A Global Leader in Gene TherapyCorporate PresentationJanuary 2020

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 presentation. 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, development of product candidates, 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 October 28, 2019. 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.

Forward-looking Statements

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Strategy to bring gene therapies to patients

Pipeline

Manufacturing

Enabling Technologies

Intellectual Property

Commercialization

Focus on liver-directed & CNS disorders

Expand & maintain our leading IP portfolio

Maintain leadership in commercial-scale manufacturing of AAV gene therapies

Invest in next-generation technologies

Retain valuable commercial rights

Commercialization Pipeline

Manufacturing

EnablingTechnologies

IntellectualProperty

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Key near-term catalysts

• Topline data from HOPE-B pivotal study in late 2020• BLA submission in 2021Hemophilia B

• Initiate dosing in Phase I/II study in early 2020 • Early efficacy data on initial patients in 2021Huntington’s

• Submit IND for AMT-180 in 2020• Begin clinical development in 2021Hemophilia A

• Initiate IND-enabling study for SCA3 in 2020• Submit IND application in 2021

Spinocerebellar Ataxia Type 3 (SCA3)

• Continue to increase manufacturing scale and capacity• Conduct manufacturing process validation for EtranaDez (AMT-061) in 2020Manufacturing

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Our proprietary pipeline

*Collaboration with Bristol-Myers Squibb

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Large-scale AAV Manufacturing• Based in Lexington, MA, expanded to 80,000 ft2

• Proprietary 3rd generation insect cell, baculovirus• Demonstrated 500L stirred-tank production• Scalable up to 2 x 2,000L• Strong intellectual property position

Potential Benefits• Control and flexibility• Consistent process from small-scale to large-scale• Highly scalable, cost-effective• High-volume capacity• Consistent, stable, high-quality product

Global leadership in AAV manufacturing

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AAV5 – Clinically demonstrated tolerability and clinical effects observed to date

• Long-term follow-up data demonstrating safety and tolerability• 25 patients have received AAV5 across 4 clinical studies1

• Observed clinical effects in the liver and brain• Low avidity of pre-existing neutralizing antibodies (NAbs)• Favorable immunogenicity profile for systemic, intravenous delivery• No confirmed T-cell-mediated immune responses to capsid

1 uniQure clinical trials in Hemophilia B, Sanfilippo B and Acute Intermittent Porphyria

Leveraging AAV5: a potentially best-in-class vector

AAV5 Vector

Hemophilia BEtranacogene dezaparvovec (AMT-061)

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1. US CDC/ATHN Hemophilia community count, March 2019. 2. Estimated based on population in Europe and prevalence reported in Iorio et al. Ann Intern Med. 2019. doi: 10.7326/M19-1208. 3. VandenDriessche T and Chuah MK. Hum Gene Ther. 2017;28(11):1013-1023. 4. Noone et al. American Society of Hematology annual meeting 2019, Poster 2118. 5. uniQure internal data, cost including factor therapy and medical costs

Hemophilia B: significant financial burden and unmet medical needs

Clinical burden Patient burden Economic burden Societal burden

Lifelong bleeding risk with current

standard of care and accrual of joint

damage3

Cumbersome treatment with

adherence issues, quality of life and

pain3

~$610,000 annual cost of factor IX

replacement therapy for severe patients in

the US4

>$20 million lifetime cost per severe

patient in the US5

Disease prevalence: ~6,000 patients in the United States1 and ~14,000 patients in Europe2

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Key Treatment Features • Demonstrated ability to increase FIX activity to

therapeutic levels • No bleeding events post-treatment• No replacement therapy for bleeds outside surgery• No requirement of immunosuppression • No exclusion of patients with pre-existing NAbs

Key Safety Features• Well-tolerated with no serious adverse events

related to treatment• No inhibitor development

Etranacogene dezaparvovec (AMT-061)

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0

10

20

0 20 40 60 80 100 120 140 160 180 200 220

FIX

activ

ity (I

U/d

L)

6 (11.1) 7 (7.1) 8 (8.5) 9 (3.9) 10 (6.7)

Cohort 2Mean FIX activity (95% CI):

