Nanobodies®

creating better medicines

May 2015

Corporate presentation

2

Forward looking statements

Certain statements, beliefs and opinions in this presentation are forward-looking, which reflect the

Company or, as appropriate, the Company directors’ current expectations and projections about

future events. By their nature, forward-looking statements involve a number of risks, uncertainties

and assumptions that could cause actual results or events to differ materially from those expressed

or implied by the forward-looking statements. These risks, uncertainties and assumptions could

adversely affect the outcome and financial effects of the plans and events described herein. A

multitude of factors including, but not limited to, changes in demand, competition and technology,

can cause actual events, performance or results to differ significantly from any anticipated

development. Forward looking statements contained in this presentation regarding past trends or

activities should not be taken as a representation that such trends or activities will continue in the

future. As a result, the Company expressly disclaims any obligation or undertaking to release any

update or revisions to any forward-looking statements in this presentation as a result of any

change in expectations or any change in events, conditions, assumptions or circumstances on

which these forward-looking statements are based. Neither the Company nor its advisers or

representatives nor any of its parent or subsidiary undertakings or any such person’s officers or

employees guarantees that the assumptions underlying such forward-looking statements are free

from errors nor does either accept any responsibility for the future accuracy of the forward-looking

statements contained in this presentation or the actual occurrence of the forecasted developments.

You should not place undue reliance on forward-looking statements, which speak only as of the

date of this presentation.

2

3

Ablynx

Corporate snapshot

• Drug discovery and development company in Ghent, Belgium

• >300 employees

• Pioneer in next generation biological drugs – Nanobodies®

• >500 granted and pending patents

• >30 programmes – six at the clinical development stage

• Three clinical proof-of-concepts (POC)

• 2 wholly-owned products in later stage clinical development (Phase III & Phase II)

• >10 new clinical programmes anticipated over the next 3 years

• AbbVie, Boehringer Ingelheim, Eddingpharm, Merck & Co, Merck Serono

and Novartis

• €193M in cash at 31 March 2015

CORPORATE

TECHNOLOGY

PARTNERS

PRODUCTS

FINANCIALS

4

2014

A year of great progress

4

Pipeline value

creation 1

Expanding

existing

collaborations 2

Corporate

development 3

• 6 clinical trial read outs – of which Phase II clinical proof-of-concept

with caplacizumab in TTP

• 4 clinical trials initiated – of which first inhaled Nanobody in patient

population

• Immune-onco deal with Merck & Co worth €20M upfront, €10.7M

research funding and up to €1.7Bn in future milestones plus royalties

• 2nd licensing agreement with Eddingpharm

• 1st step in a building commercial infrastructure with appointment of

Chief Commercial Officer

• Financial position strenghtened through oversubscribed private

placement of new shares (raised €41.7M)

What are Nanobodies?

Unique technology

6

Nanobodies

• Camelid heavy-chain only antibodies are stable and fully functional

• Nanobodies represent the next generation of antibody-derived biologics

Derived from heavy-chain only antibodies

Conventional

antibodies

Heavy chain only

antibodies

Ablynx’s Nanobody

• small

• robust

• sequence homology comparable

to humanised/human mAbs

• easily linked together

• nano- to picomolar affinities

• intractable targets

• multiple administration routes

• manufacturing in microbial cells

CH2

CH3

CH1

CL

VL

VH 12-15kDa

CH2

CH3

VHH

VHH

7

Ablynx’s platform

*Glycine-serine linkers from C-terminus to N-terminus

Rapid generation of high quality biologics

~12-18 months

Immunise llamas

with antigen or

use synthetic library

Wide range of highly

diverse Nanobodies

with 0.1-10nM affinities

Formatted*

Nanobodies ready

for in vivo testing

Cloning and production in microbial systems

8

Nanobody platform

Competitive advantages

Mix and match

Cell specificity

Immune cell

recruitment

Tissue-specific

targeting

Cell- /tissue-homing

Albumin-

binding

Nanobody Fc

Weeks/days/hours

Customised

half-life extension

Nanobodies

against ion

channels and

GPCRs

Nanobodies can

reach conserved

cryptic epitopes

Challenging and

intractable targets

Manufacturing

High-yield,

high-

concentration,

low-viscosity,

microbial

production

Inhalation

Oral-to-topical

Needle-free

Ocular

Alternative delivery routes

Nanobody-

drug

conjugates

Cell killing

Ag-1 Ag-1 Ag-2

Targeting different pathways at once

with a single Nanobody construct, e.g.

multiple checkpoint inhibitors

Product pipeline

>30 programmes in development

Two wholly-owned in later stage clinical development

10

Proprietary and partnered programmes

Multiple shots on goal

Inflammation/

Immunology

FU

LL

Y O

WN

ED

Therapeutic area Product name Target

Inflammation/

Immunology

Haematology

Oncology/

Immuno-oncology

Respiratory

Discovery

ALX-0061

Pre-clinical Phase I Phase II Phase III

IL-6R

caplacizumab vWF

ALX-0171

Neurology

Various

ALX-0141 RANKL

ALX-0761

Various

Various

Various

RSV

Various

Various

PA

RT

NE

RE

D

Bone disorders Greater China

IL-17F/IL-17A

Ocular

Oncology/

Immuno-oncology

ozoralizumab TNFα Greater China

Filing

CXCR2

Various

Other

Clinically validated targets

First-in-class

11

PARTNERED

Programme (target) Indication Key differentiating features Stage Partner

ALX-0061 (IL-6R)

RA, SLE

Best-in-class opportunity

Monovalent interaction; strong affinity

and preferential binding to soluble IL-6R

3 Phase II studies

(RA; SLE) in 2015

RA results

expected in 2016

ALX-0761 (IL-17A/F)

