Corporate Presentation

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Corporate Presentation
September 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
Corporate snapshot
Corporate
• Drug discovery and development company in Ghent, Belgium
• >300 employees
Technology
• Pioneer in next generation biologics – Nanobodies®
• >500 granted and pending patents
Products
• >30 programmes – six in clinical development
• Three clinical proof-of-concepts (POC)
• >900 healthy volunteers and patients treated with Nanobodies
Partners
• AbbVie, Boehringer Ingelheim, Eddingpharm, Merck & Co,
Merck Serono and Novartis
Financials
• €196M in cash at 30th June 2014
• Raised €41.7M through private placement (3rd July 2014)
www.ablynx.com
3
Key investment highlights
Next generation biologics
Diversified portfolio
Hybrid business model
Validating partnerships
Q2 2014 in review
www.ablynx.com
•
•
Nanobodies – antibody-derived biologics with key competitive
advantages
> 500 granted and pending patents
•
•
•
Products across various therapeutic indications
>30 products in the pipeline – 6 in the clinic
>10 new clinical programmes anticipated over the next 3 years
•
•
Balancing risk and reward
Fully-funded collaborations, 50/50 co-development deals and
proprietary programmes
•
•
•
Partnerships with leading players
>€330M cash-inflow; ~€3Bn in future potential milestones
~20 partnered programmes with 2 currently in the clinic
•
Key achievements:
achieved 3rd clinical proof-of-concept for Nanobodies
− successful completion of 2 Phase I inhalation studies (anti-RSV)
− start of Phase I bioavailability study (anti-IL-6R partnered with AbbVie)
− balance sheet further strengthened through private placement
−
4
Three-pronged business strategy
Fully-funded programmes with milestones
and royalties
• ~20 programmes in oncology, immuno-oncology,
neurology, inflammation, pulmonology and bone disorders
• 5 discovery deals
• 5 licensing deals
• >€280M in cash received with future potential value of
Co-discovery/co-development partnerships
•
•
•
•
•
3 co-co deals
3 programmes in inflammation and osteoarthritis
50:50 ownership
option to convert into licensing deals
>€50M in cash received
~€3Bn in potential milestones plus royalties
Balancing
risk and
reward
Wholly-owned product pipeline
• ~9 programmes in inflammation, ocular, autoimmune, oncology, haematology and infectious disease
• aim to retain the optionality to partner if and when appropriate
www.ablynx.com
5
Nanobodies – derived from heavy-chain only antibodies
Camelid heavy-chain only antibodies are stable and fully functional
Nanobodies represent the next generation of antibody-derived biologics
VHH
VH
CH1
VHH
VL
CL
Ablynx’s Nanobody
CH2
CH2
CH3
Conventional
antibodies
www.ablynx.com
12-15kDa
CH3
Heavy chain only
antibodies
• unique formatting flexibility (up to
penta-valent)
• speed and ease of generating
multi-specifics
• nano- to picomolar affinities
• favourable biophysical properties
(Tm, solubility, viscosity)
• tackling intractable targets
• multiple administration routes
• manufacturing in microbial cells
6
Nanobody discovery process – the power of evolution
Immunise llamas
with antigen
Wide range of
highly diverse
Nanobodies
Formatted*
Nanobodies ready
for in vivo testing
~12-18 months
www.ablynx.com
* glycine-serine linkers from C-terminus to N-terminus
7
Nanobodies – uniqueness and competitive advantages
Broad target applicability, including challenging targets
such as GPCRs and ion channels
Flexible formatting: multi-valent, multi-specific, bi-paratopic
Nanobodies
Half-life engineering technology to achieve desired
properties (acute versus chronic diseases) (T1/2 from 2h to
20 days)
Robustness allows for alternative delivery such as
nebulisation
Excellent manufacturing (yeast and bacteria), high
concentration formulations and low viscosity (excellent
syringeability)
www.ablynx.com
8
Multi-specific Nanobodies – targeting checkpoint inhibitors
Monovalent Nanobodies
against
different targets
Different multi-specific
combinations
In vivo testing
Pardoll, Nature Reviews Cancer (2012) 12:252-264
May need to interfere with
multiple pathways
www.ablynx.com
In vivo POC for different
multi-specific combinations in
18-24 months
9
Multi-specifics – Merck & Co immuno-oncology alliance
Financials
Platform validation
Responsibilities
www.ablynx.com
• €20M upfront at signing in February 2014
• €10.7M in research funding
• €1.7Bn in potential total milestones plus royalties
• Building on existing collaboration in neurology
• Opportunity in the emerging field of cancer immunotherapy