7.5 (4.2 – 10.7)

AMT-060: sustained dose-dependent increases in FIX activity

0

10

20

0 20 40 60 80 100 120 140 160 180 200 220

FIX

activ

ity (I

U/d

L)

1 (7.1) 2 (5.3) 3* (1.3) 4* (8.2) 5* (3.5)

Cohort 1Mean FIX activity (95% CI):

5.1 (1.6 – 8.6)

Weeks following AMT-060 treatment

Values in parentheses represent mean FIX activity over time. Only values at least 10 days after last FIX concentrate administration are included. FIX prophylaxis was continued after AMT-060 and tapered between Weeks 6 and 12. *Patients 3, 4 and 5 retrospectively tested positive for AAV5 neutralizing antibodies using the luciferase-based assay. Dashed line indicates sample collection occurred after the data cut (09Oct2019). Values after the data cut (Patient 4, year 3.5; Patient 10, year 4) are not included in calculations of mean FIX activity. FIX, factor IX; CI, confidence interval; IU, international units

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FIX activity measured by a one stage clotting assay conducted in a central lab. aPTT, activated partial thromboplastin time

Etranacogene dezaparvovec: Phase 2b sustained FIX activity in the functionally curative range

Mean FIX activity at 1 year: 41% of normal

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• Approximately 60 patients enrolled - severe and moderately-severe Hemophilia B • More than half of eligible patients treated • Open label, single-dose, multi-center, multi-national trial• Patients with AAV5 neutralizing antibodies not excluded• Patients serve as their own control; 6-month lead-in to establish baseline• Study objectives:

• Increase FIX activity• Reduce frequency of bleeding episodes• Decrease use of FIX replacement therapy• Assess efficacy and safety

Etranacogene dezaparvovec (EtranaDez): HOPE-B Phase III pivotal study

Huntington’s DiseaseAMT-130

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• Patient population1:• ~25,000 patients in United States• ~25,000 patients in Europe

• Underreported due to lack of treatment options

• Disease stage prevalence2: • 30.5% Early stage• 35.5% Middle stage • 34.0% Late stage

• Autosomal dominant neurodegenerative disorder

• Expansion of CAG trinucleotide huntingtin (HTT) exon1

• No disease-modifying therapies available

Huntington’s disease: prevalence and overview

1 Neuroepidemiology 2016;46:144–1532 Journal of Medical Economics. 2013 Aug;16(8):1043-50

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Huntington’sAMT-130

• No treatments available• Strong preclinical data• Near-term goal: Begin

dosing of Phase I/II trial

• One-time administration of disease-modifying therapy

• Proprietary miQURETM silencing platform• Strong mutant HTT knockdown in deep structures

and cortex• Only program to target full-length HTT protein

aggregates and highly toxic HTT exon1 protein fragments

• Potential to be first gene therapy to market

AMT-130: major gene therapy opportunity

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AMT-130: extensive preclinical validation

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

Recent publications

Model Efficacy Safety DistributionCultured human neurons

Rodents(HD rat4) (4 types HD mouse3)

NHP(Non-human primate1)

Pig(tgHD Minipig2)

5. Evers MM et al. Mol Ther. 2018;26(9):2163-21776. Spronck EA et al. Mol Ther Methods Clin Dev. 2019 Mar 16;13:334-3437. Keskin S et al. Mol Ther Methods Clin Dev. 2019 Oct 4;15:275-2848. Caron NS et al. Nucleic Acids Res. 2019 Nov 20. pii: gkz976. doi: 10.1093/nar/gkz976

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• The striatum is the primary site of pathology

• Premanifest stage: atrophy spreads and cortical thinning occurs

• Motor symptoms manifest as atrophy increases

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

Huntington’s disease: expected progression of brain pathology

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.

