Nanobodies®
creating better medicines
19 March 2015 – Brussels – Edwin Moses, CEO
KBC Healthcare Conference
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Forward looking statements
Certain statements, beliefs and opinions in this presentation are forward-looking, which reflect the
Company or, as appropriate, the Company directors’ current expectations and projections about
future events. By their nature, forward-looking statements involve a number of risks, uncertainties
and assumptions that could cause actual results or events to differ materially from those expressed
or implied by the forward-looking statements. These risks, uncertainties and assumptions could
adversely affect the outcome and financial effects of the plans and events described herein. A
multitude of factors including, but not limited to, changes in demand, competition and technology,
can cause actual events, performance or results to differ significantly from any anticipated
development. Forward looking statements contained in this presentation regarding past trends or
activities should not be taken as a representation that such trends or activities will continue in the
future. As a result, the Company expressly disclaims any obligation or undertaking to release any
update or revisions to any forward-looking statements in this presentation as a result of any
change in expectations or any change in events, conditions, assumptions or circumstances on
which these forward-looking statements are based. Neither the Company nor its advisers or
representatives nor any of its parent or subsidiary undertakings or any such person’s officers or
employees guarantees that the assumptions underlying such forward-looking statements are free
from errors nor does either accept any responsibility for the future accuracy of the forward-looking
statements contained in this presentation or the actual occurrence of the forecasted developments.
You should not place undue reliance on forward-looking statements, which speak only as of the
date of this presentation.
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3
Ablynx
Corporate snapshot
• Drug discovery and development company in Ghent, Belgium
• >300 employees
• Pioneer in next generation biological drugs – Nanobodies®
• >500 granted and pending patents
• >30 programmes – six at the clinical development stage
• Three clinical proof-of-concepts (POC)
• >10 new clinical programmes anticipated over the next 3 years
• AbbVie, Boehringer Ingelheim, Eddingpharm, Merck & Co,
Merck Serono and Novartis
• €206M in cash at December 31st 2014
CORPORATE
TECHNOLOGY
PARTNERS
PRODUCTS
FINANCIALS
4
2014
A year of great progress
4
Pipeline value
creation 1
Expanding
existing
collaborations 2
Corporate
development 3
• 6 clinical trial read outs
• Phase II clinical proof-of-concept with caplacizumab in TTP
• 4 clinical trials initiated
• Immune-onco deal with Merck & Co worth €20 upfront, €10.7M
research funding and up to €1.7Bn in future milestones plus royalties
• 2nd licensing agreement with Eddingpharm
• 1st step in a building commercial infrastructure with appointment of
Chief Commercial Officer
• Financial position strenghtened through oversubscribed private
placement of new shares (raised €41.7M)
6
Nanobodies
• Camelid heavy-chain only antibodies are stable and fully functional
• Nanobodies represent the next generation of antibody-derived biologics
Derived from heavy-chain only antibodies
Conventional
antibodies
Heavy chain only
antibodies
Ablynx’s Nanobody
• small
• robust
• sequence homology comparable
to humanised/human mAbs
• easily linked together
• nano- to picomolar affinities
• intractable targets
• multiple administration routes
• manufacturing in microbial cells
CH2
CH3
CH1
CL
VL
VH 12-15kDa
CH2
CH3
VHH
VHH
7
Ablynx’ platform
*Glycine-serine linkers from C-terminus to N-terminus
Rapid generation of high quality biologics
~12-18 months
Immunise llamas
with antigen or
use synthetic library
Wide range of highly
diverse Nanobodies
with 0.1-10nM affinities
Formatted*
Nanobodies ready
for in vivo testing
Cloning and production in microbial systems
8
Nanobody platform
Competitive advantages
Mix and match
Cell specificity
Immune cell
recruitment
Tissue-specific
targeting
Cell- /tissue-homing
Albumin-
binding
Nanobody Fc
Weeks/days/hours
Customised
half-life extension
Nanobodies
against ion
channels and
GPCRs
Nanobodies can
reach conserved
cryptic epitopes
Challenging and
intractable targets
Manufacturing
High-yield,
high-
concentration,
low-viscosity,
microbial
production
Inhalation
Oral-to-topical
Needle-free
Ocular
Alternative delivery routes
Nanobody-
drug
conjugates
Cell killing
Ag-1 Ag-1 Ag-1
Targeting different pathways at once
with a single Nanobody construct, e.g.
