Nanobodies®

creating better medicines

September 2016

Investor 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

Powerful platform generating potentially innovative medicines

• Platform technology and late-stage clinical development company

• >350 staff in Ghent, Belgium

• >45 wholly-owned and partnered programmes

• 8 Nanobodies in clinical development

• First potential launch in 2018

• AbbVie, Boehringer Ingelheim, Eddingpharm, Genzyme, Merck &Co., Inc.,

Merck KGaA, Novartis, Novo Nordisk and Taisho Pharmaceuticals

• >€380M cash received; >€7Bn in potential milestones; and royalties

• €289M in cash at 30th June 2016

• €100M of issued Convertible Bonds maturing in 2020

CORPORATE

PARTNERS

PRODUCTS

FINANCIALS

• Pioneer in next generation antibody-derived drugs – Nanobodies®

• >500 patent applications and granted patents; critical know-how

• Validation through multiple partnerships with top tier pharma companies

TECHNOLOGY

4

Ablynx

Diversified shareholder base – August 2016

• Ordinary shares listed on Euronext Brussels (ABLX)

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

• 60.9M shares outstanding

• 2.6M outstanding warrants (in number of shares)

Breakdown of share capital

US 41%

UK 21%

Belgium 24%

The Netherlands

9%

Scandinavia 1%

France 2% Other

1%

% of Institutional Shareholders by Geography (representing 78% of total S/O)

5% 5%

5%

5%

4%

4%

3%

Van Herk Investments B.V. (NL)

Bank of America (US)

Perceptive Advisors (US)

Fidelity Management Research (US)

GAM International (UK)

Boehringer Ingelheim (DE)

Oppenheimer Funds (US)

Other shareholders

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 and robust

• easily linked together

• sequence homology comparable

to humanised/human mAbs

• nano- to picomolar affinities

• able to bind and block challenging

targets

• multiple administration routes

• manufacturing in microbial cells

CH2

CH3

CH1

CL

VL

VH 12-15kDa

CH2

CH3

VHH

VHH

7

Ablynx’s drug discovery engine

Rapid generation of novel biologics

~12-18 months

and/or

Use proprietary synthetic

Nanobody phage libraries

Wide range of highly

diverse Nanobodies with

0.1-10nM affinities

Formatted

Nanobodies

Cloned into microbial

systems and produced

through fermentation

Immunise llamas

with antigen

8

Ablynx’s Nanobodies

Platform advantages

Albumin-

binding

Nanobody Fc

Hours/days/weeks

Customised

half-life extension

Nanobodies

against ion

channels and

GPCRs

Able to bind and block

challenging targets

Manufacturing

High-yield,

high-

concentration,

low-viscosity,

microbial

production

Inhalation

Oral-to-topical

Ocular

Multiple delivery routes Mix and match

Multi-specific/multivalent Nanobodies

that address multiple targets in a

single drug molecule – flexible GS

linker lengths

Broad product pipeline

10

Hybrid business model fuels the pipeline

>45 programmes, 8 Nanobodies in clinical development

Indication Product Target

aTTP

RSV

vobarilizumab

Pre-clinical Phase I Phase II Phase III

IL-6R

caplacizumab vWF

ALX-0171

ALX-0141 RANKL

ALX-0761

RSV

Bone disorders Greater China

IL-17A/IL-17F

ozoralizumab TNFα

Greater China

Filing

Japan

RA

RA

SLE

RA

Psoriasis

Immuno-Oncology

~ 15 wholly-

owned and

partnered

programmes

Up to 17

programmes

IL-6R

IL-6R

TNFα RA

Various

Various

+

CXCR2 Inflammation NA

Oncology VEGF/Ang2 BI 836880

Chronic kidney disease CX3CR1 BI 655088

Key value drivers

Vobarilizumab (anti-IL-6R)

Potential to be best-in-class in RA

13

Vobarilizumab – anti-IL-6R Nanobody

Potential to be the best-in-class in RA

• Global exclusive option licensing deal with

AbbVie

• Compelling results from 2 Phase IIb RA

studies in a total of ~600 patients

• RA open-label extension study ongoing (94%

rollover rate)

• Phase II SLE study ongoing

• Opportunity in multi-billion dollar markets

RA: rheumatoid arthritis

SLE: systemic lupus erythematosus

14

Vobarilizumab Phase IIb study results in RA High ACR responses consistent across the two studies

MTX: methotrexate

Week 12

Phase IIb monotherapy

(vobarilizumab N=187; tocilizumab: N=64)

