Beruflich Dokumente
Kultur Dokumente
February 2016
Company presentation
TABLE OF CONTENTS
Actelion at a Glance
Actelion Today
Strategy for Value Creation
Optimize Profitability
February 2016
Company presentation
ACTELION
AT A GLANCE
February 2016
Company presentation
Leader in the
science and medicine of
pulmonary arterial hypertension
(PAH)
Actelion Center, Allschwil
2,547
371
422
1,425
329
February 2016
Company presentation
2014
2007
2001
1997
Build pipeline
and commercial
Company formed,
infrastructure
development
& approval of
Tracleer
February 2016
Commercial
leverage
and prepare for
Tracleer LOE
Company presentation
Opsumit, Uptravi
and development of
new franchises
ACTELION TODAY
February 2016
Company presentation
ACTELION TODAY
A UNIQUE COMPANY
1 Based on innovation
2 Fully integrated and global
3 Highly profitable
4 Comprehensive infrastructure
5 Unencumbered assets
February 2016
Company presentation
ACTELION TODAY
A UNIQUE COMPANY
1 Based on innovation
2 Fully integrated and global
3 Highly profitable
4 Comprehensive infrastructure
5 Unencumbered assets
February 2016
Company presentation
ACTELION TODAY
FULLY INTEGRATED AND GLOBAL
A UNIQUE COMPANY
From Research to Commercialization
More than 30 operative affiliates worldwide
Product availability in >60 markets
1 Based on innovation
2 Fully integrated and global
3 Highly profitable
4 Comprehensive infrastructure
5 Unencumbered assets
Commercial Operations
R&D Centers
10
February 2016
Company presentation
ACTELION TODAY
A UNIQUE COMPANY
CORE EARNINGS
1 Based on innovation
2 Fully integrated and global
3 Highly profitable
4 Comprehensive infrastructure
5 Unencumbered assets
11
February 2016
900
800
700
600
500
400
300
200
100
0
Company presentation
2009
2010
2011
2012
2013
2014
2015
ACTELION TODAY
A UNIQUE COMPANY
1 Based on innovation
Swiss company
3 Highly profitable
Focus on quality
4 Comprehensive infrastructure
5 Unencumbered assets
12
February 2016
Company presentation
ACTELION TODAY
A UNIQUE COMPANY
1 Based on innovation
2 Fully integrated and global
3 Highly profitable
4 Comprehensive infrastructure
5 Unencumbered assets
13
February 2016
Company presentation
SUSTAIN AND
GROW THE PAH
FRANCHISE
BUILD ADDITIONAL
SPECIALTY
FRANCHISES
OPTIMIZE PROFITABILITY
14
February 2016
Company presentation
STRATEGIC PRINCIPLES
FOUR GOALS FOR ACTELION
15
February 2016
Company presentation
2015
Operational Highlights
16
February 2016
Company presentation
2015
Core EPS
PRODUCT SALES
CHF 6.16
>CHF 2
BILLION
CASH RETURNED
TO SHAREHOLDERS
CORE EARNINGS
>CHF 800
MILLION
17
February 2016
Company presentation
ALMOST
CHF 1
BILLION
SUSTAIN AND
GROW THE PAH
FRANCHISE
BUILD ADDITIONAL
SPECIALTY
FRANCHISES
OPTIMIZE PROFITABILITY
18
February 2016
Company presentation
Disease of the blood vessels carrying blood from the heart to the lungs
restricted, and the right side of the heart is put under increasing strain to pump
blood through the lungs
Normal artery
19
Artery showing
vasoconstriction
February 2016
Company presentation
SYMPTOMATIC PROFILE
Patients with pulmonary hypertension but without resulting limitation of physical activity.
Ordinary physical activity does not cause dyspnoea or fatigue, chest pain, or near
syncope.
II
III
IV
Patients with pulmonary hypertension with inability to carry out any physical activity
without symptoms. These patients manifest signs of right heart failure. Dyspnoea and/or
fatigue may even be present at rest. Discomfort is increased by any physical activity.
