1. VALENCE SOF + RBV Not randomised Open label* ≥ 18 years Chronic HCV infection Genotype 2 or 3 HCV RNA ≥ 10,000 IU/ml Treatment naïve or prior IFN-based regimen Compensated cirrhosis allowed VALENCE Study: SOF + RBV for HCV genotypes 2 and 3  Design W12 W24 N = 250 N = 72 Genotype 2 Genotype 3 * Initially randomised to 12 weeks SOF + RBV vs placebo (4:1), the study was amended with unblinding, discontinuation of placebo group and extension to 24 weeks of therapy for genotype 3 Zeuzem S. NEJM 2014;370:1993-2001 –SOF : 400 mg qd –RBV (bid dosing) : 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg  Objective –SVR 12 with 95% CI, descriptive analysis –Multivariate analysis to identify predictors of SVR 12

2. VALENCE Study: SOF + RBV for HCV genotypes 2 and 3 Baseline characteristics and patient disposition VALENCE Zeuzem S. NEJM 2014;370:1993-2001  In addition, 85 patients received placebo for a mean of 7 weeks before discontinuation of this group  11 patients, with genotype 3, initially randomised, received only 12 weeks of treatment Genotype 2 SOF + RBV 12W N = 73 Genotype 3 SOF + RBV 24W N = 250 Mean age, years5848 Female45%38% Race : white/black89% / 7%94% / 0 Body mass index, mean2625 IL28B CC genotype33 %34% HCV RNA log 10 IU/ml, mean (SD) 6.5 ± 0.76.3 ± 0.7 Cirrhosis15%24% Previous IFN treatment56%58% Discontinued for side effects4% No response14%16% Relapse or breakthrough38% Discontinued treatment, N04 (1 AE)

3. SVR 12 (HCV RNA < 25 IU/ml) 25 50 100 75 93* 97 % 90 97 TN Genotype 2 - 12 weeks Genotype 3 - 24 weeks All 100 94 78 85** 94 79 87 62 95 92 N 73 3241 302 329 250105 14592 1398 47 TNTENCC TE NCC TN AllTNTENCC TE NCC TN : Treatment-naïve ; TE : Treatment-experienced ; NC : non-cirrhotic ; C : cirrhotic * 95% CI: 85-98 **95% CI: 80-89 VALENCE Zeuzem S. NEJM 2014;370:1993-2001 VALENCE Study: SOF + RBV for HCV genotypes 2 and 3 0

4. Multivariate analysis of factors associated with SVR 12 in patients with genotype 3 OR (95% CI)p Baseline HCV RNA < 6 log 10 IU/ml4.23 (1.21 - 14.81)0.02 Female3.18 (1.22 - 8.31)0.02 Absence of cirrhosis3.46 (1.60 - 7.48)0.002 < 50 years2.82 (1.21 - 6.57)0.02 VALENCE Zeuzem S. NEJM 2014;370:1993-2001 VALENCE Study: SOF + RBV for HCV genotypes 2 and 3  Virologic breakthrough –1 in genotype 3 group (non adherent patient)  Relapse in treatment completers –5 (7%) in genotype 2 group  5/11 (45%) in genotype 3 12W-group and 35 (14%) in genotype 3 24W-group  Resistance testing (sequencing) –Done in genotype 3 group with failures: No SOF-associated mutation (S282T) NS5B substitutions : V321A in 2 patients, L159F in 6 patients (no change in SOF susceptibility)

5. VALENCE Study: SOF + RBV for HCV genotypes 2 and 3 Adverse events, N (%) VALENCE Zeuzem S. NEJM 2014;370:1993-2001 Genotype 2 + 3 SOF + RBV 12W N = 84 Genotype 3 SOF + RBV 24W N = 250 AE leading to treatment discontinuation11 Serious adverse event010 (4%) AE occurring in > 10% in either group Headache29%30% Fatigue23%30% Pruritus24%27% Asthenia25%21% Nausea31%13% Insomnia11%16% Nasopharyngitis5%14% Dry skin10%12% Dyspnea14%11% Cough10%11% Diarrhea5%12%

6. VALENCE Study: SOF + RBV for HCV genotypes 2 and 3  Summary –The oral SOF + RBV regimen resulted in high rates of SVR 12 both in genotype 2 and genotype 3 infection –High rates of response and low rates of relapse in all genotype 2 sub- groups with 12 weeks of SOF + RBV –For genotype 3, SOF + RBV 24 weeks was associated with higher SVR 12 than reported with the same regimen for 12 weeks or 16 weeks –Identification of 4 possible predictors of SVR 12 among patients with genotype 3 infection: female sex, absence of cirrhosis, younger age, and a low viral load at baseline –Severity and frequency of adverse events did not increase with longer duration of SOF + RBV treatment –SOF + RBV has a high barrier to resistance –Limitations Descriptive study Few number of patients with genotype 2 VALENCE Zeuzem S. NEJM 2014;370:1993-2001