• Focused on the discovery and development of Nanobodies
targeting immune checkpoint modulators
• Exploiting the ability to rapidly generate multi-specific
Nanobodies
• Ablynx to perform initial research during the first three
years of the collaboration
• Merck & Co responsible for further development, product
registration and commercialisation
10
Fully partnered
CoCo
Fully owned
Broad pipeline – internal and funded programmes
Therapeutic area
Product name
Target
Haematology
caplacizumab
vWF
Inflammation/
Immunology/Infection
Various
Oncology
Various
Various
Pulmonology
ALX-0171
Various
Various
Ocular
NA
Inflammation/
Immunology
NA
NA
NA
Oncology/Neurology
Immunology
Various
Various
Immunology/
Inflammation
ALX-0761
ALX-0061
ozoralizumab
IL-17F/IL-17A
IL-6R
TNFα
in Greater China
Bone disorders
ALX-0141
RANKL
in Greater China
Neurology
NA
Oncology
Phase III
RSV
Potential to evolve into at least 4 co-co programmes
NA
NA
Various
NA
NA
www.ablynx.com
Phase II
ALX-0751
Pulmonology
Immuno-oncology
Discovery Pre-clinical Phase I
Various
Validated targets (clinic)
1st in class
11
Clinical pipeline
Nanobodies® Inspired by nature
Clinical pipeline – flagship programmes
Anti-vWF – caplacizumab – bivalent Nanobody – wholly-owned
•
first-in-class opportunity with Orphan Drug Status for TTP
•
statistically significant Phase II POC in patients with acquired TTP
•
exploratory partnering discussions ongoing and started preparations for Phase III study
Anti-IL-6R – ALX-0061 – monovalent Nanobody – partnered
•
best-in-class potential; compelling POC Phase II results in patients with RA
•
global exclusive licensing deal with AbbVie (up to $840M in milestones)
•
Phase IIb studies in RA and SLE expected to start early 2015 (Ablynx responsible)
Anti-RSV – ALX-0171 – inhaled trivalent Nanobody – wholly-owned
•
first-in-class opportunity with high unmet medical need
•
3 Phase I safety studies successfully completed
•
first-in-infant study expected to start in Q4 2014
Anti-IL-17A/F – ALX-0761 – bi-specific Nanobody – partnered
www.ablynx.com
•
potent neutralisation of both IL-17A and IL-17F
•
pre-clinical POC achieved and Phase I/II in patients with psoriasis ongoing
•
exclusively licensed to Merck Serono
13
Significant unmet need in the treatment of acquired TTP
Thrombotic thrombocytopenic purpura (TTP) exists in two forms: congenital
(<10%) and acquired (>90%)
Potentially life threatening rare disorder of the blood coagulation system
•
mortality remains high (10-30%)1
•
causes extensive microscopic thrombi in small blood vessels throughout the body
Unmet medical need
•
no specifically indicated therapeutic drug available
•
primary treatment is plasma exchange (PEX) plus immune modulators
- variable duration, associated risks, expensive and time-consuming
•
potential clinical complications
•
relapses in ~ 36% of patients2
Rare disorder with an incidence of 11.3 per million2
•
~10,000 acute events annually in US and Europe
www.ablynx.com
1.Allford
et al, 2003, Kremer Hovinga, 2010; Benhamou 2012;
2. George
et al, 2008
14
Caplacizumab – prevents formation of microthrombi in TTP
caplacizumab blocks the platelet – ULvWF interaction
ADAMTS13
ULvWF
multimers
Platelet String
Formation
endothelium
caplacizumab
(anti-vWF Nanobody)
Ex vivo assay for platelet string formation
Fluorescence microscopy image of platelets adhering to UL-vWF in plasma of TTP subjects
• Without treatment, fluorescently labelled platelets
adhere to UL-vWF, observed as string-like structures
ULvWF
• Caplacizumab inhibits the formation of platelet strings
and associated microthrombi
ULvWF and anti-vWF Nanobody
www.ablynx.com
15
Caplacizumab – 1st-in-class opportunity in acquired TTP
Healthy active adult
Sudden onset
severe fatigue, headache, bizarre
behaviour, vertigo, seizures, coma
Daily plasma exchanges (PEX) in
hospital until recovery of platelet
count
Treatment with caplacizumab could potentially result in
Fewer days and volume of PEX
Reduction in exercerbations/relapses and related morbidities
Improved longer term outcomes
www.ablynx.com
16
Inclusion criteria:
subjects with
acquired TTP
requiring plasma
exchange (PEX)
Randomisation
Caplacizumab – Phase II TITAN design and schedule
PEX
30 days
placebo
1 year follow-up
1:1
Target – 110 subjects
Actual – 75 patients
Exclusion criteria:
• severe infection / sepsis
• pregnancy
• bone marrow
transplantation
• disseminated
intravascular
coagulation
• known congenital TTP
30 days
30 days
PEX
X
caplacizumab
30 days
1 year follow-up
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.
