2
Safe HarbourThis 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.
3
EUR/Million 2013 E 2014Traditional contract manufacturing and other revenue 11 12 +9,1%MMX® products, manufacturing 20 30 +50,0%MMX® products, royalties 20 23 +15,0%MMX® licence fees, up-front fees and milestones 5 18 +260,0%TOTAL OPERATING REVENUES 56 83 +48,2%
Operating expenses (34) (48) +41,2%EBITDA 22 35 +59,1%
Depreciation and amortization (9) (9) 0,0%OPERATING RESULT 13 26 +100,0%
Sale of "equity for product" stake 58 65 +12,1%Salix termination fee - 17Net financial income 1 3 +200,0%PROFIT BEFORE TAXES 72 111 +54,2%
Cash and liquid financial assets 181 182 +0,6%Equity 220 203 -7,7%Total financial debt 12 11 -8,3%Employees (n) 163 179 +9,8%
Cosmo at a glance: 2013 – E 2014
4
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
5
•Lialda
•Uceris
Two very successful products in the market
Launch in 2007First year Sales $ 50 m
second year sales $ 140 m 2013 year sales $ 529 m
Launch 2013First year sales $ 66 m
second year sales > $ 150 mPatent protection extended from 2020 to 2031
Lialda/Mezavant 2015 p 2016 p 2017 p
Cosmo Revenues in EUR m 15,7 16,9 17,9
7
Lialda: market projections
8
Lialda: litigation update
Genericising Lialda is quite challenging
• 4 par. IV litigations currently pending (first filed 2010) for counterfeiting/infringement against Zydus/Cadila, Osmotica, Mylanand 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 Tevavs. 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 rejectedfor lack of bio-equivalence
9
Uceris: market projections
Uceris 2015 p 2016 p 2017 proyalties & manufacturing income in EUR m 29.9 37.4 43.9
12
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, endoscopicand 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 effectivesteroid with no side effects) should be accelerated
13
Uceris: potential espansion beyond UC
• 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
14
Uceris Patent Protection (2020-2031)FDA Orange Book listing
Appl No Prod No Patent NoPatentExpiration
DrugSubstanceClaim
DrugProductClaim
Patent UseCode
DelistRequested
N203634 001 7410651 Jun9,2020
Y U - 1325
N203634 001 7431943 Jun9,2020
Y
N203634 001 8293273 Jun9,2020
Y
N203634 001 8784888 Jun9,2020
Y
N203634 001 8895064 Sep7,2031
Y
N203634 001 RE43799 Jun9,2020
Y U - 1325
15
Uceris Additional Patent Protectionon Pharmacokinetic Parameters (PK)
• US Patent 8,895,064 was granted on November 25, 2014 with claimscontaining 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 nowpending to strenghten the position (expiry 2031)
Uceris is thus now protected also with PK parameters
16
• 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
Uceris additional protection against ANDA Filersstemming from new Bio-Equivalence (BE) Guidance
17
Cortiment
• Cortiment was successfully launched in The Netherlands in2013. Market dynamics (units/inhabitants) equal to US
• Approval extended in 27 EU countries with MRP concluded inOctober 2014
• Launch sequence on the basis of National approvals and ofprice optimization, starting from Q1 2015
• Product presentation at 2015 ECCO in a dedicated satellitesymposium
18
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
Expected approvals in 2015:
• Australia
• Israel/Lebanon
• Jordan/Kuwait
• Russia
• Mexico
19
Cortiment: market projections
Cortiment 2015 p 2016 p 2017 proyalties & manufacturing income in EUR m 0.7 2.3 5.5
milestones in EUR m 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)
20
• 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
ZACOL NMX
22
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) ongoingTrial begun in India by Falk. After 800 patients, due to unexpected localregulatory 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
23
GI Pipeline - Rifamycinsubsequent 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 atbetter patients compliance• Seeking an earlier API delivery in the small intestine and colon
Development Timeline:Phase I/II to start in 1Q 15
24
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 tabletsand 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
25
GI Pipeline - MoAb MMX
*
From “METABOLISM” – compiled and edited by Phlip L.Altman and Dorothy S. DittmerFederation of Amer. Soc. for Exp. Biology
The colon does not host proteolytic enzymes that may destroy MoAbs
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
LNCaP TNFa-induced cell death inhibited by anti-TNFa
0,E+00
2,E+04
4,E+04
6,E+04
8,E+04
1,E+05
1,E+05
1,E+05
2,E+05
2,E+05
2,E+05
0,01 0,10 1,00 10,00 100,00
Molar Excess Antibody over TNFa
Re
lati
ve
Ce
ll N
um
be
r
MMX-48MMX-49
Inflixno TNF
z
GI Pipeline - MoAb MMX
Infliximab extracted from tablets manufactured with MMX® technology maintains the antibody biologic activity
28
Intracolontreatment
Daily dose(mg/die)
Colon weight(g)
Mucosal DamageArea (mm2) *
Inhibition(%)
P
Vehicle
Infliximab
Infliximab
---
0.008
5.0
1.81 ± 0.76
1.62 ± 0.31
1.76 ± 0.39
262 ± 209
88 ± 80
181 ± 143
---
66.73
30.63
---
0.032
0.394
* digital evaluation
GI Pipeline - MoAb MMX
Infliximab 0.008 mg/dieVehicle
Infliximab locally delivered in DNB colitis is effective
Administration of an anti-TNFα soluble receptor into the colonic lumen is effective in reducing the necrosis area in the treated mice
18,7
49,2 48,6
58,4
2,24-5,5
-10
0
10
20
30
40
50
60
70
0,0008 0,002 0,008 0,04 0,08 0,80
daily topical dose mg
% o
f
inh
ibit
ion
vs b
aseli
ne
GI Pipeline - MoAb MMX
GI Pipeline - MoAb MMXInterferon MMX tablets match MMX dissolution standards
t = 0 h
t = 4 h
t = 8 h
t = 12 h
GI Pipeline - MoAb MMX
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 colitisof moderate severity, with a Clinical Activity Index (CAI) >6 <10
Observation time
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.
Clinical remission (CAI score<4) at 6 weeks of observation
Study Aim: show clinical efficacy of topical delivery of MoAb in the intestine
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
33
GI Pipeline - MoAb MMX
Development timeline:
• 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
35
Endoscopy Pipeline
Two new powerful tools to support endoscopistsin their battle against colon cancer
Methylene Blue MMX®SIC 8000
36
Endoscopy Pipeline - Methylene Blue MMX (MB)
Methylene Blue is used in > 10% colonoscopies
via “in situ” spraying onto the colonic mucosa
*ASGE Volume 66, No 4: 2007 GASTROENINTESINAL ENDOSCOPY. Clinical Trial showed increased detection rate with Indigo Carmine.
