C-SALT Study: grazoprevir + elbasvir in genotype 1 with Child-Pugh B cirrhosis Jacobson IM. EASL 2015, Abs. O008  Design Child-Pugh B GZR 100 mg + EBR.

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C-SALT Study: grazoprevir + elbasvir in genotype 1 with Child-Pugh B cirrhosis Jacobson IM. EASL 2015, Abs. O008  Design Child-Pugh B GZR 100 mg + EBR 50 mg GZR 50 mg + EBR 50 mg Non-cirrhotic W12 Open-label SVR 12 N = 30 N = 10 ≥ 18 years Chronic HCV infection Genotype 1 Naïve or pre-treated with IFN-based regimen Child-Pugh B cirrhosis No HBV or HIV co-infection No-cirrhosis (PK intensive study)  Objective –Primary endpoint : SVR 12 (HCV RNA < 15 IU/ml), by ITT analysis C-SALT

Child Pugh-B N = 30 Non-cirrhotic (PK arm) N = 10 Mean age, years Female43.3%50% White96.7%90% Genotype 1a 1b 90% 10% 60% 40% Prior treatment status Naive Null response Partial response Relapse 63.3% 20% 0% 16.7% 60% 20% 10% 10% Child-Pugh score % 23.3% 6.7% MELD score, (mean ± SD)9.9 ± ± 1.0 C-SALT Study: grazoprevir + elbasvir in genotype 1 with Child-Pugh B cirrhosis Baseline characteristics Jacobson IM. EASL 2015, Abs. O008 C-SALT

Virologic failure2 (6.7%)0 Breakthrough00 Rebound00 Relapse ( ) 3010 Child-Pugh BNon-cirrhotic 100 ( ) C-SALT Study: grazoprevir + elbasvir in genotype 1 with Child-Pugh B cirrhosis SVR 12 (HCV RNA < 15 IU/ml), % (95% CI) % Child-Pugh B sub-groups Genotype 1a Genotype 1b Baseline HCV RNA (IU/ml) ≤ 1 M> 1 M Jacobson IM. EASL 2015, Abs. O008 C-SALT

*Relapse patients (N = 2) * * C-SALT Study: grazoprevir + elbasvir in genotype 1 with Child-Pugh B cirrhosis Child-Pugh score change from baseline to follow-up W12 § N = 18 N = 4N = 7 § 1 died at follow-up W4 Jacobson IM. EASL 2015, Abs. O008 C-SALT

GMR (90% CI) Child-Pugh B / Non-cirrhotic Grazoprevir C 2hr C 24hr AUC (0.53, 2.11) 1.71 (0.87, 3.33) 1.25 (0.70, 2.24) Elbasvir C 2hr C 24hr AUC (0.64, 1.33) 1.04 (0.67, 1.60) 0.90 (0.63, 1.60)  GZR exposure was slightly higher (not significant) in patients with Child-Pugh B cirrhosis receiving 50 mg dose compared to non-cirrhotic patients receiving 100 mg dose  EBR (50 mg) PK was similar in both patient populations C-SALT Study: grazoprevir + elbasvir in genotype 1 with Child-Pugh B cirrhosis Pharmacokinetics  Plasma samples collected over 24 hours at treatment W4 PK group (non-cirrhotic, N = 9) with GZR 100 mg Child-Pugh B (N = 9) with GZR 50 mg Jacobson IM. EASL 2015, Abs. O008 C-SALT

Child-Pugh B N = 30 Non cirrhotic (PK) N = 10 Discontinuation due to an AE, N (%)00 Serious adverse event, N (%)4 (13.3%)*0 Adverse events, N (%) Fatigue Arthralgia Nausea Pyrexia Headache 30% 16.7% 10% 30% 20% 20% 0 50% Grade 3-4 ALT/AST elevation, N (%)00 Grade 3-4 bilirubin elevation, N (%)4 (13.3)0 Death **, N (%)1 (3.3)0 C-SALT Study: grazoprevir + elbasvir in genotype 1 with Child-Pugh B cirrhosis Adverse events, N (%) * All unrelated to study treatment : hepatocellular carcinoma, N = 1; ascites and encephalopathy, N = 1 ; bacterial peritonitis, cerebral infarction and hepatic failure (**death at follow-up W4) N = 1 ; hematemesis, N = 1 Jacobson IM. EASL 2015, Abs. O008 C-SALT

C-SALT Study: grazoprevir + elbasvir in genotype 1 with Child-Pugh B cirrhosis  Summary –High rates of virologic response were observed in Child-Pugh B patients receiving a combination of once-daily GZR 50 mg + EBR 50 mg –The regimen was well tolerated with no evidence of hepatotoxicity –Plasma GZR exposure was slightly higher in Child-Pugh B patients receiving 50 mg compared to non-cirrhotic patients receiving 100 mg –EBR exposure was similar in both Child-Pugh B and non-cirrhotic groups –This regimen was highly effective and well-tolerated in a traditionally hard-to-treat patient group with no currently approved treatment options Jacobson IM. EASL 2015, Abs. O008 C-SALT