1. SAPPHIRE-I Feld JJ. NEJM 2014;370:1594-1603 SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1  Treatment regimens –Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) : 25/150/100 mg qd = 2 tablets –Dasabuvir (DSV) : 250 mg bid –RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) OBV/PTV/r + DSV + RBV Placebo Randomisation** 3 : 1 Double blind 18-70 years Chronic HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Treatment-naïve No Cirrhosis* No HBV or HIV co-infection *Liver biopsy with Metavir ≤ 3 or Ishak ≤ 4, or Fibrotest ® ≤ 0.72 + APRI ≤ 2, or Fibroscan kPa < 9.6 N = 158 N = 473 W12W24 ** Randomisation stratified on prior PEG-IFN + RBV therapy response (null, partial, relapse) and on genotype subtype (1a or 1b) OBV/PTV/r + DSV + RBV SVR 12 Open label  Design

2. SAPPHIRE-I Feld JJ. NEJM 2014;370:1594-1603 SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1  Objective –Non-inferiority and superiority of SVR 12 assessed vs estimated rate of SVR 12 with a telaprevir-based regimen in non-cirrhotic naïve patients : 78%; 95% CI : 75 to 80). –A noninferiority margin of 10.5 % of the 95% CI for the SVR 12 of the new regimen established 70% as the noninferiority threshold; the superiority threshold was 80%. –Analyses by mITT, power > 90% OBV/PTV/r + DSV + RBV Placebo Randomisation** 3 : 1 Double blind 18-70 years Chronic HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Treatment-naïve No Cirrhosis* No HBV or HIV co-infection *Liver biopsy with Metavir ≤ 3 or Ishak ≤ 4, or Fibrotest ® ≤ 0.72 + APRI ≤ 2, or Fibroscan kPa < 9.6 ** Randomisation stratified on prior PEG-IFN + RBV therapy response (null, partial, relapse) and on genotype subtype (1a or 1b) OBV/PTV/r + DSV + RBV SVR 12 Open label  Design N = 158 N = 473 W12W24

3. SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1 OBV/PTV/r + DSV (3D) + RBV N = 473 Placebo N = 158 Mean age, years49.451.2 Female42%54% Race : white/black90.5% / 5.5%91.1% / 5.1% Body mass index, mean25.726.2 Genotype : 1a / 1b68.1% / 31.9%66.5% / 33.5% Fibrosis score F2-F323.3%26.6% IL28B CC genotype30.4 %31.6% HCV RNA log 10 IU/ml, mean6.406.47 Discontinued treatment, N91 For adverse event / for virologic failure3 / 01 / 0 SAPPHIRE-I Feld JJ. NEJM 2014;370:1594-1603 Baseline characteristics and patient disposition

4. OBV/PTV/r + DSV + RBV * 95% CI : 94.5 to 97.9 : noninferior and superior to the historical SVR 12 with TVR + PEG-IFN + RBV (78.0%) ** 95% CI : 93.0 to 97.6 : noninferior and superior to the historical SVR 12 with TVR + PEG-IFN + RBV (72.0%) *** 95% CI : 95.8 to 100 : noninferior and superior to the historical SVR 12 with TVR + PEG-IFN + RBV (80.0%) 25 50 100 75 96.2* % 95.3** HCV subgenotype Overall 1 a1 b 98.0*** 97.0 96.0 96.5 N 4733221513631443297040104369 94.3 98.1 92.5 95.7 F3F2≥ 800,000< 800,000 IL28B CC F0-F1 IL28B non-CC Baseline HCV RNA (log 10 IU/ml) SAPPHIRE-I Feld JJ. NEJM 2014;370:1594-1603 SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1 SVR 12 (HCV RNA < 25 IU/ml) 0

5. SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1  Virologic failure, N = 1, at W12 (genotype 1a)  Relapse, N = 7 (1.5%) –5 by W4 post-treatment –2 by W12  Resistance testing (population sequencing) of the 7 relapses + 1 failure –All had ≥ 1 mutant resistant variants Genotype 1a (N = 7) : D168V (N = 6) in NS3 ; M28T (N = 2) and Q30R (N = 3) in NS5A ; S556G (N = 3) in NS5B Genotype 1b (N = 1) : Y56H + D168V (NS3), L31M + Y93H (NS5A) and S556G (NS5B) SAPPHIRE-I Feld JJ. NEJM 2014;370:1594-1603

6. SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1 OBV/PTV/r + DSV (3D) + RBV N = 473 Placebo N = 158 Any adverse event414 (87.5)116 (73.4) ; p < 0.05 AE leading to treatment discontinuation3 (0.6)1 (0.6) Serious adverse event10 (2.1)0 AE occurring in > 10% in either group Fatigue34.7%28.5% Headache33.0%26.6% Nausea23.7%13.3% ; p < 0.05 Pruritus16.9%3.8% ; p < 0.05 Insomnia14.0%7.6% ; p < 0.05 Diarrhea13.7%7.0% ; p < 0.05 Asthenia12.1%3.8% ; p < 0.05 Rash10.8%5.7% Grade 3-4 ALT / AST0.9% / 0.6%4.4% (p < 0.05) / 1.9% Grade 3-4 total bilirubin2.8%0 ; p < 0.05 SAPPHIRE-I Feld JJ. NEJM 2014;370:1594-1603 Adverse events, N (%)

7. SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1  Summary –Rates of response to a 12-week interferon-free combination regimen, of ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin, were more than 95% among previously untreated patients with HCV genotype 1 infection –SVR 12 was non inferior and superior to the historical control rate with telaprevir plus PEG-IFN + RBV in a similar patient population –SVR 12 was similar in patients with HCV genotype 1a or 1b infection, and in various subgroups (age, sex, fibrosis, IL28B) –Tolerability was good, with 0.6% of patients discontinuing for adverse event Nausea, pruritus, insomnia, diarrhea, and asthenia more frequent in the active group Low incidence of grade 3-4 bilirubin elevation –In conclusion, a 12-week all-oral combination regimen of OBV/PTV/r + DSV + RBV resulted in SVR 12 > 95%, regardless of HCV genotype (1a or 1b) and with low rates of treatment discontinuation, in previously untreated patients with HCV genotype 1 infection and no cirrhosis SAPPHIRE-I Feld JJ. NEJM 2014;370:1594-1603