This presentation contains forward-looking statements. All statements other than statements of historical fact

are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,”

“estimate,” “expect,” “goal,” “intend,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,”

"will,” “would” and similar expressions. Forward-looking statements are based on management's beliefs and

assumptions and on information available to management only as of the date of this press release. These

forward-looking statements include, but are not limited to, statements regarding the development of our gene

therapies, the success of our collaborations, and the risk of cessation, delay or lack of success of any of our

ongoing or planned clinical studies and/or development of our product candidates. Our actual results could

differ materially from those anticipated in these forward-looking statements for many reasons, including, without

limitation, risks associated with collaboration arrangements, our and our collaborators’ clinical development

activities, regulatory oversight, product commercialization and intellectual property claims, as well as the risks,

uncertainties and other factors described under the heading "Risk Factors" in uniQure’s Quarterly Report on

Form 10-Q filed on November 1, 2017. Given these risks, uncertainties and other factors, you should not place

undue reliance on these forward-looking statements, and we assume no obligation to update these forward-

looking statements, even if new information becomes available in the future.

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 3

1. McColgan P, Tabrizi SJ. Eur J Neurol. 2018;25(1):24-34; 2.Tabrizi SJ, et al. Lancet Neurol 2009;8(9):791-801; 3. Nopoulos PC, et al. Neurobiol Dis 2010;40(3):544-54 Figure adapted from Brundin P, et al. Nat Rev Mol Cell Biol 2010;11:301-7.

The shading and arrows

indicate the progression of

pathology. Darker shading

represents earlier onset.

Occipital

lobe

Frontal

lobe

Somatomotor

cortex

Parietal

lobe

1

2 3

3

Somatosensory

cortex

Huntington’s Disease

• Autosomal dominant neurodegenerative disorder

• Expansion of CAG trinucleotide huntingtin (HTT) exon 1

• No disease-modifying therapies available

• Prevalence of 60,000 to 70,000 patients in US and EU

• Significant additional patients undiagnosed

Expected progression of brain pathology

• The striatum is the primary site of pathology

• Premanifest stage: atrophy spread and cortical thinning

• Motor symptoms manifest as atrophy increases

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 4

One-time intracranial injection of AMT-130 into striatum (caudate nucleus and putamen)

What is AMT-130 and how do we deliver it?

1. Samaranch L, et al. Gene Ther 2017;24:253-261;

2. Evers M, et al. Mol Ther 2017;5(Suppl. 1);247. AAV5, adeno-associated viral vector serotype;

CED, convection-enhanced delivery; MRI, magnetic resonance imaging

Image reproduced from:

https://www.neuroscientificallychallenged.com/blog/know-your-brain-striatum

Caudate nucleus

Putamen

AAV5

capsid

Expression

cassette

miR-451-HTTCAG promoter

ITR

polyA

ITR

AAV5-miHTT (Company name AMT-130)

• Replication deficient AAV5

• Targeting toxic huntingtin (HTT) exon1

• miQURE® technology

• Phase I/II study to start in 2H19

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 5

Mechanism of Action of AMT-130

miQURE® technology1. PoI II expression

Tissue specificity and regulation

2. Guide strand activity only

Lower risk of off-target

3. No saturation of cellular RNAi

Increased safety profile

4. Nuclear and cytoplasmic effect

Increased efficacy

5. Indication of spread via

extracellular vesicles

Increased efficacy

[ASGCT abstract #228]

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 6

Proof-of-Concept of AMT-130 gene therapyFrom patient cells to large animals

NHP HD pigshuman neurons Diseased rodent models

Safety

Efficacy

Safety

Efficacy

Distribution

4 types HD Mouse3 tgHD Minipig2

HD Rat4

1. Samaranch L, et al. Gene Ther 2017;24:253-261; 2. Evers M, et al. Mol Ther 2017;5(Suppl. 1):247;3. Spronck EA, et al. Hum Gene Ther 2017;28:A78; 4. Miniarikova J, et al. Gene Therapy 2017;24:630-639

Non-human primate1

No off-target effects

Well tolerated in GLP-TOX studies

Safety

Efficacy

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 7

Assessment of AMT-130 persistence in a large brainLong-term study in tgHD minipigs

