Corporate Presentation

December 2020

Forward-Looking Statements

This presentation contains statements about our future expectations, plans and prospects that constitute forward-looking

statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Actual results

may differ materially from those indicated by these forward-looking statements as a result of various important factors,

including risks relating to: both our and our collaborators’ ability to successfully research, obtain regulatory approvals for,

develop and commercialize products based upon our technologies; our ability to obtain and maintain proprietary protection

for our technologies and product candidates; our reliance on third parties to manufacture our preclinical and clinical drug

supplies; competitive pressures; our ability to obtain and maintain strategic collaborations; compliance with our in-license

agreements; our ability to successfully execute on, and receive favorable results from, our proprietary drug development

efforts; market acceptance of our drug candidates; retaining members of our senior management; and our ability to raise

additional funds to finance our operations.

The forward-looking statements included in this presentation represent our views as of the date of this presentation. We

anticipate that subsequent events and developments will cause our views to change. While we may elect to update these

forward-looking statements in the future, we specifically disclaim any obligation to do so. These forward-looking statements

should not be relied upon as representing our views as of any date subsequent to the date of this presentation.

For more information regarding risks and uncertainties that could affect the results of our operations or financial condition

review our filings with the Securities and Exchange Commission (in particular, our most recent Annual Report on Form 10-K

and any subsequently filed Quarterly Reports on Form 10-Q).

2

Investment Highlights

● Focused on novel therapeutics for metabolic and endocrine diseases

o Clinical programs demonstrate best-in-class efficacy data

● Metabolic Disease Program: VK2809 for NASH

o Novel, selective thyroid receptor-β (TRβ) agonist

o Phase 2a results demonstrate significant reduction in liver fat content and lipids

o Phase 2b VOYAGE trial ongoing

● Rare Disease Program: VK0214 for X-ALD

o Novel, selective thyroid receptor-β (TRβ) agonist

o In vivo data show improvement in key biomarkers

o Phase 1 studies underway

● Other Pipeline Programs: Musculoskeletal and metabolic disorders

3

Pipeline Overview

Development Programs Indication

Stage of Development

StatusPreclin Phase 1 Phase 2 Phase 3

VK2809

(TRβ agonist)NASH

Phase 2b VOYAGE trial

ongoing

VK0214

(TRβ agonist)X-ALD Phase 1 studies ongoing

Other Programs

VK5211

(SARM)

Hip fracture, muscle

wastingPhase 2 completed

VK0612

(FBPase inhibitor)Type 2 Diabetes Phase 2a completed

VK1430

(DGAT-1 inhibitor)

Hypertriglyceridemia,

NASHPreclinical

4

Metabolic Disease ProgramVK2809: Selective Thyroid Receptor-β Agonist

Liver Disorders

Metabolic Disease Program: Selective Thyroid-β Agonists

● Proprietary platform for small molecule thyroid hormone mimetics

o Highly tissue and receptor selective

o Produce potent lipid reductions in animals and humans

o Unique chemical scaffolds, expected wider safety window vs. other approaches

● Biological profiles suggest potential benefit in multiple indications

o Broad: NASH, hypercholesterolemia, dyslipidemia

o Rare: X-linked adrenoleukodystrophy (X-ALD), other

● Lead molecules VK2809, VK0214

o Oral, once-daily formulations

o VK2809: Phase 2b ongoing, biopsy-confirmed NASH

o VK0214: Phase 1 ongoing

6

Thyroid Hormone Receptor Overview

7

Nuclear hormone receptors: 2 main types

Positive effects

● Regulates lipid metabolism

● Reduces LDL-C, triglycerides,

atherogenic proteins

● Improves metabolic control

Therapeutic goal, lipid setting: Beta receptor selectivity, minimize alpha effects

Thyroid hormone receptor beta (TRβ)Liver

Negative effects

● Proarrhythmic potential

● Elevates heart rate

● Bone/cartilage effects

Thyroid hormone receptor alpha (TRα)Heart, skeletal muscle

Thyroid Receptor β Agonists for NAFLD and NASH

● β-Receptor: Key role in lipid metabolism; systemic and liver-specific effects

● Receptor localized to liver, limited ex-hepatic expression

● In vivo evidence suggests β-activation provides anti-fibrotic benefits

● Clinical data indicate correlation between reduced liver fat, improvement in NAS

