Prosensa Therapeutics –R&D in ultra-rare disease

European Business Development

Conference

Dusseldorf, September 24, 2013

Tina C Flatau

VP Alliances and Project Management

2

This presentation may contain statements that constitute “forward-looking statements” within the meaning

of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-

looking statements are statements other than historical fact and may include statements that address future

operating, financial or business performance or Prosensa’s strategies or expectations. In some cases, you can

identify these statements by forward-looking words such as “may,” “might,” “will,” “should,” “expects,”

“plans,” “anticipates,” “believes,” “estimates,” “predicts,” “projects,” “potential,” “outlook” or “continue,”

and other comparable terminology. Forward-looking statements are based on management’s current

expectations and beliefs and involve significant risks and uncertainties that could cause actual results,

developments and business decisions to differ materially from those contemplated by these statements.

These risks and uncertainties include, but are not limited to, the timing and conduct of clinical trials of

drisapersen and Prosensa’s other product candidates, plans to pursue research and development of product

candidates for DMD and other indications, the clinical utility of Prosensa’s product candidates, the timing or

likelihood of regulatory filings and approvals, Prosensa’s intellectual property position, expectations regarding

payments under Prosensa’s collaborations and Prosensa’s competitive position. These risks and uncertainties

also include those described under the captions “Risk Factors” and “Management’s Discussion and Analysis of

Financial Condition and Results of Operations” in Prosensa’s Registration Statement on Form F-1 and future

filings with the Securities and Exchange Commission. Forward-looking statements speak only as of the date

they are made, and Prosensa does not undertake any obligation to update them in light of new information,

future developments or otherwise, except as may be required under applicable law. All forward-looking

statements are qualified in their entirety by this cautionary statement.

Forward-Looking Statements

To develop innovative,

RNA-based

therapeutics

to fill unmet medical

needs for patients with

rare genetic diseases

Our Mission

Rare disease company founded in 2002 and grown out of the University of Leiden, the Netherlands

Our lead compound is in Phase III for Duchenne Muscular Dystrophy

We have a pipeline of genotype-specific treatments for Duchenne and other neuromuscular diseases

Our technology is an RNA modulation platform, applicable to rare and common diseases

Our biggest collaboration is with GSK for selected parts of our Duchenne pipeline

4

Our story…

2001

ProsensaTherapeutics BV

PNAtix

Employees: 3

Employees: 7

Employees: 80+

BioPartner Incubator

Key collaboration

Key collaboration

Dutch AuthoritiesGMP licence

Dutch AuthoritiesGMP inspection

Start PRO044

Clinical phase I/II

Start PRO051

Clinical phase I/II

Employees: 39

Start PRO051

Clinical phase III

20022003

2004

2005

2006

2007

2008

2009

2010

2011

First human

study

University Leiden

BioPartner Accelerator

2002

2013

0 5 10 15 20 25 30

death

ventilation 24 h

ventilation at night

very limited use of arms

wheel chair - skeletal deformity

walking problems

Age

Clinical symptoms

Duchenne Muscular Dystrophy

Cause: no dystrophin protein in musclesCause: no dystrophin protein in muscles

Duchenne Muscular Dystrophy

Dystrophin

Indication Compound Discovery Pre-clinical Phase I/II Phase III

Duchenne PRO051

PRO044

PRO045

PRO053

PRO052

PRO055

PROSPECT

Myotonic Dystrophy PRO135

Huntington’s Disease PRO289

R&D Pipeline

drisapersen

License GSK Option GSK Unencumbered Prosensa

the biotech dilemma

to partner or

not to partner

11

Biopharma and the importance of collaborations

Emerging biotech companies

� Academic background and links

� Good IP basis

� Work virtually – used to

collaborations

� Innovative, energetic

Need

Good friends – advisors, investors,

backers

A flow of $$ to keep

working and grow

Guidance

A realistic growth/ game plan

Good connections

12

Why collaborate with Big Pharma?

€ €

Research Preclinical Clinical

Development is too costly for innovator companies…

13

Why collaborate with Big Pharma?

