SOF/VEL 400/100 mg qd N = 75 W24 SOF/VEL > 18 years Chronic HCV infection Genotype 1 to 6 Naïve or treatment-experienced No prior treatment with NS5A or.

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SOF/VEL 400/100 mg qd N = 75 W24 SOF/VEL > 18 years Chronic HCV infection Genotype 1 to 6 Naïve or treatment-experienced No prior treatment with NS5A or NS5B inhibitor Child-Pugh B cirrhosis ** No hepatocellular carcinoma No liver transplantation Creatinine clearance > 50 ml/min Platelets > 30,000/mm 3 Randomisation* 1 : 1 : 1 Open-label * Randomisation was stratified on HCV genotype ** Metavir F4 or Ishak 5-6 or Fibroscan > 12.5 kPa or Fibrotest > 0.75 and APRI > 2  Objectives –SVR 12 (HCV RNA < 15 UI/ml) with 2-sided 95% CI, by ITT, 99% power to detect a SVR 12 ≥ 41% ; not powered to detect significant differences in SVR among the treatment groups –Changes in MELD and CPT scores SVR 12 W12 SOF/VEL + RBV SVR 12 RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) ASTRAL-4 Curry MP. N Engl J Med 2015; 373: N = 75  Design ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease

SOF/VEL, 12W N = 90 SOF/VEL + RBV, 12W N = 87 SOF/VEL, 24W N = 90 Age, years, mean58 Female37%24%30% White88%91%90% Genotype 1a 1b 3 2 / 4 / 6 56% 20% 16% 4% / 4% / 0 52% 16% 15% 5% / 2% / 0 61% 18% 13% 4% / 2% / 1% HCV RNA, log 10 IU/ml, mean IL28B CC22%25%24% Treatment-experienced64%54%47% MELD score : median / ≥ 1510 / 4%10 / 5%11 / 16% Ascites82%75%83% Encephalopathy58%62%66% Albumin, g/dl, median Platelets/mm Discontinuation, N Lack of efficacy Adverse event Non adherence Baseline characteristics and patient disposition Charlton MR, AASLD 2015, Abs. LB13 ; Curry MP. N Engl J Med 2015; 373: ASTRAL-4 ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease

Charlton MR, AASLD 2015, Abs. LB13 ; Curry MP. N Engl J Med 2015; 373: ASTRAL-4 ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease SVR 12, % (95% CI) SOF/VEL 12W SOF/VEL + RBV 12W SOF/VEL 24W OverallGenotype 1aGenotype 3Genotype 2, 4, 6 83 (74-90) 94 (87-98) 86 (77-92) 50 (23-77) 85 (55-98) 50 (21-79) G2 22 G4 1 G6 89 (65-99) 100 (77-100) 88 (62-98) (76-96) 94 (85-99) 93 (82-98) Genotype 1b Breakthrough, N Relapse, N LTFU, N Death, N * *Patient with non-detectable drug levels at time of virological failure, LTFU, lost to follow-up 4 %

Curry MP. N Engl J Med 2015; 373: ASTRAL-4 ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease Group Type of virologic failure Age, sex, race GTIL28B HCV RNA Time of virologic failure NS5A RAVsNS5B RAVs Pre-treatmentPost-treatment SOF/VEL 12W Relapse 55, F, white3aCT5.9PT W12Y93H (> 99%) L320I (1%) 58, M, white1aCT5.1PT W12M28V (6%)None 57, M, white3aCT6.2PT W4Y93H (5%)Y93H (> 99%)None 56, M, white3aCC6.5PT W12NoneY93H (> 99%)None 62, M, white1aCT6.2PT W4None 60, M, black1bCT6.4PT W4Y93H (80%) L31M (50%), L31V (50%), Y93H (> 99%) None 57, M, white3aTT5.6PT W4NoneY93H (> 99%)None 48, M, white3aCT6.3PT4NoneY93H (> 99%)None 57, M, white1aCT6.5PT12NoneY93N (> 99%)None 57, M, white3aCT6.0PT4NoneY93H (> 99%)None 59, M, black1bTT6.1PT12 L31I (8%), L31M (3%), Y93H (60%) L31M (90%), L31V (10%), Y93H (> 99%) L159F (14%) S282T (4%) SOF/VEL + RBV 12W Relapse 59, M, white1aCT6.4PT12None 48, M, white3CT5.9PT4NoneY93H (> 99%)None Breakthrough56, M, white3aTT5.9W8W8Y93H (3%)Y93H (> 99%) N142T (3%) E237G (2%) SOF/VEL 24W Relapse 61, M, black3aCT6.3PT4NoneY93H (> 99%)None 58, M, white3aCT6.2PT4NoneY93H (99%)None 57, M, white3aCT6.3PT4NoneY93H (> 99%)None 60, M, white1a-6.9PT4 Q30H (65%), Y93H (57%), Y93N (1%) Q30H (> 99%), Y93H (> 99%) L159F (96%) S282T (3%) 51, M, white1bTT5.4PT12L31M (> 99%) L31M (98%), L31V (2%), Y93H (> 99%) None 62, M, white1aCT5.5PT12None Q30R (95%), H58D (95%), Y93N (4%) None 53, F, white3aCC6.0PT4NoneM28T (2%), Y93H (> 99%)None Breakthrough52, M, white3aCT5.3W12NoneY93H (98%)E237G (2%) Characteristics of patients with virologic failure

