Nanobodies® – creating better
medicines
Corporate Presentation – March 2014
Nanobodies® Inspired by nature
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.
www.ablynx.com
2
Overview
Technology
Pipeline
Nanobodies® Inspired by nature
Company highlights
Corporate
•
•
•
•
Drug discovery and development company - Ghent, Belgium
NYSE Euronext Brussels (ABLX)
49M shares outstanding (52M fully diluted)
>300 employees
Technology
•
•
Pioneer in next generation biologics – Nanobodies®
>500 granted and pending patents
Products
•
•
•
~30 programmes – seven in clinical development
Two clinical proof-of-concepts
>800 healthy volunteers and patients treated with Nanobodies
•
•
AbbVie, Boehringer Ingelheim, Eddingpharm, Merck & Co,
Merck Serono and Novartis
>€320M in non-dilutive cash received to date
•
•
€200.4M in cash at 31st December 2013
€20.0M net cash burn for the full year 2013
Partners
Financials
www.ablynx.com
4
Three-pronged strategy
Fully funded programmes
with milestones and royalties
•
•
•
•
~19 programmes in oncology,
immuno-oncology, neurology,
inflammation, pulmonology and
bone disorders
6 discovery deals
3 licensing deals
>€280M in cash received
Co-discovery/
co-development partnerships
•
•
•
•
4 programmes in oncology,
inflammation and
osteoarthritis
50:50 ownership
Potential to convert into
licensing deals
>€45M in cash received
Wholly-owned product
pipeline
•
•
7 programmes in
inflammation,
hematology, oncology
and infection
Aim to partner after
clinical proof-of-concept
has been achieved
Balancing risk and reward
www.ablynx.com
5
Nanobodies – proven single variable domain approach
Camelidae family has both forms
CH1
CL
VH
VL
VHH
VHH
CH2
CH2
CH3
CH3
Ablynx’s Nanobody®
• Small (1/10 size of a mAb)
• Flexible formatting
• Highly potent, robust and stable
Conventional antibody
Heavy-chain antibody
•
Heavy and light chains
•
Only heavy chains
•
Both chains required for antigen
binding and stability
•
Full antigen binding capacity
and very stable
•
Large size and relatively low
formatting flexibility
•
Administered through injection
www.ablynx.com
• Broad target applicability
• Multiple administration routes
• Ease of manufacture
• Speed of discovery
6
Nanobodies – uniqueness and competitive advantages
Broad target applicability, including challenging targets such
as GPCRs and ion channels
Flexible formatting: multivalent, multi-specific, bi-paratopic
Nanobodies in the clinic
Robustness allows for alternative delivery such as nebulisation
Half-life engineering technology to achieve desired properties
(acute vs chronic diseases) (T1/2 from 2h to 20 days)
Excellent manufacturing (yeast and bacteria), high concentration
formulations and low viscosity (excellent syringeability)
www.ablynx.com
7
Nanobody formatting - beyond antibodies and scaffolds
Combine Nanobodies into multi-paratopic and multi-specific formats
Targeting the
same epitope on
the same antigen
Targeting different
epitopes on the
same antigen
Targeting 2 or
more different
antigens
Increased potency
Increased specificity/
potency
Increased potency/
specificity
Cell killing