% r

esp

on

ders

* nominal p<0.05 vs. placebo; ** nominal p<0.01 vs placebo

Phase IIb combination therapy (+ MTX)

Week 12 Week 24

(vobarilizumab N=276; placebo: N=69)

% r

esp

on

ders

High response rates with vobarilizumab are consistent across studies

Continued improvement in ACR50 and ACR70 scores from 12 to 24 weeks

Opportunity for monthly dosing confirmed

15

Vobarilizumab Phase IIb study results in RA Strong impact on disease activity confirms best-in-class potential

Remission: DAS28CRP < 2.6; low disease activity: 2.6 ≤ DAS28CRP ≤ 3.2

Up to 49% of patients in clinical remission at week 24

Week 12

Phase IIb monotherapy

* nominal p<0.05 vs. placebo; ** nominal p<0.01 vs. placebo; *** nominal p<0.001 vs. placebo

*** *** *

*** **

***

* ** ***

** *** ***

Phase IIb combination therapy (+ MTX)

Week 12 Week 24

% s

ub

jects

% s

ub

jects

42

57 60

44

16

1 PhIIb: (sc) 150mg Q4W and 225mg Q2W + MTX; 2 Data from OPTION PhIII: (iv) 8mg/kg Q4W + MTX and BREVACTA PhIII (sc) 162mg Q2W + MTX; 3 MOBILITY PhIII: (sc) 150 mg Q2W and

200mg Q2W + MTX; 4 PhIII: (sc) 50mg Q4W and 100mg Q2W + csDMARDs; 5 Weinblatt et al, Arthritis & Rheumatology, Sept 2015; 6 DARWIN 1: (oral) 100mg QD, 200mg QD + MTX; 7

BALANCE-2 PhIIb: oral 6mg BID, 12mg BID + MTX

Potential to be the best-in-class in RA

0

10

20

30

40

50

60

% o

f p

ati

en

ts

Effect on clinically meaningful endpoints

tocilizumab

(Roche)2

vobarilizumab1

sarilumab

(SASY/REGN)3

sirukumab

(J&J/GSK)4

filgotinib

(GLPG/Gilead)6

Note: 24-week data reported in listed publications, not resulting from head-to-head studies

adalimumab

(AbbVie)5

sc

Q4W

sc

Q2W

sc

Q2W sc

Q2W

sc

Q2W

sc

Q4W sc

Q2W sc

Q2W

oral

daily

oral

daily

iv

Q4W

tocilizumab

(Roche)2

vobarilizumab1

sarilumab

(SASY/REGN)3

adalimumab

(AbbVie)5

filgotinib

(GLPG/Gilead)6

sc

Q4W

sc

Q2W

sc

Q2W

sc

Q2W

sc

Q2W

sc

Q2W

oral

daily oral

daily

iv

Q4W

DAS28CRP remission ACR70 response

17

Safety results from RA combination studies

Vobarilizumab has favourable safety profile

Note: data reported in listed publications, not resulting from head-to-head studies

18

Vobarilizumab

Potential to be the best-in-class in RA

18

µ$

µµ

µ

µ

µµ

• Very strong impact on disease activity as measured by DAS28CRP

• Favourable safety and tolerability profile across all doses tested

• Opportunity for convenient monthly dosing

Potential to become a positively differentiated treatment option for patients suffering from RA

19

Vobarilizumab

Major milestones achieved

24-week Phase IIb

RA combination

therapy study

Phase II SLE study

2015 2016 2017 2018

RA open-label

extension study

12-week Phase IIb

RA monotherapy

study

Topline results

Top line results

opt-in decision for RA

opt-in decision for SLE

Topline results

Top line results

Caplacizumab (anti-vWF)

For the treatment of acquired thrombotic

thrombocytopenic purpura

21

Caplacizumab – anti-vWF Nanobody

First-in-class potential for the treatment of aTTP

• Orphan Drug Status and patent protection to

2035

• Phase III ongoing with results expected by

end of 2017

• Planned filing for conditional approval in

Europe (Q1 2017) and BLA submission in

USA (2018)

