Presentation

Nanobodies® – creating better
medicines
JP Morgan Healthcare Conference
San Francisco – 12th-16th January 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
Outline
Company overview and proprietary Nanobody technology
Broad pipeline with multiple shots on goal
Strong cash generative partnerships
2013 achievements and upcoming news flow
www.ablynx.com
3
Ablynx – company overview and investment highlights
•
•
Drug discovery and development company - Ghent, Belgium
NYSE Euronext Brussels (ABLX)
49M shares outstanding (52M fully diluted) - €349M market cap1
280 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
>€300M in non-dilutive cash received to date
•
•
~ €200M in cash estimated at 31st December 2013
~ €20-25M net cash burn estimated for the full year 2013
Corporate
Partners
Financials
www.ablynx.com
•
•
1
6th January 2014
4
Ablynx’s strategy – three-pronged approach
Fully funded programmes with
milestones and royalties
• 19 programmes in oncology,
neurology, inflammation,
pulmonology and bone disorders
• Five discovery deals
• Three licensing deals
• >€260M 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
Ablynx’s 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
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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
Half-life engineering technology to achieve desired properties
(acute vs 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
7
Outline
Company overview and proprietary Nanobody technology
Broad pipeline with multiple shots on goal
Strong cash generative partnerships
2013 achievements and upcoming news flow
www.ablynx.com
8
Fully partnered
50% CoCo
Fully owned
Broad pipeline – internal and funded programmes
Therapeutic area
Product name
Target
Haematology
Inflammation/
Immunology/
Infection
caplacizumab
vWF
ozoralizumab
ALX-0962
Various
TNFα
IgE
Oncology
Various
Various
Bone disorders
ALX-0141
RANKL
ALX-0171
Various
Various
RSV
Pulmonary
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
Pulmonary
NA
Various
NA
NA
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
*Previously part of MS co-co deal
in Greater China
Validated targets (clinic)
1st in class
Blank boxes: non-disclosed targets
9
Programmes in Phase II clinical development
Anti-IL-6R – ALX-0061 – monovalent Nanobody with T1/2
• 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 TTP1 in H1 2014
• first-in-class opportunity with Orphan Drug Status
Anti-TNFα – ozoralizumab – bivalent Nanobody with T1/2
• 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
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ALX-0061 (anti- IL-6R) – global licensing deal with AbbVie
ALX-0061 (anti-IL-6R)
Potential best-in-class opportunity in inflammation
Phase IIa in RA successfully completed with iv formulation
26kD
Phase I with sc formulation to start in Q2 2014
Deal terms (September 2013)
Upfront payment of $175 million
Potential to receive total milestones of up to $665 million plus double-digit
royalties
Ablynx to perform sc Phase I study and Phase II sc studies in RA and SLE
AbbVie will pay a fee if they exercise the right to license ALX-0061 after the
completion of Phase II sc studies
AbbVie to perform
commercialisation
www.ablynx.com
Phase
III
development,
registration
and
global
11
ALX-0061 – compelling proof-of-concept Phase IIa results
• No increase of adverse events upon extension of treatment
• Treatment was well tolerated at all doses
• No anti-drug antibodies were detected
www.ablynx.com
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ALX-0061 – potential differentiating DAS28 remission profile
ALX-00611
Tocilizumab
(Roche)2
Sirukumab
(J&J)3
Sarilumab
(Sanofi)4
Clazakizumab
(BMS)5
1. All unmodified ALX-0061 treated patients at week 24 (N=24) and pooled ALX-0061 data at week 12 (N=28) as reported in Oct 2012
2. Data estimated from ACT-RAY, OPTION, RADIATE, ROSE, SAMURAI, SATORI and TOWARD trials, for 4 and 8 mg/kg tocilizumab + MTX,
Q4W. The data was described by a weighted non-linear regression model. [Quantify RA clinical database, Feb 2013]
3. Combined data, Phase II trial, EULAR 2012
4. Phase IIb MOBILITY trial; 100 mg Q2W, 100 mg Q1W, 150 mg Q2W, 150 mg Q1W, 200 mg Q2W (+MTX)
5. Phase IIb trial, sc Q4W: 25mg, 100 mg and 200 mg + MTX; 100mg and 200 mg without MTX
www.ablynx.com
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ALX-0061 – clinical development to be performed by Ablynx
2014
2015
2016
2017
2018
2019
Phase I sc study
Phase II in RA
top line results
potentially continues development in RA
Phase II in SLE
top line results
potentially continues
development in SLE
www.ablynx.com
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Caplacizumab (anti-vWF) – mechanism of action
