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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