Psoriasis

Potent neutralisation of both IL-17A

and IL-17F

POC achieved in primate CIA* model

Psoriasis Phase

Ib on-going:

potential clinical

POC results

expected in 2015

Leading programmes in the clinic

* Collagen induced arthritis model

Pipeline value drivers

11

PROPRIETARY

Programme (target) Indication Key differentiating features Stage

Caplacizumab (vWF)

Thrombotic

thrombocytopenic

purpura

First-in-class orphan drug

Novel mode of action

Inhibition of microthrombi formation

Start Phase III H2

2015 and MAA filing

in H1 2017 in EU for

conditional approval

ALX-0171 (RSV)

Respiratory

syncytial virus

infection

First-in-class addressing high unmet need

Inhaled Nanobody delivered to infection site

Highly potent trivalent construct

Start first-in-infant

study Q4 2014:

results expected in

H1 2016

12

Caplacizumab

Wholly-owned anti-vWF Nanobody

• First-in-class bivalent Nanobody with

Orphan Drug Status

• Developed for the treatment

of acquired thrombotic thrombocytopenic

purpura (TTP)

• Phase III study to start in H2 2015

• Filing expected in H1 2017 for conditional

approval in Europe based on Phase II

results

• Peak sales potential of €300M-€400M1

1 US, EU, Japan, other markets (Brazil, Canada, Russia, Mexico, Australia)

13

Caplacizumab

What is the biological basis of TTP?

Caplacizumab blocks the platelet –

ULvWF interaction

ULvWF and anti-vWF Nanobody

ULvWF

Ex vivo assay for platelet string formation

Fluorescence microscopy image of platelets adhering to UL-vWF in plasma of TTP patients

Without treatment, fluorescently labelled platelets adhere to

UL-vWF, observed as string-like structures

Caplacizumab inhibits the formation of platelet strings and potentially

the associated microvascular thrombi in many organs

Ultra-Large (UL)

vWF multimers Platelet string

formation in patients

with TTP

ADAMTS13 activity is

impaired

endothelium

Caplacizumab binds to A1

domain of vWF and thereby

inhibits platelet string formation

14

Acquired TTP

• Potentially life threatening rare disorder of the blood coagulation system

– incidence of 11.3 per million1

– ~10,000 acute events annually in US and Europe

• Extensive microscopic thrombi formed in small blood vessels throughout the body

• High unmet medical need

– no approved medicinal product for treatment available

– mortality remains high (10-30%)2 and ~ 36% of patients have relapses1

– major morbidities after TTP episode such as neurocognitive impairment

– standard of care is plasma exchange (PE) plus immune suppressants

1 George et al, 2008; 2 Allford et al, 2003, Kremer Hovinga, 2010; Benhamou 2012

Significant unmet medical need

HEALTHY PERSON

Daily PE in hospital

until recovery of platelet

count

Severe fatigue,

headache, coma,

abdominal pain,

weakness, nausea,

bizarre behaviour,

vertigo, seizures

SUDDEN ONSET EMERGENCY

15

Caplacizumab

Phase II TITAN design and schedule R

AN

DO

MIS

AT

ION

Primary endpoint:

time to confirmed normalisation of

platelet count

Secondary endpoints:

plasma exchange frequency and volume; relapse;

exacerbations; mortality; major clinical events (stroke, MI,

organ dysfunction); recovery from signs/symptoms; ADA

1:1

Safety & efficacy endpoints

PE

PE

Caplacizumab N=36

1 year follow-up

1 year follow-up

Long-term endpoints:

ADA; relapse; non focal neurological

symptoms

Target

110 subjects

Actual

75 subjects

Placebo N=39

30 days

30 days 30 days

30 days

16

TITAN trial summary

• Patients treated with caplacizumab achieved confirmed platelet

normalisation at more than twice the rate of the group treated with

placebo

• This effect was statistically significant (p = 0.013)

Strong clinical proof-of-concept

• 71% fewer patients with an exacerbation

• No deaths in the caplacizumab arm compared to 2 deaths in the

placebo arm

• Increased bleeding tendency (but believed to be manageable)

• Overall, caplacizumab has an acceptable safety profile

PRIMARY

ENDPOINT

SECONDARY

ENDPOINT

SAFETY

17

Caplacizumab

Current status and next steps

17

Caplacizumab could be approved for sale in Europe in 2018

• Confirmed clinical activity and good safety profile in the clinic

• Intention to file for conditional approval in EU in H1 2017 based on Phase II

• Preparations progressing to start Phase III study in H2 2015

• Intention to submit BLA in USA following Phase III study completion

• Commercialisation/partnering strategy currently under evaluation

18

ALX-0171

Wholly-owned anti-RSV Nanobody

• First-in-class trivalent Nanobody for the

treatment of respiratory syncytial virus

(RSV) infection in infants

• Delivered by inhalation

• First-in-infant Phase IIa on-going with

results expected in H1 2016

• Opportunity in multi-billion dollar market

19

RSV infection in infants

• Leading cause of infant hospitalisation and primary viral cause of infant death

– ~300,000 children* (< 5 years) hospitalised per year in 7 major markets1,2

– increased medical cost in the first year following RSV infection3

– prolonged wheezing and increased risk for asthma development4

• No widely accepted drug available to treat RSV infections

– Synagis® used as prophylaxis in high-risk pre-term infants only ($1.1Bn sales in 2013)

* Extrapolation based on estimated US prevalence 1 Hall et al, NEJM, 2009; 2 Lee et al, Human Vaccines, 2005; 3 Shi et al, J Med Econ, 2011; 4 Sigurs et al, Thorax, 2010; Backman et al, Acta Pediatr, 2014

