VK2809 in NAFLD: a phase 2 study

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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

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

VK2809 in NAFLD: a phase 2 study Placebo-Adjusted % Change in LDL-C at W12 VK2809 10 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 VK2809 10 mg QOD (N = 15) % Change P-value -23.6% 0.0121 -20.2% 0.0269 -21.8% 0.0061 VK2809-phase 2 Loomba R, AASLD 2018, Abs. LB4 3

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, % VK2809 10 mg QD (N = 11) All VK2809 treated (N = 24) -10 -20 -30 -40 -50 -60 17.1% 18.1% 17.8% VK2809 10 mg QOD (N = 13) % change p vs placebo -56.5% 0.0014 -59.7% 0.0003 -58.1% 0.0002 13.4% Placebo -8.9% VK2809 10 mg QD (N = 11) All VK2809 treated (N = 24) -2 -4 -6 -8 -10 17.1% 18.1% 17.8% VK2809 10 mg QOD (N = 13) % change (SD) p vs placebo -8.9% (6.2) 0.011 -10.6% (5.2) 0.0025 -9.7% (5.7) 0.0019 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

VK2809 in NAFLD: a phase 2 study Change in Lipoprotein(a) at W12, % Change in Apolipoprotein B at W12, % VK2809 10 mg QD All VK2809 treated -10 -20 -30 -40 14.9% 20.4% 17.7% VK2809 10 mg QOD Change p value -36.8% 0.097 -24.6% 0.049 -30.4% 0.039 15.5% Placebo 4.7% VK2809 10 mg QD All VK2809 treated -10 -20 -30 112.0% 108.5% 110.2% VK2809 10 mg QOD Change p value -23.7% 0.0021 -17.4% 0.020 -20.4% 0.0021 107.3% Placebo 0.4% VK2809-phase 2 Loomba R, AASLD 2018, Abs. LB4 5

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

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