Accumulation of fatty acids,

triglycerides; NAFLD

Oxidative stress, inflammatory

response

NASH: Steatosis, ballooning, hepatocyte

damage

NASH Progression

8

An agent that reduces liver fat, improves systemic lipids, and antagonizes

fibrotic signaling could provide multi-pronged benefits in NASH

VK2809: Unique Liver-Targeted Characteristics

● 17:1 selective for β:α

● Highly negatively charged

o Poor passive diffusion

● Not actively transported

o Due to altered chemistry

● Targeted hepatic re-uptake

o Selective liver re-absorption via

hepatic anion transporters

● 1:2 selective for β:α

● Effectively neutral charge

● Active uptake in multiple tissues

via MCT8

● Broad systemic availability

● Impractical for development due

to safety

VK2809, Novel Prodrug

VK2809A, Potent TRβ Agonist, 2.2 nM Ki

VK2809A T3 Thyroid Hormone

9

Selective activation, differentiated chemistry lends VK2809 liver selectivity;

potentially minimizes risk of systemic effects

● Cyp3A4-mediated cleavage of prodrug

● 3A4 primarily expressed in liver

● Results in targeted delivery of drug to

liver

Following oral dosing:

lym

ph(c

) th

yroid

test

es fat

bla

dder

pro

stat

esp

leen

pan

crea

sst

om

ach

lym

ph(m

)

smal

l int.

larg

e in

t. li

ver

adre

nal

kidney

sth

ymus

hea

rtlu

ngs

mar

row

musc

leey

esbra

inpituitar

ysk

inblo

od

pla

sma

bone

% o

f D

ose

0.0

0.5

1.0

1.5

2.0

2.5

Liver

VK2809: Evidence of Liver Selectivity

14C QWBA (4 h) 14C Tissue Distribution (24 h)

1) Drug Metab. Disp., 36(11), 2393-2403, (2008). 10

Liver selectivity confirmed via radiologic analysis

Heart

Liver

LargeIntestinalContents

Brain

Kidney

SmallIntestinalContents

High

Low

Heart

Liver

LargeIntestinalContents

Brain

Kidney

SmallIntestinalContents

High

Low

PO

O

OCl

O O

*

SD rat, 5mg/kg dose; approx. 30x anticipated human doses

LiverR

ela

tiv

e E

xp

res

sio

n (

fold

)

0

2

4

6

8

CYP7A ME SREBP-1c

Heart and Muscle

Re

lati

ve

Ex

pre

ssio

n (

fold

)

0

5

1015202530

MCH D1 UCP3

Heart Muscle

Pituitary and Thyroid

Re

lati

ve

Ex

pre

ssio

n (

fold

)

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

TSH D1 D1

Pituitary Thyroid

Other

Re

lati

ve

Ex

pre

ssio

n (

fold

)

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

D1 D1 D1

LiverKidneySpleen

(3 h) (24 h) (24 h) (24 h) (8 h) (24 h)

(24 h) (8 h) (24 h) (3 h) (24 h) (24 h)

VK2809: Liver-Selective Transcriptional Effects

Vehicle

T3, (0.12 mg/kg)

KB-141, (0.5 mg/kg)

VK2809, (4 mg/kg)

All 10x ED50

VK2809 shows

minimal effects on

gene expression in

extrahepatic tissues

1) Proc. Nat. Acad. Sci., 104(39), 15490-15495, (2007). 11

OtherPituitary & Thyroid

Heart & MuscleLiver

% Difference: -70.0% -64.6% -79.5% -39.7%

p-value: <0.0001 <0.0001 <0.0001 <0.0001

● Evaluation in biopsy-confirmed

diet-induced NASH model

○ Rodent model designed to reflect

progression of disease in humans

○ Animals biopsied pre-study; only

those with NASH and fibrosis

selected

○ VK2809 dosed once-daily for

8 weeks

VK2809 Significantly Reduces Steatosis in Diet-Induced NASH

Treatment with VK2809 significantly improves lipids, steatosis, NAS at 8 weeks;

