Corporate PresentationJANUARY 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 November 6, 2018. 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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Our mission

To deliver curative, one-time therapies that transform the lives of patients.

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Our strategic imperatives

Develop a proprietary pipeline of gene therapy candidates focused on liver-directed and CNS disorders

Maintain leadership in commercial-scale manufacturing of AAV gene therapies

Invest and leverage next-generation technologies that optimize and expand the applicability of gene therapy to patients

Expand and maintain our leading IP portfolio

Retain valuable commercial rights

Pipeline

Manufacturing

Enabling Technologies

Intellectual Property

Commercialization

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A pioneer in AAV gene therapy

+20 years of experience in AAV gene therapy

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Leading the way in AAV manufacturing

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

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

Benefits• Control and flexibility• Consistent process from preclinical to

commercial• 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 outcomes

• Long-term follow-up data demonstrating safety and tolerability

• 25 patients have received AAV5 across 4 clinical studies1

• Demonstrated clinical outcomes in the liver and brain

• Lowest prevalence of pre-existing neutralizing antibodies2

• Favorable immunogenicity profile for systemic, intravenous delivery

• No confirmed T-cell-mediated immune responses to capsid

1 Clinical trials in Hemophilia B, Sanfilippo B and Acute Intermittent Porphyria2 Boutin et al 2014

AAV5 Vector

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Investing in proprietary enabling technologies

Expression

Increase expression of genetic material

Immunogenicity

Mitigate immune activation

Delivery

Optimize targeting and administration

Biodistribution

Improve uniformity of transduction

BEST-IN-CLASS GENE THERAPIESIncreased patient eligibility

Applicability to more diseasesImproved safety & efficacy

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Expanding our proprietary pipeline

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Hemophilia BAMT-061

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Executing in Hemophilia B

• 10-15K patients in US/EU

• >$1B market in 20161

• Near-term goal: Complete enrollment in pivotal study

Hemophilia BAMT-061

1 GlobalData report 2016

Target product profile

• Potential for functionally-curative increases in FIX activity

• Durable and predictable outcomes

• Low risk of immune responses

• Greater patient eligibility due to low levels of NABs

• Strong intellectual property

• Potential to be first to market

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Characteristics of the Participants at BaselineAge (years) 43 50 47

Weight (kg) 89 81 82

HIV Status Negative Positive, controlled Positive, controlled

Hep B / Hep C Hep C; resolved Hep C; resolved Hep C; resolved

Hemophilia B status

Severe FIX Deficiency (<1%)

Severe FIX Deficiency (<1%)

Severe FIX Deficiency (<1%)

Pre-screening FIX treatment Prophylactic Prophylactic Prophylactic

ABR 1 year prior to screening 3 1 5

AMT-061: dose-confirmation study

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All patients experienced

increasing and sustained FIX

activity

No reported bleeding events

No infusions of FIX replacement

therapy

No immuno-suppression

required

At six weeks after the administration of AMT-061, patients achieved a mean FIX activity level of approximately 31% of normal

AMT-061: efficacy perspective with 24 weeks of cumulative patient data

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AMT-061: estimated FIX activity in humans (1)

30-50%

ESTIMATED PATIENT

VARIABILITY

20-35%

6 to 8 Weeks

52 Weeks

(1) Interim and steady state FIX estimates based on AMT-061 and AMT-060 animal data and AMT-060 Phase I/II clinical data (at one year follow-up)

//

FIX activity at 6 to 8 weeks after gene transfer expected to be 65% to 70% of peak

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AMT-061: summary of top-line data at 24 weeks of cumulative patient observation

• AMT-061 has been generally safe and well-tolerated with no serious adverse events occurring during or after vector infusion

• All patients achieved therapeutic1 levels of FIX activity 6 weeks after treatment, with mean FIX activity of 31% of normal

• No participants reported bleeds or required any infusions of factor replacement therapy

• No patients required any immunosuppression or experienced loss of FIX activity

1 Epidemiological data indicate that factor activity above 12% of normal is associated with substantial reduction or elimination of spontaneous bleeds and factor usage. Den Uijl IE et al Haemophilia 2011; 17(6):849-53

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AMT-061: HOPE-B Phase III pivotal study

• Open label, single-dose, multi-center, multi-national trial

• Approximately 50 patients with severe and moderately-severe hemophilia B

• Patients with AAV5 antibodies will not be excluded

• Patients will 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

clinical study in 2019

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

Target product profile

• One-time administration of disease-modifying therapy

• Proprietary miQURETM silencing platform

• Strong mHTT knockdown in both deep structures and cortex

• Preclinically shown to be generally safe and well-tolerated

• Potential to be first to market

Executing in Huntington’s Disease

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AMT-130: Huntington’s disease

Therapeutic Targeting

• mHTT leads to damage in the striatum, and in later stage disease, in parts of the cortex

• Therapeutic targeting of striatum (caudate nucleus and putamen), globus pallidus and cortex (sensorimotor)

Ross CA., et al. Nat Rev Neurol. 2014 Apr;10(4):204-16

Huntington’s Disease Pathway

Degenerated regions

PreservedRegions

Huntington’s disease

• Caused by expansion of CAG trinucleotide in exon 1

• No disease-modifying therapies available

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

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AMT-130: treating Huntington’s disease

AMT-130 gene therapy for Huntington’s disease (HD)

