1. Healthcare

R&D Investor Day
Lainate
January 30, 2015
1
Safe Harbour
This presentation may include forward-looking statements that are based on our
management’s beliefs and assumptions and on information currently available to our
management.
The inclusion of forward-looking statements should not be regarded as a
representation by Cosmo that any of its plans will be achieved. Actual results may
differ materially from those set forth in this presentation due to the risks and
uncertainties inherent in Cosmo’s ability to develop and expand its business,
successfully complete development of its current product candidates and current and
future collaborations for the development and commercialisation of its product
candidates and reduce costs (including staff costs), the market for drugs to treat IBD
diseases, Cosmo’s anticipated future revenues, capital expenditures and financial
resources and other similar statements, may be "forward-looking" and as such involve
risks and uncertainties and risks related to the collaboration between Partners and
Cosmo, including the potential for delays in the development programs for Methylene
Blue MMX®, Rifamycin SV MMX®, and CB-03-01. No assurance can be given that the
results anticipated in such forward looking statements will occur. Actual events or
results may differ materially from Cosmo’s expectations due to factors which include,
but are not limited to, increased competition, Cosmo’s ability to finance expansion
plans, the results of Cosmo’s research and development activities, the success of
Cosmo’s products, regulatory, legislative and judicial developments or changes in
market and/or overall economic conditions. Cosmo assumes no responsibility to
update forward-looking statements or to adapt them to future events or
developments.
You are cautioned not to place undue reliance on these forward-looking statements,
which speak only as of the date hereof, and Cosmo undertakes no obligation to revise
or update this presentation.
2
Cosmo at a glance: 2013 – E 2014
EUR/Million
Traditional contract manufacturing and other revenue
MMX® products, manufacturing
MMX® products, royalties
MMX® licence fees, up-front fees and milestones
TOTAL OPERATING REVENUES
2013
11
20
20
5
56
E 2014
12
30
23
18
83
+9,1%
+50,0%
+15,0%
+260,0%
+48,2%
(34)
22
(48)
35
+41,2%
+59,1%
Depreciation and amortization
OPERATING RESULT
(9)
13
(9)
26
0,0%
+100,0%
Sale of "equity for product" stake
Salix termination fee
Net financial income
PROFIT BEFORE TAXES
58
1
72
65
17
3
111
+12,1%
+200,0%
+54,2%
Cash and liquid financial assets
Equity
Total financial debt
Employees (n)
181
220
12
163
182
203
11
179
+0,6%
-7,7%
-8,3%
+9,8%
Operating expenses
EBITDA
3
Cosmo‘s path to organic growth
1) Expand GI pipeline
2) Expand activities to other therapeutic areas, namely:
Endoscopy & Dermatology
3) Willingness for “equity for product” deals
4) Create as much value as possible in-house and enter
deals when value maximization and risk reduction can be
achieved
4
Two very successful products in the market
• Lialda
Launch in 2007
First year Sales $ 50 m
second year sales $ 140 m
2013 year sales $ 529 m
Launch 2013
First year sales $ 66 m
second year sales > $ 150 m
Patent protection extended from 2020 to 2031
• Uceris
5
Products on the market
GI
6
Lialda: market projections
Lialda/
Mezavant
Cosmo Revenues
in EUR m
7
2015 p
2016 p
2017 p
15,7
16,9
17,9
Lialda: litigation update
Genericising Lialda is quite challenging
• 4 par. IV litigations currently pending (first filed 2010) for
counterfeiting/infringement against Zydus/Cadila, Osmotica, Mylan
and Watson (now Actavis)
• Cosmo/Shire have won in first instance against Watson (now Actavis)
as the Court ruled US6,773,720 patent covering Lialda as valid and
the ANDA formulation in infringement. Watson appealed, the federal
court amended the claim construction order, Cosmo/Shire challenged
such order to the Supreme Court, the Supreme Court ordered the
lower court to re-examine the order in light of the ruling in the Teva
vs. Sandoz case; this will significantly extend the duration of the trial
• In the meanwhile, the 30-months stay period has expired but no
ANDA filer has yet launched “at risk”, possibly because if
subsequently found guilty it would be exposed to triple damages
• Furthermore Watson (now Actavis) has seen its ANDA being rejected
for lack of bio-equivalence
8
Uceris: market projections
Uceris
royalties & manufacturing
income in EUR m
9
2015 p
2016 p
2017 p
29.9
37.4
43.9
Uceris: Santarus/Salix Add-On Study
Features
Source CCFA 2014
10
Uceris: Santarus/Salix Add-On Study
Achieving histological healing
11
Source CCFA 2014
Uceris: Cosmo’s benefits from Add-On Trial
Add-On trial shows that treatment with Uceris in addition to 5-ASA:
• is more effective than 5-ASA alone in terms of clinical, endoscopic
and hystological remission
• allows a much better mucosal healing compared to 5-ASA alone
As UC patients are normally first prescribed with 5-ASA and ≥ 40%
of them non respond to 5-ASA, in light of the efficacy of the
association:
• Uceris should be prescribed on an earlier base
• switch/upgrade to Uceris (stronger and more effective
steroid with no side effects) should be accelerated
12
Uceris: potential espansion beyond UC
•
•
•
•
•
•
•
•
13
Microscopic Colitis (MC) is an IBD, namely an inflammation of the
colon that can be detected only with a microscope
MC stems from an abnormal immune-system response to bacteria
normally living in the colon
MC includes collagenous colitis and lymphocytic colitis, whose
symptoms and treatments are similar
The most common symptom of MC is chronic, watery, non-bloody
diarrhea. Episodes of diarrhea can last for weeks, months, or even
years.
