C-SURGE: uprifosbuvir/grazoprevir/ruzasvir for genotype 1 with prior DAA-failure Design Randomisation * 1 : 1 Open-label W16 W24 > 18 years HCV infection Genotype 1 Relapse after LDV/SOF or EBR/GZR Compensated cirrhosis** allowed Well-controlled HIV co-infection allowed N = 45 MK3 + RBV MK3 N = 49 * Randomisation stratified by genotype (1a vs 1b), prior DAA regimen and cirrhosis ** Liver biopsy or Fibroscan > 12.5 kPa or Fibrotest > 0.75 + APRI > 2 MK3: Uprifosbuvir 225 mg/GZR 50 mg/RZR 30 mg FDC (MK3) = 2 tablets QD RBV dose based on body weight (< 65 kg = 800 mg/d ; 65-85 kg = 1000 mg/d ; > 85-105 kg = 1200 mg/d ; > 105 kg = 1400 mg/d) Objective SVR12 (HCV RNA < 15 IU/mL), full analysis set (≥ 1 dose of study medication) C-SURGE Wyles D. Hepatology 2017 (ePub ahead of print)

Baseline characteristics C-SURGE: uprifosbuvir/grazoprevir/ruzasvir for genotype 1 with prior DAA-failure Baseline characteristics MK3 16W + RBV N = 44 * MK3 24W N = 49 Age, years, median 61 60 Female, % 16 12 Race : white, % 70 76 Genotype 1a, % 91 82 HCV RNA log10 IU/mL, median 6.5 6.4 Cirrhosis, % 43 RASs at baseline, % NS3 NS5A NS3 + NS5A NS5B 58 72 2 71 94 65 Previous failure, % LDV/SOF 12-24W LDV/SOF 8W EBR/GZR 12W 59 20 22 63 10 33 HIV co-infection, % 5 6 * Exclusion of a participant who withdrew prior to beginning treatment C-SURGE Wyles D. Hepatology 2017 (ePub ahead of print)

SVR12 (HCV RNA <15 IU/mL) C-SURGE: uprifosbuvir/grazoprevir/ruzasvir for genotype 1 with prior DAA-failure SVR12 (HCV RNA <15 IU/mL) MK3 16W + RBV MK3 24W without RBV Full Analysis Set mFAS 98 100 80 60 40 20 44 49 % 43 * Resistance analysis population 100 80 60 40 20 31 46 12 3 25 35 % NS5A RASs NS3 RASs Present Absent 18 14 * One patient from the 16W + RBV arm withdrew from the study after taking 3 doses of study medication (this patient was excluded in the mFAS analysis) C-SURGE Wyles D. Hepatology 2017 (ePub ahead of print)

C-SURGE: uprifosbuvir/grazoprevir/ruzasvir for genotype 1 with prior DAA-failure Adverse events, % MK3 16 W + RBV N = 44 MK3 24W without RBV N = 49 Drug-related adverse event 73 47 Serious adverse event * Drug-related 2 8 Adverse event leading to discontinuation Most frequent adverse events (> 10%) Fatigue 48 24 Headache 14 12 Diarrhea 7 10 Pruritus 11 Rash 4 Laboratory abnormalities, % Hemoglobin < 10 g/dl Direct bilirubin > 5 x baseline Late AST/ALT > 5 x ULN Creatinine grade 2 (1.4 - 1.8 x ULN) 9 * N = 5 (hospitalization for cervical spine disc herniation; hospitalization for chest pain; hospitalization for dizziness; pancreatitis without hospitalization; and hospitalization for shoulder cyst surgery) C-SURGE Wyles D. Hepatology 2017 (ePub ahead of print)

C-SURGE: uprifosbuvir/grazoprevir/ruzasvir for genotype 1 with prior DAA-failure Summary MK3 (uprifosbuvir/grazoprevir/ruzasvir) ± ribavirin was highly effective in cirrhotic and non-cirrhotic genotype 1 patients who previously failed an NS5A inhibitor-containing antiviral regimen 98% (43/44) of patients receiving MK3 + RBV for 16 weeks achieved SVR12 One patient withdrew from the study after receiving 3 doses 100% (49/49) of patients receiving MK3 alone for 24 weeks have achieved SVR12 High efficacy was observed despite a high prevalence of baseline NS3 and NS5A RAVs in this population Treatment was generally safe and well-tolerated C-SURGE Wyles D. Hepatology 2017 (ePub ahead of print)