• Ablynx to lead commercialisation in Europe

and the US

• Anticipated first launch in 2018 with peak

sales potential of ~€300M1

1 US, EU, Japan and other major markets

aTTP: acquired thrombotic thrombocytopenic purpura

22

Caplacizumab unique mode of action

Rapidly stops formation of micro-clots

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 an aTTP patient

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

Caplacizumab blocks the platelet – ULvWF interaction

Ultra-Large (UL)

vWF multimers UL-vWF multimers

cause platelet string

formation

ADAMTS13 activity is

impaired

endothelium

Caplacizumab binds to A1

domain of vWF and thereby

inhibits platelet string formation

23

Acquired TTP (aTTP)

• aTTP is caused by impaired activity of ADAMTS13 (<10% of that in normal plasma1)

– extensive microclot formation in small blood vessels throughout the body

– leads to tissue ischemia and damage to vital organs

• Ultra-rare condition with incidence estimated at up to 11 per million2

• High unmet medical need with no approved therapeutic drug currently available

– high mortality in acute phase (10-20%)3 and ~ 36% of patients have a recurrence2

– significant thromboembolic complications, including brain (e.g. stroke), heart and kidney damage

– impacts life expectancy and quality of life

1 Scully et al, BJH 2012; 2 George et al, EJH 2008; 3 Allford et al, BJH 2003, Kremer Hovinga, Blood 2010; Benhamou, Haematologica 2012

Life-threatening ultra-rare acute blood clotting disorder

aTTP patient Emergency Room ICU/haematology unit

episode diagnosis treatment

Sudden onset in otherwise healthy

person (nausea, fever, coma,..)

Initial diagnosis based on

thrombocytopenia & haemolysis

Plasma exchange until normalisation of

platelet count + immune suppressants

24

TITAN Phase II study of caplacizumab

Clinical proof-of-concept achieved in aTTP patients

• Primary endpoint met with high statistical significance (p=0.005) - nearly 40% reduction in time to platelet normalisation

= faster reversion of thrombocytopenia and reduced use of plasma exchange

• 71% fewer patients with recurrences during treatment - potential prevention of organ damage

• Post-hoc analysis - caplacizumab treated patients experienced fewer major thromboembolic

events as compared to placebo (11.4% vs 43.2%)

- fewer caplacizumab treated patients refractory to plasma exchange

treatment compared to placebo (5.7% vs 21.6%)

Three aTTP experts

describe the impact of

the TITAN trial for the

aTTP community

25

HERCULES Phase III study

Started in Q3 2015 with top line results expected in Q4 2017

* iv bolus (10mg) followed by daily sc (10mg) ** incl. corticosteroids at start of daily PEX until underlying disease activity resolved

Primary endpoint: time to confirmed normalisation of platelet count

Secondary endpoints: recurrences; mortality rate; severe morbidity; organ damage biomarkers (troponin,

creatinine, LDH); PEX parameters; days in ICU/hospital; AEs; PD; PK; immunogenicity

RA

ND

OM

ISA

TIO

N

1:1

Caplacizumab* N=46

30 days

30 days

FOLLOW-UP PERIOD (4 weeks)

Potential extension of blinded study drug if recurrence, restart daily PEX and open label caplacizumab

Daily PEX

Recurrence restart daily PEX and open label caplacizumab

Placebo* N=46

TREATMENT PERIOD**

Daily PEX

132 patients

26

Caplacizumab positioning

Potential new component in standard of care for aTTP

26

Tre

ate

men

t du

ratio

n

Daily PEX Immuno-

suppression

Removes ULvWF

& auto-antibodies

Replenishes

ADAMTS13

Reduces activity

of immune

system to

resolve the

underlying

cause of aTTP

Caplacizumab

Rapidly inhibits platelet

aggregation, micro-clot formation

and small blood vessel occlusion

Reduces PEX duration

Protects during the acute phase

Prevents organ damage

Reduces recurrences

Reduces thromboembolic events

Future standard of care could be based on three pillars

Caplacizumab may become the first approved product for the

treatment of aTTP

27

Caplacizumab for the treatment of aTTP

Potentially Ablynx’s first marketed product

27

• Concentrated patient presentation

• Established KOL network and reference centres

• Modest commercial infrastructure requirements

• Contract sales, distributors and/or commercial partners in

other territories

• No direct competition in aTTP

• Potential key component in future standard of care

• Orphan Drug status with patent protection to 2035

• Peak sales potential in aTTP of ~€300M

Planned launch in 2018

Market opportunity

Strategic opportunity to

self-commercialise in

EU5 and USA

Inhaled ALX-0171 (anti-RSV)