High unmet medical need

Evolves to

distressing

symptoms

8-20%

hospitalised

Symptomatic treatment

including inhaled

corticosteroids & bronchodilator

20

ALX-0171

• Well tolerated in multiple Phase I clinical studies in adults

• In vitro and in vivo studies demonstrated

– potent anti-viral effect against recent clinical RSV isolates

– 10,000 fold reduction in viral titres and superiority over palivizumab (Synagis®)1

– daily inhalation of ALX-0171 for 3 consecutive days in neonatal lamb model for infant RSV

demonstrated markedly reduced symptoms of illness (“Malaise Score”)2

1 Vaccines of the World (Oct 2013) 2 RSV Symposium (Nov 2014) – presentations on http://www.ablynx.com/rd-portfolio/clinical-programmes/alx-0171/

Key milestones achieved

0

20

40

60

80

100

0 1 2 3 4 5 6% o

f la

mb

s w

ith

sco

re ≥

1 RSV vehicle

RSV ALX-0171

Vehicle

RSV

infection

Treatment ALX-0171 or

formulation buffer

21

ALX-0171

• Infants aged 3 to <24 months who are hospitalised for RSV infection

• 24 EU centres and additional centres Southern Hemisphere (risk mitigation)

• Custom-developed infant inhalation device (vibrating mesh)

* Data monitoring committee

First-in-infant inhalation study

RA

ND

OM

ISA

TIO

N

2:1

Placebo N=10 Inhaled ALX-0171 once/day

3 consecutive days

ALX-0171 N=20

Open-label lead-in

N=5

Review by

DMC*

Inhaled ALX-0171 once/day or placebo

3 consecutive days

Primary endpoint:

Safety and tolerability of ALX-0171

Secondary endpoints:

Clinical effect (feeding, respiratory rate,

wheezing, coughing, general appearance)

PD (viral load), PK (ALX-0171 systemic

concentration) and immunogenicity

Started Q4 2014

Results expected H1 2016

22

ALX-0171

• Strong therapeutic effect demonstrated in a neonatal animal model for infant RSV

infection

• Well tolerated in multiple Phase I studies in adults

• First-in-infant Phase IIa study initiated in Northern Hemisphere; lead-in phase

successfully completed and placebo-controlled phase of the study on-going

• Recruitment of Phase IIa study to continue in parts of Asia-Pacific region with the

goal to complete recruitment of the placebo-controlled phase by end 2015 with

results anticipated in H1 2016

Current status and next steps

22

With ALX-0171, Ablynx could potentially achieve its fifth clinical proof-of-

concept for Nanobodies, and its first for an inhaled Nanobody

23

ALX-0061

Anti-IL-6R Nanobody partnered with AbbVie

• Monovalent half-life extended Nanobody

• Best-in-class potential for the treatment of

auto-immune disorders

• Global licensing agreement with AbbVie

• Phase IIb studies in RA started and Phase

II study in SLE to start around mid 2015

• Opportunity in multi-billion dollar markets

RA: rheumatoid arthritis

SLE: systemic lupus erythematosus

24

ALX-0061

Compelling Phase IIa results in RA patients

83

71

58 63

29

0

20

40

60

80

100

% o

f p

ati

en

ts

All unmodified ALX-0061 at week 24 (N=24)

ACR20 ACR50 ACR70 DAS28 remission Boolean remission

• Treatment was highly efficacious and was well tolerated

• No increase in adverse events upon extension of treatment

• No anti-drug antibodies were reported

ACR50 score as potential

differentiating factor

25

ALX-0061

• $175M upfront at signing in September 2013

• $665M total potential milestones plus double-digit royalties

Global licensing deal with AbbVie

25

Economics

Ablynx • Perform and fund Phase I study with subcutaneous formulation

(successfully completed in 2014)

• Perform and fund Phase II studies in RA and SLE (start 2015)

AbbVie

Commercialisation

• Pay a fee for each indication if they exercise the right to

license ALX-0061 after completion of the Phase II studies

• Responsible for Phase III development and registration

• AbbVie is responsible for global commercialisation

• Ablynx retains option to co-promote ALX-0061 in the Benelux

26

ALX-0061

• First patient dosed in March 2015

• Adult subjects with moderate to severe RA despite MTX therapy

• Worldwide, randomised, double-blind, placebo-controlled 24 week dose finding study

• Eligible subjects will be invited to roll-over into open-label extension (OLE) study

* methotrexate

Phase IIb RA combination study with MTX* R

AN

DO

MIS

AT

ION

1:1:1:1:1

Placebo

ALX-0061 dose 1, Q4W

330 subjects

ALX-0061 dose 2, Q4W

ALX-0061 dose 2, Q2W

ALX-0061 dose 3, Q2W

Primary endpoint at week 12:

ACR20 response

Secondary endpoints:

ACR responses over time, disease

activity scores, EULAR DAS28

response, remission, effects on

quality of life

Other assessments:

pharmacokinetics,

pharmacodynamics,

safety/tolerability, immunogenicity

27

ALX-0061

• First patient dosed in April 2015

• Adult subjects with moderate to severe RA who are intolerant to MTX or for whom

continued MTX is inappropriate

• Worldwide, randomised, double-blind 12 week study

• (Ro)Actemra® arm to obtain parallel descriptive information on efficacy and safety

• Eligible ALX-0061 treated subjects will be invited to roll-over into an OLE study

Phase IIb RA monotherapy study

1:1:1:1

ALX-0061 dose 1, Q4W Primary endpoint at week 12: ACR20 response

Secondary endpoints: ACR responses over time, disease

activity scores, EULAR DAS28 response,

remission, effects on quality of life

228 subjects

ALX-0061 dose 1, Q2W

ALX-0061 dose 2, Q2W

(Ro)Actemra® 162mg

Q1W (EU) or Q2W (US)