20
February 2016
Company presentation
ENDOTHELIN RECEPTOR
ANTAGONISTS (ERA)
PHOSPHODIESTERASE-5INHIBITORS (PDE-5i)
PROSTACYCLIN
RECEPTOR AGONISTS
IP
RECEPTOR
AGONIST
21
February 2016
Company presentation
PGI2
ANALOGUES
1st
PGI2
1990
INCREASING DISEASE
AWARENESS
PRECLINICAL/
CLINICAL RESEARCH
22
Oral PDE-5i
2000
IMPROVEMENT IN SYMPTOMS,
MEASURED BY 6MWD
ERA:
PDE-5i:
PGI2:
Oral ERA
1st
NATIONAL
NETWORKS
February 2016
2010
REFERENCE
CENTERS
PATIENT
ASSOCIATIONS
DISEASE
REGISTRIES
therapies in 2010
CONTROLLED
CLINICAL TRIALS
EVIDENCE-BASED
GUIDELINES
PROCEEDINGS FROM
3RD WORLD
CONGRESS 2003
ESC 2004
GUIDELINES
Company presentation
SCREENING
HIGH-RISK GROUPS
PROCEEDINGS FROM
4TH WORLD
CONGRESS 2008
ESC/ERS 2009
GUIDELINES
Study
Duration
Primary endpoint
No. of
patients
Study-3511,2
12 weeks
6-MWD
32
BREATHE-13
16 weeks
6-MWD
213
EARLY4
24 weeks
PVR, 6-MWD
185
Sildenafil
SUPER-15
12 weeks
6-MWD
277
Tadalafil
PHIRST6
16 weeks
6-MWD
405
ARIES-17,8
12 weeks
6-MWD
202
ARIES-27,9
12 weeks
6-MWD
192
AMBITION10
78.6 weeks
Clinical failure
610
Macitentan
SERAPHIN11
103.9 weeks
Morbidity/Mortality
742
Selexipag
GRIPHON12
76.4 weeks
Morbidity/Mortality
1,156
Bosentan
Ambrisentan
Short-term
fixed
treatment
period trial
design
1. Channick RN, et al. Lancet 2001. 2. Badesch D, et al. Curr Ther Res 2002.
3. Rubin LJ, et al. N Engl J Med 2002. 4. Gali N, et al. Lancet 2008.
5. Gali N, et al. N Engl J Med 2005. 6. Gali N, et al. Circulation 2009.
7. Gali N, et al. Circulation 2008. 8. Oudiz R, et al. Chest 2006.
9. Oudiz RJ, et al. J Am Coll Cardiol 2009. 10. Gali N, et al. Eur Respir J 2014.
11. Pulido, et al. N Engl J Med 2013. 12. Sitbon O et al. N Engl J Med 2015.
23
February 2016
Company presentation
Not only from RCTs, but also clinical practice, including disease registries
1. Gali N, et al. Eur Heart J 2009. 2. Gali N, et al. J Am Coll Cardiol 2013.
24
February 2016
Company presentation
25
February 2016
Company presentation
February 2016
Company presentation
TRANSITION TO OPSUMIT
RESILIENCE vs. GENERICS
CHF million
- 6% in Units
-11% at CER(1)
~ 7,000
DU patients
(+9%)
1,418
1,212
~ 39,000
PAH patients
(-9%)
FY 2014
(1) Excluding
27
FY 2015
February 2016
Company presentation
28
February 2016
Company presentation
29
February 2016
Company presentation
30
February 2016
Company presentation
FC II
FC III
+/- PDE-5 inhibitor
31
February 2016
Company presentation
FC IV
ENGINE OF
TRANSFORMATION
32
February 2016
Company presentation
OPSUMIT
ENGINE OF TRANSFORMATION
February 2016
Company presentation
34
in 742 patients
February 2016
Company presentation
CHF million
across markets
2015: CHF 516 million
147
95
59
162
113
68
38
Q2
2014
35
Q3
2014
Q4
2014
Q1
2015
Q2
2015
Q3
2015
February 2016
Q4
2015
Company presentation
35 countries
36
February 2016
Company presentation
37
February 2016
Company presentation
38
February 2016
Company presentation
39
February 2016
Company presentation
Adverse reactions
occurring more frequently
(>5%) on UPTRAVI
compared to placebo are
headache, diarrhea, jaw