well-tolerated with no evidence of toxicity

12

-80

-60

-40

-20

0

Triglycerides Cholesterol Total Lipids NAS

% R

ed

uct

ion

VK

2809 t

reate

d v

s. v

eh

icle

Change in Liver Lipids

Following 8 Weeks Dosing With VK2809

% Difference: -50.2% -60.2% -46.3%

p-value: <0.01 <0.005 0.01

● Significant reductions in fibrosis,

collagen, hydroxyproline after

8 weeks

● Supports thesis that selective TRβ

activation produces broad metabolic

benefits

VK2809 Improves Fibrosis in Diet-Induced NASH Model

VK2809 significantly improved NASH and fibrosis in this model

13

-60

-40

-20

0

Fibrosis Type I Collagen Hydroxyproline

% R

ed

uct

ion

VK

2809 t

reate

d v

s. v

eh

icle

Change in Liver Fibrosis

Following 8 Weeks Dosing With VK2809

% Difference: -27.1% -36.3% -37.0% -56.3% -64.7%

p-value: 0.07 <0.05 <0.05 <0.001 <0.001

● VK2809 reduces expression and

signaling of key fibrosis drivers

● Gene expression changes align with

observed improvement in fibrosis

histology

● Improvement in genes associated

with lipid metabolism, insulin

sensitivity also observed

VK2809: Representative Gene Effects, DIO NASH Model

TRβ mechanism provides broad histologic benefits; improving steatosis,

inflammation, fibrosis14

-65

-55

-45

-35

-25

-15

-5

Col3a1 Col1a1 αSMA Autotaxin Galectin 1

% R

ed

uct

ion

VK

2809 t

reate

d v

s. v

eh

icle

Change in Pro-Fibrogenic Gene Expression

Following 8 Weeks Dosing With VK2809

Placebo-adjusted reduction,

LDL:

-15.2%p=0.026

-27.1%p=0.0003

-41.2%p<0.0001

-36.6% p<0.0001

Placebo-adjusted reduction,

triglycerides: -34.8%p=0.052

-61.0% p=0.0019

-62.1%p=0.0007

-78.6%p=0.0001

● Placebo-controlled trial (n=56), mild

hypercholesterolemia

● Results: statistically significant

reductions in LDL and triglycerides

● Encouraging safety and tolerability,

no SAEs

● Results supported a proof-of-

concept study in patients with

NAFLD and elevated LDL-C

VK2809 Early Clinical Highlights: 14-Day Phase 1b Study

15

-80

-65

-50

-35

-20

-5

5.0 mg 10.0 mg 20.0 mg 40.0 mg

Pla

ceb

o-a

dju

sted

ch

ang

e fro

m b

ase

line (%

)

LDL

Triglycerides

Baseline (mg/dL): 138 87 137 155 115 110 124 144

Placebo-Adjusted Change From Baseline (%)

Ran

do

miz

e

Placebo

Follow-up

5 mg VK2809 QD

10 mg VK2809 QOD

10 mg VK2809 QD

Double-Blind Treatment, Weeks 1-12 Weeks 13-16

VK2809-201: Phase 2a Study Design

16

● Multi-arm, dose-ranging, 12 week Phase 2a trial

o Primary endpoint: Change in LDL-C vs. placebo

o Secondary endpoint: Change in liver fat by MRI-PDFF

o Exploratory endpoints: Changes in atherogenic proteins

Screening

MRI-PDFFD1 W1 W6 W8 W12

MRI-PDFF

W4 W16

MRI-PDFF

NAFLD

patients with ≥8%

liver fat, elevated

LDL-C and

triglycerides

% Change: 2.0% -14.7% -18.9% -18.3%

p-value vs. placebo: - 0.080 0.034 0.025

● All VK2809 cohorts significantly

reduced vs. baseline

● Placebo-adjusted change from

baseline

○ 5 mg QD: -23.7 mg/dL

○ 10 mg QOD: -27.1 mg/dL

○ 10 mg QD: -28.3 mg/dL

VK2809 Significantly Reduced LDL-C After 12 Weeks

17

* p<0.05

-20

-15

-10

-5

0

5

Placebo

(n=16)

