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Nanobodies ® creating better medicines May 2016 Investor presentation

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Page 1: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

Nanobodies®

creating better medicines

May 2016

Investor presentation

Page 2: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

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

Page 3: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

3

Ablynx

Powerful platform generating potentially innovative medicines

• Platform technology and late-stage clinical development company

• 350 staff in Ghent, Belgium

• >40 wholly-owned and partnered programmes

• 1 Phase III and 4 Phase II studies ongoing in-house

• 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

• €234M in cash at 31st March 2016

• €277M raised in equity

• €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

Page 4: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

4

Ablynx

Diversified shareholder base

• Ordinary shares listed on Euronext Brussels (ABLX)

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

• 55.3M shares outstanding

• 2.7M outstanding warrants (in number of shares)

Breakdown of share capital

US 36%

UK 23%

Benelux 31%

Scandinavia 2%

France 3%

Other 5%

% of Institutional Shareholders by Geography (representing 70% of total S/O) (March 2016)

5.0% 5.0%

4.4%

3.9%

3.3%

3.0%

3.0%

72.4%

Perceptive Advisors (US)

Fidelity Management Research (US)

Taube Hodson (UK)

Boehringer Ingelheim (DE)

JP Morgan Asset Management (UK)

Oppenheimer Funds (US)

Polar Capital Funds Plc (UK)

Other shareholders

Page 5: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

Unique technology

Page 6: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

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

Page 7: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

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

Page 8: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

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

Page 9: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

Broad product pipeline

Page 10: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

10

Hybrid business model fuels the pipeline

>40 programmes, 8 Nanobodies in clinical development

Indication Product Target

aTTP

RSV

ALX-0061

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

Oncology

ozoralizumab TNFα

Greater China

Filing

Japan

VEGF/Ang2

RA

RA

SLE

RA

Psoriasis

Immuno-Oncology

~ 15 wholly-

owned and

partnered

programmes

Up to 17

programmes

IL-6R

IL-6R

TNFα RA

Various

BI 836880

Various

+

Chronic kidney disease CX3CR1 BI 655088

CXCR2 Inflammation NA

Page 11: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

Key value drivers

Page 12: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

ALX-0171 (anti-RSV)

For the treatment of RSV infections

Page 13: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

13

ALX-0171 for the treatment of RSV infections

Wholly-owned inhaled anti-RSV Nanobody

• Innovative, wholly-owned product, based on

Ablynx’s unique Nanobody® technology

• 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

• Next Phase II study in infants being planned

• Opportunity in multi-billion dollar market

Page 14: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

14

RSV infection in infants

• 60%-70% of children will have been infected by the age of 1 year1

• >3 million children (<5 years) hospitalised worldwide each year1

• 3,000-8,500 deaths in infants <2 years globally p.a.2

• No specific treatment options currently available

– Synagis® used as prophylaxis in high-risk pre-term infants only

1 Nair et al, Lancet 2010; 2 Byington et al, Pediatrics 2015; 3 Shi et al, J Med Econ, 2011; 4 Sigurs et al, Thorax, 2010; Backman et al, Acta Pediatr, 2014

Leading cause of infant hospitalisation

Evolves to

distressing

symptoms

8-20%

hospitalised

Symptomatic treatment

including inhaled

corticosteroids & bronchodilator

• Long-term disease burden

– increased medical cost in the first year following RSV infection3

– prolonged wheezing and increased risk of asthma development4

Page 15: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

15

RDD conference (May 2015); RSV Symposium (Nov 2014): presentations on Ablynx website: http://www.ablynx.com/rd-portfolio/clinical-programmes/alx-0171/

• Well tolerated in multiple Phase I clinical studies in adults

• Strong in vitro and in vivo study results

– potent anti-viral effect against recent clinical RSV isolates

– 10,000 fold reduction in viral titres and superiority in vitro compared with palivizumab (Synagis®)

– strong effect following daily inhalation for 3 consecutive days in neonatal lamb model for infant RSV

Inhaled ALX-0171

Successfully completed pre-clinical and clinical studies in adults

0

20

40

60

80

100

0 1 2 3 4 5 6

% o

f la

mb

s w

ith

sco

re ≥

1

Control

ALX-0171

RSV

infection

Treatment ALX-0171 or

formulation buffer

Malaise score - Lambs Lung viral lesions - Lambs

(day 6 post infection)