ADAMTS13
ULvWF
multimers
Platelet String
Formation
Endothelium
Microthrombi form which block
the small blood vessels in
thrombotic thrombocytopenic
purpura (TTP)
Ex vivo platelet string formation
anti-vWF Nanobody
28KDa
Target for the Nanobody is
in the bloodstream, i.v. and
s.c. formulations ensure
desired exposure
ULvWF
ULvWF and anti-vWF Nanobody
www.ablynx.com
Anti-vWF Nanobody inhibits platelet
string formation caused by UL-vWF in
plasma of TTP patients
15
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
+ caplacizumab
Daily plasma exchanges in
hospital until recovery of
platelet count
Diagnosis of TTP
Caplacizumab on top of PEX could result in:
• fewer days and volume of PEX
• reduction in relapse/exacerbations
• improved longer term outcome
www.ablynx.com
(1)
Oklahoma Registry
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Caplacizumab – current status and next steps
Worldwide Phase II study (50+ sites participating)
• caplacizumab is a combination of iv and sc dosing of the same therapeutic
Nanobody
• although some improvement in recruitment has been seen since amending the
clinical protocol in September 2013, Ablynx has decided to stop recruitment of the
trial now to allow earlier data analysis
• potential POC results in H1 2014
Simplified Phase III trial expected to start in 2015
Programme granted orphan drug status for the treatment of TTP by both
the EMA and the FDA in 2009
Currently no drugs specifically approved for the treatment of acquired TTP
Estimated peak global sales for use of anti-vWF Nanobody in acquired
TTP could be in range of €180-250 million
www.ablynx.com
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Programmes in Phase I clinical development
Anti-RSV – ALX-0171 – 1st inhaled trivalent Nanobody
• Phase I safety study in healthy volunteers successfully completed
• additional pre-clinical and Phase I studies on-going
• first-in-infant study expected to start in H2 2014
• potential transformational treatment for RSV infection in infants
Anti-RANKL – ALX-0141 – bivalent Nanobody with T1/2
• Phase I study successfully completed
• exclusively licensed to Eddingpharm in Greater China
Anti-IL-17A/F – ALX-0761 – bi-specific Nanobody with T1/2
• pre-clinical POC achieved and Phase I study on-going
• Merck Serono now 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
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Respiratory syncytial viral (RSV) infections – unmet need
~310,000 children (< 5 years) hospitalised per year in the 7 major markets
• increased medical cost in the 1st year following RSV infection(1)
• prolonged wheezing and risk for asthma development(2)
The leading cause of infant hospitalisation and leading viral cause of infant death
• ~3.5% mortality rate in those hospitalised with high-risk conditions
• estimated 400 deaths/year in US
Evolves to
distressing
symptoms
www.ablynx.com
(1) Shi
Symptomatic treatment
including inhaled
corticosteroids & bronchodilator
et al., J Med Econ, 2011
(2) Sigurs
8-20%
hospitalised
et al., Thorax, 2010; Krishnamoorthy et al., Nature Medicine 2012
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ALX-0171 – proof-of-principle in cotton rat model
RSV
Lung lavage
INFECTION
ONSET OF DISEASE
Day -1
0
1
2
3
4
5
6
TREATMENT
RSV Nanobody intratracheal instillation as mimic for nebulisation
No virus-Placebo
RSV-Placebo
ALX-0171
Protection against body weight stagnation
Reduced relative lung weights (measure of
inflammation, i.e. infection)
Beneficial effect on lung leucocyte infiltration
(measure of inflammation, i.e. infection)
www.ablynx.com
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ALX-0171 – current status and next steps
First Phase I study successfully completed
Additional Phase I studies on-going – results H1 2014
• safety study in adults with hyper-responsive airways
• local (broncho-alveolar lavage) and systemic PK study in healthy volunteers
Additional pre-clinical studies on-going – results Q1 2014
• study in juvenile animals to extend PK knowledge of ALX-0171
• additional inflammatory/histopathological endpoints
First-in-infant study – start H2 2014
Potential transformational treatment for RSV infection in infants
www.ablynx.com
21
ALX-0141 (anti-RANKL) – opportunity in bone disorders
Bivalent Nanobody with half-life extension targeting RANKL
• potentially improved tissue distribution properties
• potential to target inflamed/cancerous regions
41KDa
• highly stable and formulated at high concentrations for sc injection
Phase I study successfully completed
• marked inhibition of bone biomarkers
• well tolerated and no serious adverse events or dose limiting toxicity
