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Nanobodies ® creating better medicines February 2016 Investor presentation

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Page 1: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

Nanobodies®

creating better medicines

February 2016

Investor presentation

Page 2: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

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...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

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 + royalties

• €262M in cash at 30th September 2015

• €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...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

4

Ablynx

• Ordinary shares listed on Euronext Brussels (ABLX)

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

• 54.8M shares outstanding

• 2.7M outstanding warrants

Diversified shareholder base

Breakdown of share capital

US 35%

UK 27%

Benelux 28%

Scandinavia 2%

France 4%

Other 5%

% of institutional shareholders by geography (representing 70% of total shares outstanding)

5.1% 5.0%

4.5%

4.4%

4.0%

3.9%

3.3%

3.1%

3.0%

63.7%

Perceptive Advisors (US)

Fidelity Management Research (US)

Aviva Investors (UK)

Taube Hodson (UK)

Abingworth Management (UK)

Boehringer Ingelheim (DE)

JP Morgan Asset Management (UK)

Oppenheimer Funds (US)

Polar Capital Funds Plc (UK)

Other shareholders

Page 5: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

5

Strong performance in 2015

Excellent progress in all areas

5

Development & Discovery Financial & Commercial

• Initiated Phase III study with caplacizumab (vWF) in

acquired TTP

• Initiated 2 Phase IIb RA studies with ALX-0061 (IL-6R)

(partnership with AbbVie)

• Initiated Phase II SLE study with ALX-0061 (IL-6R)

(partnership with AbbVie)

• Completed recruitment for Phase I/IIa safety study in

infants with ALX-0171 (RSV)

• Merck KGaA completed Phase Ib study in psoriasis

patients with ALX-0761 (bi-specific IL-17A/F Nanobody)

• Achieved pre-clinical POC with bi-specific Nanobody

programme in immuno-oncology (partnership with Merck

& Co., Inc.)

• Initiated 4 new internal discovery programmes and ~10

new partnered programmes

• €100M raised through a 5-year Convertible Bond

• Expanded immuno-oncology collaboration with Merck &

Co., Inc. to include a total of 17 programmes; €5.7Bn in

potential milestones plus royalties

• Signed collaboration with Novo Nordisk to utilise multi-

specific Nanobodies in a specific indication; €5M upfront

and €182M in potential milestones plus royalties

• Signed licensing deal with Taisho Pharmaceuticals to

develop and commercialise ozoralizumab (TNFα) in

Japan

• Extended the ion channel collaboration with Merck &

Co., Inc. in Neurology

• Signed research collaboration with Genzyme to explore

the potential of a Nanobody targeting an ion channel in

Multiple Sclerosis

• Began to build a commercial organisation to support the

launch of caplacizumab in EU and USA

Page 6: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

Unique technology

Page 7: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

7

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 8: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

8

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 9: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

9

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

Mix and match

Multi-specific Nanobodies that

address different targets in a single

drug molecule

Inhalation

Oral-to-topical

Ocular

Multiple delivery routes

Page 10: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

Broad product pipeline

Page 11: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

11

Hybrid business model fuels the pipeline

~40 programmes, 6 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

+

Page 12: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

Key value drivers

Page 13: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

13

Immuno-oncology (I/O)

*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 14: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

14

Immuno-oncology (I/O)

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 15: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

15

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

• 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

• First product could enter the clinic in 2017

Page 16: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

16

Proprietary tetravalent anti-GITR Nanobody

Efficacy as monotherapy or in combination with anti-PD1 mAb

Tumour efficacy in a syngeneic mouse model

PD1 mAb

GITR Nb

Vehicle

Irrelevant Nb + PD-1 mAb

GITR Nb

GITR Nb + PD-1 mAb

CT26 colon carcinoma tumours were grown to 90 mm3 in size prior to start of treatment (Day 0)

