Nanobodies®

creating better medicines

19 March 2015 – Brussels – Edwin Moses, CEO

KBC Healthcare Conference

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.

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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)

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

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

Merck Serono and Novartis

• €206M in cash at December 31st 2014

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

• Phase II clinical proof-of-concept with caplacizumab in TTP

• 4 clinical trials initiated

• Immune-onco deal with Merck & Co worth €20 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’ 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-1

Targeting different pathways at once

with a single Nanobody construct, e.g.

multiple checkpoint inhibitors

Product pipeline

Key products in the clinic

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

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

Start Phase II

(RA; SLE) in 2015

RA results

expected 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:

results expected

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 H1

2016

12

Caplacizumab

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 PEX in hospital

until recovery of platelet

count

Severe fatigue,

headache, coma,

abdominal pain,

weakness, nausea,

bizarre behaviour,

vertigo, seizures

SUDDEN ONSET EMERGENCY

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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

PEX

PEX

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

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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

• Held consultations with regulatory authorities in USA and EU

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

• Preparations progressing to start Phase III trial in H2 2015

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

• Commercialisation/partnering strategy currently under evaluation

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ALX-0171

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

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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 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”)

1 Vaccines of the World (Oct 2013) and 2 RSV Symposium (Nov 2014) – presentations available on Ablynx website

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 confirmation from DMC to proceed with placebo-

controlled phase of the study

• Recruitment of Phase IIa study to continue in parts of the Southern Hemisphere

and Asia to complete recruitment in 2015 with results anticipated in H1 2016

Current status and next steps

22

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

of-concept for Nanobodies, and its first for an inhaled Nanobody

23

ALX-0061

Anti-IL-6R Nanobody

• 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 and Phase II

study in SLE to start in 2015

• Opportunity in multi-billion dollar markets

RA: rheumatoid arthritis

SLE: systemic lupus erythematosus

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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 resmission 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

• Study on track to have first patient dosed during Q1 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

29

Additional clinical assets

Developed with partners

• ALX-0761 – anti-IL-17A/F

Merck Serono (global)

• ALX-0141 – anti-RANKL

Eddingpharma (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

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

Target-based discovery deal

Multiple programmes on-going (1 Phase Ib) under 3 co-co deals – 2013 strategic

alliance likely to be terminated with Ablynx retaining full ownership of 5 programmes

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

Phase Ib results in psoriasis

patients in H2 2015

• Potential in vivo POC

results from initial

programmes as part of IO

collaboration with Merck &

Co

• Caplacizumab (vWF):

determine partnering and

commercialisation

strategy

• Potential milestone

payments from ongoing

partnerships

• Continuing partnering

discussions

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 (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

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ablynx.com www.ablynx.com