1. GS-9674 in NASH: a phase 2 study
Design
Randomization
2:2:1
Stratification by diabetes
GS mg PO QD (N = 56)
MRI-PDFF
GS mg PO QD (N = 56)
Placebo PO QD (N = 26)
Week 0
W12
W24
MRE
Serum markers
FibroScan
MRI-PDFF ≥ 8 % and MRE ≥ 2.5 kPa or
biopsy with NASH F1-F3
No cirrhosis (FibroTestTM < 0.75,
historical imaging and liver biopsy)
GS-9674: non-steroidal FXR agonist
Endpoints
Safety (adverse events and laboratory abnormalities)
MRI-PDFF (magnetic resonance imaging proton density fat fraction)
MRE (magnetic resonance elastometry), Fibroscan® (Echosens, Paris, France), liver biochemistry, serum markers of fibrosis (ELFTM, FibrotestTM)
GS-9674-phase 2
Patel K, AASLD 2018, Abs. 736 1

2. GS-9674 in NASH: a phase 2 study
Median changes from baseline at W24 in serum C4 and plasma bile acids, % (IQR) 80
-40
-80 40
120
p = 0.01
p = 0.14
p = 0.03
p = 0.93 C4
Total BA
Primary BA
Secondary BA
0.5
4.0
-38.5
-5.1
-36.4
-23.9
-35.5
-16.0
2.2
7.1
-38.3
-37.7
Placebo
GS mg
GS mg %
*All biomarkers assessed in patients fasted, predose; FGF19 levels were similar in fasting, predose time point among groups; p-values for comparison of GS mg vs placebo by Wilcoxon rank-sum test.
GS-9674-phase 2
Patel K, AASLD 2018, Abs. 736 2

3. Median change from baseline in liver fat by MRI-PDFF
GS-9674 in NASH: a phase 2 study
Median change from baseline in liver fat by MRI-PDFF
Relative Change*
Patients with > 30 % reduction†
-20
-30
-10
W12
W24
1.9
-1.8
-7.9
-15.0
-22.7
p = 0.01
p = 0.17
p = 0.003
p = 0.18 % 60 40 20
W12
W24
38.9
14.0
12.5
19.2
30.9
p = 0.01
p = 0.87
p < 0.001 %
Placebo
GS mg
GS mg
*p-values by Wilcoxon rank-sum test; †p-values by Mantel-Haenszel test adjusted for baseline diabetes status.
GS-9674-phase 2
Patel K, AASLD 2018, Abs. 736 3

4. GS-9674 in NASH: a phase 2 study
Median (IQR) % change from baseline at week 24 in liver biochemistry 40
-20
-60 20
-40
ALT
AST
GGT
ALP
-19
-18
Placebo
GS mg
GS mg -6
p = 0.11
p = 0.48
p < 0.001 -9
-15 -5
-37 -4 5 18
*p-values are for comparison of GS mg vs placebo by Wilcoxon rank-sum test
GS-9674-phase 2
Patel K, AASLD 2018, Abs. 736 4

5. GS-9674 in NASH: a phase 2 study
Summary
Significant improvements in hepatic steatosis and liver biochemistry and reductions in serum bile acids in patients with NASH
GS-9674 was well tolerated:
Changes in serum lipids and glycemic parameters were not observed
Grade ≥ 2 pruritus was more common in patients treated with GS mg but only one patient discontinued treatment due to pruritus
Phase 2 ATLAS study ongoing in patients with F3-F4 fibrosis due to NASH
GS-9674-phase 2
Patel K, AASLD 2018, Abs. 736 5