1. SOF/VEL + GS-9857 in genotypes 1-6 Phase II
Design W6 W8
No randomisation
Open-label
SOF/VEL + GS-9857
SVR12
> 18 years Chronic HCV infection
Genotype 1 to 6
Naïve
Compensated cirrhosis
allowed No HBV or HIV co-infection
Genotype 1-6
N = 166
SOF/VEL + GS-9857
SVR12
Genotype 1, cirrhosis
SOF/VEL + GS RBV
SVR12
N = 31
SOF/VEL: 400/100 mg qd
GS-9857: 100 mg qd
Objective
SVR12 (HCV RNA < 15 IU/ml), by ITT
SOF/VEL + GS-9857 naïve - Phase II
Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758

2. SOF/VEL + GS-9857 in genotypes 1-6 Phase II
Baseline characteristics and patient disposition
SOF/VEL + GS-9857
6 weeks
N = 67
8 weeks
N = 99
SOF/VEL + GS RBV
N = 31
Age, years, mean 53 55 59
Female
48%
38%
39%
White
87%
82%
84%
HCV RNA, log10 IU/ml, mean
6.2
6.1
6.3
IL28B CC
34%
27%
Cirrhosis
64%
100%
Genotype :
1 / 2 / 3 /
4 / 5 / 6
52% / 9 % / 31% /
7% / 0 / 0
70% / 6% / 18%
5% / 0 / 1%
100% / 0 / 0
0 / 0 / 0
Discontinuation due to adverse event 2 1
SOF/VEL + GS-9857 naïve - Phase II
Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758

3. SOF/VEL + GS-9857 in genotypes 1-6 Phase II
SVR12 by genotype, and by cirrhosis
SOF/VEL + GS W
SOF/VEL + GS W
SOF/VEL + GS RBV 8W %
100
100 96 94 81 79 81 80 71 60 40 20 N= 67 99 31 35 36 33 31
Genotype 1-6
Genotype 1
No cirrhosis
Genotype 1
Cirrhosis
Genotype 1
SOF/VEL + GS-9857 naïve - Phase II
Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758

4. SOF/VEL + GS-9857 in genotypes 1-6 Phase II
SVR12 in genotype 2, 3, 4, 6 by genotype and cirrhosis
SOF/VEL + GS W
SOF/VEL + GS W %
100
100 93 94
100 88 83 80 67 60 60 40 20 N= 67 99 31 15 15 16 4 4
Overall
Genotype 2
Genotype 3
Genotype 4
Overall
Genotype 2
Genotype 3
Genotype 4, 6
SOF/VEL + GS W
No cirrhosis
SOF/VEL + GS W
Cirrhosis
SOF/VEL + GS-9857 naïve - Phase II
Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758

5. SOF/VEL + GS-9857 in genotypes 1-6 Phase II
SVR12 according to presence of baseline RAVs
(deep sequencing with 15% threshold)
SOF/VEL + GS W
SOF/VEL + GS W
SOF/VEL + GS RBV 8W
Baseline RAVs
No : 53%
32/39 (82%)
49/51 (96%)
12/14 (86%)
Yes : 47%
21/28 (75%)
46/48 (96%)
13/17 (77%)
RAVs at virologic failure (sequencing in 23/24 relapses)
No treatment-emergent RAVs
SOF/VEL + GS-9857 naïve - Phase II
Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758

6. SOF/VEL + GS-9857 in genotypes 1-6 Phase II
Adverse events and laboratory abnormalities %
SOF/VEL + GS W
SOF/VEL + GS W
SOF/VEL + GS RBV 8W
Any adverse event
66%
69%
81%
Grade 3-4 adverse event 1% 2%
Serious adverse event
Discontinuation for adverse event * 3%
Adverse events in ≥ 10% of patients
Headache
31%
17%
26%
Nausea
16%
20%
29%
Fatigue
11%
DIarrhea
21% 9%
10%
Anemia
19%
Grade 3-4 laboratory abnormalities 4%
35%
* ALT/AST elevations (N = 1) at W2, which returned to baseline values after stopping treatment ;
diarrhea, nausea and vomiting (N = 1) ; fatigue (N = 1)
SOF/VEL + GS-9857 naïve - Phase II
Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758

7. SOF/VEL + GS-9857 in genotypes 1-6 Phase II
Summary
SOF/VEL + GS-9857 once daily for 8 weeks was highly effective in treatment-naïve, genotype 1-6 patients with and without cirrhosis
Overall SVR12 was 96%
In genotype 1, SVR12 was 100% if no cirrhosis, 94% if cirrhosis
In genotype 2-6, SVR12 was 88% if no cirrhosis, 93% if cirrhosis
Addition of RBV did not improve SVR12 in genotype 1 patients treated for 8 weeks, actually even lower
6 week treatment was associated with high relapse rate
Presence of baseline RAVs had no impact on SVR12 rate in patients with genotype 1 treated for 8 weeks
Treatment was generally well tolerated
SOF/VEL + GS-9857 naïve - Phase II
Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758