Cell / Tissue-homing
Customised half-life extension
(hours / days / weeks)
www.ablynx.com
8
Key Nanobody Advantage – Rapid and proven formatting
to make multi-specifics
Monovalent NBs against
Different targets
Clinical stage
x2
x2
~ 1 year
Combinatorial libraries
Formatting flexibility
Preclinical POC
x6
x2
x4
x3
x4
Pardoll, Nature Reviews Cancer (2012) 12:252-264
Rapid formatting of
monovalent
building blocks
www.ablynx.com
Proven
experience
Interfere with
multiple pathways at
once
9
Fully partnered
50% CoCo
Fully owned
Broad pipeline – internal and funded programmes
Therapeutic area
Product name
Target
Haematology
Inflammation/
Immunology/
Infection
caplacizumab
vWF
ozoralizumab
Various
TNFα
Oncology
Various
Various
Bone disorders
ALX-0141
RANKL
RSV
Pulmonology
ALX-0171
Various
Various
Oncology
ALX-0751
Inflammation/
Immunology
NA
NA
NA
Oncology/Neurology
Immunology
Various
Various
Immunology
ALX-0761
ALX-0061
Bone disorders
ALX-0141
Neurology
BI 1034020
NA
Oncology
NA
Pulmonology
NA
Various
NA
NA
Immuno-oncology
Various
www.ablynx.com
Discovery Pre-clinical Phase I
Phase II
Phase III
Filing
ex Greater China
Potential to evolve into at least 4 co-co programmes
IL-17F/IL-17A
IL-6R
RANKL
in Greater China
Validated targets (clinic)
1st in class
10
Clinical assets
Nanobodies® Inspired by nature
Programmes in Phase II clinical development
Anti-IL-6R – ALX-0061 – monovalent Nanobody with T1/2 extension
• Phase II POC achieved in patients with RA
• global exclusive licensing deal with AbbVie
• Ablynx responsible for next phases of development
• opportunity for differentiation in RA and SLE
Anti-vWF – caplacizumab – bivalent Nanobody
• potential Phase II POC in patients with acquired TTP(1) mid-year 2014
• first-in-class opportunity with Orphan Drug Status
Anti-TNFα – ozoralizumab – bivalent Nanobody with T1/2 extension
• Phase II POC achieved in patients with RA
• on-going licensing discussions in emerging markets
• exploring new routes of delivery with anti-TNFα Nanobodies
www.ablynx.com
(1) TTP:
thrombotic thrombocytopenic purpura
12
ALX-0061 – compelling proof-of-concept Phase IIa results
• Treatment showed strong efficacy and was well tolerated at all doses
• No increase of adverse events upon extension of treatment
• No anti-drug antibodies were detected
www.ablynx.com
13
ALX-0061 – global licensing deal with AbbVie (Sept 2013)
Ablynx received $175 million upfront; $665 million of potential total
milestones plus double-digit royalties
Ablynx will perform and fund subcutaneous Phase I study (2014) and Phase
II studies in RA and SLE (start in 2015)
AbbVie will pay a fee if they exercise the right to license ALX-0061 after the
completion of Phase II studies
• Phase II results in RA expected in 2016
• Phase II results in SLE expected in 2018
AbbVie is responsible for Phase III development, registration and global
commercialisation
Ablynx retains option to co-promote in Benelux
www.ablynx.com
14
Caplacizumab in acquired TTP – unmet medical need
Sudden onset: severe fatigue,
headache, bizarre behaviour, vertigo,
seizures, coma, etc.