pain, nausea, myalgia,
vomiting, pain in
extremity, and flushing
LAUNCH PRIORITIES
Prostacyclin
Market
Development
LAUNCH
Expand
prescriber
base
Establish as
prostacyclin of
1st choice
2
Expand
prostacyclin
therapy
patients base
2
Expand
prostacyclin
prescriber
base
11st
Establish as
prostacyclin
therapy of 1st
choice
40
February 2016
Company presentation
11st
Expand
prostacyclin
therapy
patient base
41
February 2016
Company presentation
VELETRI
I.V. THERAPY MADE A LITTLE EASIER
February 2016
Company presentation
Available in 15 markets
CHF million
83
Launch in France
> 80% new i.v. Epo patient share in US and
EU
62
Japan performance
FY 2014
(1) Excluding
43
FY 2015
February 2016
*Trade
Company presentation
SUSTAINING OUR
BUSINESS
44
February 2016
Company presentation
VENTAVIS
February 2016
Company presentation
CHF million
(1) Excluding
46
106
105
FY 2014
FY 2015
February 2016
Company presentation
MACITENTAN
47
February 2016
Company presentation
48
February 2016
Company presentation
CLINICAL CLASSIFICATION OF
PULMONARY HYPERTENSION (PH) 2015
1. PAH
1.1 Idiopathic PAH (iPAH)
1.2 Heritable PAH
1.3 Drugs and toxin induced
1.4 Associated with (APAH):
1.4.1 Connective tissue disease
1.4.2 HIV infection
1.4.3 Portal hypertension
1.4.4 CHD
1.4.5 Schistosomiasis
1.4.6 Chronic hemolytic anemia
1.5 Persistent pulmonary hypertension of
the newborn
February 2016
2. PH due to
left heart disease
3. PH due to lung disease
and/or hypoxemia
4. Chronic thromboembolic
pulmonary hypertension
and other pulmonary
artery obstructions
5. PH with unclear and/or
multifactorial mechanisms
5.1 Hematological disorders
5.2 Systemic disorders
5.3 Metabolic disorders
5.4 Other
50
February 2016
Company presentation
51
February 2016
Company presentation
based on the difference between the diastolic pulmonary artery pressure (dPAP)
and the pulmonary artery wedge pressure (PAWP), or diastolic pulmonary
vascular pressure gradient (DPG).
Phase II MELODY study complete
Goal is assessment of efficacy and safety of macitentan in CpcPH
52
February 2016
Company presentation
SUSTAIN AND
GROW THE PAH
FRANCHISE
BUILD ADDITIONAL
SPECIALTY
FRANCHISES
OPTIMIZE PROFITABILITY
53
February 2016
Company presentation
54
February 2016
Company presentation
VALCHLOR
February 2016
Company presentation
MYCOSIS FUNGOIDES
EXPANDING OUR SPECIALTY BUSINESS
56
February 2016
Company presentation
CONSISTENT PROGRESS
CHF million
3.5
4.1
7.1
8.0
4.6
57
February 2016
Company presentation
58
February 2016
Company presentation
ZAVESCA
February 2016
Company presentation
60
February 2016
Company presentation
61
February 2016
Company presentation
CHF million
102
92
US during H2 2016
FY 2014
(1) Excluding
62
FY 2015
February 2016
Company presentation
CADAZOLID
CLOSTRIDIUM DIFFICILE-ASSOCIATED
DIARRHEA
63
February 2016
Company presentation
mpact
64
February 2016
Company presentation
Narrow spectrum very limited effect on normal gut microflora potential for
selective treatment for Clostridium difficile in the gut = less recurrence
Early results indicate it may be safe and well tolerated with negligible
absorption
65
February 2016
Company presentation
C. leptum
C. difficile
10.0
Bifidobacterium
10.0
8.0
8.0
8.0
6.0
*
6.0
6.0
Prevotella
Bacteroidetes
4.0
4.0
4.0
10.0
10.0
2.0
2.0
8.0
0.0
6.0
CFU/g stool
10.0
2.0
8.0
8.0
0.0
0.0
6.0
6.0
4.0
4.0
4.0
2.0
2.0
2.0
0.0
0.0
0.0
Cadazolid is an investigational drug in development and not approved or marketed in any country
66
Lactobacillus
February 2016
Company presentation
94
86
80.0
77
60.0
55
37
40.0
19
20.0
N=
17
22
16
19
17
22
0.0
Clinical Cure
Recurrence
February 2016
Company presentation
Sustained Cure
demonstrate:
68
February 2016
Company presentation
69
February 2016
Company presentation
PONESIMOD
KEY PROPERTIES
Profile suitable for once-daily oral dosing
Selective S1P1 receptor modulator
Prevents lymphocytes from leaving lymph nodes
Lymphocyte reduction is rapid and dose-
dependent
Lymphocyte reduction is rapidly reversible upon
discontinuation
Potential in multiple immunological diseases
70
February 2016
Company presentation
PONESIMOD
71
February 2016
Company presentation
Placebo
(n=121)
Treatment
Screening
Follow-up
Follow-up
24 weeks
Core
72
February 2016
Company presentation
Extension
Per-protocol population
43% reduction
*
77% reduction
83% reduction
***
73
February 2016
Company presentation
***
0.8
52%
0.7
0.6
p<0.05
0.5
0.4
0.3
0.2
0.1
0
0.525
0.332
0.417
0.251
Placebo
Ponesimod 10 mg
Ponesimod 20 mg
Ponesimod 40 mg
February 2016
Investor Webcast
Placebo
(n=121)
Ponesimod 10 mg
(n=108)
Ponesimod 20 mg
(n=114)
Ponesimod 40 mg
(n=119)
Patients with 1 AE
90 (74.4)
83 (76.9)
88 (77.2)
88 (73.9)
310
275
304
325
Headache
18 (14.9)
15 (13.9)
15 (13.2)
15 (12.6)
Nasopharyngitis
17 (14.0)
16 (14.8)
11 (9.6)
13 (10.9)
Upper RTI
11 (9.1)
4 (3.7)
9 (7.9)
11 (9.2)
Diarrhoea
8 (6.6)
3 (2.8)
3 (2.6)
2 (1.7)
Fatigue
7 (5.8)
7 (6.5)
9 (7.9)
6 (5.0)
Arthralgia
7 (5.8)
2 (1.9)
1 (0.9)
1 (0.8)
Back pain
6 (5.0)
2 (1.9)
5 (4.4)
6 (5.0)
Nausea
6 (5.0)
2 (1.9)
3 (2.6)
4 (3.4)
UTI
6 (5.0)
2 (1.9)
1 (0.9)
3 (2.5)
Oral herpes
6 (5.0)
1 (0.9)
2 (1.7)
Sinusitis
5 (4.1)
4 (3.7)
5 (4.4)
6 (5.0)
Dyspnoea
4 (3.3)
5 (4.6)
7 (6.1)
17 (14.3)
Dizziness
3 (2.5)
8 (7.4)
7 (6.1)
11 (9.2)
Peripheral oedema
2 (1.7)
2 (1.9)
3 (2.6)
13 (10.9)
Cough
2 (1.7)
1 (0.9)
3 (2.6)
8 (6.7)
Increased ALT
1 (0.8)
5 (4.6)
7 (6.1)
7 (5.9)
AE, adverse event; ALT, alanine aminotransferase; RTI, respiratory tract infection; UTI, urinary tract infection
75
February 2016
Company presentation
76
February 2016
Company presentation
77
February 2016
Company presentation
Week 24
Week 20
Week 16
Week 12
Week 8
Week 4
Day 13
Day 8
All-treated set
78
February 2016
Company presentation
FU2
FU 1
Week 24 /
Week 20
Week 16
Week 12
Week 8
Week 4
Day 13
Day 8
DOUBLE-BLIND EXTENSION OF
THE PHASE II STUDY
PONESIMOD
79
February 2016
Company presentation
Randomization
10 mg ponesimod
Placebo
20 mg ponesimod
40 mg ponesimod
10 mg ponesimod
20 mg ponesimod
40 mg ponesimod
Treatment
Treatment Period 1
24 weeks