Other assessments: pharmacokinetics, pharmacodynamics,

safety/tolerability, immunogenicity

RA

ND

OM

ISA

TIO

N

28

ALX-0061

Key data points in clinical development

Phase I

sc study

Phase IIb

combination and

monotherapy

studies in RA

Phase II study

in SLE

2014 2015 2016 2017 2018 2019

Top line results

Top line results

potentially continues development in RA

potentially continues

development in SLE

Results announced 23 Oct 2014

ALX-0061 showed >80% bioavailability after sc injection

Phase II RA OLE

study

29

Additional clinical assets

Licensed to partners

• ALX-0761 – anti-IL-17A/F

Merck Serono (global)

• ALX-0141 – anti-RANKL

Eddingpharm (Greater China)

• Ozoralizumab – anti-TNFα

Eddingpharm (Greater China)

Partnerships

Broad platform exploitation and cash generation

31

Current partnerships

Broad platform exploitation and value creation

>20 active programmes; >€340M in non-dilutive cash received

~€3Bn in potential future milestones plus royalties

Global licensing deal for ALX-0061 (anti-IL-6R) in RA and SLE

2 discovery deals: ion channel deal; immune-onco deal with focus on multi-specifics

Strategic discovery alliance (focus on bi-specifics) – multiple programmes on-going

4 agreements: multiple programmes on-going (lead project in Phase Ib)

2 licensing deals in Greater China for ALX-0141 and ozoralizumab

Target-based discovery deal

Outlook

Potential value enhancing events

33

2015

Potential value drivers

33

Developing the pipeline Programme read outs Commercial

An important year ahead!

• Caplacizumab (vWF): i) confirm regulatory pathway

ii) start Ph III in acquired TTP

• ALX-0061 (IL-6R): dose first

patient in: i) Ph IIb RA combination therapy

ii) Ph IIb RA monotherapy

iii) Ph II in SLE

• ALX-0171 (RSV): complete

recruitment of Phase IIa

• Partnered programmes:

potential start of 3 Phase I’s

• ALX-0761 (IL-17A/F)

(Merck Serono): expect

POC Phase Ib results in

psoriasis patients in H2

2015

• Potential in vivo pre-clinical

POC results from initial

programmes as part of IO

collaboration with Merck &

Co

• Caplacizumab (vWF):

determine partnering and

commercialisation

strategy

• Potential milestone

payments from on-going

partnerships

• Continuing partnering

discussions

• Extend existing

collaborations/ enter into

new collaborations

34

Long term value creation

Some potential clinical and regulatory key events

2015

2016

2017

2018

ALX-0171 Infant Phase IIa (RSV)

Wholly-owned

ALX-0061 Phase IIb combination therapy (RA)

AbbVie have option to license worldwide

ALX-0061 Phase IIb monotherapy (RA)

AbbVie have option to license worldwide

ALX-0761 Phase Ib POC (psoriasis)

Licensed to Merck Serono (worldwide)

Caplacizumab MAA filing EU Phase III results (TTP)

Wholly-owned

ALX-0171 Infant Phase IIb (RSV)

Wholly-owned

ALX-0141 and ozoralizumab Phase I/II in China

Licensed to Eddingpharm (China)

ALX-0761 Phase IIa (psoriasis)

Licensed to Merck Serono (worldwide)

Caplacizumab conditional approval EU and BLA filing in US

Wholly-owned

ALX-0061 Phase II (SLE)

AbbVie have option to license worldwide

Results from various patient studies with partners

Clinical study results

Key regulatory events

CONTACT DETAILS

Questions

+32 9 262 00 00 Investor

Relations

investors@

ablynx.com www.ablynx.com

Addendum

37

Shareholders

• Ordinary shares listed on Euronext Brussels (ABLX)

• Sponsored level I ADRs on the US OTC market (ABYLY)

• 54.3M shares outstanding

• 2.7M outstanding warrants

• Free float is ~90%

Diversified shareholder base

Abingworth (UK); 9,03%

Boehringer Ingelheim (DE);

3,94%

Aviva Investors (UK); 5,00%

Perceptive Advisors (US);

3,82%

Polar Capital Funds Plc (UK);

3,05%

FMR LLC (US); 3,01%

Other institutional and retail

investors; 72,15%

Total shares outstanding by type

US; 33,87%

UK; 20,97%

Benelux; 32,59%

Scandinavia; 4,49%

France; 2,86%

Other; 5,23%

% of Institutional and Private Bank Owners by Geography (representing 65% of total S/O)

38

Financial summary

1 Cash, cash equivalents, restricted cash and short-term investments at the end of the period

Full year results 2014

Anticipated net cash burn for 2015 of approx. €70-80M

€M 2012 2013 2014

Revenue 26.7 35.9 49.3

Operating result (29.8) (17.7) (16.2)

Cash position1 62.8 200.4 206.2

39

Ablynx shares

Three-year performance

40

Nanobodies

Pushing the limits of antibody technology

scFv

Bi-specific,

tetra-valent

DVD-lg

Diabody lgG

1st generation

• 150 kDa

• bi-valent

• fixed half-life

• mono-specific

2nd generation

• 30-210 kDa

• mono- or bi-valent

• short or long half-life

• bi-specific

3rd generation

• 12-75 kDa

• valency of choice

• short or long half-life

• multi-specific

Nanobodies

41

Nanobodies

ND: not demonstrated

Compared to other platforms and mAbs

41

Features Nanobodies DARTS

(MacroGenics)

