SOF/VEL 400/100 mg qd N = 120 W12 SOF + RBV > 18 years Chronic HCV infection Genotype 2 Naïve or pre-treatment with IFN-based regimen Compensated cirrhosis allowed** No HBV or HIV co-infection Randomisation* 1 : 1 Open-label * Randomisation was stratified on prior treatment (naïve or experienced) and cirrhosis (yes or no) ** Metavir F4 or Ishak 5-6 or Fibroscan > 12.5 kPa or Fibrotest > 0.75 and APRI > 2 SVR 12 RBV (in 2 divided doses): 1000 mg if < 75 kg or 1200 mg/day if ≥ 75 kg ASTRAL-2 Foster GR. N Engl J Med 2015; 373:  Design ASTRAL-2 study: SOF/VEL vs SOF + RBV in genotype 2  Objective –SVR 12 (HCV RNA < 15 UI/ml), by ITT : non-inferiority of SOF/VEL with a lower bound of 95% CI for difference of - 10%, 90% power ; if non-inferiority, test for superiority with significance level of 0.05

SOF/VEL N = 134 SOF + RBV N = 132 Age, years, mean57 Female36%45% White 93%84% HCV RNA, log 10 IU/ml, mean6.5 ± ± 0.74 IL28B CC41%35% Cirrhosis14% Treatment experienced14%15% Response to previous HCV treatment No response Relapse 16% 84% 15% 85% Discontinuation, N Adverse event / lost to follow-up 1 1 / / 1 Baseline characteristics and patient disposition ASTRAL-2 ASTRAL-2 study: SOF/VEL vs SOF + RBV in genotype 2 Foster GR. N Engl J Med 2015; 373:

ASTRAL-2 ASTRAL-2 study: SOF/VEL vs SOF + RBV in genotype 2  SVR 12 according to baseline NS5A RAVs in SOF/VEL group –Absent, N = 53 : SVR 12 = 100% –Present, N = 80, SVR 12 = 100% SVR 12, % (95% CI) *adjusted absolute difference : 5.2 (95% CI : 0.2 to 10.3) ; p = 0.02 = superiority (96-100) 134 SOF/VEL 132 SOF + RBV 93.9 (88-97) 1 adverse event 6 relapses 2 lost to follow-up * % 1 discontinuation for adverse event in SOF/VEL at D1 Foster GR. N Engl J Med 2015; 373:

ASTRAL-2 Sulkowki M. AASLD 2015; Abs. 205 SVR 12 by cirrhosis and prior treatment ASTRAL-2 study: SOF/VEL vs SOF + RBV in genotype 2 SOF/VELSOF + RBV Treatment NaïveTreatment Experienced No cirrhosis CirrhosisNo cirrhosisCirrhosis relapse 2 relapses 2 lost to follow-up 3 relapses 1 lost to follow-up %

SOF/VEL N = 134 SOF + RBV N = 132 At least one adverse event69%77% Serious adverse events2 (1.5%) Grade 3-4 adverse events3 (2%) Discontinuation due to adverse event1 * (< 1%)0 Death2 ** (1%)0 (0%) Adverse events in > 10% of patients Fatigue15%36% Headache18%22% Nausea10%14% Insomnia4%14% Grade 3-4 laboratory abnormalities9%14% Hemoglobin < 10 g/dl05% Adverse events, N (%) * black male, 57, discontinued at D1 because of anxiety, headache and difficulty concentrating ** 1 cardiac arrest 131 days after the end of treatment ; 1 death of metastatic lung cancer 112 days after the end of treatment ASTRAL-2 ASTRAL-2 study: SOF/VEL vs SOF + RBV in genotype 2 Foster GR. N Engl J Med 2015; 373:

ASTRAL-2 ASTRAL-2 study: SOF/VEL vs SOF + RBV in genotype 2  Summary –Treatment with SOF/VEL for 12 weeks resulted in a 99% SVR 12 rate in patients with HCV genotype 2 infection –SOF/VEL for 12 weeks was statistically superior to SOF + RBV for 12 weeks (p = 0.02) –No patients who received SOF/VEL experienced virologic failure in a population that included patients with cirrhosis and previous treatment failure Limitation : small number of black patients –Among patients with HCV genotype 2 who received SOF/VEL, the presence of baseline NS5A or NS5B RAVs was not associated with virologic failure –SOF/VEL was well tolerated and, compared with SOF + RBV, lacked toxicities commonly associated with RBV –SOF/VEL for 12 weeks provides a single tablet, once daily, highly effective, RBV-free treatment for patients with HCV genotype 2 infection