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Delivering gene therapy to patients
FORWARD-LOOKING STATEMENTS
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historical facts, contained in this presentation, including statements regarding our strategy, future operations, future financial position, future revenues,
projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,”
“expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are
intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue
reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the
forward-looking statements we make. The forward-looking statements contained in this presentation reflect uniQure’s current views with respect to
future events, and uniQure assumes no obligation to update any forward-looking statements except as required by applicable law.
These forward-looking statements include, but are not limited to, statements regarding the risk of cessation or delay of any of the ongoing or planned
clinical studies and/or development of our product candidates, the risk of delay or failure to successfully commercialize or obtain further regulatory
approval of Glybera, and the risk that our collaborations with Chiesi or our other collaboration partners will not continue or will not be successful. Our
actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, risks
associated with our clinical development activities, regulatory oversight, product commercialization, intellectual property claims, and the risks,
uncertainties and other factors described under the heading “Risk Factors” in uniQure’s form 20-F and the prospectus dated February 5, 2014, both
documents filed with the Securities and Exchange Commission. 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, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements,
except as required by law.
2
Glybera - 1st Approved Gene Therapy in the EU
Glybera for Lipoprotein Lipase Deficiency
3
Gene Therapy and uniQure:
Changing the Future of Medicine
 1 time interventions
 Long term effect
 Highest possible patient benefit
 Highly disruptive*
 Cutting edge science
 Manufacturing leadership
 Modular portfolio development
 Regulatory expertise
 Commercialization experience
 Strong management team
4
Gene
therapy
– a real
opportunity
uniQure has
all the
building
blocks
A new
chapter in
the history
of medicine
*) MIT Review / Fierce 15:
uniQure among 50 most
disruptive companies in 2013
Establish Gene Therapy Leadership
Build a Portfolio
Milestones
Glybera – Gene Therapy for an Orphan Disease
Single intervention to restore lipoprotein lipase enzyme

Chronic disease with severe symptoms
>
>
>

High unmet medical need
>
>
>
>
>
>

Severe and life-threatening complications
Extreme levels of pain and quality of life impact
Threatens mother and child during pregnancies
Daily symptoms
Extreme diet restrictions
Significant cost burden to the medical system
Treatment goal with AAV1 gene therapy
>
>
>
6
Hyperchylomicronemia
Recurrent abdominal pain and pancreatitis
Diabetes/Atherosclerosis
Restore LPL function
Prevent complications
Control symptoms
Restoration of LPL Activity Leads to Improved Lipid
Clearance 1 Yr Post a Single Intervention
Depiction (3H-Palmitic acid tracer) of appearance and removal of newly formed
chylomicrons from the blood after a standardized meal
[3H] activity in CMs
(per cent ID per 100ml plasma)
5/5 patients pre-intervention (N=5)
3/3 patients post-intervention, week 52 (N=3)
0,8
5/5 patients post-intervention, week 14 (N=5)
0,7
Pre
0,6
0,5
0,4
0,3
52 wks. Post
0,2
0,1
14 wks. Post
0,0
0
5
10 Time after meal (hours) 15
20
NB: Tritium activity in centimorgans (cM) is an indirect measure of chylomicrons
7
25
3 year post treatment follow-up suggests reduction
in incidence and severity of pancreatitis events
6 yr follow-up head line data released in 03/2014 confirm 3 year follow-up
No. of ICU(1) stays
Pancreatitis
Patient
4
6
7
8
9
11
14
15
20
1001
1002
2001
Total
Pre-treatment2)
No. of Hospitalization(1)
Post-treatment2)
Severe
Mild
Severe
Mild
Pre-treatment
Post-treatment
Pre-treatment
Post-treatment
0
2
1
1
0
1
7
2
1
0
1
0
3
0
1
1
8
2
9
11
6
14
23
8
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
2
1
0
1
0
2
1
0
0
2
6
1
1
0
4
0
0
0
0
0
0
0
0
0
0
0
0
0
3
2
2
2
8
3
16
13
7
14
24
8
0
0
0
0
0
0
1
0
2
1
0
1
16
86
0
5
17
0
102
5
ZERO severe
pancreatitis events
in 6 years post
a single intervention
ZERO ICU stays
in 6 years post a
single intervention
Reduction in acute pancreatitis resulting in fewer ICU stays and hospitalization days
(1)
(2)
8
Table represents only ICU / hospitalizations resulting from definitive / probable pancreatitis; the overall number of
ICU / hospitalizations is significantly larger
Pre-treatment = life before treatment, post-treatment = life post treatment
EU Post-approval Commitments Foundation for
US Filing
US filing planned
based on
EU-post approval
commitments
Post-approval commitments
Clinical trials
leading to
EU Glybera
approval
Registry (incl. natural history)
Post-approval study
EU approval under
exceptional circumstances
2012
9
2013
2014
2015
2016
2017
uniQure Retains Rights in Attractive Key Markets