Darpins

(Molecular

Partners)

mAbs

Speed of discovery ++/+++ ++ ++ ++/+++

Formatting flexibility +++ ++ ++ -

Bi-specific formats ++/+++ ++ ++ ++

Manufacturability +++ ++ ++ ++

High concentration formulation ++/+++ ND ND +/-

Tailored in vivo half-life +++ ++ ++ -

Alternative routes of

administration +++ ND +/- -

Broad target

applicability incl. GPCRs and

ion channels

+++ ND ND +/-

Clinical validation Ph II Ph I Ph II Multiple

marketed

42

Nanobodies

* No. of molecules binding to more than one target or epitope in clinical development

Most versatile and clinically validated platform

Ablynx Affimed Macro-

genics Pieris

Molecular

partners F-Star Genmab

Technology Nano-

bodies TandAb DART Anticalins DARPINs mAb2-FcAb Duo-bodies

Clinical

programmes* 4 2 1 0 0 0 0

Amgen Abbvie Chugai GSK Genentech Roche Sanofi J&J BMS

Technology BiTE DvD-Ig Bispecific

mAb

Domain

Ab 2-in-1 CrossMab

Bispecific

mAb

Fyno

Mab Centyrins Adnectins

Clinical

programmes* 4 3 1 1 1 1 1 1 1 0

43

Bi-specific Nanobodies

Synergistically improve potency

• All HIV strains need the primary receptor CD4 and a chemokine co-receptor to enter and

infect host CD4+ T cells

– X4 type viruses use CXCR4; R5 type viruses use CCR5

• Synergistic improvement in HIV-1 blockade of CXCR4-CD4 bi-specific Nanobody over

monovalent Nanobodies

– up to 320-fold enhancement with bi-specific Nanobody over mono-specific

– only 2-fold enhancement with combination of monovalents in solution (1:1) over monospecific

– linking of the Nanobodies is essential for strong enhancement

Collaboration with Dr. Dominique Schols, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium

CXCR4

CD4

anti-CXCR4/CD4

anti-CXCR4

anti-CD4

anti-CXCR4 + anti-CD4 +

Blockade of HIV infection in vitro*

* Infection of HIV1 X4 NL4.3 in

human MT-4 T cells

44

10 -11 10 -10 10 -9 10 -8 10 -7 10 -6 10 -5 10 -4 0.0

0.2

0.4

0.6

0.8

1.0

Nanobodies

• Tri-valent anti-RSV (ALX-0171)

– improve activity and strain coverage by multi-valency

– superior virus neutralisation as compared to palivizumab

– 5-fold more clinical isolates neutralised below LLOD with ALX-0171 compared with palivizumab

Multi-valent formatting to improve potency

Improved potency over mAb Increased strain coverage

A-strain B-strain Total

n 32 29 61

palivizumab 0 (0%) 11 (38%) 11 (18%)

ALX-0171 30 (94%) 23 (79%) 53 (87%)

p value <0.0001 <0.0001 <0.0001

OD

45

0-5

20

nm

Concentration (M)

palivizumab

Number of strains neutralised

below lower limit of detection

7,000-fold

45

Nanobody formatting

Biparatopic format yields the required potency and efficacy

Biparatopic is both potent and efficacious

Lower potency but efficacious Potent but not efficacious

46

Caplacizumab Phase II study

Time to confirmed platelet normalisation

Primary endpoint

N = 36 N = 39

Overall Hazard Rate Ratio for caplacizumab vs. placebo

(95% CI), N = 75 2.197 (1.278, 3.778)

Stratified log-rank test p-value 0.013

Caplacizumab Placebo

Median days to confirmed platelet response – subjects with

no prior plasma exchange (95% CI)

3.00 (2.74, 3.88)

N = 34

4.92 (3.21, 6.59)

N = 35

25th & 75th percentile 2.72 & 4.31 3.01 & 11.37

Median days to confirmed platelet response – subjects with

one prior plasma exchange (95% CI)

2.44 (1.92, 2.97)

N = 2

4.31 (2.91, 5.68)

N = 4

25th & 75th percentile 1.92 & 2.97 3.37 & 5.23

The group of patients treated with caplacizumab in conjunction with the standard

of care achieved confirmed platelet normalisation at more than twice the rate

of the group receiving the standard of care plus placebo

47

Caplacizumab Phase II study

* Intention-to-Treat (ITT) population: 75 subjects, all randomised to caplacizumab (36) or placebo (39)

Secondary endpoints

Caplacizumab

N* = 36

Placebo

N* = 39

Subjects with an exacerbation within 30 days after

stopping daily PEX 3 (8%) 11 (28%)

Subjects in complete remission within 30 days after

stopping daily PEX as measured by confirmed platelet

response and absence of exacerbations

29 (81%) 18 (46%)

Subjects with an exacerbation and/or relapse at 1 month

follow-up after study drug treatment was completed 13 (36.1%) 13 (33.3%)

Deaths 0 2

These top line secondary endpoints illustrate the potential protective

effect of caplacizumab treatment in the acute phase of TTP

48

Caplacizumab

Safety profile in TITAN Phase II trials

Proportion of subjects Caplacizumab

N = 35

Placebo

N = 37

Subjects with any TEAE 97% 100%

- with bleeding event 54% 38%

Subjects with any TE Serious AEs 57% 51%

- with serious bleeding event 6% 5%

Subjects discontinued due to TEAE 8% 0%

Increased bleeding tendency in caplacizumab arm • 80% of reported events were mild

• only 3 subjects required drug treatment (tranexamic acid, methylergonovine)

• no requirement for vWF/FVIII substitution

Number of events Caplacizumab

N = 35

Placebo

N= 37

Number of TEAEs 574 545

Number of TE Serious AEs 44 36

49

Caplacizumab

• TITAN investigators, other KOLs and payers overwhelmingly positive about

caplacizumab product profile and value proposition

– Orphan Drug addressing a high unmet medical need

– innovative MOA providing specific platelet protective effect, thereby having the potential to

reduce morbidity due to organ damage

– potential for shorter duration of acute and life-threatening episodes

– potential for less exacerbations and relapses

– potential cost savings (reduction in volume and days of plasma exchange; shorter time in

intensive care)