Long-term endpoints:
relapse; non focal neurological
symptoms..
Safety & efficacy endpoints
www.ablynx.com
17
Primary endpoint – time to confirmed platelet normalisation
Median days to confirmed platelet response – subjects with
no prior plasma exchange (95% CI)
25th & 75th percentile
Median days to confirmed platelet response – subjects with
one prior plasma exchange (95% CI)
25th & 75th percentile
Overall Hazard Rate Ratio for caplacizumab vs. placebo
(95% CI), N = 75
Stratified log-rank test
p-value
caplacizumab
Placebo
3.00 (2.74, 3.88)
4.92 (3.21, 6.59)
N = 34
N = 35
2.72 & 4.31
3.01 & 11.37
2.44 (1.92, 2.97)
4.31 (2.91, 5.68)
N=2
N=4
1.92 & 2.97
3.37 & 5.23
N = 36
N = 39
2.197 (1.278, 3.778)
0.013
The group of patients treated with caplacizumab in conjunction with the standard of care
achieved confirmed platelet normalisation at more than twice the rate of the group
receiving the standard of care plus placebo
www.ablynx.com
18
Top line secondary endpoints
Caplacizumab
Placebo
N* = 36
N* = 39
Subjects with an exacerbation within 30 days after stopping
daily PEX
3 (8%)
11 (28%)
Subjects in complete remission within 30 days after stopping
daily PEX as measured by confirmed platelet response and
absence of exacerbations
29 (81%)
18 (46%)
13 (36.1%)
13 (33.3%)
0
2
Subjects with an exacerbation and/or relapse
at 1 month follow-up after study drug treatment was completed
Deaths
These secondary endpoints illustrate the potential protective effect of caplacizumab
treatment in the acute phase of TTP
www.ablynx.com
*Intention-to-Treat (ITT) population: 75 subjects, all randomised to caplacizumab (36) or placebo (39)
19
TITAN trial – overall conclusions on top line results
Clinical proof-of-concept demonstrated
• subjects in the caplacizumab arm achieved confirmed platelet normalisation at more than twice the rate
of the placebo arm (hazard ratio of 2.2)
• median days to normalised platelet counts (in patients who had not undergone a plasma exchange prior
to treament with caplacizumab): 3.0 days for the caplacizumab arm vs. 4.9 days for the placebo arm
73% reduction in number of patients with an exacerbation in the caplacizumab arm
compared to the placebo arm
76% more subjects in complete remission in the caplacizumab arm compared to the
placebo arm
No deaths in the caplacizumab arm compared to 2 deaths in the placebo arm
TEAEs and serious TEAEs consistent with serious, potentially life-threatening condition
Increased bleeding tendency, which is believed to be manageable
Increased number of immune-related TEAEs, but didn’t result in treatment
discontinuation
Caplacizumab demonstrated a potential clinical benefit for subjects with acquired TTP and
has an acceptable safety profile
www.ablynx.com
TEAE: treatment emergent adverse event
20
Caplacizumab – next steps
Complete full analysis of TITAN study and consult with KOLs and regulatory
authorities
Complete a Phase I trial to demonstrate bioequivalence between the liquid and
lyophilised formulations
Perform market access and pricing study
Continue preparations to start a Phase III study in 2015
Continue to evaluate various partnering and commercialisation options
Potential presentation of complete Phase II data set at ASH (Dec 2014)
In 2015, caplacizumab will be the first Nanobody to enter Phase III clinical
development
www.ablynx.com
21
ALX-0061 – potentially best-in-class anti-IL-6R
Features
Potential benefits
Small (26kD)
• penetrates faster and more effectively into
tissues
anti-IL-6R
anti-HSA
Targets human serum albumin
(HSA)
• prolongs half-life
• improved trafficking to inflamed tissue
Monovalent binding
• avoids target cross-linking
Preferential binding of soluble vs.
