Placebo + PR W48 Placebo + PR Yes Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4 DCV60 + PEG-IFN + RBV N = 158 No Yes No Randomisation* 2 : 2 : 1 Double blind  Design years Chronic HCV infection Genotype 1 or 4 Treatment naïve HCV RNA ≥ 100,000 IU/ml Compensated cirrhosis allowed No HBV or HIV coinfection Placebo + PEG-IFN + RBV N = 78 DCV20 + PEG-IFN + RBV N = 159 PDR (protocol-defined response) = HCV RNA < 25 IU/ml at W4 and undetectable at W10 W12 * Randomisation stratified on genotype (1 or 4) W24 Randomisation if PDR DCV20 + PR Placebo + PR DCV60 + PR PDRPDR

COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4  Dosage of drugs –DCV : 20 mg or 60 mg qd or matching placebo –PEG-IFN  -2a : 180  g SC once weekly –RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg)  Co-primary endpoints : % of genotype 1 with eRVR (undetectable HCV RNA at W4 and W12) and SVR 24 (undetectable HCV RNA) by m-ITT analysis  Resistance analyses : all baseline samples and on-treatment or follow-up samples with HCV RNA ≥ 1000 IU/ml  Objectives –eRVR of one of DCV dose superior to placebo, in genotype 1 (lower bound of the 80% CI for the difference > 35%, power of 90%) –SVR 24 of one of DCV dose superior to placebo, in genotype 1 (lower bound of the 80% CI for the difference > 0%, power of 82%) Hezode C. Gut 2015;64: COMMAND-1

DCV20 + PEG-IFN + RBV N = 159 DCV60 + PEG-IFN + RBV N = 158 Placebo + PEG-IFN + RBV N = 78 Median age, years Female33%35%30% HCV RNA log 10 IU/ml, mean Genotype 1a 1b 4 67% 26% 8% 72% 20% 8% 72% 21% 8% Cirrhosis8%5%10% IL28B CC33%28%30% Discontinued treatment Adverse event Lost to follow-up / Other Lack of efficacy In patients with PDR / 1 - In patients with PDR / / 7 25 Did not achieve PDR47 (lack of efficacy: 15)42 (lack of efficacy: 18)- Baseline characteristics and patient disposition Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4

SVR 24 (HCV RNA < 25 IU/ml) % 60 Genotype N  In genotype 1, both doses of DCV were not significantly superior to placebo (lower bound of the 80% CIs for the difference (DCV - placebo) : 33% for eRVR and 13% for SVR 24, for both DCV groups 1641 Genotype 1aGenotype 1bGenotype Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4 DCV60PlaceboDCV20 0

Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or % N Genotype 1a Genotype 1b CCCTTTCCCTTT DCV60PlaceboDCV20 0 SVR 24 (HCV RNA < 25 IU/ml) by IL28B genotype

DCV20 + PEG-IFN + RBV N = 147 DCV60 + PEG-IFN + RBV N = 146 PDR (mITT) Genotype 1a Genotype 1b 72.1% 67.0% 82.9% 72.6% 67.3% 87.1% Regimen DCV + PR 12W + PR 12W DCV + PR 24W DCV + PR 12W + PR 12W DCV + PR 24W SVR 24 among patients achieving PDR Genotype 1a Genotype 1b 75.5% 71.8% 85.7% 71.2% 71.9% 70.0% 79.2% 76.9% 85.7% 71.2% 70.3% 76.9% Rates of protocol-defined response (PDR) in genotype 1 and effect on SVR 24, N (%) Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4

DCV20 + PEG-IFN + RBV N = 147 DCV60 + PEG-IFN + RBV N = 146 Overall Virologic breakthrough Other on-treatment failure Relapse Other 40.8% 8.1% 9.5% 15.0% 8.2% 40.4% 10.3% 8.2% 15.1% 6.8% Regimen DCV + PR 12W + PR 12W N = 53 DCV + PR 24W N = 52 DCV + PR 12W + PR 12W N = 53 DCV + PR 24W N = 50 Patients achieving PDR Overall Virologic breakthrough Other on-treatment failure Relapse Other 24.5% 0 1.9% 13.2% 9.4% 28.8% 0 7.7% 19.2% 1.9% 20.8% 0 3.8% 9.4% 7.5% 30.0% % 10.5% Treatment failures in genotype 1, N (%) Virologic breakthrough was more frequent in genotype 1a Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4

DCV20 + PEG-IFN + RBV N = 159 DCV60 + PEG-IFN + RBV N = 158 Placebo + PEG-IFN + RBV N = 78 Serious adverse event7.5%8.2%7.7% Adverse event leading to discontinuation4.4% 10.3% AE in ≥ 25% of patients Fatigue55%54%59% Headache43% 46% Pruritus35%40%33% Insomnia31%34%39% Rash34%25%32% Nausea35%34%26% Myalgia28%27%32% Influenza-like illness28%31%21% Dry skin30%26%19% Irritability22%23%28% Alopecia25%26%17% Decreased appetite17%25%22% Grade 3-4 bilirubin increase101 Grade 3-4 ALT elevation06 (3.8%)1 Adverse events and hepatic liver laboratory abnormalities, N (%) Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4

 Resistance analysis –Genotype 1 At baseline : NS5A polymorphisms associated with DCV resistance (L31M/V and/or Y93H/N/S) detected in 12 genotype 1a patients and 10 genotype 1b patients –8/12 genotype 1a (L31M/V and Y93H/N/S) and 2/10 genotype 1b (Y93H) failed to achieve SVR 24 At virologic failure, DCV-associated resistant variants in all patients ; most frequent : –Q30 in genotype 1a –L31I/M/V and Y93H in genotype 1b –Genotype 4 4 virologic failures, sequencing available in 3 patients ; emergence of L28M + L30H in 1 patient, and L28M + L30S in 2 patients Hezode C. Gut 2015;64: COMMAND-1

COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4  Summary –In this phase IIb study, the combination of daclatasvir + PEG-IFN + RBV was generally well tolerated and achieved higher SVR 24 rates compared with placebo + PEG-IFN + RBV among patients infected with HCV genotype 1 or 4 Genotype 1a patients had lower rates of SVR 24 and higher rates of virologic failure compared with genotype 1b patients Although sample size was small, SVR 24 was 100% with DCV 60 mg + PEG-IFN + RBV in genotype 4 IL28B genotype predicted response, with higher rates of SVR 24 observed among patients with a CC genotype –Dose of 60 mg QD of DCV selected for Phase III studies Hezode C. Gut 2015;64: COMMAND-1