Mean

% l

un

g t

issu

e w

ith

vir

al le

sio

ns

0

10

20

30

40

50

60

Control ALX-0171

Compelling pre-clinical proof-of-concept

Page 16: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

16

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

Page 17: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

17

First-in-infant Phase I/IIa study

Safety and tolerability

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)

Study primary endpoint achieved

Safety and tolerability profile confirmed in the target population

* 1 of whom discontinued ** subject discontinued

Page 18: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

18

First-in-infant Phase I/IIa study

Anti-viral effect – viral load over time

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

All ALX-0171 (N=30)

All Placebo (N=15)

plaque assay qRT-PCR

All ALX-0171 (N=30)

All Placebo (N=15)

Page 19: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

19

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

All ALX-0171 (N=26)

All Placebo (N=15)

Page 20: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

20

Inhaled ALX-0171

Potential breakthrough for the treatment of RSV infections

20

µ$

µµ

µ

µ

µµ

• Direct delivery to the site of infection through inhalation

• No treatment-related serious adverse events

• Good safety and tolerability profile confirmed

• Anti-drug antibodies did not have an apparent effect on PK and no

apparent relation to adverse events

• Demonstrated anti-viral effect and showed encouraging trends in

Global Severity Score in infants (aged 1-24 months) who were

hospitalised with an RSV infection

Results from the first-in-infant Phase I/IIa study support advancement to a Phase II efficacy study in infants

Page 21: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

ALX-0061 (anti-IL-6R)

For the treatment of inflammatory diseases

Page 22: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

22

ALX-0061 for the treatment of RA and SLE

Anti-IL-6R Nanobody partnered with AbbVie

• Best-in-class potential for the treatment of auto-

immune disorders

• Global licensing option deal with AbbVie

• Completed recruitment of ~600 patients in 2

Phase IIb studies in RA – top line results in Q3

2016

• RA open-label study on-going

• Phase II study in SLE on-going

• Opportunity in multi-billion dollar markets

RA: rheumatoid arthritis

SLE: systemic lupus erythematosus

Page 23: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

23

The RA landscape

63

31

60

48

75

44

50

37

45

41

75

44 44 41

43

39

47

0

10

20

30

40

50

60

70

80

% o

f p

ati

en

ts

1 PhIIa study (iv) (all responders): 1mg/kg Q4W; 3mg/kg Q4W; 6mg/kg Q8W; 2 Data extracted from OPTION (iv) (4 and 8 mg/kg), AMBITION (iv) (8 mg/kg) and ADACTA (iv) (8mg/kg) trials; 3

Phase II results ACR2011/EULAR 2012: 100mg Q2W; 100mg Q4W; pooled data; 4 Phase III TARGET trial (press release Nov 2015); 150 mg Q2W and 200 mg Q2W; 5 Phase IIb trial (ACR

2013), Q4W; 25 mg, 100 mg, 200 mg; 6 2003 FDA briefing document: DE19 confirmatory Phase II/III study: 20mg QW, 40mg Q2W +MTX

ALX-0061 has best-in-class potential

Tocilizumab

(Roche)2

ALX-00611

Sarilumab

(Sanofi/Regeneron)4

Clazakizumab

(Alder)5

Sirukumab

(J&J/GSK)3

Adalimumab

(AbbVie)6

• ACR50 scores from various clinical studies

Page 24: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

24

Phase IIa RA study of ALX-0061

Demonstrated best-in-class potential

• ACR20, ACR50 and ACR70 scores of up to 100%, 75% and 63%

• First onset of remission as of week 2

• Early signs of effect on bone oedema

• No disease progression as determined by MRI

Highly efficacious

Convenient dosing

Favourable safety

profile

• Wide therapeutic window with potential to dose subcutaneously

once a month

• No dose dependent increase in frequency or severity of adverse

events

Page 25: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

25

ALX-0061

• $175M upfront at signing in September 2013

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

Global licensing option 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 (on-going)

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

license ALX-0061 after completion of the Phase II studies – then responsible for Phase III development, registration and

commercialisation

Page 27: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

Caplacizumab (anti-vWF)

For the treatment of acquired thrombotic

thrombocytopenic purpura

Page 28: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

28

Caplacizumab for the treatment of aTTP

Wholly-owned anti-vWF Nanobody

• First-in-class bivalent Nanobody with Orphan Drug

Status and patent protection up to 2035

• Developed for the treatment of acquired thrombotic

thrombocytopenic purpura (aTTP)