Experience

Guidance

Learning

Proven track record

Get you there safely

A guiding partner focused

on getting you to where you

want to be

Biotechnology….

….drug development

with more twists and

turns

Umm… I have never

done it like THIS

before

Pharma partners may be prepared to help us create the development pathway

…and prefer a quiet collaborator

Rare disease development is difficult

Rare disease biotech…

…to boldly go where no man has gone before

Expedited development and ultra-rare disease

Speed

Patient groups urge us to push ahead

with progress ‘choose speed over

perfection’

DMD is ultra-rare, disabling and

ultimately fatal

We aim to generate evidence for

expedited development of a whole

series of similar treatments

Challenges

Ultra-rare diseases tend to not be

studied well; no treatment so no

diagnostic pathway; no imperative from

payers to improve on an existing

treatment

Clinical end points yet to be validated

in regulatory submissions; no proven

surrogate

EMA PIP applies even for rare

childhood disease – so you have to start

out with an end to end plan

FDA: ‘Orphan drugs are held to the

same statutory requirements for

demonstrating effectiveness and safety’

Patients

Patient Organizations

Are partners on this journey of exploration

They put pressure on politicians, regulators and payers

They shape the development of regulatory policy

They raise $$ to support research and development

They help to educate us to understand life with the disease

They help develop measures for outcomes and quality of life

the rare disease communitythe rare disease communitythe rare disease communitythe rare disease community

newborn

screening

newborn

screening

creating disease

awareness

informing

patients

establishing

registries

communicationcommunicationcommunicationcommunication

newborn

screening

newborn

screening

enlarging

‘the market’

creating disease

awareness

generating more

revenues

informing

patients

promotion to

‘consumers’

establishing

registries

‘lining up’

patients

communication or promotion?communication or promotion?communication or promotion?communication or promotion?

talking ABOUT patientstalking ABOUT patients

patients as partnerspatients as partnerspatients as partnerspatients as partners

informationinformation

balanced balanced balanced balanced communication with communication with communication with communication with

patientspatientspatientspatients

“Hello,

We are a family from xxx. We have a son. His name is xxx and he is diagnosed

with muscular dystrophy - deletion of exons 49 and 50. We have tested him in

genetics labs in xxx, yyy and zzz. He was diagnosed when he was 11 years old.

In August xxx will be 17.

He is very determined boy, and he believes with stretching and exercising he

will walk soon again.

I am sending you all the test results we have, and if it is necessary we will

make more or different tests.

Please help our son. It is a dream of a mother and a father. We are ready to

do anything that will help our son feel better.”

USA orphan designations and approvals to 2009

A.Pariser, FDA: �Orphan drugs must demonstrate substantial evidence of effectiveness/clinical benefit (according

to 21CFR 314.50)

�Substantial evidence of benefit requires adequate and well controlled clinical trials

‘There is no one right way to do things for rare diseases’

Hurdles in Rare Disease Development

� Rare diseases are ‘complex and heterogenous’

� Costly and slow to find subjects for studies

� Difficult biology and end points

� Disease natural history not well-studied or understood

� Standards of care vary widely and affect outcomes

� In many territories there is no infrastructure to screen, record and locate subjects

� Lack of well-defined end point makes studies hard to design and regulatory and payer

‘proofs’ hard to make

� Regulators are unlikely to have an expert reviewer for the rare disease in question

� Only the potentially large markets are prioritized by pharmas

[E. Kakkis ‘CureTheProcess’ Campaign]

sustainable

pricing

European Orphan Medicinal Products Regulation

Introduced in 2000

Aims to encourage development of orphan drugs

Orphan drugs have been a very small part of the overall drugs budget. Now

there is growing concern with:

High prices of orphan drugs

Inability to meet the standard measures of cost-effectiveness used by payers

In Europe, proposals for better ways to assess in terms of value for money

to the healthcare system

Paying for the Orphan Drug System: break or bend? I s it time for a newEvaluation system for payers in Europe to take acco unt of new rare disease

treatments?

Orphanet Journal of Rare Diseases 2012, 7:74 . .