multiple checkpoint inhibitors
10
Proprietary and partnered programmes
Multiple shots on goal
Inflammation/
Immunology
FU
LL
Y O
WN
ED
Therapeutic area Product name Target
Inflammation/
Immunology
Haematology
Oncology/
Immuno-oncology
Respiratory
Discovery
ALX-0061
Pre-clinical Phase I Phase II Phase III
IL-6R
caplacizumab vWF
ALX-0171
Neurology
Various
ALX-0141 RANKL
ALX-0761
Various
Various
Various
RSV
Various
Various
PA
RT
NE
RE
D
Bone disorders Greater China
IL-17F/IL-17A
Ocular
Oncology/
Immuno-oncology
ozoralizumab TNFα Greater China
Filing
CXCR2
Various
Various
Other
Clinically validated targets
First-in-class
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PARTNERED
Programme (target) Indication Key differentiating features Stage Partner
ALX-0061 (IL-6R)
RA, SLE
Best-in-class opportunity
Monovalent interaction; strong affinity
and preferential binding to soluble IL-6R
Start Phase II
(RA; SLE) in 2015
RA results
expected 2016
ALX-0761 (IL-17A/F)
Psoriasis
Potent neutralisation of both IL-17A
and IL-17F
POC achieved in primate CIA* model
Psoriasis Phase
Ib on-going:
results expected
2015
Leading programmes in the clinic
* Collagen induced arthritis model
Pipeline value drivers
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PROPRIETARY
Programme (target) Indication Key differentiating features Stage
Caplacizumab (vWF)
Thrombotic
thrombocytopenic
purpura
First-in-class orphan drug
Novel mode of action
Inhibition of microthrombi formation
Start Phase III H2
2015 and MAA filing
in H1 2017 in EU for
conditional approval
ALX-0171 (RSV)
Respiratory
syncytial virus
infection
First-in-class addressing high unmet need
Inhaled Nanobody delivered to infection site
Highly potent trivalent construct
Start first-in-infant
study Q4 2014:
results expected H1
2016
12
Caplacizumab
Anti-vWF Nanobody
• First-in-class bivalent Nanobody with
Orphan Drug Status
• Developed for the treatment
of acquired thrombotic thrombocytopenic
purpura (TTP)
• Phase III study to start in H2 2015
• Filing expected in H1 2017 for conditional
approval in Europe based on Phase II
results
• Peak sales potential of €300M-€400M1
1 US, EU, Japan, other markets (Brazil, Canada, Russia, Mexico, Australia)
13
Caplacizumab
What is the biological basis of TTP?
