Nanobodies®
creating better medicines
March 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
• >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
• €236M in cash at 31st December 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
4
Ablynx
Diversified shareholder base
• Ordinary shares listed on Euronext Brussels (ABLX)
• Sponsored Level I ADRs on the US OTC market (ABYLY)
• 55.1M shares outstanding
• 2.5M outstanding warrants
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
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
>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
+
Key value drivers
12
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!
13
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
14
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; 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
15
Proprietary tetravalent anti-GITR Nanobody
Efficacy as monotherapy or in combination with anti-PD1 mAb
CT26 colon carcinoma tumours were grown to 90 mm3 in size prior to start of treatment (Day 0)
Tumor efficacy in a syngeneic mouse model
Vehicle
Irrelevant Nb + PD-1 mAb
GITR Nb
GITR Nb + PD-1 mAb
PD1 mAb
GITR Nb
p < 0.0001
p < 0.0001
Tetravalent
anti-GITR Nb-IgG1
16
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)
17
OPTION TO LICENSE
Programme (target) Indication Key differentiating features Stage Partner
ALX-0061 (IL-6R)
Rheumatoid
arthritis;
Systemic lupus
erythematosus
Best-in-class opportunity
Monovalent interaction; strong affinity
and preferential binding to soluble IL-6R*
3 Phase II’s (RA; SLE)
on-going; both RA trials
have completed
recruitment and results
expected in Q3 2016
Product pipeline
Most advanced clinical programmes
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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 53 patient
safety study: results expected
in Q2 2016
*Gottschalk et al, Frontiers in Immunology, Oct 2015
18
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
19
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
20
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
21
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
22
TITAN Phase II study of caplacizumab
February 2016: published in world-class medical journal
Three aTTP experts
describe the impact of
the TITAN trial for the
aTTP community
23
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
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
25
Caplacizumab for the treatment of aTTP
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
Strategic opportunity
26
ALX-0171 for the treatment of RSV infections
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
• Completed recruitment of Phase I/IIa inhalation study
in 35 infants (aged 3-24 months) and 18 infants (aged
1-5 months) – top line results in Q2 2016
• Phase II dose-ranging study expected to start in Q4
2016
• Opportunity in multi-billion dollar market
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
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
28
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
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
29
First-in-infant Phase I/IIa study of ALX-0171
• 53 infants who had been hospitalised with a RSV infection
• Study centres in Europe and Asia-Pacific region
• Adapted infant inhalation device (vibrating mesh)
• Inhaled ALX-0171 administered once/day, for 3 consecutive days
Recruitment completed with results expected in Q2 2016
* Data Monitoring Committee
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
RA
ND
OM
ISA
TIO
N
2:1
Placebo N=10
ALX-0171 N=20
Open-label lead-in
N=5
DMC*
review
DMC*
review
Infants aged 3-24
months
Placebo N=6
ALX-0171 N=12
Infants aged 1-5
months
Infants aged 5-24
months
30
ALX-0171
Next steps in clinical development
First-in-infant Phase I/IIa study
• Clinical centres in Europe and Asia-
Pacific
• Results from 35 infants, aged 3-24
months, and 18 infants, aged 1-5 months,
expected in Q2 2016
Phase II dose-ranging study
• Clinical centres in Europe, Asia-Pacific and USA
• ~120 hospitalised infants aged 1-24 months
• Start: Q4 2016
• Target recruitment completion: H2 2017
31
ALX-0171 for the treatment of RSV infections
Innovative approach with significant commercial potential
31
• Delivered via inhalation directly to the site of infection
• Highly selective and potent; 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 study expected in Q2 2016
• Currently only prophylactic and symptomatic treatment options
• ~34M infections/year resulting in ~3-4M hospitalisations/year
globally1; total estimated cost burden of ~$88Bn2
• Opportunity in a multi-billion dollar market (outpatient and
hospitalised settings; infant and elderly population)
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)
32
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
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 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
34
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
35
ALX-0061
• $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
36
ALX-0061
Key data points in clinical development
Phase IIb RA
combination study
Phase II SLE study
2015 2016 2017 2018
Phase II RA open-
label extension study
Phase IIb RA
monotherapy study Top line results
Top line results
opt-in decision for RA;
potentially continue development in RA
opt-in decision for SLE;
potentially continue
development in SLE
Top line results
Top line results
Outlook
38
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/IIa results with ALX-0171 (53 RSV-infected
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 dose-ranging study of ALX-0171
• Anti-IL-17A/F (psoriasis) – with Merck KGaA
- results of Phase Ib study (40 patients)
• Start clinical studies with partners
- up to 3 additional Phase I studies
• 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 dose-ranging 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)
• Merck KGaA starts Phase II in psoriasis with anti-IL-
17A/F
• up to 6 additional Phase I/II starts (internal +
partnered)
PLUS
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
CONTACT DETAILS
Questions
+32 9 262 00 00 Investor
Relations
investors@
ablynx.com www.ablynx.com
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