membrane bound IL-6R
• superior benefit/risk profile
Strong affinity to soluble IL-6R
• fast target engagement resulting in fast
onset of action
Low immunogenic potential
• improved safety profile
Tailored PK
• extended therapeutic window
• convenient dosing and scheduling
www.ablynx.com
22
Visual Analogue Scale
Number of involved joints
ALX-0061 – compelling Phase IIa results in RA patients
15
Tender joints
Swollen joints
10
5
0
Bl
W12
W16
W20
W24
60
Patient health
Pain
40
20
0
BL
W12
W16
W20
W24
• 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
23
ALX-0061 – global licensing deal with AbbVie
Financials
Ablynx
•
•
•
$175M upfront at signing in September 2013
$665M total potential milestones
double-digit royalties
•
to perform and fund Phase I study with subcutaneous
formulation (start Q2 2014)
to perform and fund Phase II studies in RA and SLE (start
in 2015)
•
Key data points
AbbVie
•
•
•
Phase I results subcutaneous formulation: Q4 2014
Phase II results in RA: expected in 2016
Phase II results in SLE: expected in 2018
•
to 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
•
Commercialisation
www.ablynx.com
•
•
AbbVie is responsible for global commercialisation
Ablynx retains option to co-promote ALX-0061 in the
Benelux
RA: rheumatoid arthritis
SLE: systemic lupus erythematosus
24
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 RSV1 infection2
• prolonged wheezing and risk for asthma development3
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
Symptomatic treatment
including inhaled
corticosteroids & bronchodilator
8-20%
hospitalised
*Extrapolation based on estimated US prevalence
www.ablynx.com
1 Respiratory
Syncytial Virus
2
Shi et al., J Med Econ, 2011
3
Sigurs et al., Thorax, 2010; Krishnamoorthy et al., Nature Medicine 2012
25
ALX-0171 – proof-of-concept achieved in RSV lamb model
RSV infection
Necropsy
Onset of
RSV infection
Trivalent anti-RSV
Day -1
0
1
2
3
4
5
6
7
8
Treatment ALX-0171 or formulation buffer
Mean viral titers in BALF
(day 6 post infection)
6
60
Mean % Involvement
Log10 FFU/mL BAL
7
5
4
3
2
1
Lung viral lesions
(day 6 post infection)
50
40
30
20
10
0
0
Vehicle
RSV Vehicle
RSV ALX-0171
Vehicle
RSV Vehicle
RSV ALX-0171
Daily inhalation of ALX-0171 markedly reduced viral titres
and lung lesions in RSV-infected lambs
www.ablynx.com
26
ALX-0171 – successful Phase I inhalation studies in adults
September 2012 – Phase I first-in-human study
• 60 healthy volunteers
• single–ascending dose and multiple dose up to 210 mg inhaled twice daily for 5 days
• well tolerated, with no clinically relevant adverse events or effects on lung function
May 2014 – Phase I safety study in adults with hyper-reactive airways
• 24 subjects
• single-ascending dose and multiple dose part up to 200 mg inhaled daily for five days
• some cases of mild bronchoconstriction which could be immediately reversed
May 2014 – Phase I PK study
• 41 healthy volunteers
• single and multiple dose of 200 mg inhaled daily for 5 days and single dose of 0.3 mg/kg i.v.
• local half-life of ALX-0171 is approximately 20 hours, confirming potential for once-daily dosing
First-in-infant study expected to start in Q4 2014 using a custom-developed
infant inhalation device based on a vibrating mesh
www.ablynx.com
27
ALX-0761 – opportunity in inflammatory diseases
Bi-specific anti-IL-17A/F Nanobody
• blocks both IL-17A and IL-17F
anti-IL17F
• binds HSA for improved PK
• proof-of-concept in primate CIA model*
anti-IL17A
anti-HSA
• currently in PhaseIb study in patients with psoriasis
80
Arthritis score
60
40
V e h ic le
vehicle
A L X - 0 7 6 12.8
2 .8mg/kg
m g /k g
Nanobody
20
0
-4
A L X - 0 7 6 110
1 0mg/kg
m g /k g
Nanobody
6
16
26
36
46
56
Days
• The first bi-specific Nanobody in the clinic
• Exclusively licensed to Merck Serono
www.ablynx.com
* Poster available on Ablynx website>R&D>pipeline
28
Additional clinical assets – building a presence in China
Anti-TNFα – ozoralizumab
• Phase II proof-of-concept achieved in patients with RA (Pfizer)
• opportunity in inflammation
anti-TNF
anti-TNF
anti-HSA
• Ablynx regained worldwide rights to anti-TNFα Nanobodies from Pfizer