Budesonide has proven to be the most effective API for the
treatment of MC
Best dose is 9mg and requires topical delivery in the last part of
the Gut
Uceris is the perfect candidate for an extension
Discussion are ongoing with partners
Uceris Patent Protection (2020-2031)
FDA Orange Book listing
Appl No
Prod No
N203634 001
N203634 001
N203634 001
N203634 001
N203634 001
N203634 001
14
Patent No
Patent
Expiration
7410651 Jun
9,2020
7431943 Jun
9,2020
8293273 Jun
9,2020
8784888 Jun
9,2020
8895064 Sep
7,2031
RE43799 Jun
9,2020
Drug
Drug
Substance Product
Claim
Claim
Y
Patent Use Delist
Code
Requested
U - 1325
Y
Y
Y
Y
Y
U - 1325
Uceris Additional Patent Protection
on Pharmacokinetic Parameters (PK)
•
US Patent 8,895,064 was granted on November 25, 2014 with claims
containing the in vivo pharmakinetics parameters related to the
product
•
It is important to have PK parameters granted in a US patent on an
already marketed product
•
US patent ‘064 expiry date in 2031
•
This patent is already listed in the FDA Orange Book listing
•
Two additional child patent applications with PK claims are now
pending to strenghten the position (expiry 2031)
Uceris is thus now protected also with PK parameters
15
Uceris additional protection against ANDA Filers
stemming from new Bio-Equivalence (BE) Guidance
• In response to the Citizen Petition filed by Santarus/Cosmo (2013), FDA
issued a BE Draft Guidance specific for Uceris (December 2014),
requesting two in vivo (pharmacokinetics) and one in vitro testing
parameters (dissolution)
• ANDA Filers must therefore show bioequivalence with the following testing
parameters:
In vivo : both fast and fed conditions
- partial AUC8-48 (with at least 4 non-zero points for each part);
- AUC0-t (last time point at least at 72 hours), and
- Cmax
In vitro : dissolution at 6 different pHs (at least 12 tbs per test)
- 4.5 (acetate buffer at 100 rpm);
- 6.9, 6.5, 6.8, 7.2 ad 7.5 (phosphate buffer at 100 rpm);
- alcohol and non-alcohol method (methods to be presented in detail)
• FDA requests 90% Confidence Interval (CI) for each parameter
As seen with Watson in the case of Lialda, genericizing Uceris
will be a challenging proposition from the BE standpoint
16
Cortiment
• Cortiment was successfully launched in The Netherlands in
2013. Market dynamics (units/inhabitants) equal to US
• Approval extended in 27 EU countries with MRP concluded in
October 2014
• Launch sequence on the basis of National approvals and of
price optimization, starting from Q1 2015
• Product presentation at 2015 ECCO in a dedicated satellite
symposium
17
Cortiment: RoW approval path
Cortiment marketing authorization application (MAA)
already submitted in :
• Australia
• Israel/Jordan/Kuwait/Lebanon
• Brazil
• South Africa
• Russia
• Mexico
Submissions in CH, Turkey, UAE, Chile, Canada to follow
18
Expected approvals in 2015:
• Australia
• Israel/Lebanon
• Jordan/Kuwait
• Russia
• Mexico
Cortiment: market projections
Cortiment
royalties & manufacturing
income in EUR m
milestones in EUR m
2015 p
2016 p
2017 p
0.7
2.3
5.5
1
• As per units sold, the forecast is in line with US’ (after 3
years from launch, ~12m tablets sold for each of
Cortiment and Uceris)
19
ZACOL NMX
• Jan-Apr: 3 weeks TV and 3 months radio advertising, highly successful
• 90’000 packs sold in the market in the ads period
• test confirmed the market need of products to regulate intestinal
functions in healthy subjects
Next steps:
• classification of Zacol as a medical device (ZacolMed)
• export model in EU/US with selected commercial partners
20
Products under development
GI Pipeline
21
GI Pipeline - Rifamycin
NCE (in US) antibiotic with negligible absorption after oral administration
and lower possibility of resistance. Candidate for 10 years exclusivity
in USA under GAIN Act
Indication currently sought: Travellers’ Diarrhoea
Clinical status:
Two pivotal clinical trials were required to support registration:
1 – US trial (superiority vs. placebo) completed successfully in LatAm
2 – EU trial (non inferiority vs. Cypro) ongoing
Trial begun in India by Falk. After 800 patients, due to unexpected local
regulatory issues affecting all clinical trials the trial was put on hold. Falk
has now moved the trial in LatAm (Mexico, Perù, Guatemala and Ecuador)
Development Timeline: NDA filing set for 1Q 2016
22
GI Pipeline - Rifamycin
subsequent indications
Uncomplicated Diverticulitis
• Phase II managed by Falk in Germany, Italy, Hungary and Romania.