Curry MP. N Engl J Med 2015; 373: ASTRAL-4 ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease CPT score change : baseline to follow-up W12 (% of patients) 11% 11% Worsened47% Improved < < Change in CPT score N = 17/267patients had no follow-up W12 assessment %

ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease MELD change: baseline to follow-up W12 (% of patients) Baseline MELD < 15 N = % Worsened51% Improved Change in MELD N = < Baseline MELD > 15 N = % Worsened84% Improved Change in MELD N= Curry MP. N Engl J Med 2015; 373: ASTRAL-4 17/267patients had no follow-up W12 assessment % %

SOF/VEL 12 weeks N = 90 SOF/VEL + RBV 12 weeks N = 87 SOF/VEL 24 weeks N = 90 At least one adverse event81%91%81% Serious adverse events19%16%18% Grade 3-4 adverse events18%13%19% Discontinuation due to adverse event1 (1%)4 (5%)4 (4%) Death3 (3%) 3 (3% Adverse events in > 10% of patients Fatigue26%39%23% Nausea24%25%20% Headache26%21%19% Anemia4%31%3% Diarrhea7%21%8% Insomnia10%14%10% Pruritus11%5%4% Muscle spasm3%11%4% Dyspnea4%10%2% Cough2%10%0 Hemoglobin < 10 g/dl / < 8.5 g/dl8% / 1%23% / 7% *9% / 1% Adverse events, N (%) * RBV discontinuation : 17%, dose reduction : 37% Curry MP. N Engl J Med 2015; 373: ASTRAL-4 ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease

SOF/VEL 12 weeks N = 90 SOF/VEL + RBV 12 weeks N = 87 SOF/VEL 24 weeks N = 90 Hemoglobin < 10 g/dl / < 8.5 g/dl8% / 1%23% / 7% *9% / 1% White cell count /mm 3 < 1000/mm 3 1 (1%) 4 (4%) 0 Lymphocyte count /mm 3 < 350/mm 3 10 (11%) 3 (3%) 12 (14%) 8 (9%) 6 (7%) Neutrophil count /mm 3 < 500/mm 3 2 (2%) 0 1 (1%) 1 (2%) 1 (1%) Platelet count 25,000-50,000/mm 3 < 25,000/mm 3 15 (17%) 1 (1%) 10 (11%) 0 18 (20%) 0 Hematologic abnormalities, N (%) * RBV discontinuation : 17%, dose reduction : 37% Charlton MR, AASLD 2015, Abs. LB13 ; Curry MP. N Engl J Med 2015; 373: ASTRAL-4 ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease

 Summary –Treatment with SOF/VEL for 12 or 24 weeks or SOF/VEL + RBV for 12 weeks resulted in high SVR 12 rates in HCV patients with decompensated cirrhosis caused by HCV of all genotypes –SOF/VEL + RBV resulted in the highest overall SVR 12 rates, with the lowest rates of virologic failure in HCV genotype 3 patients –Treatment was associated with improved MELD and CPT scores largely due to decreased bilirubin and improvement in synthetic function (albumin) –SOF/VEL for 12 or 24 weeks or SOF/VEL + RBV for 12 weeks was safe and well tolerated, with adverse events consistent with clinical sequelae of advanced liver disease and RBV toxicity –Limitations Study not powered to detect significant differences among the 3 treatment groups Only patients with moderate hepatic decompensation were enrolled The numbers of patients with HCV genotype 2, 4, or 6 were small Limited number of black patients Curry MP. N Engl J Med 2015; 373: ASTRAL-4 ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease