Transcript moodle.univ

23th February 2012
Justine Degeuser
Morgane Dufour
Pauline Dulouard
Olivier Héloir
Summary
From Merck to
Merck Serono
Merck Serono
nowadays
Merck Serono’s
future
2
Merck’s history
1953
1914
1668
3
Merck’s history
Merck is the world’s oldest pharmaceutical and chemical company
1668
• Friedrich Jacob Merck:
Engel-Apotheke (“Angel Pharmacy”) in
Darmstadt
1827
• Plant extracts and other chemicals by
Heinrich E. Merck
• Alkaloïdes:
morphine
codéine
Merck’s history
1887
1900
1914
1925
1933
A subsidiary in New York was created
(Georg Merck, a grandson of Heinrich
Emanuel Merck)
Merck was represented on all
continents
Confiscation : World War I, Merck &
Co. became an independent American
company
George Merck is giving direction to
his son that turns the company of
fine chemicals in pharmaceutical
company
The Merck Institute of Therapeutic
Research is based
Merck’s history
1953
1953
After the Second World War merged
with Sharp & Dohme = MSD
Establishment of Merck KGaA
For USA: Merck = EMD
From Merck to Merck Serono
Chemistry + Primary Care
7
Business sector in 2005
Chemicals
Pharmaceuticals
66%
34%
8
Sales in 2005
Sales in 2005 - EUR Million
Others
34%
Concor®
21%
Glucophage®
17%
Duoneb®
15%
Erbitux®
13%
Products
EUR million
Concor®
348.4
Glucophage®
297.2
Duoneb®
251.5
Erbitux®
218.2
others
573
9
Small molecules + Erbitux®
Development of biological molecules
Erbitux® – a first-in-class IgG1 monoclonal antibody targeting the
EGFR. Treatment of metastatic colorectal cancer and squamous cell
carcinoma of the head and neck.
1998 – Eli Lilly
Merck licensed the right to market Erbitux® outside the US and
Canada
10
Looking for a biotech company
Focus on specialist and innovative drugs
Erbitux® is a recent success of Merck Group
Development of not only new chemical but especially biological
molecules
Strategy to grow from a local, mid-sized pharmaceuticals and
chemicals company into a leading global biopharmaceuticals player
11
Serono for sale
4 therapeutic areas:
Fertility treatments : world leader (60%market share) Gonal-f®
Growth and metabolic disorders
Psoriasis
Multiple sclerosis : blockbuster Rebif® is the globalmarket leader
4th largest companies specializing in biotech
Led since 1996 by billionaire Ernesto Bertarelli
http://www.annualreports.de/documents/Merck-ar2006en.pdf
Advantages of Serono
High-quality manufacturing
Innovative
and successful products
A well-stocked
and promising development pipeline
Access to the important U.S. market
Decision to acquire the pioneering
biopharmaceutical company Serono
13
Acquisition of Serono – 2007
16,6 milliards CHF= 10,6 milliards d‘ €
On February 5th, 2007, Merck held 97% of Serono’s capital and
98% of the voting rights.
14
Serono’s pipeline
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Serono’s drugs
Serono : BIOTECH
Serono’s drugs
Neurology
Reproductive
Health
Growth &
Metabolism
Dermatology
Merck’s drugs
Merck : CHEMISTRY
Merck’s drugs
Oncology
Hypertension
DANCOR®
Growth and
metabolism
Diabetes
Merck Serono’s drugs
Merck Serono : BIOTECH
Merck Serono’s
drugs
Neurology
Reproductive
Health
Growth &
Metabolism
Dermatology
Hypertension
Oncology
Diabetes
Dancor®
18
Merck Serono
Merck had integrated the name Serono and became Merck Serono
+
Merck Serono
Merck Serono Vs EMD Serono
Divisions for innovative prescription drugs of Merck
In North America (U.S. and Canada), the activities of Merck Serono
are conducted under the name EMD Serono.
EMD: Emanuel Merck, Darmstadt
In medical biotechnology, Merck Serono is a leader in Europe.
Merck relocated on the premises of Serono
Headquarters in Geneva (Switzerland)
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Merck Serono becomes Serono
Develop and scale biologics
Strategy focused on delivering innovations to patients
Therapeutic areas: neurodegenerative diseases
oncology
fertility
endocrinology
rheumatology
Bring cardiometabolic care products in emerging markets
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Merck generics for sale
13/05/07 4.9 billion €
Mylan acquired Merck's generics
The divested Generics business represents EUR 1,802 million of
sales in 2006 and sells products in more than 90 countries
http://news.merck.de/N/0/7BDAC02AD85D7D39C125730500286E43/$File/Generics_e.pdf
Theramex for sale
10/28/2010 265 million€
Merck KGaA's European Based Women's Health Business
revenues = 100 million € in 2009
Teva Pharmaceutical has acquired Merck's Theramex
Teva Pharma take over the distribution rights of Theramex's products
sold in several countries.
http://www.worldpharmanews.com/merckkgaa/1451-merck-kgaa-sells-theramex-to-teva-for-eur-265-million
http://www.merckgroup.com/en/media/extNewsDetail.html?newsId=A52969A174686390C12577CA003EB758&newsType=1
Merck Serono nowadays
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What’s Merck group and Merck Serono now?
