1. CURRY  Design Open-label CURRY Study: SOF + RBV for HCV with liver cancer before transplantation ≥ 18 years Chronic HCV infection Any genotype HCV RNA ≥ 10,000 IU/ml Treatment naïve or not Hepatocellular carcinoma On waiting list for liver transplantation Child-Pugh ≤ 7 and MELD < 22 SOF 400 mg : 1 pill qd RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg)  Objective –Primary endpoint : post-transplant response 12 weeks after transplantation [pTVR 12 ] (HCV RNA < 25 IU/ml) in patients with HCV RNA < 25 IU/ml at last assessment before transplantation, by intention to treat, with 2-sided 90% CI and upper bound of recurrence rate of 65% SOF + RBV SVR 12 N = 61 Duration : until transplantation or 48 weeks Standard post-transplantation immunosuppressive regimen of solumedrol/prednisone, tacrolimus, and/or mycophenolate mofetil (up to 2 g/day) for the first 12W after transplantation Curry MP. Gastroenterology 2015;148:100-107

2. N = 61 Median age, years59 Female20% IL28B CC genotype22% HCV RNA log 10 IU/ml, median6.2 Genotype 1a / 1b / 2 / 3a / 4a39% / 34% / 13% / 11% / 2% Prior HCV treatment Yes Null response Partial response Breakthrough Relapse Unknown response 75% 24% 7% 20% 26% Baseline MELD score : < 8 / 9-10 / 11-1458% / 25% /18% Underwent transplantation, N with HCV RNA < 25 IU/ml 46 43 pTVR 1, N (% [90% CI])37/43 (86% [74% - 94%]) pTVR 12, N (% [90% CI])30/43 (70% [56% - 81%]) Confirmed HCV recurrence, N10/13 Baseline characteristics and outcome CURRY Study: SOF + RBV for HCV with liver cancer before transplantation Curry MP. Gastroenterology 2015;148:100-107 CURRY

3. CURRY Study: SOF + RBV for HCV with liver cancer before transplantation Curry MP. Gastroenterology 2015;148:100-107 Multivariate analysis of factors associated with absence of recurrence post-transplantation Odds ratio (95% CI)p Consecutive days HCV RNA < 25 IU/ml with target not detected prior to transplantation 1.047 (1.015 - 1.096)< 0.001 Genotype other than 1b9.83 (0.55 – 939.15)0.19 CURRY

4.  HCV Recurrence and resistance analysis –10 confirmed recurrence after liver transplantation Genotype 1a, N = 2; 1b, N = 7; 3a, N = 1 ILB28 non-CC, N = 10 Recurrence at W1 (N = 3), W2 (N = 2), W4 (N = 4), or W12 (N = 1) post-transplantation Duration of SOF+ RBV pre-transplantation < 12 weeks, N = 4 –NS5B sequencing At baseline : –4 patients with L159F variant : 4/4 relapsed –1 patient with N142T : achieved SVR 12 29 patients with failure before transplantation or recurrence after transplantation –no S282T mutant –12 patients with other variants as minor subpopulations (< 10%) in 11/12 : N142T (N = 2), L159F (N = 5), S282G (N = 1), L230F (N = 3); L159F + S282R + L230F + V321A (N = 1) CURRY Study: SOF + RBV for HCV with liver cancer before transplantation Curry MP. Gastroenterology 2015;148:100-107 CURRY

5.  Adverse events –Median duration of exposure to study regimen : 21 weeks –Serious adverse events, N = 11 –≥ Grade 3 adverse event, N = 11 –Discontinuation due to adverse event, N = 2 (pneumonia, sepsis/acute renal failure) –Most common adverse events : Fatigue (38%)Dyspnea (11%) Headache (23%)Cough (11%) Anemia (21%)Insomnia (11%) Nausea (16%)Constipation (10%) Rash (15%)Pruritus (10%) –Most common grade 3-4 laboratory abnormalities : grade 3 decrease in hemoglobin level, grade 3 hyperglycemia, grade 3-4 bilirubin elevation, lymphopenia < 500/mm 3 12 patients with RBV dose reduction, but no transfusion, no epoetin needed CURRY Study: SOF + RBV for HCV with liver cancer before transplantation Curry MP. Gastroenterology 2015;148:100-107 CURRY

6.  Summary –In this pilot study, SOF + RBV before liver transplantation prevented recurrence of HCV infection in 70% of patients with chronic HCV infection and liver cancer who achieved an HCV RNA level < 25 IU/ml before transplantation and in almost half of the total patients in the study –The rate of discontinuation owing to adverse events was low, and most adverse events were those associated with RBV therapy— fatigue, anemia, headache, and nausea—as were the laboratory abnormalities of decreased hemoglobin and increased bilirubin –Enrichment in minor resistance-associated variants, although rare, may encode for marginal reductions in susceptibility to SOF –Limitations Low sample size Exclusion of patients with decompensated liver disease CURRY Study: SOF + RBV for HCV with liver cancer before transplantation Curry MP. Gastroenterology 2015;148:100-107 CURRY