• approximately 100 patients enrolled.
• expansion to other two countries ongoing.
Development timeline:
interim analysis by end of 2015
IBS
• New formulation containing 600mg/tablet already developed aiming at
better patients compliance
• Seeking an earlier API delivery in the small intestine and colon
Development Timeline:
Phase I/II to start in 1Q 15
23
GI Pipeline - MoAb MMX
Target: to deliver MoAb topically in the intestine, in order to avoid
toxicity associated with their systemic absorption and reduce
immunoreactions
Potential indication: Ulcerative Colitis (maintenance of remission),
as an ideal follow-up to Uceris-Cortiment/Lialda
Evidence:
• Proven preservation of chemical structure of MoAb in MMX tablets
and functional activity maintained in colonic environment
• Successful efficacy model in mice
• Infliximab Bio-better under scale up process
• Phase I/II trial planned to start in 2015
24
GI Pipeline - MoAb MMX
The colon does not host proteolytic enzymes that may destroy MoAbs
*
25
From “METABOLISM” – compiled and edited by Phlip L.Altman and Dorothy S. Dittmer
Federation of Amer. Soc. for Exp. Biology
GI Pipeline - MoAb MMX
MMX® manufacturing process does not degrade or change the structural
conformation of MoAbs
Tablets manufactured with MMX® technology maintain the antibody binding
capacity
GI Pipeline - MoAb MMX
Infliximab extracted from tablets manufactured with MMX® technology
maintains the antibody biologic activity
LNCaP TNFa-induced cell death inhibited by anti-TNFa
2,E+05
2,E+05
Relative Cell Number
2,E+05
1,E+05
1,E+05
1,E+05
z
8,E+04
6,E+04
MMX-48
MMX-49
Inflix
no TNF
4,E+04
2,E+04
0,E+00
0,01
0,10
1,00
M olar Excess Antibody over TNFa
10,00
100,00
GI Pipeline - MoAb MMX
Infliximab locally delivered in DNB colitis is effective
Infliximab 0.008 mg/die
Intracolon
treatment
Daily dose
(mg/die)
Colon weight
(g)
Mucosal Damage
Area (mm2) *
Inhibition
(%)
P
---
1.81 ± 0.76
262 ± 209
---
---
Infliximab
0.008
1.62 ± 0.31
88 ± 80
66.73
0.032
Infliximab
5.0
1.76 ± 0.39
181 ± 143
30.63
0.394
Vehicle
28
Vehicle
* digital evaluation
GI Pipeline - MoAb MMX
Administration of an anti-TNFα soluble receptor into the colonic lumen is
effective in reducing the necrosis area in the treated mice
% of inhibition vs baseline
70
58,4
60
49,2
50
48,6
40
30
20
18,7
10
2,24
0
0,0008
0,002
0,008
0,04
0,08
-10
daily topical dose mg
-5,5
0,80
GI Pipeline - MoAb MMX
Interferon MMX tablets match MMX dissolution standards
t=0h
t=4h
t=8h
t = 12 h
GI Pipeline - MoAb MMX
Study Aim: show clinical efficacy of topical delivery of MoAb in the intestine
Treatment Regimen Infliximab 100 mg/100mL administered as enemas.
Three enemas one week apart, on days 0, 7, and 14.
Study Duration
42 days
Subjects characteristics
Four patients presenting with active left-sided ulcerative colitis
of moderate severity, with a Clinical Activity Index (CAI) >6 <10
Observation time
Clinical remission (CAI score<4) at 6 weeks of observation
Results
Two subjects completed the study as per protocol.
CAI remission (score<4) was observed in both subjects at day 7,
and was maintained/ improved up to day 42.