• exclusively licensed to Eddingpharm in Greater China in August 2014
- €2M upfront; development and commercial milestones; up to 20% royalties
• Pre-clinical study in China on-going
• Ablynx will have access to the clinical data generated by Eddingpharm to support potential
licensing discussions in other regions
Anti-RANKL – ALX-0141
• Phase I study successfully completed (Ablynx)
• opportunity in bone disorders
anti-RANKL
anti-RANKL
anti-HSA
• exclusively licensed to Eddingpharm in Greater China in October 2013
- €2M upfront; commercial milestones; up to 20% royalties
• pre-clinical study in China currently on-going
• Ablynx will have access to the clinical data generated by Eddingpharm to support potential
licensing discussions in other regions
www.ablynx.com
29
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)
•
4 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; immune-onco deal with €20M
upfront, €10.7M research funding and total potential milestones of up to €1.7bn plus royalties
•
2 licensing deals with Eddingpharm in Greater China for ALX-0141 (anti-RANKL) in bone
disorders and ozoralizumab (anti-TNFα) in inflammation
•
Target based discovery deal with Novartis
>€330M in non-dilutive cash received from collaborators to date
~€3Bn in potential future milestones plus royalties
www.ablynx.com
31
Outlook
Nanobodies® Inspired by nature
News flow in 2014
Completion of
clinical trials
•
Phase I results from safety
and PK studies with ALX0171 (anti-RSV)
Start of
clinical trials

•
Start of Phase I study with
s.c. ALX-0061 (anti-IL-6R)
•
Start of Phase Ib study with
ALX-0761 in patients with
psoriasis (Merck Serono)
Business
development

•
Phase II results caplacizumab
in acquired TTP
•
Completion SAD Phase I in
healthy volunteers with ALX0761 (Merck Serono)
•
Start of bio-equivalence
study with caplacizumab
(anti-vWF)
Phase I results from s.c.
study with ALX-0061 (anti-IL6R)
•
Start Phase I/II infant study
with ALX-0171 (anti-RSV)
•
Preparation to start Phase II
in RA and SLE with ALX-0061
and Phase III with
caplacizumab in 2015


•
•
Phase I results from bioequivalence study with
caplacizumab (anti-vWF)
3 trial readouts achieved
3 clinical trials initiated
2 readouts remaining
1 clinical trial to be initiated
www.ablynx.com

•
•

Potential additional
collaborative deals
Continue discussions with
potential partners in a
number of areas

cash generative
partnerships
33
Value creation – clinical data expected from patient studies
caplacizumab Phase
III (anti-vWF) in
subjects with acquired
TTP
ALX-0061 Phase
IIb s.c. (anti-IL-6R)
in subjects with RA
ALX-0171 Phase
I/II (anti-RSV) in
infants with an
RSV infection
caplacizumab
Phase II (anti-vWF)
in subjects with
acquired TTP 
Wholly-owned clinical
asset
www.ablynx.com
Wholly-owned clinical
asset
Licensed to AbbVie
(worldwide)
ALX-0761 Phase Ib
(anti-IL-17A/F) in
subjects with
psoriasis
Licensed to Merck
Serono (worldwide)
Wholly-owned clinical
asset
ALX-0171 Phase II
(anti-RSV) in infants
with an RSV infection
Wholly-owned clinical
asset
ALX-0141 and
ozoralizumab Phase
I/II results from studies
in China
Licensed to Eddingpharm
(Greater China)
34
Financials/Shareholders
Nanobodies® Inspired by nature
Financial summary
€M
2012
2013
H1 2014
Revenue
26.7
35.9
22.2
Operating Result
(29.8)
(17.7)
(7.6)
Cash Position(1)
62.8
200.4
196.0 (2)
Anticipated net cash burn for 2014: €30M - €35M
(1)
(2)
cash, cash equivalents, restricted cash and short-term investments at the end of the period
not including ABO completed on 30th June (€41.7M raised)
www.ablynx.com
36
Shareholder structure
Investors
Abingworth (UK);
9,08%
Geography
Boehringer
Ingelheim (DE);
3,97%
Biotech Value
Fund (US); 4,48%
Other
27%
US
24%
Aviva (UK); 3,19%
Perceptive
Advisors (US);
3,85%
Other institutional
and retail
investors; 72,09%
France
3%
Fidelity
Management
Research LLC
(US); 3,35%
UK
21%
Benelux
25%
Ordinary shares listed on Euronext Brussels (ABLX)
54M shares outstanding
2.7M outstanding warrants
Free float is ~90%
www.ablynx.com
37
Corporate Presentation
September 2014
Nanobodies® Inspired by nature
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