Up to 96 weeks
Core
Extension
80
February 2016
Company presentation
Randomization
10 mg ponesimod
Placebo
20 mg ponesimod
10 mg ponesimod
40 mg ponesimod
20 mg ponesimod
10 mg ponesimod
20 mg ponesimod
10 mg ponesimod
40 mg ponesimod
20 mg ponesimod
Treatment
Treatment Period 1
Treatment Period 2
24 weeks
Up to 96 weeks
Up to 432 weeks
Core
Extension
81
February 2016
Company presentation
Followup
,0.50
RR = 42.3%
p=0.045
RR = 22.5%
p=0.322
,0.40
V 10mg
V 10mg
40 mg
(n=119)
20 mg
(n=116)
,0.30
,0.20
,0.10
,0.00
10 mg
(n=108)
82
February 2016
Company presentation
Pla/40 mg
(n=32)
Pla/20 mg
(n=31)
Pla/10 mg
(n=31)
Safety profile consistent with the safety profile from the core study
Continuing in a blinded fashion with two dose groups 10 and 20 mg
More than 4 years of exposure drop-out rate minimal
Long-term data with 10 and 20mg will be very useful for registration and launch
High value of the study due to length, blinded fashion, size, and safety and
83
February 2016
Company presentation
PONESIMOD
84
February 2016
Company presentation
PHARMACODYNAMIC STUDY
scheme
Confirmed in a specific trial comparing new vs. previous titration scheme
Results presented at the European Association for Clinical Pharmacology and
85
February 2016
Company presentation
PONESIMOD
86
February 2016
Company presentation
STUDY OVERVIEW
87
February 2016
Company presentation
STUDY OBJECTIVES
Primary objective
Secondary objectives
88
February 2016
Company presentation
89
February 2016
Company presentation
PONESIMOD DIFFERENTIATION
MAXIMIZE OPPORTUNITY WITH PONESIMOD
differentiation:
Clinical utility
Differentiation
90
February 2016
Company presentation
PHASE II STUDY
IN GRAFT VS. HOST DISEASE
PONESIMOD
91
February 2016
Company presentation
Patients with chronic GvHD have a 30-50% mortality during first 5 years of
diagnosis
Scientific rationale
92
February 2016
Company presentation
these patients
30 subjects enrolled to receive escalating doses of 5, 10 and 20 mg over the
course of 24 weeks
10 sites in US expected to last approximately 18 months
Enrollment imminent
93
February 2016
Company presentation
PHASE II STUDY
IN SYSTEMIC LUPUS
ERYTHEMATOSUS
CENERIMOD
94
February 2016
Company presentation
selective profile
O
and reversible
95
February 2016
Company presentation
OH
O
N
96
February 2016
Company presentation
weeks
20 sites and expected to last approximately 20 months
97
February 2016
Company presentation
CLAZOSENTAN
CEREBRAL VASOSPASM POSTANEURISMAL SUBARACHNOID
HEMORRHAGE (aSAH)
98
February 2016
Company presentation
CONSCIOUS-3
Clazosentan is an investigational drug in development and not approved or marketed in any country
99
February 2016
Company presentation
25
Clazosentan 5 mg/h
Clazosentan 15 mg/h
-21%
(-97 to 26%)
15%
(-28 to 44%)
29%
(-9 to 54%)
-34%
(-211 to 42%)
44%
(-5 to 70%)
54%
(22 to 72%)
65%
(38 to 80%)
21
20
Event rate (%)
Placebo
35%
(-79 to 76%)
21
18
16
15
15
13
10
10
5
0
Death (within
6 weeks)
DIND = Delayed ischemic neurological deficits;
Macdonald R et al. Stroke 2012.