Opportunity in osteoporosis and bone metastases
www.ablynx.com
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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 the data generated by Eddingpharm to support
potential licensing discussions for ALX-0141 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 exploring opportunities in emerging markets
www.ablynx.com
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ALX-0761 – bi-specific Nanobody with tailored half-life
Rationale
IL-17A is the most characterised IL-17 family member but 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
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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)
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Outline
Company overview and proprietary Nanobody technology
Broad pipeline with multiple shots on goal
Strong cash generative partnerships
2013 achievements and upcoming news flow
www.ablynx.com
26
Partnerships – 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 and osteoarthritis
•
Ion channel discovery collaboration with Merck & Co in neurology
•
Licensing deal with Eddingpharm in Greater China for ALX-0141 (anti-RANKL) in bone
disorders
•
Target based discovery deal with Novartis
>€300M in non-dilutive cash received from collaborators to date
www.ablynx.com
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Partnerships – building the clinical pipeline
Potential number of partnered Nanobodies in the clinic
AbbVie (ALX-0061) in inflammation
Merck Serono (ALX-0761) in inflammation
Boehringer Ingelheim (BI 1034020) in Alzheimer’s disease
www.ablynx.com
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Outline
Company overview and proprietary Nanobody technology
Broad pipeline with multiple shots on goal
Strong cash generative partnerships
2013 achievements and upcoming news flow
www.ablynx.com
29
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)
•
•
•
•
Merck Serono and BI
initiated Phase I trials
(inflammation; Alzheimer’s)
Started additional Phase I
studies
with
anti-RSV
Nanobody
www.ablynx.com
•
AbbVie: major licensing
deal for ALX-0061 worth up
to $840M in upfronts and
milestone payments plus
double-digit royalties
Merck Serono: signed the
4th discovery collaboration
which
could
generate
>€100M in cash over the
next 6.5 years
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% to 85%
TTP: thrombotic thrombocytopenic purpura
30
Some expected news flow for 2014
Expected
Clinical Data
Start of
Clinical Trials
Business
Development
•
Potential Phase II POC
results with caplacizumab in
acquired TTP
•
Start of Phase II paediatric
study with ALX-0171 (antiRSV)
•
Potential milestone
payments from on-going
collaborations
•
Phase I results from sc
study with ALX-0061 (antiIL-6R)
•
•
Potential additional
collaborative deals
•
Phase I results from safety
and PK studies with ALX0171 (anti-RSV)
Preparation for start of
Phase II RA and SLE
studies
with
ALX-0061
(anti-IL-6R) in 2015
•
Start of up to five Phase I
studies
•
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
31
Value creation – key clinical data expected (patient studies)
2016
2015
2014
ALX-0171 Phase I/II (antiRSV) in infants with RSV
infection
Wholly-owned clinical asset
2013
Caplacizumab Phase II
(anti-vWF) in patients
with acquired TTP
Wholly-owned clinical asset
ALX-0061 Phase IIb sc
(anti-IL-6R) in patients
with RA
Licensed to AbbVie
ALX-0761 Phase IIa (antiIL-17A/F) in patients with
RA
Licensed to Merck Serono
Two partnered Phase I/II
programmes in cancer
ALX-0061 Phase IIa
iv (anti-IL-6R)
in patients with RA 
Licensed to AbbVie
www.ablynx.com
32
Investment highlights
Proprietary
Platform
Broad Pipeline
Unique, powerful and broadly validated next generation biologics
platform – Nanobodies® - with >500 granted and pending patents
~30 programmes with currently 7 in the clinic and the potential to grow
this number substantially in 2014
Clinical Data
Two clinical POCs to date and potential to have six POCs by end of 2016
>800 healthy volunteers and patients succesfully treated with Nanobodies
Commercial
Partnerships
Range of risk-reward partnerships including 23 partnered projects with
AbbVie, Boehringer Ingelheim, Eddingpharm, Merck & Co, Merck Serono
& Novartis - potentially up to 12 projects in the clinic in the next 3 years
Strong Cash
Position
~ €200M in cash estimated at 31st December 2013
~ €20-25M net cash burn estimated for the full year 2013
www.ablynx.com
33
Nanobodies® – creating better
medicines
JP Morgan Healthcare Conference
San Francisco – 16th January 2014
Nanobodies® Inspired by nature
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
35

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