Caplacizumab blocks the platelet –
ULvWF interaction
ULvWF and anti-vWF Nanobody
ULvWF
Ex vivo assay for platelet string formation
Fluorescence microscopy image of platelets adhering to UL-vWF in plasma of TTP patients
Without treatment, fluorescently labelled platelets adhere to
UL-vWF, observed as string-like structures
Caplacizumab inhibits the formation of platelet strings and potentially
the associated microvascular thrombi in many organs
Ultra-Large (UL)
vWF multimers Platelet string
formation in patients
with TTP
ADAMTS13 activity is
impaired
endothelium
Caplacizumab binds to A1
domain of vWF and thereby
inhibits platelet string formation
14
Acquired TTP
• Potentially life threatening rare disorder of the blood coagulation system
– incidence of 11.3 per million1
– ~10,000 acute events annually in US and Europe
• Extensive microscopic thrombi formed in small blood vessels throughout the body
• High unmet medical need
– no approved medicinal product for treatment available
– mortality remains high (10-30%)2 and ~ 36% of patients have relapses1
– major morbidities after TTP episode such as neurocognitive impairment
– standard of care is plasma exchange (PE) plus immune suppressants
1 George et al, 2008; 2 Allford et al, 2003, Kremer Hovinga, 2010; Benhamou 2012
Significant unmet medical need
HEALTHY PERSON
Daily PEX in hospital
until recovery of platelet
count
Severe fatigue,
headache, coma,
abdominal pain,
weakness, nausea,
bizarre behaviour,
vertigo, seizures
SUDDEN ONSET EMERGENCY
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Caplacizumab
Phase II TITAN design and schedule R
AN
DO
MIS
AT
ION
Primary endpoint:
time to confirmed normalisation of
platelet count
Secondary endpoints:
plasma exchange frequency and volume; relapse;
exacerbations; mortality; major clinical events (stroke, MI,
organ dysfunction); recovery from signs/symptoms; ADA
1:1
Safety & efficacy endpoints
PEX
PEX
Caplacizumab N=36
1 year follow-up
1 year follow-up
Long-term endpoints:
ADA; relapse; non focal neurological
symptoms
Target
110 subjects
Actual
75 subjects
Placebo N=39
30 days
30 days 30 days
30 days
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TITAN trial summary
• Patients treated with caplacizumab achieved confirmed platelet
normalisation at more than twice the rate of the group treated with
placebo
• This effect was statistically significant (p = 0.013)
Strong clinical proof-of-concept
• 71% fewer patients with an exacerbation
• No deaths in the caplacizumab arm compared to 2 deaths in the
placebo arm
• Increased bleeding tendency (but believed to be manageable)
• Overall, caplacizumab has an acceptable safety profile
PRIMARY
ENDPOINT
SECONDARY
ENDPOINT
SAFETY
17
Caplacizumab
Current status and next steps
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Caplacizumab could be approved for sale in Europe in 2018
• Confirmed clinical activity and good safety profile in the clinic
• Held consultations with regulatory authorities in USA and EU
• Intention to file for conditional approval in EU in H1 2017 based on Phase II study
• Preparations progressing to start Phase III trial in H2 2015
• Intention to submit BLA in USA following Phase III study completion
• Commercialisation/partnering strategy currently under evaluation
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ALX-0171
Anti-RSV Nanobody
• First-in-class trivalent Nanobody for the
treatment of respiratory syncytial virus
(RSV) infection in infants
• Delivered by inhalation
• First-in-infant Phase IIa on-going with
results expected in H1 2016
• Opportunity in multi-billion dollar market
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RSV infection in infants
• Leading cause of infant hospitalisation and primary viral cause of infant death
– ~300,000 children* (< 5 years) hospitalised per year in 7 major markets1,2
– increased medical cost in the first year following RSV infection3
– prolonged wheezing and increased risk for asthma development4
• No widely accepted drug available to treat RSV infections
– Synagis® used as prophylaxis in high-risk pre-term infants only ($1.1Bn sales in 2013)
Extrapolation based on estimated US prevalence 1 Hall et al, NEJM, 2009; 2 Lee et al, Human Vaccines, 2005; 3 Shi et al, J Med Econ, 2011; 4 Sigurs et al, Thorax, 2010; Backman et al, Acta Pediatr, 2014