• Phase III (92 patients) on-going 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 USA

• Anticipated first launch in 2018

• Peak sales potential of ~€300M1

1 US, EU, Japan and other major markets

Page 29: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

29

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 Platelet string

formation in patients

with aTTP

ADAMTS13 activity is

impaired

endothelium

Caplacizumab binds to A1

domain of vWF and thereby

inhibits platelet string formation

Page 30: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

30

Acquired TTP (aTTP)

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

– extensive micro-clot formation in small blood vessels throughout the body

– leads to tissue ischemia and damage to vital organs

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

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

– high acute mortality (10-20%)3, vast majority within 2 weeks post diagnosis, and ~ 36% of patients with recurrences2

– major morbidities, 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

Page 31: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

31

TITAN Phase II study of caplacizumab

Clinical proof-of-concept achieved in aTTP patients

Primary endpoint:

time to confirmed normalisation of

platelet count

Secondary endpoints:

recurrences; PEX parameters; mortality;

major clinical events RA

ND

OM

ISA

TIO

N

1:1

PEX

PEX

Caplacizumab N=36

75 patients

Placebo N=39

30 days

30 days 30 days

30 days

• 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 (PEX)

• 71% fewer patients with recurrences during caplacizumab treatment

- potential prevention of organ damage

PEX = plasma exchange

Page 33: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

33

HERCULES Phase III study of caplacizumab

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

PEX = plasma exchange

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

92 patients

Page 34: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

34

Caplacizumab positioning

Potential new component in standard of care for aTTP

34

Tre

ate

men

t du

ratio

n

Daily PEX Immuno-

suppression

Removal of ULvWF

& auto-antibodies

Replenishment of

ADAMTS13

Reduces activity

of immune

system to

resolve the

underlying

cause of aTTP

Caplacizumab

Rapid inhibition of platelet

aggregation, micro-clot formation

and small blood vessel occlusion

Reduction in duration of PEX

treatment

Protection during the acute

phase of the disease

Prevention of organ damage

Reduction in recurrences

Future standard of care could be based on three pillars

Caplacizumab may become the first approved product for the

treatment of aTTP

Page 35: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

35

Caplacizumab for the treatment of aTTP

Potentially Ablynx’s first marketed product

35

• Concentrated patient presentation

• Established KOL network and reference centres

• Modest commercial infrastructure requirements

• Retain direct control over commercialisation in EU5 and USA

• 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

Potential launch in 2018

Market

Strategic opportunity

Page 36: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

Immuno-oncology

Major collaboration with Merck & Co, Inc. and

wholly-owned programmes

Page 37: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

37

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!

Page 38: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

38

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

Page 39: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

39

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 in

October 2015 with a bi-specific Nanobody

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

Page 40: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

Outlook

Page 41: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

41

Potential news flow 2016-2017

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)

• Q3 2016

- ALX-0061 results from Phase IIb monotherapy study

- ALX-0061 results from Phase IIb combination study

- start follow-up study with HERCULES patients

• Q4 2016

- opt-in decision by AbbVie for ALX-0061 in RA

- start Phase II efficacy study of ALX-0171

• Start 1 additional Phase I study with partner

• Pre-clinical milestones

PLUS

• Caplacizumab (aTTP) – wholly-owned

- filing for conditional approval in Europe (H1)

- HERCULES Phase III study results (H2)

• ALX-0061 (RA) – AbbVie have an option

- potential start of Phase III RA study (H2)

• ALX-0171 (RSV) – wholly-owned

- complete recruitment of Phase II efficacy study (H2)

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

- start of multiple IND enabling studies

- pre-clinical milestones

• BI starts Phase II with anti-VEGF/Ang2 (BI)

• Up to 6 additional Phase I/II starts (internal +

partnered) PLUS

Page 42: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

42

Ablynx

Investment thesis

Unique and powerful validated technology platform which has

been used to generate potential medicines in a wide range of

therapeutic areas

Very well funded hybrid business model which supports >40

programmes, some together with pharmaceutical partners,

offering a balanced range of risk and reward

A number of short and medium term pre-clinical, clinical and

commercial catalysts

Page 43: Investor presentation - Ablynx · • Recruitment from Q4 2014 to Q1 2016 • Study centres in Europe and Asia-Pacific region • Adapted infant inhalation device (vibrating mesh)

CONTACT DETAILS

Questions

+32 9 262 00 00 Investor

Relations

investors@

ablynx.com www.ablynx.com