2016 half-year results and business update · 2018. 9. 13. · webcast presentation – 25 august...
TRANSCRIPT
Nanobodies®
creating better medicines
Webcast presentation – 25 August 2016
2016 half-year results and business update
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Ablynx 2016 half-year results presentation
Participants on the call
Dr Robert K. Zeldin
CMO
Dr Edwin Moses
CEO
Wim Ottevaere
CFO
3
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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4
Ablynx 2016 half-year results presentation
Agenda
• Welcome and introduction
• Significant achievements year-to-date
• Financial highlights
• Operational performance
• Outlook for the remainder of the year
• Q&A
• Conclusion
Financial highlights
Financial results and shareholder information
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Financial summary
€ million H1 2016 H1 2015 % change
Total revenue and grant income 53.5 38.4 39%
R&D income 53.1 38.0 40%
Grants 0.4 0.4 -
Operating expenses (55.5) (45.9) 21%
R&D (49.0) (40.3) 22%
G&A (6.5) (5.6) 16%
Operating result (2.0) (7.4) 73%
Net financial result 24.9 (7.7) >100%
Net result 22.8 (15.2) >100%
Net operational cash flow (19.0) (1) (35.1) (2) 46%
Cash position at 30 June (5) 288.7 (3) 268.4 (4) 8%
(1) Excluding €71.4 million net proceeds from the private placement of new shares (announced on 1 June 2016)
(2) Excluding €97.2 million net proceeds from the convertible bond (announced on 20 May 2015)
(3) Including €1.3 million in restricted cash
(4) Including €1.6 million in restricted cash
(5) Cash, cash equivalents, restricted cash and short-term investments at the end of the period
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Shareholders
Diversified shareholder base – August 2016
• Ordinary shares listed on Euronext Brussels (ABLX)
• Sponsored Level I ADRs on the US OTC market (ABYLY)
• 60.9M shares outstanding
• 2.6M outstanding warrants (in number of shares)
Breakdown of share capital
US 41%
UK 21%
Belgium 24%
The Netherlands
9%
Scandinavia 1%
France 2% Other
1%
% of Institutional Shareholders by Geography (representing 78% of total S/O)
5% 5%
5%
5%
4%
4%
3%
Van Herk Investments B.V. (NL)
Bank of America (US)
Perceptive Advisors (US)
Fidelity Management Research (US)
Taube Hodson Stonex Partners (UK)
Boehringer Ingelheim (DE)
Oppenheimer Funds (US)
Other shareholders
Product pipeline
Significant clinical pipeline achievements
>15 new pre-clinical programmes started
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Hybrid business model fuels the pipeline
>45 programmes with 8 Nanobodies in clinical development
Indication Product Target
aTTP
RSV
vobarilizumab
Pre-clinical Phase I Phase II Phase III
IL-6R
caplacizumab vWF
ALX-0171
ALX-0141 RANKL
ALX-0761
RSV
Bone disorders Greater China
IL-17A/IL-17F
ozoralizumab TNFα
Greater China
Filing
Japan
RA
RA
SLE
RA
Psoriasis
Immuno-Oncology
~ 15 wholly-
owned and
partnered
programmes
Up to 17
programmes
IL-6R
IL-6R
TNFα RA
Various
Various
+
CXCR2 Inflammation
Oncology VEGF/Ang2 BI 836880
Chronic kidney disease CX3CR1 BI 655088
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Vobarilizumab – anti-IL-6R Nanobody
Potential to be the best-in-class in RA
• Global exclusive option licensing deal with
AbbVie
• Compelling results from 2 Phase IIb RA
studies in a total of ~600 patients
• RA open-label extension study ongoing (94%
rollover rate)
• Phase II SLE study ongoing
• Opportunity in multi-billion dollar markets
RA: rheumatoid arthritis
SLE: systemic lupus erythematosus
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Vobarilizumab
2016 achievements
• Compelling results from the 12 week Phase IIb monotherapy study in
251 patients with moderate to severe RA
August July
• Compelling results from the 24 week Phase IIb combination therapy study
in 345 patients with moderate to severe RA
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Vobarilizumab Phase IIb study results in RA High ACR responses consistent across the two studies
• Strong effect on clinically meaningful efficacy endpoints resulting in high ACR50 and
ACR70 responses at week 12 (both as monotherapy and in combination with MTX)
• Continued improvement in ACR50 and ACR70 scores from week 12 to week 24 (in
combination with MTX)
MTX: methotrexate
Week 12
Phase IIb monotherapy