New cerebral
infarct
Vasospasm-related
Clazosentan is an investigational drug in development and not approved or marketed in any country
100
February 2016
DIND
Company presentation
Rescue
therapy
Vasospasm
2 days of Tx
101
February 2016
Company presentation
EXTENSIVE RESEARCH
& DEVELOPMENT
102
February 2016
Company presentation
A CHAIN OF EXPERTISE
371 PROFESSIONALS (DECEMBER 2015)
Pharmacologists
Toxicologists
Cell Biologists
Molecular Biologists
DRUG
DISCOVERY
ORGANIZATION
Biochemists
Formulation Specialists
Clinical Scientists
Medicinal Chemists
103
Pharmacokineticists
February 2016
Company presentation
Structural Biologists
104
February 2016
Company presentation
105
Single-center approach
Fully integrated research informatics
Focus on small molecules
Few platforms of expertise
Multiple therapeutic areas
High medical input
February 2016
Company presentation
Clinical Science
CLINICAL
DEVELOPMENT
106
February 2016
Biometry
Global Clinical Operations
Strategic Clinical Development
Company presentation
Phase II
Macitentan
OPUS
Macitentan
ORCHESTRA
Macitentan
SOPRANO
Macitentan
SYMPHONY
Macitentan
PORTICO
Macitentan & Selexipag
TRITON
Selexipag
GRIPHON
Macitentan
MAESTRO
Macitentan
MELODY
Macitentan
MERIT
107
February 2016
Company presentation
Phase III
Phase IV
DIVERSIFICATION
Phase I
Cadazolid
Clostridium difficile assoc. diarrhea
Ponesimod
Multiple Sclerosis
Clazosentan
Reversal of vasospasm post-aSAH
Ponesimod
Graft vs. host disease
Cenerimod
Systemic lupus erythematosus
Endothelin Receptor Antagonist
Specialty cardiovascular disorders
Lucerastat
Fabrys disease
108
February 2016
Company presentation
Phase II
Phase III
need
Current clinical pipeline to build solid portfolio for future revenue growth
109
February 2016
Company presentation
SUSTAIN AND
GROW THE PAH
FRANCHISE
BUILD ADDITIONAL
SPECIALTY
FRANCHISES
OPTIMIZE PROFITABILITY
110
February 2016
Company presentation
FINANCIAL OVERVIEW
BY REPORTING PERIOD
111
February 2016
Company presentation
FY
2015
STRONG PERFORMANCE
Variance
FY 2015
CHF
CER
1,956
2,042
4%
7%
11%
743
814
9%
14%
25%
5.58
6.16
10%
15%
26%
570
656
15%
21%
5.11
4.91
-4%
1%
Product sales
CHF million
Core earnings
CHF million
Operating income
CHF million
112
CER
FY 2014
February 2016
Company presentation
Ex US rebate
reversals
CORE EARNINGS
BY REPORTING PERIOD
113
February 2016
Company presentation
FY
2015
CORE EARNINGS
INTRINSIC GROWTH + 25%
CHF million
32
168
66
814
743
FY '14 Core
earnings as
reported
114
US rebate reversals
February 2016
677
677
FY'14 Core
earnings
excluding US
rebate reversals
FY '15 intrinsic
growth
Company presentation
FX
FY'15 Core
earnings
115
February 2016
Company presentation
FY
2015
Variance
FY 2014
FY 2015
CHF
CER
648
693
11
5.58
6.16
116.2
112.5
10
15
594
552
-7
-3
5.11
4.91
116.2
112.5
-4
116
February 2016
Company presentation
SHAREHOLDER
RETURNS
117
February 2016
Company presentation
927
588
358
133
2012
2013
118
February 2016
Company presentation
2014
2015
FINANCIAL GUIDANCE
February
2016
119
February 2016
Company presentation
2016
FINANCIAL GUIDANCE
120
February 2016
Company presentation
MANAGEMENT &
BOARD
121
February 2016
Company presentation
Otto Schwarz
COO
Joined in 2008
Nicholas Franco
Chief BD Officer
Joined in 2011
Guy Braunstein
Head of Global CD
Joined in 2009
Martine Clozel
Founder, CSO
Joined in 1997
Christian Albrich
Head of Global HR
Joined in 2005
Rudi Frank
Head of Global Quality Management
Joined in 2000
Marian Borovsky
General Counsel
Joined in 2003
122
Andr Muller
CFO
Joined in 2013
February 2016
Company presentation
Andrew Weiss
Head of IR & CC
Joined in 2014
Juhani Anttila
Joined in 2005
John J. Greisch
Joined in 2013
Robert J. Bertolini
Joined in 2011
Peter Gruss
Joined in 2012
Jean Malo
Joined in 2004
123
David Stout
Joined in 2015
February 2016
Company presentation
Jean-Paul Clozel
Joined in 2000
Michael Jacobi
Joined in 2009
Herna Verhagen
Joined in 2015
124
February 2016
Company presentation