forward-looking statements

Delivering gene therapy to patients
FORWARD-LOOKING STATEMENTS
This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of
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.
We have filed a registration statement (including a prospectus) with the Securities and Exchange Commission, or SEC, for the offering to which this
presentation relates. Forward-looking statements represent our management’s beliefs and assumptions only as of the date of the prospectus. You
should read the prospectus, including the Risk Factors set forth therein, and the documents that we have filed as exhibits to the registration
statement, of which the prospectus is a part, completely and with the understanding that our actual future results may be materially different from what
we expect. We have included important factors in the cautionary statements included in the prospectus, particularly in the Risk Factors section, that
we believe could cause actual results or events to differ materially from the forward-looking statements that we make. Except as required by law, we
assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from
those anticipated in the forward-looking statements, even if new information becomes available in the future.
We have filed a registration statement (File No. 333-193158), including a prospectus, with the SEC for the offering to which this communication
relates. Before you invest, you should read the prospectus in that registration statement and other documents the issuer has filed with the SEC for
more complete information about the issuer and this offering. You may get these documents for free by visiting EDGAR on the SEC website at
www.sec.gov. Alternatively, the issuer, any underwriter, or any dealer participating in the offering will arrange to send you the prospectus if you request
it by calling Jefferies LLC at 1-877-547-6340 or Leerink Partners LLC at 1-800-808-7525.
2
Gene therapy and uniQure:
Changing the future of medicine
!  Life changing
!  Disruptive*
!  Validated
!  Cutting edge science
!  Manufacturing leadership
!  Modular portfolio development
!  Regulatory expertise
!  Commercialization experience
!  Strong management team
3
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
3 core strategies to build world leader in gene therapy
3
2
1
Establish
gene therapy
4
Develop
gene therapy
portfolio
Maintain
gene therapy
leadership
Building blocks of gene therapy
Gene
“Blueprint”
Vector
THERAPEUTIC
DELIVERY
VEHICLE
5
Manufacturing
GENE /
VECTOR
COPIES
1
2
3
Administrating
“Protein Factory”
in the body
GENE/VECTOR
COPIES INTO
THE CELLS
PROTEIN
FACTORY
Modular concept
Product development with reduced time to patient, lower cost
Muscle
Liver
CNS
Building blocks
Functional Gene
Vector
LPLD
Porphyria
Hemophilia B
Sanfilippo B
LPL
PBGD
Factor IX
NaGlu
AAV1
AAV5
Manufacturing
Administration
6
Insect Cell Manufacturing
Intramuscular (IM)
Intravenous (IV)
1
2
3
Intra-cranial / CSF
Lipoprotein lipase deficiency – an orphan disease
Glybera – single intervention to restore lipoprotein lipase enzyme
! 
Chronic disease with severe symptoms
>  Hyperchylomicronemia
>  Recurrent abdominal pain and pancreatitis
>  Diabetes/Atherosclerosis
! 
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
>  Restore LPL function
>  Prevent complications
>  Control symptoms
7
1
2
3
What evidence has been collected over 8 years?
Introduction of the LPL gene leads to consistent results
Gene
Protein
! 
! 
8
! 
Vector DNA in muscle sustained after
single dose
! 
Restoration of LPL enzyme activity
documented
! 
LPL mediated lipid uptake
re-established
Improvement of postprandial
chylomicron metabolism
Enzyme Function
! 
Clinical
improvement
! 
Strong safety profile
EU regulatory approval of manufacturing platform established
1
2
3
Reduction in risk of acute pancreatitis,
hospital and ICU stay
Restoration of LPL activity leads to improved
lipid clearance post treatment
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
9
1
2
3
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
Pancreatitis
Patient
Pre-treatment2)
No. of ICU(1) stays
No. of Hospitalization(1)
Post-treatment2)
Severe
Mild
Severe
Mild
Pre-treatment
Post-treatment
Pre-treatment
Post-treatment
4
6
7
8
9
11
14
15
20
1001
1002
2001
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
Total
16
86
0
5
17
0
102
5
Reduction in acute pancreatitis resulting in fewer ICU stays and hospitalization days
(1) 
(2) 
