1. VK2809 in NAFLD: a phase 2 study
Design
Placebo (N = 15)
Follow-up
NAFLD patients with LDL-C > 110 mg/dL
Liver fat content > 8% (MRI-PDFF)
Randomization
10 mg VK2809 QOD (N = 16)
10 mg VK2809 QD (N = 16)
Double-Blind Treatment
Screening MRI-PDFF D1 W1 W4 W6 W8
W12 MRI-PDFF
W16 MRI-PDFF
VK2809: selected liver-targeted thyroid receptor β agonist
Endpoints
Primary: change in LDL-cholesterol vs placebo
Secondary: change in liver fat by MRI-PDFF
Exploratory: changes in atherogenic lipoproteins
VK2809-phase 2
Loomba R, AASLD 2018, Abs. LB4 1

2. VK2809 in NAFLD: a phase 2 study
Baseline characteristics
Placebo N = 15
VK2809
10 mg QOD
N = 16
10 mg QD
All VK2809 patients N = 32
Mean age, years
50.5
53.8
49.8
51.8
Female : Male
60 : 40
63 : 37
50 : 50
58 : 42
White
73%
81%
100%
91%
Mean BMI (kg/m²) 30 32 34 33
Mean ALT (IU/L) 39 38 50 44
Mean AST (IU/L) 31
Mean Alkaline Phosphatase (IU/L) 87 90 82 86
Mean MRI-PDFF
13,4%
17,1%
18,1%
17,8%
Mean LDL-C (mg/dL)
143
150
140
145
Mean triglycerides (mg/dL)
173
189
211
200
Mean fasting glucose (mg/dL) 98
100 91 96
Mean HbA1c (%)
5,6
5,8
5,7
Mean Systolic BP (mmHg)
127
125
126
Mean Diastolic BP (mmHg) 80 79
VK2809-phase 2
Loomba R, AASLD 2018, Abs. LB4 2

3. VK2809 in NAFLD: a phase 2 study
Placebo-Adjusted % Change in LDL-C at W12
VK mg QD
(N = 16)
All VK2809 treated
(N = 31) -5
-10
-15
-20
-25
-30
-35
Baseline (mg/dl)
150.3
140.4
145.2
VK mg QOD
(N = 15)
% Change
P-value
-23.6%
-20.2%
-21.8%
VK2809-phase 2
Loomba R, AASLD 2018, Abs. LB4 3

4. VK2809 in NAFLD: a phase 2 study
Relative change in MRI-PDFF
liver fat content at W12, %
Absolute change in MRI-PDFF
liver fat content at W12, %
VK mg QD
(N = 11)
All VK2809 treated
(N = 24)
-10
-20
-30
-40
-50
-60
17.1%
18.1%
17.8%
VK mg QOD
(N = 13)
% change
p vs placebo
-56.5%
-59.7%
-58.1%
13.4%
Placebo
-8.9%
VK mg QD
(N = 11)
All VK2809 treated
(N = 24) -2 -4 -6 -8
-10
17.1%
18.1%
17.8%
VK mg QOD
(N = 13)
% change (SD) p vs placebo
-8.9% (6.2) 0.011
-10.6% (5.2)
-9.7% (5.7)
13.4%
Placebo
-0.9% (2.8)
Baseline LFC
66.7% of patients treated with VK2809 experienced a > 50% decrease in liver fat content vs 18.2% in placebo-treated patients
VK2809-phase 2
Loomba R, AASLD 2018, Abs. LB4 4

5. VK2809 in NAFLD: a phase 2 study
Change in Lipoprotein(a) at W12, %
Change in Apolipoprotein B at W12, %
VK mg QD
All VK2809 treated
-10
-20
-30
-40
14.9%
20.4%
17.7%
VK mg QOD
Change
p value
-36.8% 0.097
-24.6% 0.049
-30.4% 0.039
15.5%
Placebo
4.7%
VK mg QD
All VK2809 treated
-10
-20
-30
112.0%
108.5%
110.2%
VK mg QOD
Change
p value
-23.7%
-17.4% 0.020
-20.4%
107.3%
Placebo
0.4%
VK2809-phase 2
Loomba R, AASLD 2018, Abs. LB4 5

6. VK2809 in NAFLD: a phase 2 study
Summary of adverse events
Placebo N = 15
VK2809
10 mg QOD
N = 16
10 mg QD
Number of reported adverse events 36 21 31
Number (%) of subjects with at least one reported
Treatment-emergent AE (TEAE)
9 (60)
11 (69)
10 (62)
Serious TEAEs
0 (0)
Drug-related serious TEAE
Good tolerability and safety
No serious adverse events observed in any arm
No dose-related trends in AEs
Excellent gastro-intestinal tolerability
VK2809-phase 2
Loomba R, AASLD 2018, Abs. LB4 6

7. VK2809 in NAFLD: a phase 2 study
Summary
VK2809 produced robust reduction in liver fat on MRI-PDFF in NAFLD patients after 12 weeks of oral dosing
Up to 91% of patients dosed with VK2809 experienced a response as demonstrated by liver fat reductions ≥ 30% relative to baseline ; 67% experienced liver fat reductions ≥ 50%
VK2809 produced significant reduction in LDL-C, triglycerides, Apo B, and Lp(a) relative to placebo in NAFLD patients
VK2809 was safe and well-tolerated
VK2809-phase 2
Loomba R, AASLD 2018, Abs. LB4 7