1. ARV-trial.com
SURVEYOR-II study – Part 3: glecaprevir/pibrentasvir + RBV in genotype 3 with treatment experience and/or cirrhosis
Design
Randomisation
Open-label
W12
W16
N = 22
GLE/PIB
≥ 18 years
HCV genotype 3
HCV RNA > 1000 IU/mL
Naïve or treatment-experienced with IFN/PEG-IFN + RBV or SOF + RBV + PEG-IFN
Compensated cirrhosis allowed
No HBV or HIV co-infection
Treatment-experienced
with no cirrhosis
N = 22
GLE/PIB
No randomisation
Open-label
Naive
N = 40
GLE/PIB
Cirrhosis
GLE/PIB
Experienced
N = 47
GLE/PIB: 100/40 mg 3 tablets QD
Objective
SVR12 (HCV RNA < 25 IU/mL), no formal statistical hypothesis
SURVEYOR-II – Part 3
Wyles D. Hepatology 2017 (epub ahead of print) 1

2. Baseline characteristics
ARV-trial.com
SURVEYOR-II study – Part 3: glecaprevir/pibrentasvir + RBV in genotype 3 with treatment experience and/or cirrhosis
Baseline characteristics
No cirrhosis, treatment-experienced
Randomisation 1 : 1
Cirrhosis
No randomisation
GLE/PIB
12 weeks
N = 22
16 weeks
Naïve
N = 40
Treatment-experienced
N = 47
Median age, years 56 59
Female, % 36 40 23
Race : white, % 77 91 93 89
Mean BMI, kg/m2 26 28 29 27
Median HCV RNA, log10 IU/mL
6.6
6.1
6.2
6.5
Fibrosis stage :
F0-F1 / F2 / F3 / F4, %
50 / 18 / 32 / 0
68 / 9 / 23 / 0
0 / 0 / 0 / 100
Treatment-experienced, %
IFN/PEG-IFN + RBV
SOF + RBV + PEG-IFN
100
64 36 41 47 53
SURVEYOR-II – Part 3
Wyles D. Hepatology 2017 (epub ahead of print) 2

3. Treatment-experienced Treatment-experienced Treatment-experienced
SURVEYOR-II study – Part 3: glecaprevir/pibrentasvir + RBV in genotype 3 with treatment experience and/or cirrhosis
SVR12 % 98
100 95 96 91 80 60 40
1:1 randomized 20 22 22 40 47 N=
12 weeks
No cirrhosis
Treatment-experienced
16 weeks
No cirrhosis
Treatment-experienced
12 weeks
Cirrhosis
Treatment-naive
16 weeks
Cirrhosis
Treatment-experienced
Breakthrough
Relapse
Lost to follow-up 2 1 1 1
SURVEYOR-II – Part 3
Wyles D. Hepatology 2017 (epub ahead of print)

4. SURVEYOR-II study – Part 3: glecaprevir/pibrentasvir + RBV in genotype 3 with treatment experience and/or cirrhosis
Virologic failures 1 2 3 4 5
Type of failure
Relapse
Breakthrough
GLE/PIB duration
12W
16W
Treatment-experienced
Yes
Fibrosis stage F2
F0-F1 F4
Compensated cirrhosis No
Baseline HCV RNA, IU/mL
8.1 M
15.7 M
18.9 M
2.8 M
17.4 M
Treatment compliance NA
NS3 RAVs *
at baseline
at failure
None
Y56H + Q168R
A166S
A156G + A166S
NS5A RAVs *
Y93H
A30K
A30K + Y93H
L31F + Y93H
* RAVs detected by next-generation sequencing at 15% threshold:
NS3 : 36, 43, 54, 55, 56, 80, 155, 156, 166, and 168
NS5A : 24, 28, 29, 30, 31, 32, 58, 92, and 93
SURVEYOR-II – Part 3
Wyles D. Hepatology 2017 (epub ahead of print)

5. Adverse events and laboratory abnormalities
ARV-trial.com
SURVEYOR-II study – Part 3: glecaprevir/pibrentasvir + RBV in genotype 3 with treatment experience and/or cirrhosis
Adverse events and laboratory abnormalities
No cirrhosis,
treatment-experienced
Randomisation 1 : 1
Cirrhosis
No randomisation
GLE/PIB
12 weeks
N = 22
16 weeks
Naïve
N = 40
Treatment-experienced
N = 47
Serious adverse event, N * 1 3
AE leading to discontinuation, N
Adverse event in ≥ 10% of patients, %
Fatigue
Headache
18 23 18 13 25 34
Laboratory abnormalities, N
AST grade 3 (> 5 x ULN)
Total bilirubin grade 3 (> 3 x ULN) 2
0 0
* Umbilical hernia, colon cancer, pleural effusion, squamous cell carcinoma of the skin, schizophrenia, angina pectoris
SURVEYOR-II – Part 3
Wyles D. Hepatology 2017 (epub ahead of print) 5

6. ARV-trial.com
SURVEYOR-II study – Part 3: glecaprevir/pibrentasvir + RBV in genotype 3 with treatment experience and/or cirrhosis
Summary
High efficacy with GLE/PIB in patients with HCV genotype 3 infection with compensated cirrhosis and/or prior treatment experience
SVR12 rates of 98% and 96% in treatment-naïve and treatment- experienced patients with cirrhosis following 12 and 16 weeks of the QD combination, respectively
SVR12 rate of 96% in treatment-experienced patients without cirrhosis following 16 weeks of treatment, or 91% after 12 weeks
GLE/PIB was well tolerated
with mostly mild adverse events
no drug related-related serious adverse event
few occurrences of grade 3 or higher laboratory abnormalities
and no study drug discontinuation
SURVEYOR-II – Part 3
Wyles D. Hepatology 2017 (epub ahead of print) 6