GI Pipeline - MoAb MMX
Assessment and assumptions for MMX® application
1-
Protein and peptide degrading proteolytic enzymes or peptidases are less
abundant in the colon than in the upper GI tract
2 - Drug delivery into the colonic region, also in the left side of it, through MMX®
tablets is validated
3-
MMX® formulation auxiliary substances are compatible with the chemical nature of
peptides and proteins: no compatibility major problems
4-
MMX® manufacturing process thermic and mechanical stresses do not degrade or
change the structural conformation of proteins or peptides
5-
Proteins delivered by MMX® tablets have been proven to retain their binding
capacity and their peculiar biologic activities
GI Pipeline - MoAb MMX
Development timeline:
33
•
Formulation and analytical development ongoing with model APIs
•
Generation by AIMM of a series of stable Remicade bio-better clones
•
AIMM bio-better with physico-chemical and biological properties similar to
Remicade (before and after lyophilization)
•
Selected clone has been transferred to a protein mfrg company for large scale
production
•
Batches available for MMX manufacturing by end of Q2 2015
Products under development
Endoscopy Pipeline
34
Endoscopy Pipeline
Two new powerful tools to support endoscopists
in their battle against colon cancer
Methylene Blue MMX®
35
SIC 8000
Endoscopy Pipeline - Methylene Blue MMX (MB)
Methylene Blue is used in > 10% colonoscopies
via “in situ” spraying onto the colonic mucosa
Suspicious
area according
to endoscopist
survey
2-3 fold increased
procedure time*
[~80$ cost of single use spray catheter]
Localized
and partial
staining*
*ASGE Volume 66, No 4: 2007 GASTROENINTESINAL ENDOSCOPY.
36 Clinical Trial showed increased detection rate with Indigo Carmine.
Increased
Detection
Rate in the
area*
37
Endoscopy Pipeline - MB
MB: a revolutionary diagnostic tool for early cancer detection
Normal
Procedure
Time
* According to Phase II Clinical Data, 51% more polyps and
47% more adenomas were found with MB
38
Whole Colon
stained,
overcoming
operator
subjectivity
Sharp increase in
Detection Rate,
especially for
flat/small lesions*
39
MB Main Target
Polyps not otherwise
visible
MB Main Target
Polyps not otherwise
visible
INVISIBLE
WITHOUT
MB
Endoscopy Pipeline - MB development timeline
• Phase III ongoing, expanded from 13 sites between US and EU
to 20
• Primary endpoint: proportion of subjects with at least one
histologically proven adenoma or carcinoma vs. white light
endoscopy
• 1,270 patients to be treated within H1 2015
• Data available Q3 2015
• Centralized Registration Application granted in EU under EMA
• Special Protocol Assessment (SPA) granted by FDA
43
310
330
431
Dr. Alessandro Repici, Istituto Clinico
Humanitas
Rozzano, Italy
Dr. Renato Cannizzaro, Centro di
Riferimento Oncologico
Aviano, Italy
Dr. Ralph Kiesslich, Klinikum der
Landeshauptstadt Wiesbaden und der
HELIOS Kliniken Gruppe
Drittmittelverwaltung
Wiesbaden, Germany
510
Dr. James East, John Radcliffe Hospital
Oxford, UK
610
Dr. Evelien Dekker, AMC Amsterdam
Amsterdam, Netherlands
611
Dr. Peter D. Siersema, UMC Utrecht
Utercht, Netherlands
630
Dr. Manon Spaander, Erasmus Medical
Centre, Rotterdam, Netherlands
730
Dr. Limas Kupcinskas, Kaunas University of
Medicine, Kaunas, Lithuania
820
44
MB Phase III
Clinical Trial Sites: EU
Dr. Raf Bisschops, Belgium University
Hospital, Leuven, Belgium
730
610
510
611
630
820
431
310
330
45
130
Dr. Michael Wallace
Mayo Clinic Jacksonville, FL
131
Dr. Prateek Sharma
University of Kansas School
of Medicine, Kansas City, MO
110
Dr. Francisco Ramirez
Mayo Clinic, Scottsdale, AZ
111
Prof David Bruining
Mayo Clinic, Rochester, MN
114
Dr David Gatof, Clinical
Research of the Rockies
Lafayette, CO
132
Dr. Marcia (Mimi) Canto
J Hopkins, Baltimore, MD
230
Dr. Norman Marcon, St.