Wills Hughes-Wilson (wills.hughes-wilson@sobi.com) . . .Ana Palma (apalma@shire.com) .

Ad Schuurman (ASchuurman@cvz.nl) .Steven Simoens (steven.simoens@pharm.kuleuven.be ) .

Health Technology Assessments –Rare Disease

Proposed evaluation criteria:

�Rarity

�Investments

�Efficacy uncertainty

�Manufacturing complexity

�Follow-up measures being undertaken

�Disease severity

�Lack of alternative therapies

�Impact of treatment/ disease modification

�Unique target disease

small biotechsmall biotechsmall biotechsmall biotech

AchievementsAchievementsAchievementsAchievements…………

Speed vs reach

+ big pharma+ big pharma+ big pharma+ big pharma

�development capabilities

�contacts with regulators

�payer relationships

�manufacturing know-how

�commercial infrastructure

� research capabilities

� patient proximity

� fast decision making

� entrepreneurial spirit

� sense of urgency

Big Pharmavs Small Biotech

Adapted for standardized R&D-

Commercialization

Specialized, adaptive and inter-

connected for Rare Disease R&D

Extension study ongoing (more than 3 years)

12 Subjects; 6mg/kg/week

Extension study ongoing (more than 3 years)

12 Subjects; 6mg/kg/week

DEMAND IV/DMD114349

Extension study for

DEMAND II and III

DEMAND IV/DMD114349

Extension study for

DEMAND II and III

Repeat dose escalation (5wks)

12 Subjects, 0.5-2-4-6 mg/kg/week

Repeat dose escalation (5wks)

12 Subjects, 0.5-2-4-6 mg/kg/week

Pivotal study, placebo-controlled (2:1)

186 Subjects; 6mg/kg/week, 48 weeks

Pivotal study, placebo-controlled (2:1)

186 Subjects; 6mg/kg/week, 48 weeks

Dose regime comparison, placebo-controlled (2:2:1:1)

53 Subjects; 6mg/kg, 24 wks efficacy/48 wks safety

Dose regime comparison, placebo-controlled (2:2:1:1)

53 Subjects; 6mg/kg, 24 wks efficacy/48 wks safety

Dose-escalation, placebo controlled (3:1)

18 Non-ambulant subjects -> 12mg/kg single dose – PK/safety

Dose-escalation, placebo controlled (3:1)

18 Non-ambulant subjects -> 12mg/kg single dose – PK/safety

DEMAND III/DMD114044

DEMAND II/DMD114117

Dose comparison, placebo-controlled (2:2:1:1)

51 Subjects; 3 or 6mg/kg/week, 48 weeks

Dose comparison, placebo-controlled (2:2:1:1)

51 Subjects; 3 or 6mg/kg/week, 48 weeks DEMAND V/DMD114876

PRO051-CLIN-02

DMD114118

Natural History study

250 subjects (aged 3 – 18 years), 3 year follow-up

Natural History study

250 subjects (aged 3 – 18 years), 3 year follow-upDEMAND VI

CompletedCompleted

EnrolledEnrolled

Drisapersen Clinical Program

More than 300 patients in fully enrolled or completed studiesMore than 300 patients in fully enrolled or completed studies

the larg

est R&D

effort

the larg

est R&D

effort

the larg

est R&D

effort

the larg

est R&D

effort

ever in

DMD

ever in

DMD

ever in

DMD

ever in

DMDthe

largest

R&D effo

rt

the larg

est R&D

effort

the larg

est R&D

effort

the larg

est R&D

effort

ever in

DMD

ever in

DMD

ever in

DMD

ever in

DMD

More than 50 trial sites in 25 countries on 5 continentsMore than 50 trial sites in 25 countries on 5 continents

Drisapersen Clinical Program

the most

global ef

fort

the most

global ef

fort

the most

global ef

fort

the most

global ef

fort

ever in

DMD

ever in

DMD

ever in

DMD

ever in

DMDthe

most glob

al effort

the most

global ef

fort

the most

global ef

fort

the most

global ef

fort

ever in

DMD

ever in

DMD

ever in

DMD

ever in

DMD

Thank you