Retreatment study: SOF/VEL + RBV in prior NS5A failure - Phase II

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Retreatment study: SOF/VEL + RBV in prior NS5A failure - Phase II Design Open-label W24 > 18 years Failure to SOF/VEL or SOF/VEL + VOX (LEPTON study) Any genotype Compensated cirrhosis allowed No HBV or HIV co-infection N = 69 SOF/VEL + RBV SVR12 SOF/VEL: 400/100 mg FDC QD ; RBV: weight based in twice daily dose (1000 mg/day if < 75 kg, 1200 mg/day if ≥ 75 kg) Objective SVR12 (HCV RNA < 15 IU/mL), by ITT RETREATMENT STUDY Gane EJ, Hepatology 2017 (Epub ahead of print)

Retreatment study: SOF/VEL + RBV in prior NS5A failure - Phase II Baseline characteristics, disposition and outcome SOF/VEL + RBV N = 69 Age, years, mean 57 Female, % 23 White, % 88 HCV RNA, log10 IU/mL, mean 6.4 IL28B CC, % 33 Cirrhosis, % 26 Genotype 1a / 1b / 2 / 3, % 46 / 7 / 20 / 26 Prior SOF/VEL + VOX, % 41 Prior VEL dose : 25 mg / 50 mg, % 41 / 59 Prior treatment duration, 4-6W / 8W /12W, % 36 / 39 / 25 Relapse of prior treatment, % 99 Mean time to retreatment, days 356 Discontinuation, N 3 (adverse event, incarceration, withdrew consent) SVR12 * 63/69 (91% [95% CI : 82-97]) * 4 patients excluded from analysis (still in follow-up) RETREATMENT STUDY Gane EJ, Hepatology 2017 (Epub ahead of print)

Retreatment study: SOF/VEL + RBV in prior NS5A failure - Phase II SVR12 by genotype, and by baseline RASs Genotype 3 20 40 60 80 100 97 37 93 78 14 18 % N= Genotype 2 Genotype 1 SVR12 in cirrhosis : 78% vs 96% if no cirrhosis Failures Genotype 1: 1 on-treatment virological failure after discontinuation for AE Genotype 2: 1 post-treatment relapse after discontinuation at W8 (pre-treatment with SOF/VEL) Genotype 3: 1 non-response ((pre-treatment with SOF/VEL), 2 relapses (pre-treatment with SOF/VEL in 1, SOF/VEL + RBV in 1) , 1 withdrew consent N SVR12 No RASs 32 97% 5 100% 4 RASs 5 (14%) 9 (64%) 89% 13 (76%) 77% RETREATMENT STUDY Gane EJ, Hepatology 2017 (Epub ahead of print)

Retreatment study: SOF/VEL + RBV in prior NS5A failure - Phase II Adverse events and laboratory abnormalities, % SOF/VEL + RBV Any adverse event 88 Grade 3 adverse event 4 Serious adverse event 1 Discontinuation for adverse event 1 (N = 1, irritability) Death Adverse events in ≥ 10% of patients Fatigue 32 Nausea 22 Headache 17 Insomnia 16 Rash Pruritus 14 Irritability 13 Upper respiratory tract infection Grade 3 laboratory abnormalities Grade 4 laboratory abnormalities Hemoglobin < 10 g/dL 6 RETREATMENT STUDY Gane EJ, Hepatology 2017 (Epub ahead of print)

Retreatment study: SOF/VEL + RBV in prior NS5A failure - Phase II Summary SOF/VEL + RBV for 24 weeks resulted in high SVR12 rates in patients with genotype 1 or 2 who had failed prior SOF/VEL-containing regimens Genotype 1: no impact of RASs on SVR12 Genotype 3: SVR12 of 100% in patients without NS5A RASs, but low SVR12 among those with NS5A RASs Good tolerability RETREATMENT STUDY Gane EJ, Hepatology 2017 (Epub ahead of print)