Page 17: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

17

Proprietary tetravalent anti-GITR Nanobody

Efficacy as monotherapy or in combination with anti-PD1 mAb

Individual tumor efficacy plots

Reg = regressed below baseline volume

Irr Nb + PD-1 mAb

0/10 Reg

GITR Nb

1/10 Reg

GITR Nb + PD-1 mAb

5/10 Reg

Vehicle

0/10 Reg

CT26 colon carcinoma tumours were grown to 90 mm3 in size prior to start of treatment (Day 0)

Page 18: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

18

OPTION TO LICENSE

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’s (RA; SLE) on-

going; RA results expected

in H2 2016

Product pipeline

Most advanced clinical programmes

18

PROPRIETARY

Programme (target) Indication Key differentiating features Stage

Caplacizumab (vWF)

Acquired

thrombotic

thrombocytopenic

purpura

First-in-class orphan drug

Inhibits micro-clot formation

More rapidly restores normal platelet counts

Phase III on-going and MAA

filing planned in H1 2017 in EU

for conditional approval

ALX-0171 (RSV)

Respiratory

syncytial virus

infection

Inhaled Nanobody delivered directly to

infection site

First-in-class therapeutic addressing high

unmet medical need

Completed recruitment of first-

in-infant Phase I/IIa 35 patient

safety study: results expected

in H1 2016. Expansion study

on-going in infants aged 1-5

months

*Gottschalk et al, Frontiers in Immunology, Oct 2015

Page 19: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

19

Caplacizumab

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 II (75 patients) successfully completed; Phase

III (92 patients) on-going with results expected by

end of 2017

• Planned filing for conditional approval in Europe (H1

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, other major markets

Page 20: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

20

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 21: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

21

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 22: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

22

Caplacizumab (anti-vWF) proven clinical benefit

TITAN Phase II study – achieved clinical proof-of-concept

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 subjects

Placebo N=39

30 days

30 days 30 days

30 days

• Primary endpoint met with high statistical significance (p=0.005)

- 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 23: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

23

Caplacizumab (anti-vWF)

Hercules Phase III study (Q3 2015 to 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 subjects

Page 24: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

24

Caplacizumab positioning

Potential new component in standard of care for aTTP

24

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 25: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

25

Caplacizumab (anti-vWF)

Potentially Ablynx’s first marketed product

25

• 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 potential

Strategic opportunity

Page 26: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

26

ALX-0171

Wholly-owned anti-RSV Nanobody

• First-in-class trivalent Nanobody, delivered by inhalation

• Potential breakthrough for the treatment of Respiratory

Syncytial Virus (RSV) infection in infants

• 3 Phase I studies in 106 adults* successfully completed

• First-in-infant Phase I/IIa safety results in H1 2016

• Expansion cohort in younger infants within the Phase I/IIa

safety study on-going during H1 2016

• Phase II dose-ranging study to start in H2 2016

• Opportunity in multi-billion dollar market

* Including 24 adults with hyper-reactive airways

Page 27: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

27

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 ($900M sales in 2014)

1 Nair et al, Lancet 2010; 2 Byington et al, Pediatrics 2014; 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 28: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

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Vaccines of the World (Oct 2013); 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

ALX-0171 (anti-RSV Nanobody)

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

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 29: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

29

ALX-0171 (anti-RSV Nanobody)

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

• Study centres in Europe and Asia-Pacific region

• Adapted infant inhalation device (vibrating mesh)

First-in-infant Phase I/IIa safety study – recruitment completed

* Data Monitoring Committee

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 or placebo once/day

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

Results in H1 2016

Review

by DMC*

Page 30: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

30

ALX-0171 (anti-RSV Nanobody)

Next steps in clinical development

Phase I/IIa expansion cohort

• Expansion of Phase I/IIa safety study

• ~10-18 hospitalised infants aged 1-5 months

• Generate additional data in younger children

• On-going

• Results: H2 2016

Phase II dose-ranging

• Clinical centres in EU, Asia-Pacific and USA

• ~100 hospitalised infants aged 1-36 months

• Primary endpoint: nasal viral load

• Secondary endpoints: clinical effect (e.g. feeding

and respiratory parameters) and duration of

hospitalisation

• Start: H2 2016

• Target recruitment completion: end 2017

Page 31: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

31

ALX-0171 (anti-RSV Nanobody)