10
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
1
2
3
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
11
2013
2014
2015
1
2
3
2016
2017
3 core strategies to build world leader in gene therapy
3
2
1
Establish
gene therapy
12
Develop
gene therapy
portfolio
Maintain
gene therapy
leadership
Pipeline 2014
Preclinical
I
II
Glybera EU
Glybera US
Hemophilia B
Acute Intermittent Porphyria
Sanfilippo B
Parkinson’s Disease
6 Preclinical Programs (Hem A, ….)
13
1
2
3
III
Market
AAV8/FIX containing uniQure gene cassette
results in marked reduction of prophylactic treatment(1)
St Jude/UCL trial started 4 yrs. ago shows sustained, dose dependent effect:
6/8 patients off prophylaxis, 2/8 significantly lower frequency after single treatment
% Expression
of normal
Mid-dose
Low-dose
12
11
10
9
8
7
High-dose
Oral Presentation
Presented in New England Journal of Medicine 12/2011
Mild
6
5
4
3
2
1
Moderate
1
2
3
4
5
6
Patient
1) Third party trial conducted by St. Jude’s Children Research Hospital and UC London
14
Disease
Severity
1
2
3
7
8
Severe
AAV5/FIX Phase I/II dose escalation study in 2014
AAV8 mammalian
cell-based
AAV5 insect cell
production
High
(2.0 × 1013)
uniQure
! 
Population
> 
1% of normal plasma
factor IX levels
>  On prophylactic therapy
! 
Objectives
Dose (gc/kg)
>  Assess safety/tolerability
>  Define optimal therapeutic dose
uniQure
Mid
(2.0 ×
1012)
! 
>  Factor IX plasma levels
>  Need for FIX replacement
therapy
ST Jude
ST Jude
Low
(2.0 ×
15
Key efficacy assessments
>  Incidence of spontaneous
bleeding
>  Health related quality of life
ST Jude
1011)
1
2
3
AAV5/FIX efficacy in primates, dose dependent efficacy
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
16
1
1
100
10
1
Key
50
5 e 1 1 g c /k g
01
50
9 .3 e 1 3 g c /k g
0 .1
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 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
100
9 .3 e 1 3 g c /k g
50
100
150
D a1y5s0a fte r v e c to r in fu s io n
1 0 0 D a y s1 5a 0fte r v e c to r in fu s io n
1 0 0D a y s1 5a 0fte r v e c to r in fu s io n
D a y s a fte r v e c to r in fu s io n
2 .5 e 1 3 g c /k g
5 e 1 1 g c /k g
2 503
5 e 1 2 g c /k g
1
10
0
0 .1
0
10
9 .3 e 1 3 g c /k g
0 .1
0 .1
0
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 )
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
10
Preclinical data suggests
AAV5 works
as well as AAV8
100
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
10
(% 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
100
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
h F IX p ro te in
! 
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 )
! 
2 .5 e 1 3 g c /k g
9 .3 e 1 3 g c /k g
3 core strategies to build world leader in gene therapy
3
2
1
Establish
gene therapy
17
Develop
gene therapy
portfolio
Maintain
gene therapy
leadership
Vector design - evolution of uniQure’s vector platform
TROPISM
natural AAV
DIRECTED EVOLUTION
4D Therapeutics
AAV1
Muscle
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
AAV2
AAV5
Exclusivity for
LIVER / CNS
AAV6
AAV8
AAV9
18
optimized AAV
1
2
3
Manufacturing – uniQure’s leading 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
19
1
2
3
World-leading manufacturing capabilities in EU and US
Building the world’s largest dedicated AAV manufacturing unit in the US
! 
2x 500 Liters
(Expansion up to 2x 2,000 Liters)
Amsterdam Plant
(EU)
1x 50 Liters
(Expansion up to 250 Liters)
Capacity
Lexington Plant
(US)
20
1
2
3
Building out US facility
>  Lexington, MA
>  Copy / scale up existing technology
>  Hiring of 50 experienced employees
planned
>  Estimated time of completion of
facility qualification and ready for first
test batches by end of 2014
Raised net proceeds of US$ 82 m in NASDAQ IPO
to reach multiple clinical milestones
2014
H1
Glybera – EU launch
Porphyria results
2015
H2
H1
2016
H2
"
"
Sanfilippo B results
"
21
H2
"
Hemophilia B results
Glybera Data to Support
U.S. Filing
H1
"
Gene therapy and uniQure:
Changing the future of medicine
!  Life changing
!  Disruptive*
!  Validated
!  Cutting edge science
!  Manufacturing leadership
!  Modular portfolio development
!  Regulatory expertise
!  Commercialization experience
!  Strong management team
22
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

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