Michael's Hospital
Toronto, Canada
MB Phase III
Clinical Trial Sites:
North America
111
112
230
132
131
110
130
Endoscopy Pipeline
MB market potential estimate
MB Market potential
non SSRI
colonoscopies in US in
m
46
2017
2018
2019
2020
2021
12.6
12.8
12.9
13.1
13.2
market penetration
5%
10%
15%
20%
20%
minimum price
120
120
120
120
120
colonoscopies in EU
17.4
17.6
17.8
18.0
18.3
market penetration
5%
10%
15%
20%
20%
minimum price
50
50
50
50
50
colonoscopies in RoW
24.8
26.8
29.0
31.5
34.2
market penetration
0%
2,5%
5,0%
7,5%
10,0%
minimum price
30
30
30
30
30
total revenues in
EUR m
119.1
261.2
409.6
564.8
602.4
Endoscopy Pipeline - SIC
After the lesion is found, it must be removed
47
Total time for lesion removal: 40 minutes
Endoscopy Pipeline - SIC
Polyps removal tecniques
Endoscopic Mucosal Resection (EMR)
•
Most commonly used technique for the removal of mucosal lesions,
smaller than 2 cm, or piecemeal removal of larger lesions (> 2 cm)
•
A cushion is needed to lift the lesion and facilitate its removal,
minimizing the risks of mechanical or electrocutlery damage to the deep
layers of the GI wall
Injection in the
submucosa
48
Capture with the
snare
Removal
Endoscopy Pipeline – SIC
Polyps removal tecniques
Endoscopic Submucosal Dissection (ESD)
•
Developed specifically for removing larger lesions (> 2 cm)
•
Predicted to replace conventional surgery
•
Higher rate of perforation and bleeding complications
•
Submucosal injection is essential in ESD, and a high and long lasting
submucosal cushion is needed for a safe cutting
Circumferential injections
49
Mucosal elevation
Submucosal dissection
Endoscopy Pipeline - SIC
•
To avoid risk of perforation, particularly for flat polyps, endoscopists need
to create a ’’safety cushion‘‘ between the lesion and the deep layers of
the GI wall
•
Current procedures foresee the injection of normal saline solution, which
is easy to inject but dissipates quickly
•
Longer lasting cushions are obtained with expensive Hyaluronic Acid
solutions or self made cocktails
•
Strong need to obtain similar long lasting effect with alternative solutions:
ideal product should:
• have low viscosity to facilitate injection
• Provide a long lasting cushion (> 30 min)
• Include a dye to enhance borders definition
• be safe and bio-compatible
• Affordable in terms of pricing
50
Endoscopy Pipeline - SIC
• SIC 8000 (SIC) is a Submucosal Injectable Composition, easy to
be injected, developed to be used in endoscopic resection procedures in
the GI tract
• SIC creates a long lasting cushion which is essential for a successful
Endoscopic Mucosal Resection (EMR) or Endoscopic Submucosal
Dissection (ESD)
• SIC is dyed with methylene blue, so it helps in visualizing the lesion
and performing the resection procedure, minimizing risk of perforation
• SIC is covered by two international and one US patent
applications filed in 2014 (priority 2013)
51
Endoscopy Pipeline - SIC
SIC satisfies an unmet need
• No products for this indication currently available in the US market
• Most commonly used submucosal injectable solution is normal saline, but
several injections needed to maintain the cushion
• Hyaluronic acid solutions are known to be long lasting, but expensive
Sigmavisc® in EU costs 50€ for 5 ml, Muco-up® in Japan costs 55€ for 5
ml
• Other patented compositions not on US market for impracticality
• Easy to use: no additional or customized devices (such as
syringe pumps or other pumps) needed to administer SIC 8000
No currently used solutions meet medical needs
in endoscopic practice
52
Endoscopy Pipeline – SIC
Practical application
53
Endoscopy Pipeline – SIC
Practical application
54
Endoscopy Pipeline – SIC
Practical application
55
Endoscopy Pipeline – SIC
Development as agreed with FDA is completed
•
3 biocompatibility studies (as per ISO 10993 standard)
 In vitro cytotoxicity
 Acute intracutaneous reactivity study in rabbits
 Delayed dermal sensitization in guinea pigs
 Biocompatibility studies demonstrated that SIC 8000 is biocompatible: not
cytotoxic, not irritating, not sensitizing
•
5 preclinical GLP studies on animals:
 Tolerability study in minipigs
 Tolerability study in dogs
 Tolerability study in pigs
 EMR/ESD procedures using SIC 8000 in pigs (stomach + colon)
 Feasibility study of EMR/ESD procedures in pigs (stomach + colon + esophagus)
•
Aim of the preclinical studies: full characterization of the product (efficacy/safety
profile) in conditions simulating and mimicking the actual use of the product on
human patients
•
Animal species selection based on the animal models currently used for endoscopic
training procedures
56
Endoscopy Pipeline - SIC
Development Timeline
SIC is a medical device classified as a class II medical device in US and
as either a class IIa or IIb medical device in EU
Approval timeline:
• 510(k) filing in US scheduled by end Q1 2015
• FDA approval scheduled by end Q2 2015
• European CE mark filing scheduled by Q2 2015
• European approval scheduled by Q4 2015
57
Endoscopy pipeline: SIC
market potential estimate (colonoscopies only)
SIC market estimates
polyps/adenomas per
colonoscopy in phase II
% of polyps/ adenomas
removal requiring SIC
Minimum vials per
colonoscopy
58
2016
2017
2018
2019
2020
1,75
1,75
1,75
1,75
1,75
20%
20%
20%
20%
20%
1,5
1,5
1,5
1,5
1,5
estimated price in US
100
100
100
100
100
market penetration in US
10%
20%
30%
40%
50%
estimated price in EU
40
40
40
40
40
market penetration in EU
7%
15%
25%
30%
30%
estimated price in RoW
30
30
30
30
30
market penetration
3,5%
7,5%
12,5%
15,0% 15,0%
Revenue (millions)
68,5
143,1
227,8
298,6
353,6
Endoscopy pipeline: SIC
market potential (additional indications)
The tissues of the esophagus, stomach and duodenum are quite similar to
those of the colon. Inspection of these three tracts is conducted by
Esophagogastroduodenoscopy (ECG). SIC can be used in all these tracts.