VK2809

5 mg QD

(n=10)

VK2809

10 mg QOD

(n=15)

VK2809

10 mg QD

(n=16)

% C

hang

e fro

m B

ase

line

Baseline (mg/dL) 142.1 140.0 150.3 140.4

* *

Mean % Change in LDL-C at 12 Weeks

% Change: -9.4% -53.8% -56.5% -59.7%

p-value vs. placebo: - 0.0001 0.0018 0.0004

● Significant relative reductions from

baseline in liver fat by MRI-PDFF

● Maximal reductions at Week 12

○ 5 mg QD: 78%

○ 10 mg QOD: 72%

○ 10 mg QD: 76%

VK2809 Produced Significant Relative Reductions in Liver Fat

18

**p<0.01; ***p<0.001

-60

-50

-40

-30

-20

-10

0

Placebo

(n=12)

VK2809

5 mg QD

(n=9)

VK2809

10 mg QOD

(n=13)

VK2809

10 mg QD

(n=11)

% C

hang

e fro

m B

ase

line

Median baseline liver fat 12.0% 11.7% 14.7% 18.0%

*****

***

Median Relative

% Change in Liver Fat at 12 Weeks

Responders: 16.7% 100% 76.9% 90.9% 87.9%

p-value vs. placebo: - 0.0002 0.0048 0.0006 <0.0001

● Up to 100% of VK2809 patients experienced

response, as defined by ≥30% decrease in

liver fat at Week 12

● 88% of combined VK2809 cohorts

demonstrated a response rate

● 70% of all patients receiving VK2809

demonstrated liver fat reductions ≥50%

● Reduction in liver fat correlated with

improved odds of long-term histology

benefit1

VK2809 Cohorts Demonstrated High Relative Response Rates

191) Ther. Adv. Gastroenterol., 9(5), 692-701, (2016).

0

15

30

45

60

75

90

Placebo

(n=12)

VK2809

5 mg QD

(n=9)

VK2809

10 mg QOD

(n=13)

VK2809

10 mg QD

(n=11)

VK2809

Combined

(n=33)

% R

esp

ond

ers

***

***

***

**

**p<0.01; ***p<0.001

Patients with ≥30%

Relative Reduction in Liver Fat at 12 Weeks

Representative Fat Reduction, VK2809 and Placebo Subject

20

20

Su

bje

ct A

, Seg

men

t 4

aSu

bje

ct B

, Seg

men

t8

Baseline Week 12

50%25% 33%15%5% 100%

13.77%

7.91%21.54%

15.57%

50%25% 33%15%5% 100% 50%25% 33%15%5% 100%

22.80%18.68%23.20%

50%25% 33%15%5% 100%

● Placebo: minimal change to liver

color, fat content

● VK2809: dramatic change in liver

shade, indicating reduced fat

Subject,

DoseBaseline Week 12

Absolute

Change

Relative

Change

Subject A,

Placebo20.3% 22.6% 2.3% 11.4%

Subject B,

10 mg QD24.6% 6.0% -18.6% -75.6%

Overall Mean Hepatic Fat Values

≤ xULN < 30 kg/m2 BP<140mmHg Not Hispanic

-49.6%p=0.027

-58.0%p=0.0002

-52.7%p=0.0003

-56.7%p=0.0001

*p<0.05; **p<0.01; ***p<0.001

> xULN ≥ 30 kg/m2 BP≥140mmHg Hispanic

-57.4%p=0.0001

-51.3%p=0.0151

-54.9% p=0.0167

-49.0%p=0.0054

Consistent Week 12 MRI-PDFF Reductions Across Key Subsets

21

● Consistent MRI-PDFF reduction

independent of risk factors:

○ ALT >xULN

○ BMI ≥30 kg/m²

○ Baseline BP ≥140 mmHg

○ Hispanic ethnicity

Mean % Change in Liver Fat

at 12 Weeks in VK2809 Treated Patients

-60

-50

-40

-30

-20

-10

0

Baseline ALT Baseline BMI Hypertension Hispanic

% C

hang

e fro

m B

ase

line

* ***

Baseline (%): 13.9 20.8 17.7 16.8 18.1 13.0 15.1 18.7

N: 18 15 9 24 26 7 15 18

***

**

***

**

***

% Change: -18.7% -48.7% -33.4% -32.6% -45.4% % Change: -2.0% -8.2% -7.9% -6.6% -7.5%

p-value: - 0.0016 0.0206 0.1519 0.0053 p-value: - 0.0006 0.0360 0.0674 0.0027

Durable Liver Fat Reduction Observed at 16 Weeks

22

Significant reduction in MRI-PDFF maintained 4 weeks after last dose

-10

-8

-6

-4

-2

0

Placebo

(n=9)

VK2809

5 mg QD

(n=8)

VK2809

10 mg QOD

(n=8)

VK2809

10 mg QD

(n=11)

VK2809

Combined

(n=27)

% C

hang

e F

rom

Base

line

Median Relative % Change in Liver Fat at 16 Weeks Mean Absolute % Change in Liver Fat at 16 Weeks

-50

-40

-30

-20

-10

0

Placebo

(n=9)

VK2809

5 mg QD

(n=8)

VK2809

10 mg QOD

(n=8)

VK2809

10 mg QD

(n=11)

VK2809

Combined

(n=27)

% C

hang

e F

rom

Base

line

****

*

*p<0.05; **p<0.01; ***p<0.001

Median Baseline: 11.3% 14.0% 14.7% 18.2% 17.9% Mean Baseline: 12.3% 15.1% 16.3% 17.8% 16.6%

****

**

Responders: 22.2% 100% 62.5% 54.5% 70.4%

p-value vs. placebo: - 0.0023 0.0698 0.1968 0.0083

Durable Response Rates Maintained 4-Weeks Post-Treatment

23

● Up to 100% of VK2809 patients

experienced response, as defined

by ≥30% decrease in liver fat at

Week 16

● Combined VK2809 cohorts

demonstrated 70% response rate at

Week 16 (p=0.0083)

● Opens potential intermittent dosing

or cycling strategies

Patients with ≥30%

Relative Reduction in Liver Fat at 16 Weeks

0

15

30

45

60

75

90

Placebo

(n=9)

VK2809

5 mg QD

(n=8)

VK2809

10 mg QOD

(n=8)

VK2809

10 mg QD

(n=11)

VK2809

Combined

(n=27)

% R

esp

ond

ers

**

**

**p<0.01

% Change: -32.7% -56.6% -42.7% -48.0% -54.7%

p-value: 0.0003 - 0.0121 0.0095 0.0099

% Change: -46.1% -42.9% -63.9% -54.3% -61.8%

p-value: <0.0001 0.0347 <0.0001 0.0005 0.0001

24

Week 16 Liver Fat Reduction Maintained Across Baseline Levels

-65

-55

-45

-35

-25

-15

-5

8%-12%

(n=12)

>12%-16%

(n=3)

>16%-20%

(n=6)

>20%-24%

(n=7)

>24%

(n=5)

% C

hang

e F

rom

Base

line

-65

-55

-45

-35

-25

-15

-5

8%-12%

(n=11)

>12%-16%

(n=1)

>16%-20%

(n=6)

>20%-24%

(n=5)

>24%

(n=4)

% C

hang

e F

rom

Base

line

Mean % Change in Liver Fat at 12 Weeks

*p<0.05; **p<0.01; ***p<0.001*p<0.05; ***p<0.001

****

***

******

***

**

***

Potent, durable reduction in MRI-PDFF across range of baseline fat content

Mean % Change in Liver Fat at 16 Weeks

% Change: -0.2% -18.8% -22.6% -18.5%

p-value: - 0.21 0.0023 0.0081

% Change: 3.0% -17.1% -36.8% -26.1%

p-value: - 0.21 0.048 0.060

-25

-20

-15

-10

-5

0

Placebo

(n=16)

VK2809

5 mg QD

(n=10)

VK2809

10 mg QOD

(n=15)

VK2809

10 mg QD

(n=16)

Perc

ent

Ch

ang

e F

rom

Base

line

-40

-30

-20

-10

0

Placebo

(n=16)

VK2809

5 mg QD

(n=10)

VK2809

10 mg QOD

(n=15)

VK2809

10 mg QD

(n=16)