Incidence: 11.3 per million(1); 10,000
acute events p.a. in EU + US
Healthy active adult
Currently no drugs specifically
approved to treat acquired TTP
+ caplacizumab
Daily plasma exchanges in
hospital until recovery of
platelet count
Diagnosis of TTP
Caplacizumab on top of PEX could potentially result in:
•
•
•
www.ablynx.com
fewer days and volume of PEX
reduction in relapse/exacerbations
improved longer term outcome
(1)
Oklahoma Registry
15
Caplacizumab – current status and next steps
Confirmed biological activity and safety in the clinic
Potential Phase II proof-of-concept (POC) results in June 2014
Positive data would allow further exploration of partnering opportunities
Phase III trial could start in 2015
• planning a simpler study protocol compared to the Phase II trial
Orphan drug status for the treatment of TTP in the US and Europe
We believe approximately 10,000 patients present each year
• there is no specific drug treatment available, only multiple plasma exchanges
www.ablynx.com
16
Ozoralizumab – proof-of-concept and OLE study results
Phase II proof-of-concept study
N=253
Open-label extension (OLE) study
N=266
% of patients
% of patients
Primary endpoint: ACR20
Pooled results
• Ozoralizumab 80mg Q4W significantly improved ACR20 at week 16
• High ACR responses at week 48
www.ablynx.com
17
Ozoralizumab OLE – overall summary
Treatment over 48 weeks was well tolerated (86% of patients completed
the study)
Adverse event rates within expectations and serious infections remain rare
(i.e. 3 events in 100 patient years)
High ACR20 rate (84%) at week 48 augmented by high translation to
ACR50 and even ACR70 rates
61% of patients reached low or no disease activity during study including
38% of patients in DAS28 remission
No clinically meaningful immunogenicity
BD discussions focused on emerging markets
www.ablynx.com
18
Programmes in Phase I clinical development
Anti-RSV – ALX-0171 – 1st inhaled trivalent Nanobody
• Phase I safety study in healthy volunteers successfully completed
• additional Phase I studies on-going
• first-in-infant study expected to start in H2 2014
• potentially transformational treatment for RSV infection in infants
Anti-RANKL – ALX-0141 – bivalent Nanobody with T1/2 extension
• Phase I study successfully completed
• exclusively licensed to Eddingpharm in Greater China
Anti-IL-17A/F – ALX-0761 – bi-specific Nanobody with T1/2 extension
• pre-clinical POC achieved and Phase I study on-going
• Merck Serono has an exclusive license to the programme
Alzheimer’s – BI 1034020
• Phase I study initiated in October 2013
• Boehringer Ingelheim fully responsible for the programme
www.ablynx.com
19
ALX-0171 to treat RSV infection in infants – unmet need
~310,000 children (< 5 years) hospitalised per year in the 7 major markets
• increased medical cost in the 1st year following RSV(1) infection(2)
• prolonged wheezing and risk for asthma development(3)
The leading cause of infant hospitalisation and leading viral cause of infant death
• ~3.5% mortality rate in hospitalised high-risk infants
• estimated 400 deaths/year in US
Evolves to
distressing
symptoms
www.ablynx.com
(1)
Symptomatic treatment
including inhaled
corticosteroids & bronchodilator
Respiratory Syncytial Virus
(2)
Shi et al., J Med Econ, 2011
(3)
8-20%
hospitalised
Sigurs et al., Thorax, 2010; Krishnamoorthy et al., Nature Medicine 2012
20
ALX-0171 – current status and next steps
Pre-clinical POC recently achieved in neonatal lamb model
• daily inhalation of ALX-0171 resulted in a strong reduction of viral titres in lung fluid and a
marked reduction in inflammation in the lungs (viral lesions)
• treatment with ALX-0171 also appeared to significantly improve various clinical signs and
symptoms such as behavioural activity and general well-being
First Phase I study successfully completed
• inhalation of ALX-0171 was well tolerated and did not induce any significant clinically
relevant adverse events or clinically significant changes in lung function