Occipitallobe

Frontal lobe

Somatomotor cortex

Parietal lobe

1

2 3 3

Somatosensory cortex

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AMT-130: well-tolerated and widespread distribution in the non-human primate (NHP) brain

NHP MRI-guided frontalconvection-enhanced delivery

No procedure-related neurological symptoms following infusion into the striatum

Distribution throughout NHP brain

Putaminal delivery AAV5-GFP

Caudate nucleus

Putamen

Globuspallidus

Thalamus

Hippocampus

uniQure, data on file. MRI, magnetic-resonance imaging Samaranch L. et al, Gene Ther. 2017 Apr;24(4):253-261. Figure 3

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AMT-130: strong reduction of mutant HTT in the minipig brain

Libechov transgenic (tgHD) minipigs:• Lifespan: 12-20 years• Body weight: 50-140 kg• Brain weight: 90-100 g• Highly developed immune system

MRI-guided Convection-enhanced delivery

Comparable mutant huntingtin protein knockdown at 6 and 12 months

Bars represent average ± SEM of n=3-4 animals/group

Prefro

ntal

Somato-S/M

Temporal

Caudate

Putamen

Amygdala

Thalamus

Pons

Cerebell

um

0

25

50

75

100

125

mut

ant

HTT

prot

ein

(% fr

om n

aive

)

6 months12 months

Cortex Striatum

30%

50%

70%

putamen

caudate

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AMT-130: neuropathology in diseased mouse model

Leavitt BR, Vallès. et al., Manuscript in preparation

Mea

n co

ncen

tratio

ntN

AA (m

M)

WT contro

l

Formulat

ion buffer

5.2X

109

1.3X10

114.0

4.5

5.0

5.5

6.0

***

gc AMT-130

Q175FDN

Mea

n co

ncen

tratio

nm

I (m

M)

WT contro

l

Formulat

ion buffer

5.2X10

9

1.3X10

113

4

5

6

7

*

gc AMT-130

Q175FDN

Myo-Inositol (MI)Gliosis marker

N-Acetyl Aspartate (tNAA)Neuronal integrity marker

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AMT-130: full-length and exon1 HTT lowering in striatum and cortex in diseased mouse model

5UTR Exon 1-2 Exon 640.0

0.5

1.0

1.5Full lenght HTT in Striatum

Rel

ativ

e ex

pres

sion

to F

orm

ulat

ion

Buffe

r

5UTR Exon 1-2 Exon 640.0

0.5

1.0

1.5Full-length HTT in Cortex

Rela

tive

expr

essi

on to

For

mul

atio

n Bu

ffer

Early intron 1 Intron 10.0

0.5

1.0

1.5

Rel

ativ

e ex

pres

sion

to F

orm

ulat

ion

Buf

fer Exon1 HTT in Striatum

Early intron 1 Intron 10.0

0.5

1.0

1.5

Rel

ativ

e ex

pres

sion

to F

orm

ulat

ion

Buffe

r

Exon 1 HTT in Cortex

(AAAA)n

(CAG)n

5’UTR E1 E2 E67

Intron 1

(CAG)n

5’UTR (AAAA)nE1

Full-length HTT mRNA

Exon-1 HTT mRNA

Full length HTT in Striatum Full length HTT in Cortex

Exon1 HTT in Striatum Exon1 HTT in Cortex

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AMT-130: significant differentiating features

No immune-related toxicity

No cytotoxic T cells recognizing AAV5 epitopes

Reversal of pathology in a relevant HD animal model

Reversal of neuronal integrity and partial reversal of gliosis (inflammation) in Q175FDN mice

Long-term silencing after a single administration

No need for repeated intrathecal injections

No direct miRNA toxicity and no off-target effects

miHTT expression is well-regulated and the technology does not generate a passenger strand

No long-term neurofilament-light increase in HD pig study (18 months follow-up)

Silences mutant Huntington protein as well as the more toxic small fragments

Uniquely silences exon1 toxicity

Silences mutant Huntington protein species at the site of the pathology

Significant, long-term and therapeutic knock-down in the striatum and sensorimotor cortex

miQURE technology spreads throughout the target CNS region via extracellular vesicles

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Adapted from Ross CA, et al. Nat Rev Neurol 2014;10:204-16

AMT-130: goal of clinical treatment

Premanifest

Motordiagnosis Manifest

Presymptomatic Prodromal Early Moderate Advanced

I II III IV V

100

0

← F

unct

ion

(%)

