1. COSMOS SOF + SMV + RBV SOF + SMV Randomisation 2 : 1 : 2 : 1* Open-label * Randomisation was stratified on genotype (1a or 1b) in both cohorts, IL28B in cohort 1 and treatment history (naïve or non-responder) in cohort 2 COSMOS Study: SOF + SMV + RBV for genotype 1 – Phase IIa  Design W12 W24 N = 24 ≥ 18 years Chronic HCV infection Genotype 1 HCV RNA ≥ 10,000 IU/ml Cohort 1 : prior non responders, Metavir F0-F2 Cohort 2 : treatment-naïve and prior non responders, Metavir F3-F4 –SOF : 400 mg (2 x 200 mg) qd in cohort 1, 400 mg qd in cohort 2 –SMV : 150 mg qd –RBV weight based (bid dosing) : 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg Lawitz E. Lancet 2014;384:1756-65 SOF + SMV + RBV SOF + SMV SOF + SMV + RBV SOF + SMV SOF + SMV + RBV SOF + SMV Cohort 1 Cohort 2 N = 16 N = 15 N = 27 N = 14 N = 30 N = 27 N = 14

2. COSMOS Study: SOF + SMV + RBV for genotype 1 – Phase IIa  Objective –Exploratory study –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI –ITT analysis –No sample size calculation –Analyses within each cohort and on pooled cohort data COSMOS Lawitz E. Lancet 2014;384:1756-65

3. Drug regimenn Genotype 1a / 1b Treatment history No response / Naïve Metavir F0-F1 / F2 / F3 / F4 (%) HCV RNA, log 10 IU/ml, median IL28B CC Cohort 1 SOF + SMV + RBV 24W2483% / 17%100% / 046 / 54 / 0 / 06.70 SOF + SMV 24W1573% / 27%100% / 020 / 80 / 0 / 06.713% SOF + SMV + RBV 12W2778% / 22%100% / 041 / 59 / 0 / 06.711% SOF + SMV 12W1471% / 29%100% / 057 / 43 / 0 / 06.70 Cohort 2 SOF + SMV + RBV 24W3077% / 23%57% / 43%0 / 0 / 57 / 436.227% SOF + SMV 24W1675% / 25%50% / 50%0 / 0 / 38 / 636.512% SOF + SMV + RBV 12W2782% / 19%56% / 44%0 / 0 / 59 / 416.615% SOF + SMV 12W1479% / 21%50% / 50%0 / 0 / 50 / 506.719% Baseline characteristics Female : 36%, median age : 57 years ; white : 81%, black : 19% ; median BMI : 28.0 kg/m 2 NS3 Q80K polymorphism mutation present in 45% of genotype 1a COSMOS COSMOS Study: SOF + SMV + RBV for genotype 1 – Phase IIa Lawitz E. Lancet 2014;384:1756-65

4. SVR 12 (HCV RNA < 25 IU/ml) in Cohort 1 Prior non responders, Metavir F0-F2 % By subgenotype and G80K mutation (genotype 1a) COSMOS COSMOS Study: SOF + SMV + RBV for genotype 1 – Phase IIa Lawitz E. Lancet 2014;384:1756-65 79 100 75 100 93 67 100 89 96 88 100 93 83 100 0 20 40 60 80 100 Overall 4N24152714412844769 46 1b1a Q80K 1a no Q80K 1b1a Q80K 1a no Q80K 1b1a Q80K 1a no Q80K 1b1a Q80K 1a no Q80K SOF + SMV + RBV 24WSOF + SMV 24WSOF + SMV + RBV 12WSOF + SMV 12W

5. SVR 12 (HCV RNA < 25 IU/ml) in Cohort 2 Treatment naïve and non responders, Metavir F3-F4 COSMOS COSMOS Study: SOF + SMV + RBV for genotype 1 – Phase IIa Lawitz E. Lancet 2014;384:1756-65 93 86 100 88 93 92 100 93 0 20 40 60 80 100 By subgenotype and G80K mutation (genotype 1a) Overall 1b1a Q80K 1a no Q80K 1b1a Q80K 1a no Q80K 1b1a Q80K 1a no Q80K 1b1a Q80K 1a no Q80K 100 88 100 % N30162714711124575814338 SOF + SMV + RBV 24WSOF + SMV 24WSOF + SMV + RBV 12WSOF + SMV 12W

6.  SVR 12 similar in patients with IL28B CC and non-CC genotypes, irrespective of whether they received RBV, in treatment-naïve or previous non-responders, with 12 or 24 weeks of SMF + SOF, also high in F4 patients  Relapse in patients with HCV RNA < 25 IU/ml at end of completed treatment : 6 (all genotype 1a) Relapses Cohort 1Cohort 2 123123 Treatment groupSSR24SSR12SS12SSR12 SS12 Treatment historyNR Naïve MetavirF2 F0-F1F4F3F4 IL28B genotypeTT CTTTCC Baseline HCV RNA, log 10 IU/ml777656 Time of relapse, week444488 Baseline Q80KYes No Emergence of SMV resistance mutations N174S R155K NoD168E R155K D168E I170T SSR : SOF + SMV + RBV ; NR : null responder COSMOS COSMOS Study: SOF + SMV + RBV for genotype 1 – Phase IIa Lawitz E. Lancet 2014;384:1756-65

7. Adverse events, N (%) 24 weeks12 weeks SOF + SMV + RBV N = 54 SOF + SMV N = 31 SOF + SMV + RBV N = 54 SOF + SMV N = 28 Adverse event grade 3 / 49% / 2%3% / 10%9% / 2%7% / 0 Serious adverse event6%3%00 Death1* (2%)000 AE leading to discontinuation2 (4%)2 (7%)00 * Toxicity to alcohol and narcotics ; Aggression Raised CK ; Renal failure AE of clinical interest Rash19%16%20%11% Pruritus17%3%9%14% Neutropenia03%00 Anemia30%3%13%0 Photosensitivity4%7%6%7% AE of special interest Increased bilirubin11%3%9%0 COSMOS COSMOS Study: SOF + SMV + RBV for genotype 1 – Phase IIa Lawitz E. Lancet 2014;384:1756-65

8. COSMOS Study: SOF + SMV + RBV for genotype 1 – Phase IIa  Summary –High Rates of SVR 12 with SOF + SMV, even in difficult to treat groups, including patients with compensated cirrhosis and prior non response to therapy –Rapid virologic response did not predict SVR 12 –Addition of RBV did not improve SVR 12 rates –Extending treatment to 24 weeks did not improve SVR 12 rates, except possibly in patients with prior relapse and advanced fibrosis –Patients with baseline G80K mutation had high SVR 12 rates, including those with compensated cirrhosis, with no impact of RBV –Regimen well tolerated: fatigue, headache, and nausea were the most common side effects –Overall, SOF + SMV shows high efficacy and tolerability in patients with chronic HCV genotype 1 infection, either naïve or non-responders to previous IFN-based therapy COSMOS Lawitz E. Lancet 2014;384:1756-65