Perc

ent

Ch

ang

e F

rom

Base

line

Mean Change in Lipoprotein(a) at Week 12

VK2809 Improved Atherogenic Protein Levels at 12 Weeks

25

*p<0.05; **p<0.01; ***p<0.001

Mean Change in Apolipoprotein B at Week 12

Baseline (mg/dL): 19.5 19.8 14.9 20.4 Baseline (mg/dL): 107.7 112.6 112.0 108.5

* **

***

Reductions in Lp(a), ApoB suggest potential long-term cardiovascular benefit

26

● No SAEs observed

● Mean ALT, AST levels in VK2809-treated

subjects reduced relative to placebo at

Week 12

● No other liver function tests significantly

different from placebo

● No clinically meaningful changes in other

key markers among VK2809-treated

patients relative to placebo

● Excellent tolerability

No SAEs reported in any VK2809 clinical study to date

Patients with elevated baseline ALT demonstrated greater

improvement relative to placebo at Weeks 12 and 16

Direct bilirubin, indirect bilirubin, alkaline phosphatase, INR

Thyroid hormones (fT4, tT3, TSH); cardiovascular markers

(troponin, CK-MB, NT proBNP); vital signs (BP, heart rate,

weight)

GI and nausea events numerically lower vs. placebo

VK2809-201: Encouraging Safety Profile Through 12 Weeks

VK2809: Phase 2a Summary and Conclusions

27

● VK2809 produced robust reduction in liver

fat on MRI-PDFF in NAFLD patients after 12

weeks of dosing

● Consistent effects observed across common

NASH risk factors

● Liver fat reduction maintained 4 weeks post-

dosing

● VK2809 produced significant reduction in

plasma lipids, suggesting long-term CV

benefit

● VK2809 was safe and well-tolerated in this

12-week study

88% of patients receiving VK2809 experienced ≥30%

reduction in liver fat content, including all patients

receiving 5 mg doses; 70% experienced reductions ≥50%

70% of VK2809 patients remained responders 28 days after conclusion of dosing

LDL-C, triglycerides, and atherogenic proteins: Apo B, Lp(a)

No SAEs observed, discontinuations well-balanced across cohorts

Elevated ALT, BMI, hypertension, Hispanic ethnicity

VK2809 Clinical Highlights and Current Status

28

● Phase 1 studies demonstrated safety, predictable PK, robust lipid-lowering

effects

● 12-Week Phase 2 study demonstrated potent, durable liver fat reduction

● Consistent efficacy demonstrated across key high-risk subsets

● No drug-drug interaction when co-administered with atorvastatin

● Profile supports further development in biopsy-confirmed NASH

● VOYAGE 12-Month Phase 2b NASH study initiated 4Q19

VK2809: Phase 2b VOYAGE Study

VOYAGE Study: 12-Month Phase 2b Study of VK2809

30

D1 M3

MRI-PDFF

M13

Safety

Ran

do

miz

e

Placebo (n=75)

Follow-up

1.0 mg VK2809 QD (n=37)

2.5 mg VK2809 QD (n=75)

5 mg VK2809 QOD (n=75)

10 mg VK2809 QOD (n=75)

Double-Blind Treatment, 12 months 4 Weeks

Biopsy-confirmed

NASH

Screening,

Biopsy MRI-PDFF

● Multi-arm, dose-ranging, 12-month Phase 2 trial

o Primary endpoint: Change in MRI-PDFF vs. placebo at 3 months

o Secondary endpoint: Change in histology at 12 months (NAS, fibrosis markers, etc.)

M12

Biopsy,

MRI-PDFF

VOYAGE Study: 12-Month Phase 2b Study of VK2809

● Key inclusion criteria:

o Biopsy-confirmed NASH with NAS ≥4

o Liver fat content ≥8%

o F2-F3 fibrosis, up to 25% F1

● Primary endpoint: Change in liver fat content at week 12

● Secondary, exploratory endpoint: Change in histology at 12 months

31

Closing Comments: VK2809 Competitive Advantages

● Currently >40 NASH programs in Phase 2 or Phase 3 development

● What differentiates VK2809 from the crowd?

