1. Reddy KR. Lancet Infect Dis. 2015;15:27-35 ATTAIN SMV + TVR placebo + PEG-IFN + RBV TVR + SMV placebo + PEG-IFN + RBV Randomisation* 1 : 1 Double-blind ≥ 18 years HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Null or partial responders to previous PEG-IFN + RBV Compensated cirrhosis allowed No HBV or HIV co-infection ATTAIN Study: simeprevir versus telaprevir, with PEG-IFN + RBV in previous non responders with genotype 1  Design N = 384 N = 379 W12W48 * Randomisation was stratified on genotype (1a or 1b) and previous response to PEG-IFN + RBV (partial or null) PEG-IFN + RBV  Treatment regimens –SMV : 150 mg qd, or placebo ; TVR : 750 mg tid, 7-9h apart, or placebo –PEG-IFN  -2a : 180  g SC once weekly –RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg)  Primary efficacy endpoint –Non inferiority of SMV : SVR 12 (HCV RNA < 25 IU/ml) by intention to treat (lower margin of the 2-sided 95% CI for the difference with TVR = 12%)

2. SMV N = 379 TVR N = 384 Median age, years5052 Female36%42% Genotype 1a (Q80K present /Q80K absent) 1b Other 43% (23% / 77%) 57% < 1% 42% (17% / 83%) 57% 1% IL28B CC genotype 4%5% HCV RNA log 10 IU/ml, median6.566.57 Metavir fibrosis score F0-F2 / F3-F456% / 44%55% / 45% Prior treatment with PEG-IFN + RBV Null response62% Partial response38% Discontinued treatment, n Adverse event Lost to follow-up Withdrawal 21 0 10 11 29 4 6 19 Baseline characteristics and patient disposition Reddy KR. Lancet Infect Dis. 2015;15:27-35 ATTAIN ATTAIN Study: simeprevir versus telaprevir, with PEG-IFN + RBV in previous non responders with genotype 1

3. SVR 12 (HCV RNA < 25 IU/ml) difference : - 1.1% (95% CI : -7.8 to 5.5) SMVTVR On treatment failure34%20% Viral breaktrough22%20% Relapse17% Reddy KR. Lancet Infect Dis. 2015;15:27-35 ATTAIN ATTAIN Study: simeprevir versus telaprevir, with PEG-IFN + RBV in previous non responders with genotype 1 % SMV TVR N3791453842342201461333727215220 54 44 70 44 27 64 34 55 46 68 40 26 67 39 0 20 40 60 80 100 AllPrevious null response Previous partial response 1a Q80K-1a Q80K+1bCirrhosis 238124215

4. NS3 Sequencing SMVTVR Sequencing available148/176 failures134/176 failures Emerging mutations142/148111/134 Main mutations detected (positions) 80 122 155 168 36 54 155 156 Reddy KR. Lancet Infect Dis. 2015;15:27-35 ATTAIN ATTAIN Study: simeprevir versus telaprevir, with PEG-IFN + RBV in previous non responders with genotype 1

5. SMV, N = 379TVR, N = 384 AE leading to treatment discontinuation12 (3%)39 (10%) Grade 3 adverse event72 (19%)84 (22%) Grade 4 adverse event14 (4%)21 (5%) Serious adverse event8 (2%)33 (9%) Adverse event of interest Rash (any type)81 (21%)119 (31%) Pruritus122 (32%)170 (44%) Photosensitivity8 (2%)1 (< 1%) Neutropenia69 (18%)52 (14%) Anemia51 (13%)144 (38%) Dyspnea27 (7%)36 (9%) Increased bilirubin30 (8%)28 (7%) Additional AE in ≥ 20% of patients in either group Fatigue120 (32%)146 (38%) Pyrexia81 (21%)94 (24%) Headache95 (25%)111 (29%) Nausea64 (17%)109 (28%) Adverse events, N (%) Reddy KR. Lancet Infect Dis. 2015;15:27-35 ATTAIN ATTAIN Study: simeprevir versus telaprevir, with PEG-IFN + RBV in previous non responders with genotype 1

6.  Summary –SMV + PEG-IFN + RBV showed non-inferiority with regard to SVR 12 to TVR + PEG-IFN + RBV in patients with chronic HCV genotype 1 infection and compensated liver disease who were null or partial responders to previous treatment with PEG-IFN + RBV Non-inferiority was met for null or partial responders separately as well Rates of on-treatment failure, viral breakthrough, and relapse were similar between the two treatment groups –The incidence of adverse events deemed at least possibly related to SMV or TVR was noticeably lower in the SMV group, and most adverse events were grade 1 or 2 –Serious adverse events were infrequent and less common in the SMV group, and fewer patients needed to discontinue SMV compared with TVR because of an adverse event Reddy KR. Lancet Infect Dis. 2015;15:27-35 ATTAIN