Study 337-1119: LDV/SOF in genotype 5 Design Open-label W12 ≥ 18 years Chronic HCV infection Genotype 5 HCV RNA ≥ 10,000 IU/ml Treatment-naïve or experienced Compensated cirrhosis allowed Creatinine clearance ≥ 60 ml/min No HBV or HIV co-infection N = 41 LDV/SOF SVR12 Co-formulated ledipasvir-sofosbuvir (LDV 90 mg/SOF 400 mg): 1 pill QD Objective Primary endpoint: SVR12 (HCV RNA < 15 IU/ml), with 2-sided 95% CI 337-1119 Abergel A. Lancet Infect Dis. 2016;16:459-64

Study 337-1119: LDV/SOF in genotype 5 Baseline characteristics, patient disposition and outcome Treatment- naïve N = 21 Treatment-experienced N = 20 Mean age, years 61 64 Female 48% 50% Body mass index < 30 kg/m2 100% 85% HCV RNA log10 IU/ml, mean 6.2 6.6 Cirrhosis 14% 30% IL28B CC genotype 62% Previous HCV treatment response Relapse/breakthrough Non-response Intolerance to IFN - 70% 25% 5% Creatinine clearance (Cockroft-Gault), ml/min, mean 85.4 85.1 Discontinuation, N SVR12 (95% CI) Relapse, N 95% (76-100) 1 95% (75-100) 337-1119 Abergel A. Lancet Infect Dis. 2016;16:459-64

Study 337-1119: LDV/SOF in genotype 5 Adverse events, N (%) N = 41 Any adverse events 33 (80) Serious adverse events 1 (2) : depression Treatment discontinuation due to adverse event Adverse events in ≥ 5% of patients Asthenia 39% Headache 27% Fatigue 10% Upper abdominal pain 7% Arthralgia Diarrhea Dizziness Musculoskeletal pain Myalgia Nasopharyngitis Urinary tract infection Cough 5% 337-1119 Abergel A. Lancet Infect Dis. 2016;16:459-64

Study 337-1119: LDV/SOF in genotype 5 Additional outcome No grade 3 or 4 laboratory abnormalities Emergent laboratory abnormalities: total bilirubin < 1.5 ULN: 10% ; hemoglobin 100-109 g/dl: 2% ; lipase > 1.5-3.0 ULN: 2% ; platelets 100 000 to 125 000/mm3: 2% Successful deep sequencing in 39/41 patients NS5A: 8/39 (21%) had RAVs at baseline (SVR12 in 7/8 patients) Q30R/L (N = 2 ; 2.5% and 3.9% of viral population) L31M/F (N = 4 ; 29.5% to > 99% of viral population) P58S (N = 2 ; 9.9% and 94.6% of viral population) NS5B: 9/39 (23%) had RAVs at baseline (SVR12 in 9/9 patients) N142T (N = 7 ; 1.1% to 19.2% of viral population) M289I (N = 2 ; 7.6% and 98.3% of viral population) 337-1119 Abergel A. Lancet Infect Dis. 2016;16:459-64

Study 337-1119: LDV/SOF in genotype 5 Viral relapse (n = 2) Man, 72-year old, treatment-experienced (partial response), IL28B TT genotype, cirrhosis, HCV RNA 170 000 IU/ml. At baseline: NS5A RAV L31M (> 99% of viral population). HCV RNA < limit of quantification at W1 and undetectable from W2 to the end of treatment. Relapse at post-treatment W4 At relapse NS5A: L31M, no additional RAV NS5B: emergence of S282T (2% viral population) and M289I (16% viral population) Woman, 56-year old, naïve, no cirrhosis, IL28B TT genotype, HCV RNA 180 000 UI/ml. HCV RNA < limit of quantification at W1 and undetectable from W2 to the end of treatment. Relapse at post-treatment W4. Failure to baseline and post-treatment NS5A and NS5B amplification 337-1119 Abergel A. Lancet Infect Dis. 2016;16:459-64

Study 337-1119: LDV/SOF in genotype 5 Summary This prospective, open-label study is the first to assess a regimen consisting of only directly acting antivirals in patients with HCV genotype 5 infection A fixed-dose combination regimen with ledipasvir-sofosbuvir once per day for 12 weeks resulted in SVR12 in 39 (95%) of 41 patients The 2 relapses had the IL28B TT genotype, one was naïve with no cirrhosis, one was treatment-experienced with cirrhosis and NS5A RAV L31M at baseline Overall, the presence of NS5A RAVs and NS5B N142T and M289I had no meaningful effect on the SVR12 for LDV/SOF in genotype 5 No patients discontinued treatment because of an adverse event. Only one serious adverse event, worsening depression, was reported, and was deemed to be unrelated to study treatment 337-1119 Abergel A. Lancet Infect Dis. 2016;16:459-64