(vobarilizumab N=187; tocilizumab: N=64)
% r
esp
on
ders
* nominal p<0.05 vs. placebo; ** nominal p<0.01 vs placebo
Phase IIb combination therapy (+ MTX)
Week 12 Week 24
(vobarilizumab N=276; placebo: N=69)
% r
esp
on
ders
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Vobarilizumab Phase IIb study results in RA Strong impact on disease activity confirms best-in-class potential
Remission: DAS28CRP < 2.6; low disease activitiy: 2.6 ≤ DAS28CRP ≤ 3.2
• Vobarilizumab as a monotherapy induces clinical remission in up to 41% of patients as
compared to 27% for tocilizumab-treated patients
• Vobarilizumab in combination with MTX induces clinical remission in up to 49% of
patients at week 24
Week 12
Phase IIb monotherapy
* nominal p<0.05 vs. placebo; ** nominal p<0.01 vs. placebo; *** nominal p<0.001 vs. placebo
*** *** *
*** **
***
* ** ***
** *** ***
Phase IIb combination therapy (+ MTX)
Week 12 Week 24
% s
ub
jects
% s
ub
jects
42
57 60
44
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Vobarilizumab Phase IIb study results in RA Favourable safety profile confirmed in a larger patient population
• Side effect profile did not change with increased dosing
• Treatment-related serious adverse events occurred in:
- 0.5% of vobarilizumab-treated patients in the monotherapy study
(vs. 3.1% for tocilizumab-treated patients)
- 1.8% of vobarilizumab-treated patients in the combination therapy study
(vs. 2.9% for placebo-treated patients)
• In both studies, only infrequent abnormalities in laboratory parameters were
observed
• No negative effect on mean LDL/HDL cholesterol ratio across all doses
tested in both studies
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Vobarilizumab
Potential to be the best-in-class in RA
15
µ$
µµ
µ
µ
µµ
• Very strong impact on disease activity as measured by DAS28CRP
• Favourable safety and tolerability profile across all doses tested
• Opportunity for convenient monthly dosing
Potential to become a positively differentiated treatment option for patients suffering from RA
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Vobarilizumab
Major milestones achieved – key upcoming catalysts on track
24-week Phase IIb
RA combination
therapy study
Phase II SLE study
2015 2016 2017 2018
RA open- label
extension study
12-week Phase IIb
RA monotherapy
study
Top line results
Top line results
opt-in decision for RA
opt-in decision for SLE
Top line results
Top line results
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ALX-0171 – inhaled anti-RSV Nanobody
First-in-class potential for treatment of RSV infections
• Biological drug delivered by inhalation – major
platform advantage
• Most advanced product in clinical development
to treat RSV infections in infants
• Critical pre-clinical and clinical milestones
achieved
• Phase II dose-ranging efficacy study in infants
planned to start in Q4 2016
• Opportunity in multi-billion dollar market
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Inhaled ALX-0171
• Recruitment from Q4 2014 to Q1 2016
• Study centres in Europe and Asia-Pacific region
• Adapted infant inhalation device (vibrating mesh)
• Inhaled ALX-0171 administered once/day, for 3 consecutive days
Phase I/IIa study in 53 hospitalised RSV-infected children
Primary endpoint:
Safety and tolerability of ALX-0171
Secondary endpoints:
Assessment of clinical effect (feeding, respiratory rate, O2
saturation, wheezing, coughing, general appearance), PD,
PK and immunogenicity
RA
ND
OM
ISA
TIO
N
2:1
Placebo N=10
ALX-0171 N=20 Open-label lead-in
N=5 Infants aged 3-24
months
Placebo N=6
ALX-0171 N=12
Infants aged 1-5
months Infants aged 5-24
months
DMC*
review
DMC*
review
* Data monitoring committee
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First-in-infant Phase I/IIa study
Safety and tolerability confirmed in the target population
Open-label group
ALX-0171 (N=5)
Randomised group
ALX-0171 (N=30)
Randomised group
Placebo (N=16)
Adverse events (AEs)
- number (%) of subjects with an AE 4 (80.0) 9 (30.0) 4 (25.0)
- number (%) of subjects with a treatment-related AE 1 (20.0) 2 (6.7) 0 (0.0)
Serious adverse events (SAEs)
- number (%) of subjects with an SAE 3* (60.0) 1** (3.3) 0 (0.0)
- number (%) of subjects with treatment-related SAEs 0 (0.0) 0 (0.0) 0 (0.0)
* 1 of whom discontinued ** subject discontinued