As many ECGs are performed as colonoscopies, both in the US and
Europe.
During ECG, removal of tissues/polyps is frequently necessary and will
require SIC as per below examples:
Barrett Esophagus
• Caused by GERD, ~ 1,6% of population affected
• Requires an ECG every 3 years
• Tissue removal required in ~ 10% all cases
Stomach & duodenal polyps
• polyps requiring extraction are found in around 0,7% of all procedures
59
Endoscopy Pipeline – SIC
Additional Indications - Stomach
60
Endoscopy Pipeline – SIC
Additional Indications - Esophagus
61
Products under development
Dermatology Pipeline
62
Dermatology pipeline
Product
CB-03-01
ACNE
CB-03-01
ALOPECIA
CB-06-02
AS 101
CB-06-04
ACNE ANTIBIOTIC
Pre-clinical
Phase I
Phase II
Phase III
MA
Launch
Dermatology:
a market with little innovation and many opportunities
• No NCE in Acne in the US market in the last 15 years
• Dermatologists generally prescribe 2-3 products at the same time
as they look for new therapeutic options
• Historically dermatology has had the lowest product failure rate in
clinical trials
• Probability of success in phase III clinical trials is high
• Market has important cosmetic and life-style implications
64
Dermatology Pipeline
Acne market dynamics & opportunity
85% of all persons age 12-24 get acne, characterized as a chronic disease
In US 17 m person have acne, 35 m prescriptions are written p.a. primarily
generics as there are no new drugs
WW market ~ $ 3 b; US Market at $ 2.3 b, growing by ~ 1% p.a.
• Topical antibiotics market share ~ 29%
• Topical retinoid market ~ 25%
• Oral antibiotic market ~ 41%
Excellent opportunity for new topical drugs with
novel treatment forms and very low side effects
65
Dermatology pipeline – CB-03-01 (Acne)
CB-03-01 (Cortexolone 17α-propionate) is a NCE
with a new mechanism of action, acting on the
sebum secretion control.
It can prevent the cascade of physiological
events:
follicle closure by sebum overproduction ->
colonization by Prop. acnes ->
Inflammation that leads to Acne formation,
through evidence of
Comedones -> papules -> pustules -> nodules ->
cysts
Differently from other Acne drugs, CB-03-01 is
topically effective without systemic side
effects (no relevant AEs detected on the >450
subjects treated up today)
66
Dermatology pipeline – CB-03-01 (Acne)
Phase II overview
Phase II dose ranging trial completed in US
360 patients – 4 doses + vehicle
Best dose identified (1% BID)
No adverse events
67
Dermatology pipeline – CB-03-01 (Acne)
Phase II overview
•
•
•
•
•
•
•
•
68
CB-03-01 is a NCE
FDA requires at least 1000 patients treated for safety evaluation
110 patients treated in Phase I/IIa
290 patients treated in Phase IIb
Primary Endpoints: reached
700 treated patients planned for Phase III (2 pivotal studies of 350 vs
vehicle)
CB-03-01 has shown statistical significance in Phase II with only 72
patient per cohort
CB-03-01 has therefore very high potential for showing statistical
superiority vs vehicle
Dermatology pipeline – CB-03-01 (Acne)
Phase II overview
statistical significance in IGA improvement (co-primary endpoint)
BID 1.0%
cream
VEHICLE
%
%
2-Point Improvement
17.1%
6.7%
No Change
35.7%
61.3%
%
%
2-Point Improvement
21.8%
8.5%
No Change
23.6%
59.3%
ITT
PP
69
P value
0,0321
Dermatology pipeline – CB-03-01 (Acne)
Phase II overview
CB–03–01 Phase II: statistical significance in total lesion count
(co-primary endpoint)
CB-03-01 1% cream
VEHICLE
P-value
-13.1%
0.0173
BID
ITT
MEAN
70
-35.7%
Dermatology pipeline – CB-03-01 (Acne)
Phase II overview
successful also in secondary endpoint
showing reduction in Inflammatory Lesion Counts
ITT
MEAN
* Kruskal Wallis test
71
CB-03-01 1% cream BID
VEHICLE
%
%
-37.2%
-27.0%
P-value*
0.0384
Dermatology pipeline – CB-03-01 (Acne)
Phase II overview
successful also in secondary endpoint
showing reduction in Non-Inflammatory Lesion Counts
CB-03-01 1% cream
VEHICLE
P-value
-16.1%
0.0178
BID
ITT
MEAN
72
-32.9%
Dermatology pipeline – CB-03-01 (Acne)
Development timeline
• EOP2 achieved on Jan 28th
• Special Protocol Assessment to be discussed with FDA in
Q2 2015
• Phase III trials program:
- 2 pivotal trials (US + EU) with > 700 patients/each
FPI in Q3 15
- 1 extension trial
- data available Q3 17
73
LPO in Q1 17
Dermatology Pipeline
Alopecia market dynamics & opportunity
20% of all men and 10% of all women between 20-64 lose
part of their hair
~ 17% of persons affected use at least one substance
• <1% of affected men and women have done hair transplants
• <1% of affected men and 5% of affected women use hairpieces
US Market estimated at $ 1 b and EU market at EUR 1.5 b,
growing by ~ 2% p.a.