Slow or haltdiseaseprogression

AMT-130

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Study Overview

• Objectives: assess safety, tolerability and efficacy

• Multicenter, randomized, double-blinded study

• Controlled with imitation surgery

• Two dose cohorts with a total of 26 patients

• Early manifest patients

• 18-month follow-up (5 years for treated patients)

AMT-130: Phase I/II clinical trial

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*Unified Huntington’s Disease Rating Scale

AMT-130: Phase I/II efficacy endpoints

Clinical Parameters*• Total motor score• Total functional capacity

Imaging (MRI and MRS)• Measures of neural function• Striatal volume (atrophy)

Biomarkers• NF-L (neurofilament light)• mHTT in CSF• Other exploratory markers

Quantitative Motor Function• Finger, hand and foot tapping• Grasping and lifting (chorea)

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AMT-130: Phase I/II clinical trial design

Cohort 1: 10 patients (6 dosed, 4 control) Cohort 2: 16 patients (10 dosed, 6 control)

3-month enrollment

stagger followed by

DSMB Review #1

3-month enrollment

stagger followed by

DSMB Review #2

1-month enrollment

stagger followed by

DSMB Review #3

1-month enrollment

stagger followed by

DSMB Review #4

Subject 1&21:1

randomization1 dosed

1 control

Subject 3&41:1

randomization1 dosed

1 control

Subject 5-102:1

randomization4 dosed

2 control

Subject 13&141:1

randomization1 dosed

1 control

Subject 11&121:1

randomization1 dosed

1 control

Subject 15-262:1

randomization8 dosed

4 control

1-month enrollment

stagger followed by

DSMB Review #5

ResearchPipeline

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Novel Approach• Product Construct – AAV5 including C7 Promoter and FIX-Super9™• Super9™ is a proprietary modified FIX that, when activated through normal

mechanisms, activates FX independently of FVIII

AMT-180: a novel approach to Hemophilia A

Long-term and stable expression

Effective in all HemA patients

Compatible with bypass agents

Comparable with emicizumab

• Hepatocyte-friendly• Non-thrombogenic

• Sufficient thrombin generation to stop bleeding episodes

• Not neutralized by FVIII inhibitors

• Safe in combination with rFVIIa and/or FEIBA and emicizumab

• Comparable efficacy in HemA with and without inhibitors

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More effective than replacement therapy

Patients with and without inhibitors

Non-immunogenic

• More stable in plasma• More efficient uptake • Better end-organ

distribution

• Many Fabry patients develop inhibitors to α-gal replacement therapy

• NAGA is not neutralized by α-gal inhibitors

• No loss of activity due to α-gal inhibitors

Novel Approach• Product Construct – AAV5 including modified NAGA• Modified NAGA has therapeutic α-gal activity and gB3 reduction

AMT-190: a new approach to Fabry disease

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• CAG repeat expansion in ATXN3 gene

• Ataxin-3 protein acquires toxic properties

• Brain degenerationcerebellum andbrainstem

• More widespread in later stages

• Ataxia• Dystonia/rigidity• Muscular atrophy• Paralysis

• No medication that slows the progressive course of the lethal disease

AMT-150: a gene therapy for SCA3

Cause Damage Symptoms Unmet Need

Novel Approach• AAV5, SCA3 miRNA administered by intrathecal or cisterna magna injection • Leverages HD platform and experience, including miQURE™ gene silencing technology• Potential to be first to market

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Key near-term catalysts

• Topline data from HOPE-B pivotal study in late 2020• BLA submission in 2021Hemophilia B

• Initiate dosing in Phase I/II study in early 2020 • Early efficacy data on initial patients in 2021Huntington’s

• Submit IND for AMT-180 in 2020• Begin clinical development in 2021Hemophilia A

• Initiate IND-enabling study for SCA3 in 2020• Submit IND application in 2021

Spinocerebellar Ataxia Type 3 (SCA3)

• Continue to increase manufacturing scale and capacity• Conduct manufacturing process validation for EtranaDez (AMT-061) in 2020Manufacturing