• Ablynx estimates peak sales for caplacizumab to be in the range of €300M-

€400M*

* US, EU5, Japan, other mkts / Jefferies estimates: $400 million peak sales (14 Oct 2014)

Commercial opportunity

“If the manufacturer can achieve these data at

launch, this is a winning product” – US payer

50

RSV therapeutics

* Based on 375 mg dosing schedule in adult challenge trial (see press release Jul 2014)

** Assuming abstract from 8th RSV conference Oct 2012 refers to ALS-8176 but not explicitly mentioned (Deval et al.)

Studies currently on-going in infants

ALS8176 (Alios/J&J) ALX-0171 (Ablynx)

Administration oral

suspension

pulmonary

nebulisation

Entity NCE

nucleoside analogue

biologic

Dosing 2/day

5 mg/kg*

1/day

MOA polymerase inhibitor fusion inhibitor

In vitro potency

serotype A

200 nM** IC50 ≈ 0.1 nM

Development status PhII infant study started July

2014 (SAD/MAD; N=168)

Results: Nov 2015

PhIIa infant study to start Q4

2014 (MD; N=35)

Results: Q3 2015

51

RSV pipeline

* Other Medimmune vaccine candidates for infants in NIAID sponsored studies

Therapeutics and vaccines currently in development

Product Company Class Target population Phase

RI-002 ADMA Biologics Anti-RSV antibody

prophylaxis

Immune-compromised

patients

Phase III ongoing

RSV vaccine Novavax RSV F-vaccine Infants (maternal

immunisation)

Phase II in pregnant women initiated

Q3 ‘14

GSK-3003891 GSK RSV vaccine Infants and children Phase I in adults

MEDI-7510* MedImmune/

AstraZeneca

RSV vaccine Older adults Phase I in older adults

MEDI-8897 MedImmune/

AstraZeneca

Anti-RSV antibody

prophylaxis

Infants and children Phase I in adults

RSV-001 Okairos/GSK RSV vaccine Infants and immune-

compromised adults

Phase I completed

ALS-8176 Alios/J&J Nucleoside

analogue

Infants Phase II in infants

GS-5806 Gilead RSV fusion inhibitor (Older) adults and bone

marrow transplant patients

(BMT)

First-in-infant study withdrawn

Phase IIb in (older) adults and BMT on-

going

ALX-0171 Ablynx Anti-RSV Nanobody Infants and children 3 Phase I’s in adults completed; Phase

IIa in infants ongoing

ALN-RSV01 Alnylam/Hyowa

Hakko Kirin

Nucleocapsid gene

siRNA

Immune-compromised

adults

Phase II in lung transplant patients but

no longer mentioned as part of pipeline

MDT-637 Microdose

/Teva

RSV fusion inhibitor Infants and children Healthy adult volunteer challenge study

ongoing

52

ALX-0171

Suitability of neonatal lamb model compared with human challenge model

• Lambs develop lower respiratory tract infection which is associated with general malaise and specific

lung pathology (comparable to infants)

• Treatment at peak of viral load on day 3 post infection (symptoms and lung pathology are already clearly

present)

• Lambs develop clinical symptoms such as wheezing (comparable to infants)

In vivo proof-of-concept achieved

0

1

2

3

4

5

6

7

Vehicle RSV Vehicle RSV ALX-0171

Lo

g10

FF

U/m

L B

AL

Mean viral titers in BALF

(day 6 post infection)

0

10

20

30

40

50

60

Vehicle RSV Vehicle RSV ALX-0171

Me

an

% I

nvo

lve

me

nt

Lung viral lesions

(day 6 post infection)

53

ALX-0171

* 0 = no clinical signs; 4 = animals down

Highly effective in RSV infected lambs

0

20

40

60

80

100

0 1 2 3 4 5 6

% o

f la

mb

s w

ith

sc

ore

≥ 1

“Malaise” Score

RSV vehicle

RSV ALX-0171

Vehicle

Daily inhalation of ALX-0171 markedly reduced symptoms

of illness in RSV infected neonatal lambs

RSV

infection

Treatment ALX-0171 or

formulation buffer

• Subjective scoring

(0 to 4*) of parameters that measure

general health

– “Malaise” score: weakness, depression,

lethargy, drooping of ears, and not eating

• Daily inhalation of ALX-0171 markedly

reduced symptoms of illness

54

ALX-0171

• September 2012 – Phase I first-in-human study

– 60 healthy volunteers

– single-ascending dose and multiple dose up to 210 mg inhaled twice daily for 5 days

– well tolerated, with no clinically relevant adverse events or effects on lung function

• May 2014 – Phase I safety study in adults with hyper-reactive airways

– 24 subjects

– single-ascending dose and multiple dose part up to 200 mg inhaled daily for five days

– some cases of mild bronchoconstriction which could be immediately reversed

• May 2014 – Phase I PK study

– 41 healthy volunteers

– single and multiple dose of 200 mg inhaled daily for 5 days and single dose of 0.3

mg/kg iv

– local half-life of ALX-0171 is approximately 20 hours, confirming potential for once-daily

dosing

Successful Phase I inhalation studies in adults

54

55

ALX-0171

• First-in-class potential addressing a disease with a high unmet medical need

– no adequate therapeutic treatment for RSV infections in infants

• Most infants are infected with RSV during their first year of life

• Nearly all children will have had an RSV infection by the age of 2

• Opportunity to treat RSV infection in infants

– hospitalised setting (~300,000 infants per year in the 7 major markets)

– out-patient setting (~2 million infants <1 year of age per year in 7 major markets)