2-3 fold increased procedure time*[~80$ cost of single use spray catheter]
Localized and partial staining*
Suspicious area according to endoscopistsurvey
Increased Detection Rate in the area*
38
Endoscopy Pipeline - MB
MB: a revolutionary diagnostic tool for early cancer detection
* According to Phase II Clinical Data, 51% more polyps and47% more adenomas were found with MB
Normal Procedure
Time
Whole Colon stained,
overcoming operator
subjectivity
Sharp increase in Detection Rate, especially for
flat/small lesions*
43
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
44
MB Phase IIIClinical Trial Sites: EU
510 630
610
431
310
310Dr. Alessandro Repici, Istituto ClinicoHumanitasRozzano, Italy
330Dr. Renato Cannizzaro, Centro di Riferimento Oncologico Aviano, Italy
431
Dr. Ralph Kiesslich, Klinikum der Landeshauptstadt Wiesbaden und der HELIOS Kliniken GruppeDrittmittelverwaltungWiesbaden, Germany
510Dr. James East, John Radcliffe HospitalOxford, UK
610Dr. Evelien Dekker, AMC Amsterdam Amsterdam, Netherlands
611Dr. Peter D. Siersema, UMC Utrecht Utercht, Netherlands
630Dr. Manon Spaander, Erasmus Medical Centre, Rotterdam, Netherlands
730Dr. Limas Kupcinskas, Kaunas University of Medicine, Kaunas, Lithuania
820Dr. Raf Bisschops, Belgium University Hospital, Leuven, Belgium
611
820
730
330
45
MB Phase IIIClinical Trial Sites:
North America
110
131
130
111
132
230
130Dr. Michael WallaceMayo Clinic Jacksonville, FL
131Dr. Prateek SharmaUniversity of Kansas School of Medicine, Kansas City, MO
110Dr. Francisco RamirezMayo Clinic, Scottsdale, AZ
111Prof David BruiningMayo Clinic, Rochester, MN
114Dr David Gatof, Clinical Research of the RockiesLafayette, CO
132Dr. Marcia (Mimi) CantoJ Hopkins, Baltimore, MD
230Dr. Norman Marcon, St. Michael's HospitalToronto, Canada
112
MB Market potential 2017 2018 2019 2020 2021
non SSRI colonoscopies in US in m 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 46
Endoscopy PipelineMB market potential estimate
Endoscopy Pipeline - SICAfter the lesion is found, it must be removed
47 Total time for lesion removal: 40 minutes
Endoscopy Pipeline - SICPolyps removal tecniques
Endoscopic Mucosal Resection (EMR)
48
• 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
Capture with the snare
Removal
Endoscopy Pipeline – SICPolyps removal tecniques
Endoscopic Submucosal Dissection (ESD)
49
Circumferential injections Mucosal elevation Submucosal dissection
• 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
Endoscopy Pipeline - SIC
50
• To avoid risk of perforation, particularly for flat polyps, endoscopists needto 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
51
• 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 SubmucosalDissection (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)
Endoscopy Pipeline - SIC
Endoscopy Pipeline - SICSIC satisfies an unmet need
52
• 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 needsin endoscopic practice
56
Endoscopy Pipeline – SICDevelopment 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
57
Endoscopy Pipeline - SICDevelopment 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
SIC market estimates 2016 2017 2018 2019 2020
polyps/adenomas per colonoscopy in phase II 1,75 1,75 1,75 1,75 1,75
% of polyps/ adenomas removal requiring SIC 20% 20% 20% 20% 20%
Minimum vials per colonoscopy 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
58
Endoscopy pipeline: SICmarket potential estimate (colonoscopies only)
59
Endoscopy pipeline: SICmarket 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
Product Pre-clinical Phase I Phase II Phase III MA Launch
CB-03-01ACNE
CB-03-01ALOPECIA
CB-06-02AS 101
CB-06-04 ACNE ANTIBIOTIC
Dermatology pipeline
64
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
65
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 withnovel treatment forms and very low side effects
66
Dermatology pipeline – CB-03-01 (Acne)
CB-03-01 (Cortexolone 17α-propionate) is a NCEwith a new mechanism of action, acting on thesebum secretion control.It can prevent the cascade of physiologicalevents:follicle closure by sebum overproduction ->colonization by Prop. acnes ->Inflammation that leads to Acne formation,through evidence ofComedones -> papules -> pustules -> nodules ->cysts
Differently from other Acne drugs, CB-03-01 istopically effective without systemic sideeffects (no relevant AEs detected on the >450subjects treated up today)
67
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
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
69
statistical significance in IGA improvement (co-primary endpoint)
BID 1.0%
cream
VEHICLE P value
ITT % %
2-Point Improvement 17.1% 6.7% 0,0321
No Change 35.7% 61.3%
PP % %
2-Point Improvement 21.8% 8.5%
No Change 23.6% 59.3%
Dermatology pipeline – CB-03-01 (Acne)Phase II overview
CB–03–01 Phase II: statistical significance in total lesion count(co-primary endpoint)
70
CB-03-01 1% cream
BID
VEHICLE P-value
ITT
MEAN -35.7% -13.1% 0.0173
Dermatology pipeline – CB-03-01 (Acne)Phase II overview
successful also in secondary endpointshowing reduction in Inflammatory Lesion Counts
71
CB-03-01 1% cream BID VEHICLE P-value*
ITT % %
MEAN -37.2% -27.0% 0.0384
* Kruskal Wallis test
Dermatology pipeline – CB-03-01 (Acne)Phase II overview
72
CB-03-01 1% cream
BID
VEHICLE P-value
ITT
MEAN -32.9% -16.1% 0.0178
successful also in secondary endpointshowing reduction in Non-Inflammatory Lesion Counts
Dermatology pipeline – CB-03-01 (Acne)Phase II overview
73
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 LPO in Q1 17
- 1 extension trial
- data available Q3 17
Dermatology pipeline – CB-03-01 (Acne)
74
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
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)
Rinaldi 2010 - International Hair Research Foundation (IHRF)
80
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
81
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 patientsatisfaction.