32

o Orally available

o Liver-targeted

o Potently reduces liver fat

o Well tolerated

Preferred route of administration for chronic therapy

o Reduces systemic lipids, may improve

overall metabolic profile

Bodes well for potential long-term CV benefit

No elevations in other lipids that may require polypharmacy

Weight loss and reduced liver fat correlate with NASH

resolution, improved fibrosis markers

No GI impact, no pruritis or other tolerability issues to date

Reduces risk of undesired effects in other tissues

Rare Disease Program

VK0214

X-Linked Adrenoleukodystrophy

VK0214 for X-ALD

34

● X-Linked adrenoleukodystrophy (X-ALD)

o Orphan neurodegenerative disorder

o X-linked: Carried by females, primarily manifesting in males

o No cure, no approved therapy

● Most severe form: Cerebral ALD

o Rapidly progressive inflammatory demyelination; disruption of BBB

o Affects ~35% before age 12 (CCALD), ~20% between age 20 – 35 (CALD)

o Deterioration in speech, cognition; vegetative state within 3-5 years

● Most common form: Adrenomyeloneuropathy (AMN)

o Affects spinal cord, motor neurons; no inflammatory component or brain involvement

o Affects nearly all adult patients; considered “default” manifestation of ALD

o Progressive motor impairment; wheelchair confinement, leg paralysis common

1) Biochimie, 98 (2014) 135-142. 2) Ann. Neurol. 49:512-517 (2001). 3) Biochim. Biophys. Acta 1822 (2012) 1465-1474. 4) Orphanet J. Rare Dis. 7:51 (2012). 5) Brain Pathol. 20(4): 845-856 (2010).

TRβ: X-Linked Adrenoleukodystrophy

Caused by mutation in gene for the ATP-Binding Cassette transporter D1 (ABCD1)

● Peroxisomal transporter of very long chain fatty acids (VLCFA)

Graphic adapted from http://www.x-ald.nl/origin-and-metabolism-of-vlcfa/.

ABCD1: Normal function to transport VLCFA

into peroxisome for degradation

X-ALD: Defective ABCD1 leads to accumulation

of VLCFA in tissues

High VLCFA levels disrupt cell membranes;

inflammatory demyelination in brain tissue;

motor neuron deterioration

TRβ Agonists: Stimulate expression of

compensatory transporters ABCD2, 3; may

mitigate VLCFA elevation

35

VK0214: Chemical Characteristics

● >20:1 selective for β:α

● Highly negatively charged

o Poor passive diffusion

● Altered chemical geometry

o Not actively transported via MCT8

● Targeted hepatic re-uptake

o Selective liver re-absorption via

hepatic OATP1B1, OATP1B3

● 1:2 selective for β:α

● Effectively neutral charge

● Active uptake in multiple tissues

via MCT8

● Broad systemic availability

● Impractical for development

due to safety

VK0214 T3 Thyroid Hormone

36

Broader systemic availability may be appropriate for diffuse disease

settings like X-ALD

37

0

2

4

6

DMSO VK0214 4PBA Sobetirome

Fo

ld c

han

ge (D

MSO

set

as

1)

● Alternative VLCFA transporters ABCD2,-3

are induced by TRβ receptor

o Mechanistically compensate for ABCD1

deficiency

● Over-expression of ABCD2 corrects VLCFA

elevation in vitro and in vivo

● TRβ agonists such as VK0214 hold promise

● In vitro PoC established in X-ALD

fibroblasts

VK0214 successfully induces ABCD2 expression in human X-ALD cells

VK0214: Potent ABCD2 Induction in X-ALD Fibroblasts

Strong Rationale for TRβ Role in X-ALD

(1) Eur. J. Cell Biol. 87, 933-945, 2008 (2) J. Steroid Biochem. Mol. Biol., 116, 37-43, 2009 (3) Short call oral presentation 6, 84th American Thyroid Association, November 1, 2014.