Commercial opportunity

“Current prophylaxis with a mAb is expensive and

only partially protective. Any new treatment strategy

for RSV bronchiolitis is very welcome” – BE KOL

56

ALX-0061

Potentially best-in-class anti-IL-6R

Features Potential benefits

Small (26kD)

• Penetrates faster and more effectively into

tissues

Targets human serum albumin (HSA) • Prolongs half-life

• Improved trafficking to inflamed tissue

Monovalent binding • Avoids target cross-linking

Preferential binding of soluble vs.

membrane bound IL-6R

• Superior benefit/risk profile

Strong affinity to soluble IL-6R • Fast target engagement resulting in fast onset

of action

Low immunogenic potential • Improved safety profile

Tailored PK • Extended therapeutic window

• Convenient dosing and scheduling

anti-HSA anti-IL-6R

57

IL-6(R) and JAK inhibitors

25

32

46

32

27

44

55

71

32

60

37

48

34

44 46

45

37 38

43

37 35

0

10

20

30

40

50

60

70

80

% o

f p

ati

en

ts

Week 12 Week 24

1 All pooled/unmodified ALX-0061 treated patients (pooled) at week 12 and week 24; 2 Data extracted from LITHE (4 and 8 mg/kg), OPTION (4 and 8

mg/kg), TOWARD (8 mg/kg) trials; 3 Smolen JS, et al. Ann Rheum Dis 2014 (100 mg Q2W); 4 Phase III MOBILITY trial; 150 mg Q2W and 200 mg

Q2W; 5 Phase IIb trial (ACR 2013), Q4W; 25 mg, 100 mg, 200 mg; 6 Data extracted from Phase III Scan, Sync and Standard trials; 5 mg BID and 10

mg BID; 7 Data presented by Galapagos (100 mg BID) on 14th-15th April 2015

ACR50 scores from different clinical studies

Tocilizumab

(Roche)2

ALX-00611

Sarilumab

(Sanofi)4

Clazakizumab

(BMS)5

Sirukumab

(J&J)3

Tofacitinib

(Pfizer)6

Filgotinib

(Galapagos)7

58

50%

0%

4%

0%

20%

40%

60%

80%

100%

Pbo Pooled

ALX-0061, 12w Data

Remission Low disease activity

7%

36%

7%

14%

0%

20%

40%

60%

80%

100%

Pbo 100mg BID

DARWIN1, 12w Data

Remission Low disease activity

DAS28CRP Response of ALX-0061 vs. filgotinib

ALX-0061 as presented on October 4, 2012

DARWIN1 as presented by Galapagos on April 14/15, 2015

Pooled data vs. highest reported responses

59

ALX-0061

• Potential to treat moderate to severe RA

– first line biologic

– monotherapy or in combination with methotrexate (MTX)

– patients refractory or intolerant to anti-TNFα

• (Ro)Actemra® (the only marketed IL-6R blocker) generated sales of $840M in

2013 and sales are expected to grow to ~$1.5B in 20161 and ~$4.8B by 20202

• ALX-0061 as a novel option for the treatment of severe SLE

– high unmet medical need among moderate and severe SLE populations

– ~5 million people worldwide suffer from a form of lupus

– SLE market expected to grow to $4B in 20213

1 Decision Resources 2014 2 SG Cross Asset Research 2012 3 Decision Resources 2014

Commercial opportunity

“I would definitely consider it as a first line

biologic RA treatment.” – IT KOL

60

Global RA market

• In 2013, Humira (AbbVie) for the treatment of auto-immune disorders, was the world’s largest selling

drug with ~$11B in sales (approved in 7 indications)

• (Ro)Actemra (Roche/Genentech/Chugai) is currently the only IL-6R inhibitor on the market (used as

2nd and 1st line biologic)

• (Ro)Actemra generated sales of $840M in 2013 and sales are expected to grow to ~$1.5B in 20161 and

~$4.8B by 20202

Source: First Word Pharma 2012 1 Decision Resources 2014; 2 SG Cross Asset Research 2012

Opportunity for anti-IL6(R) drugs

60

Global RA market – market share and CAGR for the different drug classes*

2011 2016

Class

Sales

($m)

CAGR (2006–11)

(%)

Market share

(%)

Sales

($m)

CAGR (2011–16)

(%)

Market share

(%)

TNF inhibitor 13.721 17% 84% 16,076 4% 69%

B-cell depletion 1,221 0.5% 7.5% 1,285 1% 6%

T-cell modulator 910 59% 5.6% 2,010 17% 9%

IL-6 inhibitor 679 178% 4.2% 2,034 24% 9%

JAK inhibitor 0 0% 0% 1,566 0% 7%

Syk inhibitor 0 0% 0% 313 0% 1.3%

IL-17 inhibitor 0 0% 0% 90 0% 0.4%

61

Therapeutics targeting IL-6(R)

* Graft versus host disease; ** Neuromyelitis optica

Drugs currently in development

61

Drug Target Company Disease Dosing Stage

SAR153191

REGN88

IL-6R Sanofi/

Regeneron

RA, uveitis 150 or 200 mg

q2w

PhIII/Phii

Launch RA mid-2017

CNTO 136 IL-6 J&J/

GSK

RA 50 mg q4w, 100

mg q2w

PhIII

Launch end 2017

ALD518 IL-6 Alder RA,

NSCLC,

GVHD*

25-100-200 mg

q4w

PhII dose finding

Launch >2018 (following BMS

returning the asset)

CDP6038 IL-6 R-Pharm/

UCB

RA 60-120-240 mg

q2w

PhII

PF-04236921 IL-6 Pfizer SLE, CD,

RA

RA q4w

SLE, CD q8w

RA PhI

SLE, CD PhII

SA237 Actemra

follow-on

IL-6R Chugai RA, NMO Q4w or less

frequent

RA PhI

NMO/NMOSD PhIII

FE999301 IL-6 Ferring Various Phase II (Crohn’s)

