CONCERTO-2 Study: SMV + PEG-IFNa-2a + RBV for genotype 1 HCV-trial.com CONCERTO-2 Study: SMV + PEG-IFNa-2a + RBV for genotype 1 Design Randomisation * 1:1 Open-label 20-70 years, Japanese Chronic HCV infection Genotype 1 HCV RNA ≥ 100 000 IU/ml IFN-based pre-treated, non-responders No prior DAA therapy No cirrhosis No HBV or HIV co-infection N = 53 SMV 12W + PEG-IFN + RBV 24-48W ** SMV 24W + PEG-IFN + RBV 24-48W ** N = 53 * Randomisation was stratified on age (< 65 or ≥ 65 years old) and IL28B ** Response-guided therapy SMV: 100 mg 1 capsule qd PEG-IFNa-2a: 180 mg SC once weekly RBV: 600 or 1000 mg/day according to body weight Dosage adjustment of PEG-IFN and RBV permitted Objective Primary endpoint: SVR12 (HCV RNA < 1.2 log10 IU/ml), with 2-sided 95% CI, significant difference vs null hypothesis proportion ≤ 14% of success, 90% power CONCERTO-2 Izumi N, J Gastroenterol 2014;49:941-53 1

CONCERTO-2 Study: SMV + PEG-IFNa-2a + RBV for genotype 1 Baseline characteristics, and disposition SMV12 N = 53 SMV24 Median age, years 60 Female 49 51 Genotype : 1a / 1b, % 0 / 100 6 / 94 IL28B CC genotype, % 15 11 HCV RNA log10 IU/ml, median 6.4 Metavir stage in patients with biopsy : F0 / F1 / F2 / F3, % 0 / 55 / 15 / 30 18 /18 / 36 / 27 Prior therapy, % IFN only PEG-IFN only IFN + RBV PEG-IFN + RBV 7.5 0 7.5 84.9 3.8 1.9 86.8 Discontinuation during follow-up, % Withdrawal of consent 4.7 Completion of all treatment, % Discontinuation PR / SMV / both, N 77.8 3 / 9 / 10 CONCERTO-2 Izumi N, J Gastroenterol 2014;49:941-53 2

CONCERTO-2 Study: SMV + PEG-IFNa-2a + RBV for genotype 1 Virologic response, ITT (%) SMV12 N = 53 SMV24 SVR12 95% CI, p * 52.8 38.6-66.7, p < 0.0001 35.8 23.1-50.2, p = 0.0001 Virologic breakthrough 13.2 11.3 Relapse 38.6 51.1 Met RGT criteria and completed 24W of PEG-IFN + RBV 81.1 60.5 73.6 48.7 Failure to achieve SVR12 HCV RNA detectable at end of treatment HCV RNA detectable at SVR12 assessment Missing at SVR12 timepoint 47.2 17.0 30.2 64.2 15.1 43.4 5.7 * One sample test for binomial distribution versus null hypothesis proportion ≤ 14 % for each treatment group Of the 57 failures, 56 had NS3 sequence available: ≥ 1 emerging NS3 mutation in 46/56 (82.1% ; SMV12 = 80.0% , SMV24 = 83.9%) CONCERTO-2 Izumi N, J Gastroenterol 2014;49:941-53 3

CONCERTO-2 Study: SMV + PEG-IFNa-2a + RBV for genotype 1 Adverse events (entire treatment period) SMV12 N = 53 SMV24 Treatment discontinuation due to adverse event SMV only, N All study medication, N 2 Grade3-4 adverse events, N 11 17 Serious adverse event, N 3 Common adverse events, % Pyrexia White blood cell count decreased Anemia Neutrophil count decreased Malaise Platelet count decreased Headache Rash Alopecia Pruritus Decreased appetite Arthralgia Hemoglobin decresaed Myalgia Hematocrit decreased Nasopharyngitis 62 62 53 57 51 43 38 40 30 23 25 13 15 19 59 45 28 CONCERTO-2 Izumi N, J Gastroenterol 2014;49:941-53

CONCERTO-2 Study: SMV + PEG-IFNa-2a + RBV for genotype 1 Summary In treatment-experienced patients with HCV genotype 1 infection who failed to respond to previous IFN-based therapy, re-treatment with 12 weeks of oral SMV QD in combination with PEG-IFN +RBV achieves high SVR rate This study was not able to determine whether there is an additional efficacy benefit by prolonging SMV therapy beyond 12 weeks Limitation: prior partial response versus null-response status to previous IFN-based therapy was not clearly documented SMV was generally well tolerated the incidences of serious adverse events or grade 3/4 rash or anemia were low, as were the rates of treatment discontinuations due to these adverse events CONCERTO-2 Izumi N, J Gastroenterol 2014;49:941-53 5