• Rogaine and Propecia are only approved products in both markets
• Patents for both products have lapsed
Excellent opportunity for new topical drugs with
novel treatment forms and very low side effects
74
Dermatology Pipeline – CB-03-01 (Alopecia)
Dermatology Pipeline – CB-03-01 (Alopecia)
Rinaldi 2010 - International Hair Research Foundation (IHRF)
76
Dermatology Pipeline – CB-03-01 (Alopecia)
Rinaldi 2010 - International Hair Research Foundation (IHRF)
77
Dermatology Pipeline – CB-03-01 (Alopecia)
Rinaldi 2010 - International Hair Research Foundation (IHRF)
78
Dermatology Pipeline – CB-03-01 (Alopecia)
Rinaldi 2010 - International Hair Research Foundation (IHRF)
79
Dermatology Pipeline – CB-03-01 (Alopecia)
• Only topical anti-androgen for treatment of Androgenetic Alopecia
(Propecia® is a tablet)
• Kinetic proof of scalp penetration obtained
• Same mechanism and safety as for acne
80
Dermatology Pipeline – CB-03-01 (Alopecia)
Development timeline
•
POC Phase II ongoing in USA: 90 patients, double blind, 3 parallel arms, placebo and
Minoxidil controlled, 26 weeks of treatment, endpoints on scalp darkness and patient
satisfaction.
•
The Modified Norwood-Hamilton Scale is used to assess the eligibility of subjects at
the Screening Visit. Subject has to have mild to moderate AGA in temple and vertex
region rating Modified Hamilton-Norwood Scale III vertex to V (IIIv, IV, V) with
ongoing hair loss to be eligible for this study
•
Recruitment is in progress and treatment
will be completed by end of 2015
81
Dermatology Pipeline – CB-06-02 (HPV)
market dynamics & opportunity
>20 m persons are infected with HPV in the US, around 1% of
sexually active persons in US have visible external genital warts
(AGW)
HPV can lead to cancer and should be eradicated
In western countries many young children are vaccinated against the
Papillomavirus
• the vaccine is ineffective on persons that already have the virus
Current market
•
around 360’000 persons develop AGW each year in US
• there are ~ 600’000 TRX each year
• main products prescribed are Imiquimod based
82
Dermatology Pipeline – CB-06-02 (HPV)
• Anogenital warts (AGWs) is a common, highly infectious disease
caused by the human papillomavirus (HPV)
• Tellurium based compound for treatment of HPV and genital
warts
• HPV vaccination is currently in regression because of fertility
concerns
83
Dermatology Pipeline – CB-06-02 (HPV)
American family Physician December 15, 2004, 70 (12)
84
Dermatology Pipeline – CB-06-02 (HPV)
Development timeline
• POC Phase II ongoing in Israel on 30 + 30 patients, double blind,
parallel arms, 12 weeks of treatment + 3 months of follow up,
endpoints on remission and recurrence rates
• Trial Completion foreseen by Q1 2016
85
Dermatology Pipeline – CB-06-01 (Acne)
• Topical antibiotic for the treatment of Acne
• Ideal complement to CB-03-01
• NCE with very potent and selective properties
• Effective with bacterial strains resistant to other antibiotics
86
Dermatology Pipeline – CB-06-01 (Acne)
Antibacterial spectrum
87
Dermatology Pipeline – CB-06-01 (Acne)
Activity against antibiotic-resistant P. acnes
88
Dermatology Pipeline – CB-06-01 (Acne)
Development timeline
• POC Phase II ongoing with a gel formulation, completion by Q1
2016
89
Cosmo Corporate Matters
90
Cosmo Corporate Matters
No impact of FX turmoil on Cosmo
No costs in CHF
Only 9% of costs in $, rest in EUR
49% of revenues in $; 51% in EUR
All liabilities are in EUR
91
Cosmo Corporate Matters
Cash & Liquid Investments
as of 1/12/2015
EUR 123.6 m
USD 63.7 m
92
Cosmo Corporate Matters
Financial position
151,5 m
investments
35,7 m
cash
74% in EUR;
26% in $
64% in EUR
36% in $
11 m debt
100% in EUR
93
Cosmo Corporate Matters
Completed Capital Reduction
• annullment of 576’760 shares
• total capital unchanged by increasing nominal