Tocilizumab

biosimilar

IL-6R BioXpress Research

Tocilizumab

biosimilar

IL-6R Panpharma-

ceuticals

Research

62

Rheumatoid arthritis

Source: AbbVie; Decision Resources 2014

Current and emerging therapies

• TNFα inhibitors dominate the RA market; but for >30% of patients, alternative

treatment approaches are needed (patients may not respond or may not tolerate

the drug, or become refractory)

• Anti-IL-6R treatment is clinically validated with (Ro)Actemra®; ALX-0061 falls within

the anti-IL-6R drug class

• AbbVie is committed to various drugs with differents MOAs (transcript Q1 2015

conf call): “Behind HUMIRA we have a rich pipeline of mid- and late-stage immunology

assets in clinical development. We're also working to advance several other mid-stage

immunology programs, including ABT-122 (our anti-IL-17 TNF combination) and an anti-IL-6

antibody, among others. All of our R&D efforts are focused on advancing the standard of care

in each of our areas of immunology leadership.”

Total RA market 2013: $14bn

Expected to grow to $18bn by 2023

1%

6% 6%

9%

7%

71%

JAK inhibitors

IL-6R inhibitors

B-Cell therapies

Selective costimulationmodulators

Conventional DMARDs

TNFα inhibitors

Source: AbbVie; Decision Resources 2014

63

ALX-0761

• ALX-0761 blocks both IL-17A and IL-17F (involved in

inflammation); binds HAS for improved PK

• Targeting both IL-17A and IL-17F could be more effective

in blocking the inflammatory response

– IL-17F forms homodimer and heterodimers with IL-17A

– IL-17F exerts similar in vitro biological activity as IL-17A but is

secreted by different cell types

• Developed by Merck Serono

– completed Phase I SAD study in healthy volunteers

– ongoing Phase Ib study in patients with psoriasis (results

expected in 2015)

• Secukinumab (Novartis) most advanced anti-IL-17A in

development (registration phase) with estimated peak

sales of ~$500M*

* Analysts estimates 2014 1 Poster available on Ablynx website: R&D>pipeline

Bi-specific Nanobody in psoriasis

anti-HSA

anti-IL17A anti-IL17F

Proof-of-concept achieved in primate

collagen induced arthritis model1

Art

hri

tis s

co

re

Days

–4 6 16 26 36 46 56 0

20

40

60

80

Vehicle ALX-0761 (2.8mg/kg)

ALX-0761 (10mg/kg)

64

Unmet need in psoriasis

Rationale for targeting IL-17-Th17

64 Source: Nature Biotechnology, Jan 2015; Hilary Bartlett & Ryan Million, Nature Reviews, Drug Discovery, Jan 2015

• IL-17A and TNFα are pro-inflammatory cytokines, produced by lineages of TH1 and TH17 cells, which are found in

blood and skin lesions of people with psoriasis

• ~50% of patients with moderate to severe psoriasis receive only topical or no treatment at all and >50% of

patients dissatisfied with current treatments

• Novartis’ Cosentyx (secukinumab) will be the first anti-IL-17A therapeutic on the market (2015 expected)

• Research suggests that IL-17A(F) blockers maybe more efficacious than anti-TNFα drugs for the treatment of

psoriasis

65

Therapeutics targeting IL-17A/F

Drugs in development

65

Drug Target Company Disease Stage

secukinumab IL-17A Novartis Psoriasis

Psoriatic arthritis; ankylosing spondylitis;

RA in patients IR to TNF

Filed

PhII and PhIII

ixekizumab Il-17A Eli Lilly Psoriasis

Psoriatic arthritis

PhIII completed

PhIII

brodalumab IL-17RA Amgen/Astra

Zeneca

Psoriasis

Psoriatic arthritis

Asthma

PhIII

PhIII

PhII

RG4934 IL-17A Roche Psoriatic arthritis PhI but no update since

2010

RG7624 IL-17A/F Roche Autoimmune

(no specific indication)

PhII to start early 2015

UCB-4940 IL17A/F UCB Psoriasis PhIb MAD in patients

CNTO 6785 IL-17A Janssen RA PhII

ABT-122 IL-17A/

TNFα

AbbVie RA in patients with an inadequate response

to methotrexate

PhII

COVA-322 IL-17A/

TNFα

Janssen/

Covagen AG

Psoriasis PhI/II

Sales potential of $500M - $1Bn for anti-IL-17 drugs in psoriasis1

1Trinity Partners, Nature Reviews, Drug Discovery, Jan 2015

66

Clinical stage products licensed in China

• Anti-TNFα – ozoralizumab – inflammation

– Phase II proof-of-concept achieved in patients with RA (Pfizer)

– Ablynx regained worldwide rights to anti-TNFα Nanobodies from Pfizer

– exclusively licensed to Eddingpharm in Greater China in Aug 2014

• €2M upfront; development and commercial milestones; up to 20% royalties

– pre-clinical study in China on-going

– Ablynx will have access to the clinical data generated by Eddingpharm

• Anti-RANKL – ALX-0141 – bone disorders

– Phase I study successfully completed (Ablynx)

– exclusively licensed to Eddingpharm in Greater China in Oct 2013

• €2M upfront; commercial milestones; up to 20% royalties

– pre-clinical study in China currently on-going

– Ablynx will have access to the clinical data generated by Eddingpharm

1 Espicom

Chinese Pharma market to grow to $163B by 20171

anti-HSA

anti-TNF anti-TNF

anti-HSA

anti-RANKL anti-RANKL