• no bronchoconstriction, no dose-limiting toxicity or treatment-emergent local or systemic
immunogenicity was observed
Additional Phase I safety and PK studies on-going – results Q2 2014
Potential transformational treatment for RSV infection in infants
www.ablynx.com
21
ALX-0141 – Phase I clinical study results
Target: RANKL – opportunity in 120
bone disorders
Objectives: safety, pharmacological
profile, biological effective dose and
100
immunogenicity
80
42 women dosed in 6 dose levels60(sc injection) – 0.003 mg/kg to 1 mg/kg
Well tolerated with no serious adverse
events or dose limiting toxicity
40
20 4 out of 6 subjects showed statistically
Following a single dose of 1mg/kg,
significant suppression of the bone
biomarker CTX-1 at 9 months
0
0
40
80
120
160
200
240
280
320
Serum CTX-1 (% of baseline)
140
ALX-0141
120
Placebo
Series3
1 mg/kg
100
80
60
40
20
0
0
40
80
120
160
200
240
280
320
Time after dosing (days)
www.ablynx.com
RANKL: Receptor Activator of Nuclear factor Kappa-B Ligand
22
ALX-0141 – licensing deal with Eddingpharm
Exclusive license to Eddingpharm in Greater China in all indications,
including osteoporosis and bone metastases
Eddingpharm responsible for clinical development, registration and
commercialisation
Ablynx gets access to clinical data generated by Eddingpharm to support
potential licensing discussions in other regions
Ablynx received €2 million at signing
Ablynx entitled to potentially receive commercial milestone payments plus
tiered, double-digit royalties of up to 20% on net sales
First step in exploiting opportunities in emerging markets
www.ablynx.com
23
ALX-0761 – bi-specific Nanobody with tailored half-life
Rationale
IL-17A is the most characterised IL-17 family member and IL-17F has similar
activity and possibly even a non-redundant role in vivo
Targeting both IL-17A and IL-17F could provide a more effective way to block
inflammatory responses
ALX-0761
Bi-specific half-life extended Nanobody that blocks both IL-17A and IL-17F
Programme entered Phase I in healthy volunteers in H1 2013
First bi-specific Nanobody that entered the clinic
Merck Serono has an exclusive license and pays milestones and royalties to
Ablynx
www.ablynx.com
24
ALX-0761 – proof-of-principle in animal RA model
bone erosi on score
Arthriti s scor e
20
60
40
20
0
-4 1 7 14 21 28 35 42 49 56
Time (Days)
Vehicle
ALX-0761 2.8mg/kg
ALX-0761 10mg/kg
15
10
5
0
-6
1
8
15 22 29 36 43 50
Time (Days)
ALX-0761 significantly improved clinical endpoints (arthritis score, bone
erosion) in a cynomolgus monkey RA model(1)
www.ablynx.com
(1) Ablynx
poster presentation at ACR 2013 (available on www.ablynx.com)
25
Bi-paratopic Nanobody with tailored half-life
Pre-clinical model for Alzheimer’s: APP transgenic mice exhibit high levels of Ab
peptide
Bi-paratopic Nanobody is superior over bivalent antibody benchmarks in achieving
efficient depletion of free Ab peptide levels in plasma
fold reduction free Ab in plasma
+ half-life extension
anti-Abeta
APP transgenic mice
8-20 fold
improvement*
anti-Abeta
N-terminus
C-terminus
t 0h
dosing
2h
measure
free Ab
Bi-paratopic half-life extended Nanobody binds to two different epitopes on amyloidbeta peptide (N-terminus and central) with extremly high affinity (≤1pM)*
www.ablynx.com
* WO 2011/107507
26
Partnerships
Nanobodies® Inspired by nature
Broad platform exploitation and cash generation
•
Global licensing deal with AbbVie for ALX-0061 (anti-IL-6R) in RA and SLE: $175M upfront and
total potential value of $840M plus royalties
•
Strategic discovery alliance with Boehringer Ingelheim (8 pre-clinical programmes on-going)
and a collaboration in Alzheimer’s (Phase I)
•
4 discovery deals with Merck Serono: 10 programmes (1 Phase I) on-going in inflammation,
immunology, oncology, immuno-oncology, neurology and osteoarthritis
•
2 discovery deals with Merck & Co: ion channel deal in neurology; cancer immunotherapy deal
with €20M upfront, €10.7M research funding and total potential milestones of up to €1.7bn plus