• Most common AEs were infections and respiratory disorders
• 3 AEs related to ALX-0171: mild cough, mild rhinorrhoea, mild fever 11 days after last dose
• 5 SAEs reported: hypo-responsiveness, hypotonia, pneumonia (2) and atelectasis
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First-in-infant Phase I/IIa study
Anti-viral effect – time to undetectable virus in culture
Pro
po
rtio
n o
f p
atie
nts
with
de
tecta
ble
RS
V
All Placebo (N=13)
All ALX-0171 (N=22)
Time (hours)
Treatment with ALX-0171 had an immediate and significant impact on viral replication in RSV-infected infants
Cox model to compare ALX-0171 and placebo with respect to time to first undetectable virus in culture (undetectable at 2
consecutive time points) from time of start of treatment
Time to undetectable virus ALX-0171 Placebo
Median hours 25.3 51.9
Nominal p-value 0.014
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First-in-infant Phase I/IIa study
Overall disease severity assessment – Global Severity Score*
Encouraging initial indication of therapeutic effect
* Overall disease severity assessment including feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general
condition and fever
Nominal p-value=0.0092
based on longitudinal analysis comparing ALX-0171
and placebo with respect to the Global Severity
Score, adjusting for baseline score and time
All ALX-0171 (N=26)
All Placebo (N=15)
Glo
ba
l S
eve
rity
Sco
re (
me
an
+ S
E)
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Inhaled ALX-0171
Potential breakthrough for the treatment of RSV infections
22
µ$
µµ
µ
µ
µµ
• Direct delivery to the site of infection through inhalation
• Good safety profile and no treatment-related SAEs in hospitalised
RSV infected infants
• Demonstrated anti-viral-effect in pre-clinical and clinical studies
• Encouraging indication of therapeutic effect in the clinic
Phase II dose-ranging efficacy study in ~180 hospitalised RSV-infected infants planned to start in Q4 2016
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Caplacizumab – anti-vWF Nanobody
First-in-class potential for treatment of aTTP
• Orphan Drug Status and patent protection to
2035
• Phase III ongoing with results expected by
end of 2017
• Planned filing for conditional approval in
Europe (Q1 2017) and BLA submission in
USA (2018)
• Ablynx to lead commercialisation in Europe
and the US
• Anticipated first launch in 2018 with peak
sales potential of ~€300M1
1 US, EU, Japan and other major markets
aTTP: acquired thrombotic thrombocytopenic purpura
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Caplacizumab
2016 achievements
• Publication of the Phase II TITAN study in patients with acquired TTP in The
New England Journal of Medicine
• Recruitment in HERCULES Phase III proceeding well with target enrolment
increased to approximately 130 patients (from 92 originally planned) with
topline results still expected before the end of 2017
• Preparations on-track to file for conditional approval of caplacizumab in
Europe in Q1 2017
Outlook confirmed
Potential value enhancing events
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2016-2017 outlook confirmed
Focus on sustainable value creation
2016 2017
• Q1 2016
- Phase I start with VEGF/Ang2 (BI) - €8M
- publication of data from TITAN study in the NEJM
• Q2 2016
- Phase I start with CX3CR1 (BI) - €8M
- Phase I start with CXCR2 (Novartis)
- Phase I/IIa results with ALX-0171 (53 infants)
- successfully raised €74M in a Private Placement
• Q3 2016
- vobariluzumab PhIIb RA monotherapy study results
- vobariluzumab PhIIb RA combination study results
- start follow-up study with HERCULES patients
• Q4 2016
- opt-in decision by AbbVie for ALX-0061 in RA
- start Phase II dose-ranging efficacy study of ALX-0171
- pre-clinical milestones
• Caplacizumab (aTTP) – wholly-owned
- filing for conditional approval in Europe (H1)
- HERCULES Phase III study results (H2)
- life cycle management activities
• Vobarilizumab (RA) – preparations for
Phase III study initiation
• ALX-0171 (RSV) – wholly-owned
- life cycle management activities
• Immuno-oncology – with Merck & Co., Inc.
- start of multiple IND enabling studies
- pre-clinical milestones
• Various partnered programmes
advancing in the clinic
CONTACT DETAILS
Questions
+32 9 262 00 00 Investor
Relations
investors@
ablynx.com www.ablynx.com