No prior therapy with PI ARV-trial.com TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis Randomisation** 1 : 1 Open-label Design W12 W24 18-70 years HCV genotype 1 Naïve or pre-treated Cirrhosis* Child-Pugh A < 7 HCV RNA ≥ 10,000 IU/ml No prior therapy with PI N = 208 OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV + RBV N = 172 * Liver biopsy with Metavir > 3 or Ishak > 4, or Fibroscan kPa > 14.6 ** Randomisation stratified on prior Peg-IFN + RBV therapy ; Naïve patients, stratified on genotype (1a vs 1b) and IL-28B (CC vs non-CC) Experienced patients stratified on genotype subtype, prior response (null, partial, relapse) Treatment regimens Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (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) TURQUOISE-II Poordad F, NEJM 2014;370:1973-82 1

No prior therapy with PI TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis Randomisation 1 : 1 Open-label Design W12 W24 18-70 years HCV genotype 1 Naïve or pre-treated Cirrhosis* Child-Pugh A < 7 HCV RNA ≥ 10,000 IU/ml No prior therapy with PI N = 208 OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV + RBV N = 172 * Liver biopsy with Metavir > 3 or Ishak > 4, or Fibroscan kPa > 14.6 Primary efficacy endpoint Sustained virologic response (HCV RNA < 25 IU/ml) 12 weeks after end of treatment, with two-sided 97.5% CI Non-inferiority of SVR12 assessed vs estimated rate of SVR24 with a telaprevir-based regimen (47%; 95% CI : 41 to 54). A noninferiority margin of 10.5 % established 43% as the noninferiority threshold; the superiority threshold was 54% Analyses by mITT TURQUOISE-II Poordad F, NEJM 2014;370:1973-82

TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis HCV RNA : COBAS TaqMan real-time RT–PCR assay, v 2.0 (Roche) Virologic failure 2 consecutive HCV RNA > 1 log10 IU/ml above the nadir at any time during treatment, HCV RNA ≥ 25 IU/ml at all assessments during treatment among patients who received at least 6 weeks of treatment, confirmed HCV RNA ≥ 25 IU/ml after a level < 25 IU/ml during treatment Virologic relapse : confirmed HCV RNA ≥ 25 IU/ml between the end of treatment and 12 weeks after the last dose of study drug among patients who completed treatment and had an HCV RNA < 25 IU/ml at the final visit during the treatment period Exploratory analysis : stepwise logistic-regression model to assess the association between the rate of SVR12 and continuous and categorical subgroup variables TURQUOISE-II Poordad F, NEJM 2014;370:1973-82

Baseline characteristics and patient disposition ARV-trial.com TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis Baseline characteristics and patient disposition 12 weeks N = 208 24 weeks N = 172 Mean age, years 57.1 56.5 Female 30% Race : white/black 95.7% / 2.9% 93.6% / 3.5% Body mass index 27.9 ± 4.1 27.9 ± 4.3 Genotype : 1a / 1b 67.3% / 32.7% 70.3% / 29.7% IL28B non-CC genotype 83.2 % 80.2% HCV RNA log10 IU/ml 6.41 ± 0.62 6.53 ± 0.52 Prior treatment with PEG-IFN + RBV, N 122 98 Null response 75 62 Partial response 18 13 Relapse 29 23 Platelet count x 10-9/l, median (IQR) 140 (104-188.5) 142.5 (105-183) Serum albumin, g/l, median (IQR) 40 (37-42) 39 (37-42) Discontinued treatment, N 4 9 For adverse event / for virologic failure 4 / 0 4 / 3 TURQUOISE-II Poordad F, NEJM 2014;370:1973-82 4

SVR12 (HCV RNA < 25 IU/ml) ARV-trial.com TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis SVR12 (HCV RNA < 25 IU/ml) 12 weeks 24 weeks 25 50 100 75 91.8 95.9 % p = 0.09 88.6 94.2 HCV subgenotype Overall 1a No prior treatment 1b 98.5 94.6 96.6 86.7 95.2 94.4 Relapse Partial response Null Prior treatment N 208 172 140 121 68 51 86 74 29 23 18 13 62 TURQUOISE-II Poordad F, NEJM 2014;370:1973-82 5

Outcomes for patients without SVR12 TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis Outcomes for patients without SVR12 12 weeks N = 208 24 weeks N = 172 N (%) 17 (8.2%) 7 (4.1%) On-treatment virologic failure 1 3 Relapse 12 (5.9%) * 1 (0.6%) Other 4 * 7/12 had genotype 1a and prior null response to PEG-IFN + RBV Resistance testing (population sequencing) of the 17 virologic failures (on-treatment or relapse) No resistance, N = 2 Resistance, N = 15 D168V (NS3) and Q30R (NS5A) most frequent in genotype 1a D168V (NS3), Y93H (NS5A) and C316Y + M414I (NS5B) in the single genotype 1b case TURQUOISE-II Poordad F, NEJM 2014;370:1973-82

TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis SVR12 (HCV RNA < 25 IU/ml), according to genotype and prior treatment 12 weeks N = 208 24 weeks N = 172 N/ total N (%) Genotype 1a No prior treatment 59/64 (92.2) 52/56 (92.9) Prior treatment Null response 40/50 (80) 39/42 (92.9) Partial response 11/11 (100) 10/10 (100) Relapse 14/15 (93.3) 13/13 (100) Genotype 1b 22/22 (100) 18/18 (100) 25/25 (100) 20/20 (100) 6/7 (85.7) 3/3 (100) 14/14 (100) TURQUOISE-II Poordad F, NEJM 2014;370:1973-82

TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis Multivariate Analysis of Association of Variables with a SVR12 Estimated odds ratio (95% CI) p Model including former injection-drug use * Previous PEG-IFN + RBV treatment (null response vs partial response, relapse or no prior treatment) 0.39 (0.16 - 0.94) 0.04 Genotype (1a vs 1b) 0.12 (0.02 - 0.90) Former injection-drug use (yes vs no) 0.35 (0.14 - 0.86) 0.02 Model excluding former injection-drug use ** 0.33 (0.13 - 0.80) 0.10 (0.01 - 0.80) 0.03 * Also adjusted for baseline Child–Pugh score and ethnic group; ** also adjusted for geographic region and treatment duration Continuous variables : age, BMI, platelet, albumin, alpha-foetoprotein, HCV RNA level Categorical variables : treatment duration, genotype, IL28B genotype, previous PEG-IFN + RBV, sex, race, ethnicity, geographic region, Child–Pugh score, diabetes, history of depression or bipolar disorder , former injection-drug use TURQUOISE-II Poordad F, NEJM 2014;370:1973-82

TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis Adverse events, N (%) 12 weeks, N = 208 24 weeks, N = 172 Any adverse event 191 (91.8) 156 (90.7) AE leading to treatment discontinuation 4 (1.9) 4 (2.3) Serious adverse event 13 (6.2) 8 (4.7) AE occurring in > 10% in either group Fatigue 32.7% 46.5% (p < 0.01) Headache 27.9% 30.8% Nausea 17.8% 20.3% Pruritus 18.3% 19.2% Insomnia 15.4% 18.0% Diarrhea 14.4% 16.9% Asthenia 13.9% 12.8% Rash 11.1% 14.5% Irritability 7.2% 12.2% Anemia 7.7% 10.5% Dyspnea 5.8% 12.2% (p<0.05) Death 1 (0.5) TURQUOISE-II Poordad F, NEJM 2014;370:1973-82

TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis AE leading to discontinuation 12 weeks, N = 208 24 weeks, N = 172 N = 4 Acute hepatitis, Mental status change Extradural hematoma Lactic acidosis Anemia, COPD, Suicidal ideation, CNS symptoms + asthenia + dehydration Laboratory abnormalities, N (%) 12 weeks, N = 208 24 weeks, N = 172 ALT, grade 3-4 6 (2.9%) 0 (p < 0.05) AST, grade 3-4 1 (0.5%) Alkaline phosphatase, grade 3-4 Total bilirubin, grade 3-4 28 (13.5%) 9 (5.2%) (p < 0.01) Hemoglobin Grade 1 49.5% 56.4% Grade 2 5.8% 10.5% Grade 3 1.0% 0.6% Grade 4 0.5% TURQUOISE-II Poordad F, NEJM 2014;370:1973-82

ARV-trial.com TURQUOISE-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV with cirrhosis Summary In both treatment groups of 3D + RBV, the primary efficacy end points met the prespecified criteria for noninferiority and superiority to the historical rate with telaprevir plus PEG-IFN + RBV among patients with HCV genotype 1 infection and cirrhosis 12 or 24 weeks of treatment with coformulated ombitasvir/paritaprevir/ritonavir and dasabuvir, administered with RBV, resulted in high rates of SVR12 (91.8% and 95.9%, respectively) Patients with cirrhosis and a prior null response had SVR12 of 86.7% and 95.2% in the 12-W and 24-W groups, respectively. Patients with genotype 1a and a prior null response had a SVR12 of 80% with 12 weeks of treatment and 92.9% with 24 weeks of treatment. All other subgroups with genotype 1a, including previously naïve patients, those with a prior partial response, with a prior relapse, had rates of SVR12 of 92 to 100% with 12 weeks or 24 weeks of treatment Patients with genotype 1b and a prior null response had a SVR12 of 100% with either treatment duration Drug discontinuations due to adverse events were infrequent TURQUOISE-II Poordad F, NEJM 2014;370:1973-82 11