royalties
•
Licensing deal with Eddingpharm in Greater China for ALX-0141 (anti-RANKL) in bone
disorders
•
Target based discovery deal with Novartis
>€320M in non-dilutive cash received from collaborators to date
www.ablynx.com
28
Further building the clinical pipeline
Potential number of partnered Nanobodies in the clinic
up to
12
up to
7
3
2013
www.ablynx.com
2014
2015
29
Achievements 2013
Outlook 2014
Nanobodies® Inspired by nature
2013 has been transformational for Ablynx
Business
Development
Clinical Trials
•
Strong Phase IIa results for
anti-IL-6R Nanobody
•
Continued Phase II
recruitment for TTP with
caplacizumab (anti-vWF)
•
•
•
AbbVie: deal for ALX-0061
worth up to $840M in
upfronts and milestones
plus double-digit royalties
•
Merck Serono: signed the
4th discovery collaboration
which could generate
>€100M in cash over the
next 6.5 years
Merck Serono and BI
initiated Phase I trials
(inflammation; Alzheimer’s)
Started additional Phase I
studies with anti-RSV
Nanobody
www.ablynx.com
•
Eddingpharm: licensing of
anti-RANKL Nanobody in
Greater China
Corporate
Development
•
Strengthened management
team and Board of
Directors
•
Raised €31.5M through a
private placement of new
shares
•
17 million VC shares
successfully placed
•
Free float increased from
53% at the end of 2012 to
85% today
TTP: thrombotic thrombocytopenic purpura
31
Evolution in the shareholder structure
Listed on NYSE Euronext Brussels (ABLX)
49M shares outstanding
2.8M outstanding warrants
Free float increased from 53% end 2012 to 85% today
www.ablynx.com
32
Expected news flow for 2014
Expected
Clinical Data
•
•
Potential Phase II POC
results with caplacizumab in
acquired TTP
Phase I results from sc
study with ALX-0061 (antiIL-6R)
•
Phase I results from safety
and PK studies with ALX0171 (anti-RSV)
•
Phase I results from BI for
Nanobody for use in
Alzheimer’s disease
•
Phase I results from Merck
Serono for ALX-0761 (antiIL-17A/F)
www.ablynx.com
Start of
Clinical Trials
•
Start of Phase I study with
sc ALX-0061 (anti-IL-6R)
•
Start of Phase II paediatric
study with ALX-0171 (antiRSV)
•
Preparation for start of
Phase II RA and SLE
studies with ALX-0061
(anti-IL-6R) in 2015
•
Start of up to four partnered
Phase I studies
Business
Development
•
Potential milestone
payments from on-going
collaborations
•
Potential additional
collaborative deals

33
Value creation – clinical data expected from patient studies
ALX-0061 Phase
IIb sc (anti-IL-6R) in
patients with RA
Licensed to AbbVie
2013
Caplacizumab
Phase II (anti-vWF)
in patients with
acquired TTP
clinical
ALX-0061 Phase IIa Wholly-owned
asset
iv (anti-IL-6R)
in patients with RA 
ALX-0171 Phase
I/II (anti-RSV) in
infants with RSV
infection
ALX-0761 Phase
IIa (anti-IL-17A/F)
in patients with RA
Wholly-owned clinical
asset
Licensed to Merck
Serono
Two partnered
Phase I/II
programmes in
cancer
Licensed to AbbVie
www.ablynx.com
34
Investment highlights
Proprietary
Platform
Broad Pipeline
Nanobodies® – unique, powerful and broadly validated next generation
biologics platform with >500 granted and pending patents
~30 programmes with 7 in the clinic with the potential for substantial
growth in 2014
Clinical Data
Two clinical POCs to date with the potential of six POCs by end-2016
>800 healthy volunteers and patients succesfully treated with Nanobodies
Commercial
Partnerships
~23 partnered programmes of which three in the clinic
Potentially up to 12 programmes in the clinic in the next 3 years
Strong Cash
Position
€200.4M in cash at 31st December 2013
€20.0M net cash burn for the full year 2013
www.ablynx.com
35
Contact Investor Relations:
Edwin Moses - CEO
Tel: +32 (0)9 262 00 07
edwin.moses@ablynx.com
Marieke Vermeersch – Ass. Dir. Investor Relations
Tel: +32 (0)9 262 00 82
marieke.vermeersch@ablynx.com
@AblynxABLX
Contact Media Relations:
Mary-Jane Elliott, Amber Bielecka, Lindsey Neville
Tel: +44 207 920 2345
ablynx@consilium-comms.com
Ablynx Corporate Presentation – March 2014
Nanobodies® Inspired by nature