Asselah T. AASLD 2015, Abs. 1179 OSIRIS  Design SMV + PEG-IFN + RBV Open label Chronic HCV infection Genotype 4 Treatment-naïve Mild to moderate fibrosis.

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Asselah T. AASLD 2015, Abs OSIRIS  Design SMV + PEG-IFN + RBV Open label Chronic HCV infection Genotype 4 Treatment-naïve Mild to moderate fibrosis No HBV or HIV co-infection OSIRIS Study: SMV + PEG-IFN + RBV in genotype 4 W24 SVR 12 –SMV 150 mg qd –PEG-IFN  -2a 180  g once weekly ; RBV: dose adjusted to body weight  Objective –SVR 12 (HCV RNA < 15 IU/ml) PEG-IFN + RBV W12 12 weeks of treatment if IL28B CC: HCV RNA < 25 IU/ml at W2 (undetectable or not) + HCV RNA undetectable at W4 and W8 IL28B CT or TT: HCV RNA undetectable at W2, W4 and W8 12 weeks of treatment if IL28B CC: HCV RNA < 25 IU/ml at W2 (undetectable or not) + HCV RNA undetectable at W4 and W8 IL28B CT or TT: HCV RNA undetectable at W2, W4 and W8

12 weeks N = weeks N = 33 Median age, years48 Female32%30% Race : white / black77% / 10%83% / 14% IL28B CC genotype41%3% Genotype subtype 4a 4d 4 other 41% 38% 21% 39% 36% 24% HCV RNA, log 10 IU/ml, median Metavir score F0-F1 F2 F3 85% 15% 0 76% 21% 3% Discontinued therapy SMV (adverse event / virologic endpoint) PEG-IFN + RBV (adverse event / virologic endpoint) 09 (27%) 5 (3 / 2) 9 (4 / 2) Baseline characteristics Asselah T. AASLD 2015, Abs OSIRIS OSIRIS Study: SMV + PEG-IFN + RBV in genotype 4

SVR 12 by baseline characteristics in the 12W group MaleFemale4a4d4/other SexHCV subtype Fibrosis stage Baseline HCV RNA (IU/ml) RegionIL28B genotype F0–F1F3≤ 800K> 800KCCCTTTEuropeMiddle East/ Africa All Asselah T. AASLD 2015, Abs OSIRIS OSIRIS Study: SMV + PEG-IFN + RBV in genotype 4 %

SVR 12 by baseline characteristics in the 24W group MaleFemale4a4d4/other SexHCV subtype Fibrosis stage Baseline HCV RNA (IU/ml) Region IL28B genotype F0–F1F3≤ 800K> 800KCCCTTTEuropeMiddle East/ Africa All 33 Asselah T. AASLD 2015, Abs OSIRIS OSIRIS Study: SMV + PEG-IFN + RBV in genotype 4 %

12 weeks N = weeks N = 33 Serious adverse event06% Adverse event possibly related to SMV29%45% Adverse event leading to discontinuation of all study drugs09% Grade 3-4 adverse events18%42% Adverse events in ≥ 20% in either group Pruritus Neutropenia Asthenia Fatigue Decreased appetite Influenza-like illness Headache 26% 15% 18% 9% 15% 21% 27% 24% 27% 21% Adverse events  2 serious adverse events, not related to SMV: acute sinusitis (N = 1) and phlebitis (N = 1)  3 grade 3/4 adverse events were considered related to SMV (all grade 3, all in W24 group): asthenia (N = 2) and increased serum bilirubin (N = 1) Asselah T. AASLD 2015, Abs OSIRIS OSIRIS Study: SMV + PEG-IFN + RBV in genotype 4

 Summary –Overall, 51% of patients with genotype 4 met the eligibility criteria for shortening treatment duration (W2 virologic response), and were assigned to receive 12 weeks of SMV + PEG-IFN + RBV SVR 12 was 97% (33/34) in this sub-group Genotype 4 subtype, sex, geographical region, and race did not appear to affect eligibility –SVR 12 was 82% in patients assigned to receive 24 weeks of SMV + PEG-IFN + RBV –The safety profile of SMV in patients with genotype 4 is comparable to previous data in patients with genotype 1 Asselah T. AASLD 2015, Abs OSIRIS OSIRIS Study: SMV + PEG-IFN + RBV in genotype 4