High unmet medical need
Evolves to
distressing
symptoms
8-20%
hospitalised
Symptomatic treatment
including inhaled
corticosteroids & bronchodilator
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ALX-0171
• Well tolerated in multiple Phase I clinical studies in adults
• In vitro studies demonstrated
– potent anti-viral effect against recent clinical RSV isolates
– 10,000 fold reduction in viral titres and superiority over palivizumab (Synagis®)1
• Daily inhalation of ALX-0171 for 3 consecutive days in neonatal lamb model for infant
RSV demonstrated markedly reduced symptoms of illness (“Malaise Score”)
1 Vaccines of the World (Oct 2013) and 2 RSV Symposium (Nov 2014) – presentations available on Ablynx website
Key milestones achieved
0
20
40
60
80
100
0 1 2 3 4 5 6% o
f la
mb
s w
ith
sco
re ≥
1 RSV vehicle
RSV ALX-0171
Vehicle
RSV
infection
Treatment ALX-0171 or
formulation buffer
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ALX-0171
• Infants aged 3 to <24 months who are hospitalised for RSV infection
• 24 EU centres and additional centres Southern Hemisphere (risk mitigation)
• Custom-developed infant inhalation device (vibrating mesh)
* Data monitoring committee
First-in-infant inhalation study
RA
ND
OM
ISA
TIO
N
2:1
Placebo N=10 Inhaled ALX-0171 once/day
3 consecutive days
ALX-0171 N=20
Open-label lead-in
N=5
Review by
DMC*
Inhaled ALX-0171 once/day or placebo
3 consecutive days
Primary endpoint:
Safety and tolerability of ALX-0171
Secondary endpoints:
Clinical effect (feeding, respiratory rate,
wheezing, coughing, general appearance)
PD (viral load), PK (ALX-0171 systemic
concentration) and immunogenicity
Started Q4 2014
Results expected H1 2016
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ALX-0171
• Strong therapeutic effect demonstrated in a neonatal animal model for infant
RSV infection
• Well tolerated in multiple Phase I studies in adults
• First-in-infant Phase IIa study initiated in Northern Hemisphere; lead-in phase
successfully completed and confirmation from DMC to proceed with placebo-
controlled phase of the study
• Recruitment of Phase IIa study to continue in parts of the Southern Hemisphere
and Asia to complete recruitment in 2015 with results anticipated in H1 2016
Current status and next steps
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With ALX-0171, Ablynx could potentially achieve its fourth clinical proof-
of-concept for Nanobodies, and its first for an inhaled Nanobody
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ALX-0061
Anti-IL-6R Nanobody
• Monovalent half-life extended Nanobody
• Best-in-class potential for the treatment of
auto-immune disorders
• Global licensing agreement with AbbVie
• Phase IIb studies in RA and Phase II
study in SLE to start in 2015
• Opportunity in multi-billion dollar markets
RA: rheumatoid arthritis
SLE: systemic lupus erythematosus
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ALX-0061
Compelling Phase IIa results in RA patients
83
71
58 63
29
0
20
40
60
80
100
% o
f p
ati
en
ts
All unmodified ALX-0061 at week 24 (N=24)
ACR20 ACR50 ACR70 DAS28 resmission Boolean remission
• Treatment was highly efficacious and was well tolerated
• No increase in adverse events upon extension of treatment
• No anti-drug antibodies were reported
ACR50 score as potential
differentiating factor
25
ALX-0061
• $175M upfront at signing in September 2013
• $665M total potential milestones plus double-digit royalties
Global licensing deal with AbbVie
25
Economics
Ablynx • Perform and fund Phase I study with subcutaneous formulation
(successfully completed in 2014)
• Perform and fund Phase II studies in RA and SLE (start 2015)
AbbVie
Commercialisation
• Pay a fee for each indication if they exercise the right to
license ALX-0061 after completion of the Phase II studies
• Responsible for Phase III development and registration
• AbbVie is responsible for global commercialisation
• Ablynx retains option to co-promote ALX-0061 in the Benelux
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ALX-0061
• First patient dosed in March 2015
• Adult subjects with moderate to severe RA despite MTX therapy
• Worldwide, randomised, double-blind, placebo-controlled 24 week dose finding study