Innovative therapeutic approach with significant commercial potential

31

• Delivered via inhalation directly to the site of infection

• Highly potent and selective

• Neutralises broad range of RSV strains

• Compelling proof-of-concept in animal model of infant RSV

• Good safety profile demonstrated

• Data from first-in-infant Phase I/IIa safety study expected in H1 2016

• Currently only prophylactic and symptomatic treatment options

• Vaccines and improved antibodies in development for prophylactic

use, but with potential limitations

• Small molecule therapeutics in development but ALX-0171 appears

to be the most advanced programme for the treatment of infant RSV

infections

• ~34M infections/year resulting in ~3-4M hospitalisations/year

globally1; total estimated cost burden of ~$88Bn2

Market potential

Unique product

1 Nair et al, Lancet 2010; 2Novavax November 2015: estimated value of life lost, future health implications and lost earnings (both elderly and infant populations)

Page 32: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

32

ALX-0061

Anti-IL-6R Nanobody partnered with AbbVie

• Half-life extended Nanobody

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

immune disorders

• Global licensing agreement with AbbVie

• 2 Phase IIb studies in RA on-going with results

expected in H2 2016

• Phase II study in SLE on-going with results

expected in 2018

• Opportunity in multi-billion dollar markets

RA: rheumatoid arthritis

SLE: systemic lupus erythematosus

Page 33: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

33

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 (anti-IL-6R) 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 34: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

34

ALX-0061 (anti-IL-6R Nanobody)

Phase IIa RA study 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

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35

ALX-0061 (anti-IL-6R Nanobody)

• $175M upfront at signing in September 2013

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

Global licensing option deal with AbbVie

35

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 36: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

36

ALX-0061 (anti-IL-6R Nanobody)

Key data points in clinical development

Phase I study subcutaneous (sc) ALX-0061

Phase IIb RA

combination study

Phase II SLE study

2014 2015 2016 2017 2018

Phase II RA open

label extension

(OLE) study

Phase IIb RA

monotherapy study 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

Top line results

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Outlook

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38

2016 – an exciting year ahead

Potential key events

Clinical study results Building the pipeline

• Results of first-in-infant Phase I/IIa

safety study with ALX-0171 (RSV)

(35 infants aged 3-24 months)

• Results from the expansion cohort

of the first-in-infant Phase I/IIa

safety study with ALX-0171 (RSV)

(infants aged 1-5 months)

• Results from the Phase IIb RA

combination therapy study with

ALX-0061 (IL-6R)

• Results from the Phase IIb RA

monotherapy study with ALX-0061

(IL-6R)

• Results from the Phase Ib study

with ALX-0761 (IL-17A/F) in

psoriasis patients (licensed to

Merck KGaA)

• Continuation of Phase III study

with caplacizumab

• Continuation of Phase II study in

SLE with ALX-0061 (IL-6R)

• Initiation of Phase II dose-

ranging study with ALX-0171

(RSV)

• Initiation of up to 4 Phase I

studies in partnered programmes

• Start of IND enabling studies with

immuno-oncology programmes

(partnered with Merck & Co.,

Inc.)

• Initiation and continuation of ~40

internal and partnered discovery

and pre-clinical programmes

Commercial

• Opt-in decision by AbbVie for

global exclusive license of

ALX-0061 in RA

• Continuing preparations for

commercialisation of

caplacizumab

• Expand existing collaborations

and/or initiate new

partnerships

• Payment to Ablynx of multi-

millions in up-fronts, FTE

payments and milestones

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39

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 40: Investor presentation - Ablynx...February 2016 Investor presentation 2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,

CONTACT DETAILS

Questions

+32 9 262 00 00 Investor

Relations

investors@

ablynx.com www.ablynx.com