% Chg: -45% -61% -74% -82%

p-value: <0.0001 <0.0001 <0.0001 <0.0001

% Chg: 48% -51% -55% -57%

p-value: <0.0001 <0.0001 <0.0001 <0.0001

% Chg: -29% -21% -43% -54%

p-value: <0.0001 <0.005 <0.0001 <0.0001

VK0214: In Vivo Proof-of-Concept Data, ABCD1 KO Mouse

● ABCD1 Knockout model: Mimics biochemical features of human X-ALD

● VK0214: Durable and progressive reductions in plasma VLCFAs

o Tissue effects suggest encouraging CNS activity following long-term exposure

Reductions in Plasma VLCFA-LPC, ABCD1 Knockout Model

38

12 Weeks6 Weeks 25 Weeks

-80

-60

-40

-20

0

C26:0 C24:0 C22:0 C20:0

% R

ed

uct

ion

VK

0214

tre

ate

d v

s. c

on

tro

l

-80

-60

-40

-20

0

C26:0 C24:0 C22:0 C20:0

% R

ed

uct

ion

VK

0214

tre

ate

d v

s. c

on

tro

l

-80

-60

-40

-20

0

C26:0 C24:0 C22:0 C20:0

% R

ed

uct

ion

VK

0214

tre

ate

d v

s. c

on

tro

l

% Difference: -19% -15% -34% -11%

p-value: <0.05 <0.01 <0.0001 0.07

VK0214: Reduces VLCFA Levels in Key Tissues

39

● Significant VLCFA reductions observed in

multiple tissues

● Encouraging evidence of CNS activity

● Reductions in multiple VLCFAs consistent

with plasma observations

● Suggests potential benefit in both

cerebral and AMN forms of X-ALD

● Phase 1 study ongoing in healthy

volunteers

● Phase 1b PoC planned 2021

Change in Tissue VLCFAs:

CNS and Peripheral Tissue

-35

-25

-15

-5

Liver

C26:0

Spinal Cord

C26:0

Brain

C20:0

Brain

C26:0

% R

ed

uct

ion

VK

0214

tre

ate

d v

s. v

ehic

le

VK0214 Summary and Current Status

40

● Potential to be best in-class oral, small molecule TRβ therapeutic for X-ALD

● Encouraging efficacy with rapid (6 weeks) and progressive (up to 25 weeks)

VLCFA reductions in plasma and tissues: brain, spinal cord and liver

● Activation of the thyroid beta receptor can lead to an improved metabolic

profile in X-ALD setting given its durable and sustained response

● Compelling PoC in genetic model supports development as a potential

treatment for X-ALD

● Viking Therapeutics has received Orphan Status for this program

● Phase 1 study ongoing in healthy volunteers

● Phase 1b PoC planned 2021

VK0214-101: SAD-MAD Study Design

41

● Phase 1 study to evaluate the safety, tolerability and pharmacokinetics of

VK0214, a selective thyroid receptor-β agonist, in a single ascending dose

(SAD) and multiple ascending dose (MAD) study in healthy adults

● Sample size:

o VK0214: N= 84, Placebo: N=28; healthy male and female participants

● Data from this study will be used in the design of a Phase 1b trial to evaluate

the safety, tolerability and pharmacokinetics of VK0214 in adult patients with

adrenomyeloneuropathy (AMN)

● Study starting dose: 5 mg

Financial Summary

Capital Structure 1 In ‘000s FinancialsSeptember 30, 2020

($’000s)

Shares outstanding 72,921Cash burn YTD 3Q

2020$20,334

Options, RSUs 4,002Cash and ST

Investments$255,304

Warrants 5,525

Total shares,

options, RSUs,

warrants

82,448

Notes: 1) As of September 30, 2020

42

● Capital structure and summary financials

Investment Highlights

● Focused on novel therapeutics for metabolic and endocrine diseases

o Clinical programs demonstrate best-in-class efficacy data

● Metabolic Disease Program: VK2809 for NASH

o Novel, selective thyroid receptor-β (TRβ) agonist

o Phase 2a results demonstrate significant reduction in liver fat content and lipids

o Phase 2b VOYAGE trial ongoing

● Rare Disease Program: VK0214 for X-ALD

o Novel, selective thyroid receptor-β (TRβ) agonist

o In vivo data show improvement in key biomarkers

o Phase 1 studies underway

● Other Pipeline Programs: Musculoskeletal and metabolic disorders

43

Corporate Presentation

December 2020