• Eligible subjects will be invited to roll-over into open-label extension (OLE) study
* methotrexate
Phase IIb RA combination study with MTX* R
AN
DO
MIS
AT
ION
1:1:1:1:1
Placebo
ALX-0061 dose 1, Q4W
330 subjects
ALX-0061 dose 2, Q4W
ALX-0061 dose 2, Q2W
ALX-0061 dose 3, Q2W
Primary endpoint at week 12:
ACR20 response
Secondary endpoints:
ACR responses over time, disease
activity scores, EULAR DAS28
response, remission, effects on
quality of life
Other assessments:
pharmacokinetics,
pharmacodynamics,
safety/tolerability, immunogenicity
27
ALX-0061
• Study on track to have first patient dosed during Q1 2015
• Adult subjects with moderate to severe RA who are intolerant to MTX or for whom
continued MTX is inappropriate
• Worldwide, randomised, double-blind 12 week study
• (Ro)Actemra® arm to obtain parallel descriptive information on efficacy and safety
• Eligible ALX-0061 treated subjects will be invited to roll-over into an OLE study
Phase IIb RA monotherapy study
1:1:1:1
ALX-0061 dose 1, Q4W Primary endpoint at week 12: ACR20 response
Secondary endpoints: ACR responses over time, disease
activity scores, EULAR DAS28 response,
remission, effects on quality of life
228 subjects
ALX-0061 dose 1, Q2W
ALX-0061 dose 2, Q2W
(Ro)Actemra® 162mg
Q1W (EU) or Q2W (US)
Other assessments: pharmacokinetics, pharmacodynamics,
safety/tolerability, immunogenicity
RA
ND
OM
ISA
TIO
N
28
ALX-0061
Key data points in clinical development
Phase I
sc study
Phase IIb
combination and
monotherapy
studies in RA
Phase II study
in SLE
2014 2015 2016 2017 2018 2019
Top line results
Top line results
potentially continues development in RA
potentially continues
development in SLE
Results announced 23 Oct 2014
ALX-0061 showed >80% bioavailability after sc injection
29
Additional clinical assets
Developed with partners
• ALX-0761 – anti-IL-17A/F
Merck Serono (global)
• ALX-0141 – anti-RANKL
Eddingpharma (Greater China)
• Ozoralizumab – anti-TNFα
Eddingpharm (Greater China)
31
Current partnerships
Broad platform exploitation and value creation
> 20 active programmes; >€340M in non-dilutive cash received
~€3Bn in potential future milestones plus royalties
Global licensing deal for ALX-0061 (anti-IL-6R) in RA and SLE
2 discovery deals: ion channel deal; immune-onco deal with focus on multi-specifics
Strategic discovery alliance (focus on bi-specifics) – multiple programmes on-going
2 licensing deals in Greater China for ALX-0141 and ozoralizumab
Target-based discovery deal
Multiple programmes on-going (1 Phase Ib) under 3 co-co deals – 2013 strategic
alliance likely to be terminated with Ablynx retaining full ownership of 5 programmes
33
2015
Potential value drivers
33
Developing the pipeline Programme read outs Commercial
An important year ahead!
• Caplacizumab (vWF): i) confirm regulatory pathway
ii) start Ph III in acquired TTP
• ALX-0061 (IL-6R): dose first
patient in: i) Ph IIb RA combination therapy
ii) Ph IIb RA monotherapy
iii) Ph II in SLE
• ALX-0171 (RSV): complete
recruitment of Phase IIa
• Partnered programmes:
potential start of 3 Phase I’s
• ALX-0761 (IL-17A/F)
(Merck Serono): expect
Phase Ib results in psoriasis
patients in H2 2015
• Potential in vivo POC
results from initial
programmes as part of IO
collaboration with Merck &
Co
• Caplacizumab (vWF):
determine partnering and
commercialisation
strategy
• Potential milestone
payments from ongoing
partnerships
• Continuing partnering
discussions
34
Long term value creation
Some potential clinical and regulatory key events
2015
2016
2017
2018
ALX-0171 Infant Phase IIa (RSV)
Wholly-owned
ALX-0061 Phase IIb combination therapy (RA)
AbbVie have option to license worldwide
ALX-0061 Phase IIb monotherapy (RA)
AbbVie have option to license worldwide
ALX-0761 Phase Ib (psoriasis)
Licensed to Merck Serono (worldwide)
Caplacizumab MAA filing EU Phase III results (TTP)
Wholly-owned
ALX-0171 Infant Phase IIb (RSV)
Wholly-owned
ALX-0141 and ozoralizumab Phase I/II in China
Licensed to Eddingpharm (China)
ALX-0761 Phase IIa (psoriasis)
Licensed to Merck Serono (worldwide)
Caplacizumab conditional approval EU and BLA filing in US
Wholly-owned
ALX-0061 Phase II (SLE)
AbbVie have option to license worldwide
Results from various patient studies with partners
Clinical study results
Key regulatory events
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