For the treatment of RSV infections

29

ALX-0171 – inhaled anti-RSV Nanobody

First-in-class potential for the treatment of RSV infections

• Biological drug delivered by inhalation – major

platform advantage

• Most advanced product in clinical development

to treat RSV infections in infants

• Critical pre-clinical and clinical milestones

achieved

• Phase II dose-ranging efficacy study in infants

planned to start in Q4 2016

• Opportunity in multi-billion dollar market

30

RSV infection in infants

• 90% of children infected by 2 years of age1

• 33.8 million episodes (infants <5 years) globally p.a.1

• 3.4 million hospital admissions (infants <5 years) globally p.a.1

• 66,000-199,000 deaths (infants <5 years) globally p.a.1

• No approved therapeutic

1 Mazur et al, Lancet 2015; 2 Shi et al, J Med Econ, 2011; 3 Sigurs et al, Thorax, 2010; Backman et al, Acta Pediatr, 2014

Leading cause of infant hospitalisation

Evolves to

distressing

symptoms

Up to 20%

hospitalised Symptomatic treatment

• Long-term disease burden

– increased medical cost in the first year following RSV infection2

– prolonged wheezing and increased risk of asthma development3

31

Anti-RSV Nanobody – ALX-0171

Incorporating unique Nanobody platform advantages

Platform advantage Product features

Multivalent formatting

• 3 Nanobodies linked together that bind to the F-protein of RSV

• 7,000 fold increase in potency over monovalent construct

• 10,000 fold reduction in viral titres in vitro

• Neutralises 87% of a broad range of clinical RSV isolates

Delivery via inhalation • Biological activity maintained after nebulisation

• Delivered directly to the site of infection

• Very encouraging efficacy in neonatal lamb model for infant RSV

infection

• Safe and well-tolerated in healthy adults and adults with hyperreactive

airways

• Phase I/IIa study in 53 infants successfuly completed

32

Inhaled ALX-0171

• Recruitment from Q4 2014 to Q1 2016

• Study centres in Europe and Asia-Pacific region

• Adapted infant inhalation device (vibrating mesh)

• Inhaled ALX-0171 administered once/day, for 3 consecutive days

Phase I/IIa study in 53 hospitalised RSV-infected children

Primary endpoint:

Safety and tolerability of ALX-0171

Secondary endpoints:

Assessment of clinical effect (feeding, respiratory rate, O2

saturation, wheezing, coughing, general appearance), PD,

PK and immunogenicity

RA

ND

OM

ISA

TIO

N

2:1

Placebo N=10

ALX-0171 N=20 Open-label lead-in

N=5 Infants aged 3-24

months

Placebo N=6

ALX-0171 N=12

Infants aged 1-5

months Infants aged 5-24

months

DMC*

review

DMC*

review

* Data monitoring committee

33

First-in-infant Phase I/IIa study

Safety and tolerability

Excellent safety and tolerability profile confirmed in the target population

Open-label group

ALX-0171 (N=5)

Randomised group

ALX-0171 (N=30)

Randomised group

Placebo (N=16)

Adverse events (AEs)

- number (%) of subjects with an AE 4 (80.0) 9 (30.0) 4 (25.0)

- number (%) of subjects with a treatment-related AE 1 (20.0) 2 (6.7) 0 (0.0)

Serious adverse events (SAEs)

- number (%) of subjects with an SAE 3* (60.0) 1** (3.3) 0 (0.0)

- number (%) of subjects with treatment-related SAEs 0 (0.0) 0 (0.0) 0 (0.0)

* 1 of whom discontinued ** subject discontinued

• Most common AEs were infections and respiratory disorders

• 3 AEs related to ALX-0171: mild cough, mild rhinorrhoea, mild fever 11 days after last dose

• 5 SAEs reported: hypo-responsiveness, hypotonia, pneumonia (2) and atelectasis

34

First-in-infant Phase I/IIa study

Anti-viral effect – time to undetectable virus in culture

Pro

po

rtio

n o

f p

atie

nts

with

de

tecta

ble

RS

V

All Placebo (N=13)

All ALX-0171 (N=22)

Time (hours)

Treatment with ALX-0171 had an immediate and significant impact on viral replication in RSV-infected infants

Cox model to compare ALX-0171 and placebo with respect to time to first undetectable virus in culture (undetectable at 2

consecutive time points) from time of start of treatment

Time to undetectable virus ALX-0171 Placebo

Median hours 25.3 51.9

Nominal p-value 0.014

35

First-in-infant Phase I/IIa study

Overall disease severity assessment – Global Severity Score*

Encouraging initial indication of therapeutic effect

* Overall disease severity assessment including feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general

condition and fever

Nominal p-value=0.0092

based on longitudinal analysis comparing ALX-0171

and placebo with respect to the Global Severity

Score, adjusting for baseline score and time

All ALX-0171 (N=26)

