Jefferies Healthcare Conference 2015 - Jefferies - The … NV...Product pipeline >30 programmes in...
Transcript of Jefferies Healthcare Conference 2015 - Jefferies - The … NV...Product pipeline >30 programmes in...
Nanobodies® creating better medicines
1-4 June 2015, New York
Dr Edwin Moses – CEO Ablynx
Jefferies Healthcare Conference 2015
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 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) • 2 wholly-owned products in later stage clinical development (Phase III & Phase II) • >10 new clinical programmes anticipated over the next 3 years
• AbbVie, Boehringer Ingelheim, Eddingpharm, Genzyme, Merck & Co, Merck Serono and Novartis
• €193M in cash at 31 March 2015 • €100M raised through issuance of 5 year Convertible Bond in May 2015 (3.25%
coupon, 26.5% premium)
CORPORATE
TECHNOLOGY
PARTNERS
PRODUCTS
FINANCIALS
What are Nanobodies?
Unique technology
5
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
6
Ablynx’s 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
7
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-2
Targeting different pathways at once with a single Nanobody construct, e.g. multiple checkpoint inhibitors
Product pipeline
>30 programmes in development Two wholly-owned in later stage clinical development
9
Proprietary and partnered programmes Multiple shots on goal
Inflammation/ Immunology
FULL
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
PAR
TNER
ED
Bone disorders Greater China
IL-17F/IL-17A
Ocular
Oncology/ Immuno-oncology
ozoralizumab TNFα Greater China
Filing
CXCR2
Various
Other
Clinically validated targets First-in-class
10
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
3 Phase II studies (RA; SLE) in 2015 RA results expected in 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: potential clinical POC results expected in 2015
Leading programmes in the clinic
* Collagen induced arthritis model
Pipeline value drivers
10
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
Started first-in-infant study Q4 2014: results expected in H1 2016
11
Caplacizumab Wholly-owned 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)
12
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
13
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 PE in hospital until recovery of platelet
count
Severe fatigue, headache, coma, abdominal pain,
weakness, nausea, bizarre behaviour, vertigo, seizures
SUDDEN ONSET EMERGENCY
14
Caplacizumab Phase II TITAN design and schedule
RAN
DO
MIS
ATIO
N
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
PE
PE 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
15
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
16
Caplacizumab Current status and next steps
16
Caplacizumab could be approved for sale in Europe in 2018
• Confirmed clinical activity and good safety profile in the clinic
• Intention to file for conditional approval in EU in H1 2017 based on Phase II
• Preparations progressing to start Phase III study in H2 2015
• Intention to submit BLA in USA following Phase III study completion
• Commercialisation/partnering strategy currently under evaluation
17
ALX-0171 Wholly-owned 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
18
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
19
ALX-0171
• Well tolerated in multiple Phase I clinical studies in adults
• In vitro and in vivo 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”)2
1 Vaccines of the World (Oct 2013) 2 RSV Symposium (Nov 2014) – presentations on http://www.ablynx.com/rd-portfolio/clinical-programmes/alx-0171/
Key milestones achieved
020406080
100
0 1 2 3 4 5 6% o
f lam
bs w
ith s
core
≥ 1
RSV vehicle
RSV ALX-0171
Vehicle
RSV infection
Treatment ALX-0171 or formulation buffer
20
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
RAN
DO
MIS
ATIO
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
21
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 placebo-controlled phase of the study on-going
• Recruitment of Phase IIa study to continue in parts of Asia-Pacific region with the goal to complete recruitment of the placebo-controlled phase by end 2015 with results anticipated in H1 2016
Current status and next steps
21
Potential POC for an inhaled Nanobody
22
ALX-0061 Anti-IL-6R Nanobody partnered with AbbVie
• 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 started and Phase
II study in SLE to start in mid-2015 • Opportunity in multi-billion dollar markets
RA: rheumatoid arthritis SLE: systemic lupus erythematosus
23
ALX-0061 Compelling Phase IIa results in RA patients
83
71
58 63
29
0
20
40
60
80
100
% o
f pat
ient
s
All unmodified ALX-0061 at week 24 (N=24) ACR20 ACR50 ACR70 DAS28 remission Boolean remission
ACR50 score as potential differentiating factor
Data published 13 February 2013: press release available on Ablynx ‘s website
24
ALX-0061
• $175M upfront at signing in September 2013 • $665M total potential milestones plus double-digit royalties
Global licensing deal with AbbVie
24
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 (ongoing)
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
25
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
AND
OM
ISAT
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
26
ALX-0061
• First patient dosed in April 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
RAN
DO
MIS
ATIO
N
27
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
Phase II RA OLE study
28
Additional clinical assets Licensed to partners
• ALX-0761 – anti-IL-17A/F Merck Serono (global)
• ALX-0141 – anti-RANKL Eddingpharm (Greater China)
• Ozoralizumab – anti-TNFα Eddingpharm (Greater China)
Partnerships
Broad platform exploitation and cash generation
30
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
4 agreements: multiple programmes on-going (lead project in Phase Ib)
2 licensing deals in Greater China for ALX-0141 and ozoralizumab
Target-based discovery deal
Research collaboration in multiple sclerosis
Outlook
Potential value enhancing events
32
2015 Potential value drivers
32
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 POC Phase Ib results in psoriasis patients in H2 2015
• Potential in vivo pre-clinical POC results from initial programmes as part of IO collaboration with Merck & Co
• Caplacizumab (vWF): determine partnering and commercialisation strategy
• Potential milestone payments from on-going partnerships
• Continuing partnering discussions
• Extend existing collaborations/ enter into new collaborations
33
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 POC (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
CONTACT DETAILS
Questions +32 9 262 00 00 Investor
Relations
investors@ ablynx.com www.ablynx.com