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 O C T O B E R 2 0 1 9 | 1

Corporate PresentationOctober 2019

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Forward-looking StatementsThis 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 July 29, 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.

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• Demonstrated clinical proof of concept in Hemophilia B; achievement of patient enrollment in HOPE-B pivotal study, with potential to be first- and best-in-class

• Proprietary CNS platform with lead program AMT-130 in Huntington’s disease expected to initiate dosing in Phase I/II study this year

• Strong pipeline of additional product candidates approaching the clinic including in Hemophilia A, Fabry disease, and SCA3

• Global commercial rights retained for all core programs

• Leadership in large-scale, cGMP manufacturing of AAV gene therapies

Key corporate achievements and capabilities

• Portfolio of enabling technologies and IP, including miQURE™ gene silencing, FIX-Padua variant, re-administration, manufacturing processes and AAV5 and other novel vectors and promoters

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Our proprietary pipeline

*Collaboration with Bristol-Myers Squibb

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Leading the way in AAV manufacturing

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

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Leveraging AAV5: a potentially best-in-class vector

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

AAV5 Vector

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Hemophilia BEtranacogene dezaparvovec(AMT-061)

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Increases in FIX activity up to 54% of normalMean FIX activity at 36 weeks of 45% of normalMain Efficacy Findings:

• Sustained increases in FIX activity

• No bleeding events post-treatment

• No infusions of replacement therapy for bleeds

• No requirement of immunosuppression

• No exclusion of patients with pre-existing NAbs

Main Safety Findings:• Well-tolerated

• No serious adverse events related to treatment

• No inhibitor development

Etranacogene dezaparvovec (EtranaDez): FIX activity at 36 weeks post-treatment in Phase 2b study

54.1

30.1

50.9

0

10

20

30

40

50

60

70

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36

FIX

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ity o

ne-s

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Week

Participant 1

Participant 2

Participant 3

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

• Achieved enrollment of 62 patients with severe and moderately-severe Hemophilia B

• 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

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Huntington’s DiseaseAMT-130

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Huntington’sAMT-130

• 3-7 per 100K people1

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

dosing of Phase I/II

1 Rawlins, MD. Neuroepidemiology 2016;46:144-153

Target product profile

• One-time administration of disease-modifying therapy

• Proprietary miQURETM silencing platform

• Strong mutant HTT knockdown in deep structures and cortex

• Targets full length HTT protein aggregates and highly toxic HTT exon1 protein fragments

• Potential to be first to market

Executing in Huntington’s Disease

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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

Huntington’s disease: expected progression of brain pathology

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.

Occipitallobe

Frontal lobe

Somatomotor cortex

Parietal lobe

1

2 3 3

Somatosensory cortex

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AMT-130: goal of clinical treatment to slow or halt disease progression from an early stage

1 Lower Limit of Detection

Vector DNA distribution

1 x 1 01 3

g c A A V 5 - m iH T T

3 x 1 01 3

g c A A V 5 - m iH T T

1

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Samaranch L. et al, Gene Ther. 2017 Apr;24(4):253-261. Figure 3

Penetration throughout non-human primate brain

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AMT-130: strong reduction of mutant HTT

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

N=12

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

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ntal

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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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AMT-130: Phase I/II clinical trial

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 with ≥ 44 CAG repeats

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

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AMT-130: Phase I/II clinical trial endpoints

Clinical Parameters*• Total motor score• Total functional capacity• Composite score

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

Volumetric MRI and MRS• Measures neuronal atrophy

and function

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

Patient-reported outcomes• Neuro-QoL• HD QLIFE

Efficacy Endpoints

*Unified Huntington’s Disease Rating Scale

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AMT-130: Phase I/II clinical trial design

Cohort 1 Cohort 2

DSMB Review #1

at 3 months follow-up

DSMB Review #2

at 3 months follow-up

DSMB Review #3

at 3 months follow-up

DSMB Review #4at 1 month follow-up

DSMB Review #5at 1 month follow-up

Subject 1&21:1

randomization1 AMT-1301 control

Subject 3&41:1

randomization1 AMT-1301 control

Subject 5-102:1

randomization4 AMT-1302 control

Subject 13&141:1

randomization1 AMT-1301 control

Subject 11&121:1

randomization1 AMT-1301 control

Subject 15-262:1

randomization8 AMT-1304 control

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Research Pipeline

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AMT-180: a novel approach to Hemophilia A

Long-term and stable expression

Effective in all HemApatients

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

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

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More effective than replacement therapy

Patients with and without inhibitors

• 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

AMT-190: a new approach to Fabry disease

Novel Approach

• Product Construct – AAV5 including modified NAGA

• Modified NAGA has therapeutic α-gal activity and gB3 reduction

Non-immunogenic

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

• Initiate dosing in Phase I/II study before end of 2019• Preliminary biomarker data on initial patients in 2020

• Submit IND for AMT-180 in 2020

• Initiate IND-enabling study for SCA3 in 2019• Targeting one new IND-submission each year

Hemophilia B

Huntington’s

Hemophilia A

Other Programs

Key corporate goals