1. FUSION  Design  Objectives –SVR ≥ 20% compared with historical control of 25%, 97% power –Difference of SVR > 20% between the 2 groups, 82% power SOF + RBV Randomisation 1 : 1* Blinded, active-control HCV genotype 2 or 3 No response to prior treatment with IFN-based regimen HCV RNA ≥ 10,000 IU/ml Compensated cirrhosis allowed * Randomisation was stratified on cirrhosis (presence vs absence) and genotype (2 vs 3) FUSION Study: SOF + RBV (12 vs 16 weeks) for HCV genotypes 2 and 3 W12 SVR 12 W16 Placebo SVR 12 W24W28 –SOF : 400 mg qd –RBV (bid dosing) : 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg N = 98 N = 103 Jacobson IM. NEJM 2013;368:1867-77

2. SOF + RBV 12 W N = 103 SOF + RBV 16 W N = 98 Mean age, years54 Female29%32% Race : white/black85% / 5%88% / 1% Body mass index, mean2829 HCV genotype 1* / 2 / 33% / 35% / 62%3% / 33% / 64% IL28B CC genotype30%31% HCV RNA log 10 IU/ml, mean (SD) 6.5 ± 0.676.5 ± 0.63 Cirrhosis35%33% Response to previous IFN treatment Non response Relapse 24% 76% 26% 74% Discontinued treatment, N1 (AE)0 Returned for post-treatment W4 visit9995 Returned for post-treatment W12 visit5473 Baseline characteristics and patient disposition * Excluded from efficacy analysis FUSION FUSION Study: SOF + RBV (12 vs 16 weeks) for HCV genotypes 2 and 3 Jacobson IM. NEJM 2013;368:1867-77

3. HCV RNA < 25 IU/ml FUSION FUSION Study: SOF + RBV (12 vs 16 weeks) for HCV genotypes 2 and 3 Jacobson IM. NEJM 2013;368:1867-77 W4W12W4W12No cirrhosisCirrhosisNo cirrhosisCirrhosis During treatmentPost treatment (SVR)Genotype 2Genotype 3 SOF + RBV 12 weeks SOF + RBV 16 weeks SVR 12 by genotype and cirrhosis

4.  Virologic breakthrough during treatment : none  Relapse in patients with HCV RNA < 25 IU/ml at end of completed treatment –46/99 (46%) in 12W group vs 26/95 (27%) in 16W group  Resistance testing (sequencing) –73 relapses : No SOF-associated mutation (S282T) 11 NS5B substitutions in > 2 subjects (no change in susceptibility to SOF) FUSION FUSION Study: SOF + RBV (12 vs 16 weeks) for HCV genotypes 2 and 3 Jacobson IM. NEJM 2013;368:1867-77 SOF + RBV 12 WSOF + RBV 16 W OR (95% CI)p p Genotype 2 (vs 3)21.49 (6.14 – 75.14)< 0.000110.52 (2.25 – 49.17)0.0028 Weight-based RBV dose1.47 (1.09 – 1.98)0.012- Cirrhosis (no vs yes)3.12 (1.02 – 9.54)0.046- Female vs male-3.98 (1.17 – 13.54)0.027 Multivariate analysis of factors associated with SVR 12

5. SOF + RBV 12W N = 103 SOF + RBV 16W N = 98 AE leading to treatment discontinuation10 Serious adverse event53 AE occurring in > 10% in either group Fatigue Nausea Headache Insomnia Pruritus Anemia Irritability Cough Diarrhea Rash Arthralgia 45% 21% 25% 20% 12% 11% 15% 10% 15% 7% 11% 47% 20% 33% 29% 7% 4% 11% 13% 6% 12% 9% Adverse events, N (%) FUSION FUSION Study: SOF + RBV (12 vs 16 weeks) for HCV genotypes 2 and 3 Jacobson IM. NEJM 2013;368:1867-77

6.  Summary –In this phase III study, 12 or 16 weeks of treatment with SOF and RBV resulted in a SVR 12 in 50 to 73% of patients with prior treatment failure In genotype 2, high response rates (SVR 12 > 96%) were observed in patients with no cirrhosis ; those with cirrhosis had lower SVR 12 (60 to 78%) In genotype 3 infection, response rates were sub-optimal, whether patients had or not cirrhosis –No virologic resistance was detected in patients who did not have a sustained virologic response –The rate of premature discontinuation of treatment with SOF and RBV due to adverse events was low (1%) –In conclusion, 12 weeks of treatment with SOF and RBV can be an effective option for patients with HCV genotype 2 infection who failed prior IFN-based therapy, in the absence of cirrhosis FUSION FUSION Study: SOF + RBV (12 vs 16 weeks) for HCV genotypes 2 and 3 Jacobson IM. NEJM 2013;368:1867-77