Baxa et al., J Huntingtons Dis (2013) 2:47 | Evers et al., Mol Ther (2018) 26:2163

Human

HTT promoter

124 CAG/CAA repeat

Truncated human HTT

(Exon 1 to 12)

Libechov minipig:

Life-span: 12-20 years

Body weight: 50-140 kg

Brain weight: 90-100 g

Highly developed immune system

• Good model to assess biodistribution and target engagement in large brain

• Ubiquitous expression of human mtHTT(548aa N-terminal fragment)

putamen

caudate

• Treatment groups:

Control (untreated)

AAV5-miHTT (1.2 x 1013 gc/animal)

(100μL/structure, max rate 3 μL/min)

• CSF collection

• Per treatment group, interim sacrifices:

6 months (n=3/group)

12 months (n=4/group)

>24 months (n=8/group) [in-life]MRI-guided CED

Study design

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 8

• Brains cut in n=12 (4mm-thick) slices (4mm punches)

• One hemisphere used for bioanalysis

6 months interim sacrifice → n=54 punches (alternate slices)

12 months interim sacrifice → n=170 punches (all slices)

Assessment of AMT-130 biodistribution and efficacyExtensive brain dissection and bioanalysis

sagittal view

coronal view

• DNA isolation → vector DNA (Q-PCR)

• RNA isolation → miHTT (RT-QPCR)

• Tissue lysate and CSF → mHTT protein

(2B7-MW1 Singulex immunoassay)

Bioanalysis

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 9

Widespread vector DNA distribution across cortical regions

2 41

01

22

42

62

8 81

43

43

64

6

20

48

72

38

58

78

98 6

16

30

32

54

74

76

50

52

88

90

11

01

14

11

61

32

12

21

48

70

86

11

2

94

11

81

36

14

6

102

103

104

105

106

107

108

VG

co

pie

s /

μg

DN

A

Pre

front

al

Mot

or

Cin

gulate

Insu

lar

Som

atose

nsory

Som

atom

otor

Visual

Perir

hinal

Retr

osple

nial

Tempo

ral

Cortex

LLoQ

12

m

6m

2 41

01

22

42

62

8 81

43

43

64

6

20

48

72

38

58

78

98 6

16

30

32

54

74

76

50

52

88

90

11

01

14

11

61

32

12

21

48

70

86

11

2

94

11

81

36

14

6

102

103

104

105

106

107

108

VG

co

pie

s / μ

g D

NA

Pre

front

al

Mot

or

Cin

gulate

Insu

lar

Som

atose

nsory

Som

atom

otor

Visual

Perir

hinal

Retr

osple

nial

Tempo

ral

Cortex

LLoQ

T31

T29

T34

T55

T58

T62

T63

2 41

01

22

42

62

8 81

43

43

64

6

20

48

72

38

58

78

98 6

16

30

32

54

74

76

50

52

88

90

11

01

14

11

61

32

12

21

48

70

86

11

2

94

11

81

36

14

6

102

103

104

105

106

107

108

VG

co

pie

s / μ

g D

NA

Pre

front

al

Mot

or

Cin

gulate

Insu

lar

Som

atose

nsory

Som

atom

otor

Visual

Perir

hinal

Retr

osple

nial

Tempo

ral

Cortex

LLoQ

T31

T29

T34

T55

T58

T62

T63

Animal ID#

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 10

Widespread vector DNA distribution across cortical regions

prefronta

l

moto

r

cingula

te

insu

lar

som

atose

nsory

som

atom

otor

perirh

inal

/ret

rosp

lenia

l

tem

poral

visu

al

103

104

105

106

107

Cortex

VG

co

pie

s / μ

g D

NA

LLoQ

12 months

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 11

Vector DNA in subcortical regions:detected in all brain regions except brainstem and cerebellum