• Non-selective knockdown of huntingtin protein (HTT) in the brain

• Utilizes proprietary miRNA that binds to and degrades HTT mRNA

• One-time injection in the striatum, the primary affected structure in HD

• AAV5 has been shown to have widespread distribution in brain, including cortex

• MRI-guided stereotactic administration directly into deep structures of brain

• Demonstrated preclinical PoC in multiple small and large animal models

• AMT-130 leverages same manufacturing platform and process used for AMT-061

Caudate nucleusPutamen

AMT-130

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AMT-130: widespread distribution in brain

1 Lower Limit of Detection

Vector DNA distribution

1

Vect

or g

enom

e co

pies

per

g DN

A

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

Penetration throughout NHP brain

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AMT-130: strong reduction of mHTT

Mutant huntingtin protein knockdown at 6 months

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

Median. Each dot represents the average value of 3 tgHD minipig animals

47.0% 67.5% 28.2% 46.5%12.0% 40.7%

N=12 N=21 N=9 N=9 N=12 N=6 N=12

MRI-guided CED

putamen

caudate

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AMT-130: considerations for Phase I/II dose escalation study

• Early manifest / stage 1 patients

• ≥ 44 HTT CAG repeats

• 3 surgical sites in U.S.

• At least 2 non-surgical sites

• Randomized, double-arm, blinded study with sham control

• CSF mHTT protein, miHTT, other biomarkers measured over 9-18 months

• Other exploratory endpoints

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AMT-130: considerations for Phase I/II dose escalation study

HD patients

Screening / Randomization

Measurements over 9-18 months

CSF levels at baseline and over time will be monitored with other exploratory parameters

Clinical Parameters (e.g. UHDRS, HD-

CAB)

Quantitative Motor Function

Volumetric MRI and MRS

Patient-reported outcomes

Biomarkers of neuronal injury

Open-labelaccess

Sham controls

15M 18M1M 3M 6M 12M9M 15M

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AMT-130: status and next steps

• Established pre-clinical proof of concept

• Completed safety toxicology studies

• Granted Orphan Drug Designation by FDA

• Granted Orphan Medicinal Drug Designation by EMA

Current Status

• Clearance of IND for AMT-130

• Begin first-in-human clinical study

Next Steps

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Research Pipeline Expansion

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Long-term and stable expression

Effective in all hemophilia A

patients

Compatible with bypass agents

Comparable with emicizumab

• Hepatocyte-friendly• Stable long-term

expression• Non-immunogenic

• 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 HemAwith and without inhibitors

AMT-180: Super9™ – A new approach to hemophilia A

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AMT-180: expression levels in NHPs expected to translate to therapeutically relevant FVIII mimetic activity in humans

male Cynomolgus macaquen=2IV, 9e13 gc/kgadapted delivery

1) AAV5-LP1-Super92) AAV5-P-IDAV3) AAV5-P-Super9

1 vehicle treated NHP• Wk 13: FEIBA injection• Wk 15: FVIIa injection

AAV5-P-Super9AAV5-P-IDAVAAV5-LP1-Super9vehicle

-1 0 1 2 3 4 5 6 7 8

50

100

150

200

250

hFIX protein (%) in NHPs

weeks post-injection

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Hepatocyte-friendly

Not immunogenic

ManufacturabilitySufficient thrombin

generation

Expected to prevent bleeding

Long-term expression in mice

Proven record manufacturing FIX mutant

proteins

AMT-180: preclinical data findings

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In Fabry disease Gb3 and lyso-Gb3 accumulate in tissues throughout the body, resulting in a wide range of debilitating symptoms

• Patients suffer from pain, angiokeratomas, hypohidrosis, corneal opacity, gastrointestinal tract disorder, hearing loss, renal failure, cardiac involvement and cerebrovascular disorder

• Two Fabry phenotypes depending on the α-Gal A levels:

• Classic Fabry: <1% of α-Gal A activity: early onset

• Variant Fabry: >1% of α-Gal A activity: late onset

in black: early symptomsin red: late symptoms

AMT-190: Fabry disease, a lysosomal storage disease

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AMT-190: injection of the modified NAGA protein in Fabry mice, superior GLA activity in the liver, kidneys and heart

Tajima Y et al. Am J Human Genetics 2009

Wild typeFabryModified NAGAFabrazymeReplagal

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More stable in plasma and better end-organ

distribution

Preclinical Proof of Concept

AAV/modNAGAcauses

therapeutic GLA activity and gB3

reduction

Non-immunogenic long-term replacement product

for Fabry

Potentially more effective than current replacement

therapy

Ready for toxicology studies

AMT-190: preclinical data findings

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Cause Damage Symptoms Unmet need

AMT-150: halt brain degeneration in SCA3 patients

CAG repeat expansion in ATXN3 gene:

Ataxin-3 protein acquires toxic

properties

Brain degenerationCerebellum and

BrainstemMore widespread in

later stages

AtaxiaDystonia/RigidityMuscular atrophy

Paralysis

No medication that slows the progressive course of the lethal

disease

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SCA3 mouse model

• N = 3 per group• In-life 6 weeks

AMT-150: 65% ataxin-3 lowering in brainstem of SCA-concept3 mice after cisterna magna injection of miQURE

miQURETM

Control miQURE_A miQURE_B miQURE_C0

25

50

75

100

SCA3 mouse brainstem

Mut

ant a

taxi

n-3

prot

ein

(%)

Rel

ativ

e to

con

trol

* *

Up to 65% ataxin-3 loweringin SCA3 mice

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Ataxin-3 lowering in SCA3 mice

Widespread brain

transduction

Strong target

engagementNo off-target

effects

Candidate selection Proof-of-mechanism Enhancing intrathecal delivery

AMT-150: halt ataxia with our proprietary miQURE therapy