GZR/EBR 100/50 mg qd N = 201 N = 100 W12W24 W16 PlaceboGZR/EBR W28 > 18 years HCV infection Genotype 1, 4, 6 Treatment-naïve ≥ 3 months opioid replacement Compensated cirrhosis allowed HIV co-infection allowed Randomisation 2 : 1 Double blind  Design C-EDGE CO-STAR: grazoprevir/elbasvir for HCV infected drug users on opiod replacement therapy  Objective –SVR 12 (HCV RNA < 15 IU/ml) by intention to treat analysis : includes all patients, reinfection = failure by modified ITT (primary efficacy endpoint) : re-infection = success ; exclusion of discontinuations for reasons other than virologic failure and lost-to-follow-up C-EDGE CO-STAR Dore G. AASLD 2015, Abs. 40

GZR/EBR N = 201 Placebo N = 100 Age, years, median4847 Female24%23% Black / White / Asian 79% / 15% / 6%84% / 7% / 9% Genotype 1a 1b % 15% 6% 3% 75% 15% 6% 4% HCV RNA > 2,000,000 IU/ml56.7%51.0% Fibrosis stage F419.9%22.0% HIV co-infection8.0%5.0% Urine drug screen positive at D1 (excluding opiate)60.7%52.0% Discontinuation, N5NA Baseline characteristics and patient disposition C-EDGE CO-STAR Dore G. AASLD 2015, Abs. 40 C-EDGE CO-STAR: grazoprevir/elbasvir for HCV infected drug users on opiod replacement therapy

Non-virologic failure Relapse Reinfection ( ) 96.6 ( ) 100 ( ) 60 ( ) All patientsGenotype 1aGenotype 1bGenotype 4Genotype % Primary endpoint : SVR 12 (HCV RNA < 15 IU/ml), % (95% CI), ITT mFAS* SVR 12, ITT, Full analysis set 91.5%93.5%93.3%91.7%20% C-EDGE CO-STAR Dore G. AASLD 2015, Abs. 40 C-EDGE CO-STAR: grazoprevir/elbasvir for HCV infected drug users on opiod replacement therapy * ITT, mFAS : reinfection = success, unrelated discontinuation = excluded

SVR 12 (HCV RNA < 15 IU/ml) by subgroup, % (95% CI), ITT, mFAS MalePositiveNegativeNoYesFemaleNoYes (91-98) 95.5 (90-98) 95.4 (87-99) 95.6 (91-98) 95 (83-99) % (86-100) 97.6 (92-100) 93.8 (88-98) 113 SexDrug screenCirrhosisHCV RNA > 2,000,000 IU/ml C-EDGE CO-STAR Dore G. AASLD 2015, Abs. 40 C-EDGE CO-STAR: grazoprevir/elbasvir for HCV infected drug users on opiod replacement therapy

 Urine drug screen results, from D1 to treatment W12 –At each time point, in both groups > 50% of patients with positive urine drug screen of any drug among the 8 following classes : amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, phencyclidine, propoxyphène Around 20% with positive screen for opiates  Adherence to study drugs C-EDGE CO-STAR Dore G. AASLD 2015, Abs. 40 GZR/EBRPlacebo Adherence > 95% during the 12 weeks96.5%100% % of patients who missed ≤ 2 doses92.5%96.9% % of patients who missed ≥ 6 doses3%0%

GZR/EBR N = 201 Placebo N = 100 Serious adverse event3.5%4.0% Serious drug-related adverse event0.5%1.0% Adverse event leading to discontinuation1.0%2.0% Most frequent adverse events Fatigue15.9%20.0% Headache12.9%14.0% Nausea11.4%9.0% Diarrhea10.0%9.0% Late AST/ALT > 5 x ULN00 Total bilirubin > 2.6 x ULN00 Adverse events, N (%) C-EDGE CO-STAR Dore G. AASLD 2015, Abs. 40 C-EDGE CO-STAR: grazoprevir/elbasvir for HCV infected drug users on opiod replacement therapy

 Summary –EBR/GZR demonstrated high efficacy in genotype 1 and 4- infected patients receiving Opiate Agonist Therapy Limitation : small number of genotype 6-infected patients –Acceptable safety profile with comparable adverse event rates between the immediate and deferred treatment arms –High study medication adherence –Stable ongoing drug use throughout the initial treatment phase in both groups –Data demonstrate support for treating HCV among subjects receiving Opiate Agonist Therapy C-EDGE CO-STAR Dore G. AASLD 2015, Abs. 40 C-EDGE CO-STAR: grazoprevir/elbasvir for HCV infected drug users on opiod replacement therapy