• 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
Dermatology Pipeline – CB-03-01 (Alopecia)
82
Dermatology Pipeline – CB-06-02 (HPV)market dynamics & opportunity
>20 m persons are infected with HPV in the US, around 1% ofsexually 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
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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
85
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
Dermatology Pipeline – CB-06-02 (HPV)
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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
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Dermatology Pipeline – CB-06-01 (Acne)
Development timeline
• POC Phase II ongoing with a gel formulation, completion by Q1 2016
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Cosmo Corporate MattersNo 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
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Cosmo Corporate MattersFinancial position
35,7 m cash
74% in EUR; 26% in $
151,5 m investments
64% in EUR36% in $
11 m debt100% in EUR
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Cosmo Corporate MattersCompleted 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
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Cosmo Corporate MattersNext 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
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Cosmo Corporate MattersTransfer 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
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Cosmo Corporate MattersConsequences 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
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• 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
Cosmo Corporate MattersSecond Plant in Ireland
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• 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
Cosmo Corporate MattersSecond Plant in Ireland - Features
100
Cosmo Corporate MattersPotential 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 shareholderspre-emptive rights
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Cosmo Corporate MattersNext Deals Opportunities
EndoscopySIC (w/w rights) MB (w/w)
GIRifamycin (rights in US and selected RoW countries)Monoclonal Antibody MMX (w/w)
DermatologyCB-03-01 for Acne (w/w)CB-03-01 for Alopecia (w/w)CB-06-02 for HPV-Genital Warts (w/w)CB-06-01 for Acne (w/w)
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Cosmo Corporate Matters2015 Projected Clinical News Flow
EndoscopySIC: approvalMB: end of phase III
GIRifamycin: end of phase III
DermatologyCB-03-01 for Acne: start of phase IIICB-03-01 for Alopecia: end of POC – phase II
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EUR/Million E 2014 E 2015 E 2016
Traditional contract manufacturing and other revenue 12 12 12
MMX® products manufacturing 30 34 38
MMX® products royalties 23 (1) 24 (2) 29 (3)
MMX® licence fees, up-front fees and milestones 18 - 1
Revenues from products under development - 80 (4) 163 (4)
Total Revenues 83 150 243
Operating expenses (48) (5) (54) (5) (67) (5)
EBITDA 35 96 176
Depreciation and amortization (9) (9) (3)
Operating result 26 87 173
Sale of "equity for product" stake 65 (6)
Salix termination fee 17 - -
Net financial income 3 3 6
Profit before taxes 111 90 179
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
2014 – 2016 Guidance
104
Cosmo Pharmaceuticals
Information Contacts
• Number of shares: 14,418,983
• Listing: SIX Swiss exchange, Main board
• ISIN: IT0004167463
• Alessandro Della Cha , [email protected]
• Chris Tanner, [email protected]: +39-02-9333’7276
• Giuseppe Cipriano, [email protected]
• Luigi Moro, [email protected]