uniQure retains key markets including
North America and Japan

Commercialization in
North America by
uniQure

Distribution agreements in
other geographies based on
business case vs. own organization

Chiesi have European
commercialization rights
>
>
EUR 31 m down payment
20 – 30% royalty from Chiesi
uniQure Territories
Chiesi Territories
10
Glybera EU Launch Preparations Led by Chiesi
Preparations for launch in mid-2014

1st wave: Germany, UK, Holland, Sweden and Austria
> Product released for patient treatment
> Centers of Excellence prepared for first LPLD patients
 Site preparations including Registry set-up finalized
 Health care staff training on track
 LPLD patients identified, consent procedure ongoing
> European Pricing Strategy and implementation plan finalized

In Germany negotiation between hospital and sick fund (in-patient) in progress
> AMNOG process for out-patient treatment, core value dossier close to final
11
Gene Therapy Platform Building Blocks
Gene
“Blueprint”
Vector
THERAPEUTIC
DELIVERY
VEHICLE
12
Manufacturing
GENE /
VECTOR
COPIES
Administrating
“Protein Factory”
in the body
GENE/VECTOR
COPIES INTO
THE CELLS
PROTEIN
FACTORY
uniQure’s Vector Platform Evolution
TROPISM
natural AAV
AAV1 Exclusive
for LPLD in Muscle
AAV2
AAV5
Exclusivity for
LIVER / CNS
AAV6
AAV8
AAV9
13
DIRECTED EVOLUTION
optimized AAV
4D Therapeutics
Synthetic
Synthetic
AAV
Mutants
Synthetic
AAV
Mutants
Synthetic
AAV
Mutants
Synthetic
AAV
Mutants
Synthetic
AAV
Mutants
Synthetic
AAV
Mutants
Synthetic
AAV
Mutants
Synthetic
AAV
Mutants
Synthetic
AAV
Mutants AAV
Synthetic
AAV
Mutants
Super Mutants
uniQure’s Leading Manufacturing Platform
uniQure
Baculo-based
Plasmid-based
adherent cultures
Plasmid-based
Suspension cultures
Herpes-based
Adenovirus-based
Suspension
Cell Culture
++
-
++
+
++
Efficiency
DNA Transfection
++
+
-
++
++
Scalability
++
--
-
+
++
Safety
++
-
-
concerns
concerns
Low COGs
++
-
-
+
+
EU Regulatory Approved
++
-
-
-
-
FTO / IP Protection
++
-
-
complex
complex
14
World-leading Manufacturing Capabilities in EU and US
Building the world’s largest dedicated AAV manufacturing unit in the US

US manufacturing site
> Lexington, Ma
> 2 x 500 L (expansion to 2 x 2000
L possible)
> Copy/scale of exisitng technology
> Estimated time of completion for
test batches end of 2014

Amsterdam, NL
> 2 x 50 L, EMA approved facility
15
Establish Gene Therapy Leadership
Build a Portfolio
Milestones
Pipeline 2014
PRECLINICAL
I
II
III
GLYBERA EU
GLYBERA US
HEMOPHILIA B
ACUTE INTERMITTENT PORPHYRIA
SANFILIPPO B
PARKINSON’S DISEASE
6 PRECLINICAL incl. (HEMOPHILIA A, ….
uniQure sponsored
17
investigator led
MARKET
Hemophilia B
Spontaneous bleeds, joint damage, compliance
18
Hemophilia B
Gene therapy can become treatment of choice