value per share from EUR 0.25 to EUR 0.26
• Total shares outstanding now 14’418’983 shares
• Accretion of 4% which is an implicit dividend
94
Cosmo Corporate Matters
Next Strategic Steps
• Change of registered office to Luxembourg
• Set-up of second plant in Ireland
• Potential strategic spin-off of derma franchise by means of
IPO or private placement
• Initiate discussion for deals re pipeline products
• evaluate possibility of setting up own distribution
company in US
95
Cosmo Corporate Matters
Transfer of Seat to Luxembourg
• Filing for registration in Luxembourg early February
• Registration takes place in 10-20 days
• After registration in Luxembourg, filing for cancellation in
Italy
96
Cosmo Corporate Matters
Consequences of shareholders‘ withdrawal
• 104’931 shares put to the company at CHF 156.03
• shareholders who have tendered shares will receive payment
value May 5, 2015
• shareholders who did not tender shares have pre-emptive
rights to purchase tendered shares at CHF 156.03 until
February 13
• no need of a convertible/loan to finance redemption
97
Cosmo Corporate Matters
Second Plant in Ireland
• a second FDA approved plant is being built in Dublin, Ireland
• Scope:
• ensure production continuity
• enhance manufacturing franchise
• grant second line of supply to strategic partners
• Plant will occupy a newly constructed “shell” bordering Dublin airport to ease
logistics
98
Cosmo Corporate Matters
Second Plant in Ireland - Features
• 3’000 sqm surface, 12m height
• MMX tablets production line (500k batch size) + bottle and blister
packaging lines
• expected timeline:
• Q1 2015 planning permission filing
• Q4 2015 fit-out works start, around 12 months duration
• H2 2017 FDA inspection
• total investment: approx EUR 15m in 2016-2017
99
Cosmo Corporate Matters
Potential IPO of Cosmo Derma
• Newco is being set up
• Newco to be funded by Cosmo Pharma
• Plan to list on SIX
• Plan to give existing Cosmo Pharma shareholders
pre-emptive rights
100
Cosmo Corporate Matters
Next Deals Opportunities
Endoscopy
SIC (w/w rights)
MB (w/w)
GI
Rifamycin (rights in US and selected RoW countries)
Monoclonal Antibody MMX (w/w)
Dermatology
CB-03-01
CB-03-01
CB-06-02
CB-06-01
101
for
for
for
for
Acne (w/w)
Alopecia (w/w)
HPV-Genital Warts (w/w)
Acne (w/w)
Cosmo Corporate Matters
2015 Projected Clinical News Flow
Endoscopy
SIC: approval
MB: end of phase III
GI
Rifamycin: end of phase III
Dermatology
CB-03-01 for Acne: start of phase III
CB-03-01 for Alopecia: end of POC – phase II
102
2014 – 2016 Guidance
EUR/Million
Traditional contract manufacturing and other revenue
MMX® products manufacturing
MMX® products royalties
MMX® licence fees, up-front fees and milestones
Revenues from products under development
Total Revenues
Operating expenses
EBITDA
Depreciation and amortization
Operating result
Sale of "equity for product" stake
Salix termination fee
Net financial income
Profit before taxes
Potentially replaceable with “equity for product” transactions
(1) includes EUR 5.7 M royalties on Lialda/Mezavant: royalty cap reached in 2Q 2014
(2) includes EUR 23,4 M roy on Uceris/Cortiment
(3) includes EUR 28,4 M roy on Uceris/Cortiment
(4) assumes MB and SIC are licensed in 2015 and Rifamycin is licensed in US in 2016
(5) includes SOP and profit bonus
(6) gain on sale of SNTS shares
103
E 2014
E 2015
E 2016
12
30
23
18
12
34
24
12
38
29
1
163
243
(67)
176
(3)
173
(1)
(2)
-
83
(48)
35
(9)
26
65
17
3
111
(5)
80
150
(54)
96
(9)
87
(4)
(5)
(6)
3
90
6
179
(3)
(4)
(5)
Cosmo Pharmaceuticals
Information
Contacts
• Number of shares: 14,418,983
• Alessandro Della Cha , CEO
[email protected]
• Listing: SIX Swiss exchange,
Main board
• ISIN: IT0004167463
• Chris Tanner, CFO
[email protected]
ph: +39-02-9333’7276
• Giuseppe Cipriano, COO
[email protected]
• Luigi Moro, CSO
[email protected]
104