks or LDV/SOF for 24 weeks, with no statistical differences in rates between groups –They were 5 relapses, and no baseline characteristics were predictive –The 2 treatment regimens were safe and well tolerated Patients receiving LDV/SOF alone had higher rates of headache and fatigue than patients receiving LDV/SOF + RBV or placebo –Limitation Exclusion of patients with decompensated liver disease SIRIUS Bourlière M. Lancet Infect Dis 2015;15:397-404