Preferred therapy today: enzyme replacement
> 2 treatments / week / patient
= > 6,000 treatments over a lifetime
> Total number of hospital days over 10 years
(156 severe hemophilia patients, 1989–1999)*
= On demand: 320 hospital days/10 years
= Prophylaxis: 246 hospital days/10 years
> Cost per severe patient: > US$ 300 k p.a./patient
= > US$ 15 million

Future: Gene Therapy, single interventions, long lasting effect
* On-demand vs. prophylactic treatment for severe haemophilia in Norway and Sweden: differences in treatment
characteristics and outcomeK. STEEN CARLSSON et al, Haemophilia (2003), 9, 555–566
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AAV8/FIX Single Intervention Using uniQure Gene
Cassette Reduces Need for Prophylactic Treatment(1)
St Jude/UCL trial started 4 yrs. ago demonstrated sustained, dose dependent effect:
after single treatment 6/8 patients off prophylaxis, 2/8 significantly lower frequency
% Expression
of normal
Mid-dose
Low-dose
12
11
10
9
8
7
6
5
4
3
2
1
High-dose
Presented in New England Journal of Medicine 12/2011
Mild
Moderate
1
2
3
4
5
Patient
1) Third party trial conducted by St. Jude’s Children Research Hospital and UC London
20
Oral Presentation
Disease
Severity
6
7
8
Severe
AAV5/FIX Phase I/II Dose Escalation Study in 2014
AAV8 mammalian
cell-based
AAV5 insect cell
production
Population
>
>
High
(2.0 × 1013)
Dose (gc/kg)

uniQure

Objectives
>
>
uniQure
Mid
(2.0 × 1012)
ST Jude
ST Jude
Low
(2.0 × 1011)
21
ST Jude

≦ 1% of normal plasma
factor IX levels
On prophylactic therapy
Assess safety/tolerability
Define optimal therapeutic dose
Key efficacy assessments
>
>
>
>
Factor IX plasma levels
Need for FIX replacement
therapy
Incidence of spontaneous
bleeding
Health related quality of life
AAV5/FIX - Efficacy in Primates
h F IX p ro te in
A M T - 0 6 0 in C y n o m o lg u s m o n k e y s
100
in C y n o m o lg u s m o n k e y s
100
22
1
0 .1
1
h F IX p ro te in
10
h F IX p ro te in
h F IX p ro te in
(% o f n o rm a l h u m a n le v e ls )
(% o f n o rm a l h u m a n le v e ls )
h F IX p ro te in
100
Preclinical data suggests AAV5 works
as well as AAV8
10
100
10
A M T - 0 6 0 in C y n o m o lg u s m o n
keys
Porphyria
Porphyria
A M T - 0 6 0 in C y n o m o lg u s m o n k e y s
100
(% o f n o r m a l h u m a n le v e ls )
Human AAV5/FIX levels in dose
escalating GLP tox study show
linear dose response
A M T -0 6 0
AMT-060
A M T -0in6 0Cynomolgus
in C y n o m oMonkeys
lg u s m o n k e y s
AMT-060 in Rhesus Monkeys
10
1
Key
(% o f n o rm a l h u m a n le v e ls )

Human AAV5/FIX expression
levels in macaques similar to
those achieved in humans from
current AAV8 clinical study
(UCL/St Jude’s)
(% o f n o rm a l h u m a n le v e ls )

1
0 .1
10
0
50
100
150
5 e 1 1 g c /k g
D a y s a fte r v e c to r in fu s io n
5 e 1 2 g c /k g
5 e 1 1 g c /k g
1
5 e 1 1 g c /k g
5 e 1 2 g c /k g
5 e 1 1 g c /k g
5 e 1 2 Porphyria
g c /k g
2 .5 e 1 3 g c /k g
5 e 1 2 g c /k g
2 .5 e 1 3 g c /k g
2 .5 e 1 3 g0c.1
/k g
9 .3 e 1 3 g c /k g
9 .3 e 1 3 g c /k g
9 .3 e 1 3 g c /k g
0 .1
0
0 .1
01
2 503
100
50
100
150
D a1y5s0a fte r v e c to r in fu s io n
2 .5 e 1 3 g c /k g
9 .3 e 1 3 g c /k g
AAV5/FIX Competitive Position
uniQure timeline puts AA5-FIX as first to market –
no other gene therapy competitor has full FTO or validated manufacturing
uniQure validated
and scalable
Competitors:
uniQure AAV5
manufacturing
exclusive Spark,
from Baxter,
NIH Dimension,
Biomarin
process
uniQure gene
cassette exclusive
from St. Jude
23
Hemophilia Enzyme Replacement Market
Big market volume to protect for current ERT competitors
Market Volume (in US$ bn)
Market:
US$ 8 bn
Growth
Hemophilia A
Hemophilia B
6% p.a.
Sources: Morningstar Estimates
24
Establish Gene Therapy Leadership
Build a Portfolio
Milestones
Raised net proceeds of US$ 85 m in NASDAQ IPO
to reach multiple clinical milestones
2014
H1
Glybera – EU launch
Porphyria results
2015
H2
H1
2016
H2