40

60

62

80

42

64

66

82

84

44

68

10

01

02

12

4

12

01

44

102

103

104

105

106

107

108

VG

co

pie

s /

μg

DN

A

Caudate

Puta

men

Glo

bus palli

dus

Acc

umbe

ns

Am

ygda

la

Hip

pocam

pus

Striatum andLimbic areas

LLoQ

10

41

26

13

8

10

6

10

81

28

13

0

14

0

14

2

15

2

15

0

16

4

17

0

15

41

56

15

81

60

16

61

68

18

22

56

92

96

13

41

62

102

103

104

105

106

107

108

Thalamus, Mesencephalon,Brainstem and Cerebellum

LLoQ

Thala

mus,

L

Thala

mus

, MD

Thala

mus

, VL

Tha

lam

us, Z

I

Thala

mus

, VPM

/VPL

Red n

ucleus

Mes

enceph

alon

Pons

Med

ulla

Cere

bellum

Whi

te m

atte

r

12

m

6m

2 41

01

22

42

62

8 81

43

43

64

6

20

48

72

38

58

78

98 6

16

30

32

54

74

76

50

52

88

90

11

01

14

11

61

32

12

21

48

70

86

11

2

94

11

81

36

14

6

102

103

104

105

106

107

108

VG

co

pie

s / μ

g D

NA

Pre

front

al

Mot

or

Cin

gulate

Insu

lar

Som

atose

nsory

Som

atom

otor

Visual

Perir

hinal

Retr

osple

nial

Tempo

ral

Cortex

LLoQ

T31

T29

T34

T55

T58

T62

T63

2 41

01

22

42

62

8 81

43

43

64

6

20

48

72

38

58

78

98 6

16

30

32

54

74

76

50

52

88

90

11

01

14

11

61

32

12

21

48

70

86

11

2

94

11

81

36

14

6

102

103

104

105

106

107

108

VG

co

pie

s / μ

g D

NA

Pre

front

al

Mot

or

Cin

gulate

Insu

lar

Som

atose

nsory

Som

atom

otor

Visual

Perir

hinal

Retr

osple

nial

Tempo

ral

Cortex

LLoQ

T31

T29

T34

T55

T58

T62

T63

Animal ID#

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 12

Highly comparable vector DNA brain distributionat 6 and 12 months post-administration

Pre

fronta

l

Som

ato-S

/M

Tempora

l

Cau

date

Puta

men

Am

ygdal

a

Thalam

us

Pons

Cer

ebel

lum

White

mat

ter

102

103

104

105

106

107

108

VG

co

pie

s / μ

g D

NA

12 months

6 monthsCortex Striatum

LLoQ

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 13

Expression of therapeutic miHTT strongly correlates with vector DNA levels in all brain regions

2 41

01

22

42

62

8 81

43

43

64

62

04

87

23

85

87

89

8 61

63

03

25

47

47

65

05

28

89

01

10

11

41

16

13

21

22

14

87

08

61

12

94

11

81

36

14

64

06

06

28

04

26

46

68

28

44

46

81

00

10

21

24

12

01

44

10

41

26

13

81

06

10

81

28

13

01

40

14

21

52

15

01

64

17

01

54

15

61

58

16

01

66

16

81

82

25

69

29

61

34

16

2

10 -1

100

101

102

103

104

105

miH

TT

(m

ole

c/c

ell

)

Pre

front

al

Mot

or

Cin

gulate

Insu

lar

Som

atose

nsory

Som

atom

otor

Visual

Perir

hinal

Retr

osple

nial

Caudate

Puta

men

Glo

bus palli

dus

Acc

umbe

ns

Am

ygda

la

Hip

pocam

pus

Thalam

ic n

ucle

i

Tempo

ral

Mes

enceph

alon

Pons

Med

ulla

Cortex

Striatum and

Limbic areas Thalamus

Mesenceph., Brainst.,

Cerebellum

Cere

bellum

Whi

te m

atte

r

LLoQ

102 103 104 105 106 107 108

10 -1

100

101

102

103

104

105

VG copies/ug DNA

miH

TT

(m

ole

cu

les/c

ell) 0.8963Pearson r

<0.0001p

12

m

2 41

01

22

42

62

8 81

43

43

64

6

20

48

72

38

58

78

98 6

16

30

32

54

74

76

50

52

88

90

11

01

14

11

61

32

12

21

48

70

86

11

2

94

11

81

36

14

6

102

103

104

105

106

107

108

VG

co

pie

s / μ

g D

NA

Pre

front

al

Mot

or

Cin

gulate

Insu

lar

Som

atose

nsory

Som

atom

otor

Visual

Perir

hinal

Retr

osple

nial

Tempo

ral

Cortex

LLoQ

T31

T29

T34

T55

T58

T62

T63

Animal ID#

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 14

Strong long-term lowering of mutant HTT protein in the tgHD minipig brain, comparable at 6 and 12 months