All Placebo (N=15)

Glo

ba

l S

eve

rity

Sco

re (

me

an

+ S

E)

36

Inhaled ALX-0171

Potential breakthrough for the treatment of RSV infections

36

µ$

µµ

µ

µ

µµ

• Direct delivery to the site of infection through inhalation

• Good safety profile and no treatment-related SAEs in hospitalised

RSV infected infants

• Demonstrated anti-viral-effect in pre-clinical and clinical studies

• Encouraging indication of therapeutic effect in the clinic

Phase II dose-ranging efficacy study in ~180 hospitalised RSV-infected infants planned to start in Q4 2016

Immuno-oncology

Major collaboration with Merck & Co, Inc. and

wholly-owned programmes

38

Immuno-oncology

*BofA Merrill Lynch July 2015

Changing the cancer treatment paradigm

• Market expected to grow to >$43bn by 2020*

• I/O drugs expected to treat 60% of cancers*

• Proven substantial survival impact

Huge market potential

• Increasing number of targets

• Combination therapies are the future

Multiple targets

Nature Reviews - 2012

• Bind multiple targets (2, 3, 4 or 5) with one Nanobody molecule

• Potential to increase efficacy and avoid escape mechanisms

• Technology allows rapid exploration of combinations

• Manufacturing simplicity and cost-effectiveness

Multi-specific Nanobodies -

the next wave!

39

Immuno-oncology

Multi-specific Nanobodies versus combination mAbs

One tri-specific Nanobody is 4x smaller than a mAb

mAb

Tri-specific

Nanobody

mAb 3

mAb 2

mAb 1

More difficult for mAbs to bind to

different targets simultaneously

Target 1

Target 2 Target 3

Multi-specific Nanobodies may block

multiple targets simultaneously

Target 3

Target 1 Target 2

40

Multi-specific Nanobodies

• Heavily investing in I/O R&D pipeline (~80% of total R&D budget*)

• Keytruda® approved in advanced melanoma (first line) and metastatic

NSCLC

• Sales of Keytruda® estimated to reach $6Bn by 2020**

• >160 clinical studies for Keytruda® in >30 tumor types

*Bryan Garnier Oct 2015 **Leerink August 2015

Major immuno-oncology collaboration with Merck & Co., Inc.

First in vivo pre-clinical milestone (€3.5M) achieved and

first clinical studies planned to start in 2017

Merck & Co., Inc.

leader in the field

Merck & Co., Inc. and

Ablynx in collaboration

• Initially signed in Feb ‘14; significantly expanded in July ‘15

• Targeting multiple immune-checkpoint modulators

• Up to 17 fully-funded Nanobody programmes; focus on multi-specific

combinations

• €33M upfront; up to €5.7Bn in potential future milestones plus royalties

Outlook

42

2016-2017 outlook confirmed

Focus on sustainable value creation

2016 2017

• Q1 2016

- Phase I start with VEGF/Ang2 (BI) - €8M

- publication of data from TITAN study in the NEJM

• Q2 2016

- Phase I start with CX3CR1 (BI) - €8M

- Phase I start with CXCR2 (Novartis)

- Phase I/IIa results with ALX-0171 (53 infants)

- successfully raised €74M in a Private Placement

• Q3 2016

- vobariluzumab PhIIb RA monotherapy study results

- vobariluzumab PhIIb RA combination study results

- start follow-up study with HERCULES patients

• Q4 2016

- opt-in decision by AbbVie for vobarilizumab in RA

- start Phase II dose-ranging efficacy study of ALX-0171

- pre-clinical milestones

• Caplacizumab (aTTP) – wholly-owned

- filing for conditional approval in Europe (H1)

- HERCULES Phase III study results (H2)

- life cycle management activities

• Vobarilizumab (RA) – preparations for

Phase III study initiation

• ALX-0171 (RSV) – wholly-owned

- life cycle management activities

• Immuno-oncology – with Merck & Co., Inc.

- start of multiple IND enabling studies

- pre-clinical milestones

• Various partnered programmes

advancing in the clinic

CONTACT DETAILS

Questions

+32 9 262 00 00 Investor

Relations

investors@

ablynx.com www.ablynx.com