Sanfilippo B results

26
H2

Hemophilia B results
Glybera Data to Support
U.S. Filing
H1

Gene therapy and uniQure:
Changing the future of medicine
 1 time interventions
 Long term benefit
 Highest possible patient benefit
 Highly disruptive*
 Cutting edge science
 Manufacturing leadership
 Modular portfolio development
 Regulatory expertise
 Commercialization experience
 Strong management team
27
Gene
therapy
– a real
opportunity
uniQure has
all the
building
blocks
A new
chapter in
the history
of medicine
*) MIT Review / Fierce 15:
uniQure among 50 most
disruptive companies in 2013
The Leader in Gene Therapy
Chiesi – strategic partner for EU commercialization

Chiesi – strategic focus on advanced therapeutics
>
>
€1.1 bn in revenues, 3,800 employees
Acquired Cornerstone (US) Sep 2013 (for $250m), Zymenex in Aug 2013

EU-focused partnership for Glybera and Hemophilia B

Key partnership terms
>
>
Effective June 2013
Financial terms
Development-related
€17m / (US$22m)
Equity Investment
€14m / (US$18m)
Upfront
Glybera
20-30%
Hemophilia B
25-33%
Estimated uniQure share of Net Sales
Milestones
>
>
29
Up to €42m / (US$57m)
Glybera (Commercial)
Full commercialization costs to be born by Chiesi
Chiesi carries 50% of HemB development cost
1
2
3
uniQure’s leading manufacturing capability
Safe Manufacturing System
 Serum-free manufacturing system
 No need for using pathogenic viruses

Cost-effective Platform
 Yield per production cell equal or higher than

such as herpes simplex or adenovirus for
AAV production
No co-production of replication competent
AAV (regulatory requirement)
uniQure
manufacturing
Platform
High Degree Of Validation By
EU Regulators and Pharma
 Meeting requirements of Good Manufacturing
Improved Quality Product
 Low ratio of so-called "empty


30




mammalian cell based production systems
Suspension cell line that can be grown at high
densities leading to high volumetric yields
Easily scalable technology
No need for expensive raw materials
No need for stable cell lines (difficult to make)
Significantly less FTEs required
particles” (without need for
centrifugation steps)
Favorable impurity profile
Monomeric duplex technology (double
stranded, self-complementary)



1
2
3
Practices (GMP)
Licensed by EMA
Cell line and baculovirus technology accepted
by FDA (approved BLA from Protein Sciences)
FTO / Strong IP position
AAV5/FIX Competitive Landscape
uniQure timeline puts AA5-FIX as first to market - no other gene therapy competitor
has validated manufacturing
Gene Therapy
Non-gene Therapy Products
Marketed
BeneFIX® RT
(Pfizer)
Nonafact®
(Sanquin)
Rixubis
(Baxter)
rFIXFc
(Biogen / Syntonix)
rIX-FP
(CSL Behring)
N9-GP (NN7999)
(Novo Nordisk)
Phase III
BAY86-6150 (FVIIa)
Bayer
Phase I / II
IB1001
(Inspiration Bio)
AAV8-hFIX
(CH Philadelphia / Spark Therapeutics –
Phase I/II to October 2019)
PF-05280602 (FVIIa)
Pfizer
AAV8-FIXco
(St Jude CH – Phase I to Feb 14)
AAV8-FIX’
(AskBio / Baxter – Phase I/III to Aug 17)
AAV5-FIX
(uniQure)
Pre-clinical
ZFP Hemophilia Program
(Shire / Sangamo)
Enzyme Replacement
31
Non-final product
Full freedom-to-operate

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