Pre

fronta

l

Moto

r

Cin

gulate

Insu

lar

Som

atose

nsory

Som

atom

otor

Vis

ual

Per

irhin

al

Ret

rosp

lenia

l

Tempora

l

Cau

date

Puta

men

Glo

bus pal

lidus

Acc

umben

s

Am

ygdal

a

Hip

pocam

pus

Thalam

us, L

Thalam

us, M

D

Thalam

us, V

PL

Thalam

us, V

PM

Thalam

us, V

L

Thalam

us, Z

I

Red

nucl

eus

Mes

ence

phalon

Pons

Med

ulla

Cer

ebel

lum

White

mat

ter

0

20

40

60

80

mu

tan

t H

TT

(p

g/μ

g t

ota

l p

rot.

)

Control (untreated) AAV5-miHTT (12 months)

CortexStriatum and

Limbic areas ThalamusMesenceph., Brainst.,

Cerebellum

***

**

**

##

#

*

***

*******

**

***

****

* *

** ***

**

*

*

* *

****

Pre

fronta

l

Som

ato-S

/M

Tempora

l

Cau

date

Puta

men

Am

ygdal

a

Thalam

us

Pons

Cer

ebel

lum

White

mat

ter

0

25

50

75

100

125

mu

tan

t H

TT

pro

tein

(% f

rom

na

ive

)

6 months

12 months

Cortex Striatum

30%

50%

70%

Two-tailed t-test (#p<0.1, *p<0.05, **p<0.005, ***p<0.0005, ****p<0.0001)

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 15

Mutant HTT protein in CSF is also lowered, but does not accurately reflect mHTT lowering in brain tissue

Increase in CSF mHTT levels with age

predose 6 12

0

100

200

300

400

Time post-injection (months)C

SF

mH

TT

(fM

)

Control (untreated)

AMT-130

6 9 12 15 18

0

100

200

300

400

tgHD minipig age (months)

CS

F m

tHT

T(f

M)

AMT-130 datapoints from 3-12 months post-injection

predose 6m 12

m

0

25

50

75

100

125

CS

F m

HT

T (

% f

rom

co

ntr

ol)

70%

50%

30%

→ Prefrontal cortex

→ Caudate

→ Putamen

→ Thalamus

40%

80%

85%

45%

45%

75%

70%

55%

Brain mHTT lowering

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 16

Conclusions

• Strong and sustained target engagement and efficacy of one-time intrastriataladministration of AMT-130 in tgHD minipigs

• Significant correlation between vector DNA, miHTT and mHTT protein lowering

• Highly comparable between 6 and 12 months post-administration

• First time that sustained and non-toxic mHTT protein lowering is shown in a large brain

• Widespread effects, both in target regions (striatum) and more distal areas (thalamus and cortex)

D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S A A V 5 - m i H T T m e d i a t e d H T T l o w e r i n g i n t g H D m i n i p i g s | A S G C T M a y 1 , 2 0 1 9 | 17

Acknowledgements

Institute of Animal Physiology and Genetics (Czech Republic)

Jiri Klima | Bozena Bohuslavova | Zdenka Ellederova | Jan Motlik

CHDI (USA)

Doug Macdonald | David Howland

IRBM (Italy)

Roberta Pintauro | Valentina Fodale | Alberto Bresciani

uniQure (The Netherlands)

Anouk Stam | Cynthia Brouwers | Lieke Paerels

Marina Sogorb-Gonzalez | Bas Blits

Melvin Evers | Pavlina Konstantinova | Sander van Deventer