Sales of Merck KGaA - 2011
Pharmaceuticals : 63%
Merck Serono
92%
Consumer Health
Care
8%
27
Merck Serono
Regular increase of the activity
Increase of sales
Sales
6000
5000
Gross margin
5000
4500
4000
3500
3000
2500
2000
1500
1000
500
0
+29%
4000
3000
2000
1000
0
2007
2008
2009
2010
+27%
2007
2008
2009
201028
Merck Serono – R&D expenses
R&D
1200
1000
800
600
400
200
0
2007
2008
2009
2010
2010 : 1167 millions €
2007-2010 : increase of 32%
29
Patent cliff
Revenues lost due to patent expiries - a % of 2010 revenue
Key products protected for next three years -patent expiries:
Rebif ® : EU 2015, US 2022
Erbitux ® : EU 2014, Japan 2016
Gonal-f ® : EU 2009, USA 2015
http://www.merckgroup.com/company.merck.de/en/images/IR_2012_01_09_JPM_EN_tcm1612_85236.pdf?Version=
http://www.ema.europa.eu/docs/fr_FR/document_library/EPAR_-_Summary_for_the_public/human/000071/WC500023742.pdf
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Pipeline & Products
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Strategy of Merck Serono
Strategic focus
Enhance the productivity of our drug discovery activities with
innovative and emerging technologies
Expand upon our Multiple Sclerosis franchise to enter other
neurodegenerative disease areas
Expand our pipeline in Rheumatology with complementary product
opportunities offering a broad indication potential
35
Strategy merck serono
Assessment of Therapeutique Areas
36
Sales - 2010
Products
31%
36%
Neurodegenerative Rebif®
diseases
31%
1 668
Oncology
Erbitux®
15%
820
Fertility
Gonal-f®
9%
504
Endocrinology
Concor®
franchise
7%
373
Glucophage®
franchise
6%
316
15%
6%
12%
Biologics
% Sales
Eur
Million
Cardiometabolic
Care / Others
Other
products
32%
1 727
Small molecules
~60% of portfolio based on biologically manufactured products
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Phase I
Phase II
ARX 424
Long-acting interferon
Multiple sclerosis
ONO - 4641
Oral S1P receptor modulator
Multiple sclerosis
ATX-MS-1467
Immune tolerizing agent
Multiple sclerosis
Cilengitide
Integrin inhibitor
SCCHN
Extended-release formulation of
interferon beta-1a
Multiple sclerosis
PI –2301
Second-generation peptide copolymer
Multiple sclerosis
MEK inhibitor
(AS703026/MSC1936369B)
Solid tumors and hematological
malignancies
Novel combinations of MEK inhibitor
(AS703026/MSC1936369B) with one of
two sanofi-aventis PI3K inhibitors**
Solid tumor
MEK inhibitor
(AS703988/MSC2015103B)
Solid tumors
c-Met kinase inhibitor
(EMD 1214063)
Solid tumors
NHS-IL12***
Cancer immunotherapy
Solid tumors
Fibroblast Growth Factor 18
Osteoarthritis
Atacicept
anti-Blys/anti-APRIL fusion protein
Lupus nephritis
Cilengitide
Integrin inhibitor
NSCLC
Anti-integrin mAb (DI17E6)
Metastatic colorectal cancer
Anti-integrin mAb (DI17E6)
Metastatic prostate cancer (mCRPC),
setting prior to chemotherapy
Hypoxia-targeted drug (TH-302)
Pancreatic cancer
Fibroblast Growth Factor 18
Cartilage injury repair
Phase III
Erbitux® (cetuximab)
Anti-EGFR mAb (PETACC-8*)
Adj colon cancer
Erbitux® (cetuximab)
Anti-EGFR mAb (EXPAND)
Gastric cancer
Cilengitide
Integrin inhibitor (CENTRIC)
Glioblastoma
In Registration
Rebif® HSA-free formulation
(interferon beta-1a) for patients
with early signs of MS (REFLEX)
EMA: Approved
Erbitux® (cetuximab)
Anti-EGFR mAb
NSCLC (1st line therapy)
EMA: Application submitte
Stimuvax®
Cancer immunotherapy
(START, INSPIRE)
NSCLC
Hypoxia-targeted drug (TH-302)
Soft tissue sarcoma
Kuvan
Sapropterin dihydrochloride
(SPARK****)
PKU in pediatric patients < 4year
Atacicept
anti-Blys/anti-APRIL fusion protein
Systemic lupus erythematosus
Oncology
Neurodegenerative Diseases
Rheumatology
Endocrinology
38
Therapeutic areas
CardioMetabolic
care and others
Oncology
Neuro
Endocrinology
degenerative
Diseases
Fertility
39
Oncology
Colorectal cancer CRC
The third most deadly cancer among women and the fourth in men.
Worldwide, it is responsible for around 529,000 deaths per year.
Metastatic bowel or mCRC : start in colon or rectum but has spread to
another part of the body - metastasizes. About a quarter of people
diagnosed with CRC already have metastatic CRC.
Head and Neck cancer
Flat "squamous" cells that line the surfaces in the head and neck area, such
as the mouth, nose and throat, and are thus termed "squamous cell
carcinomas of the head and neck" (SCCHN).
Significant increase in the worldwide incidence of SCCHN over the past
decade, particularly among women.
Globally, there are almost 650,000 new cases of head and neck cancer each
year, and over 350,000 deaths.
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Oncology
Erbitux® Cetuximab
IgG1 monoclonal antibody targeting EGFR.
Approved in many countries all over the world for KRAS wild-type
mCRC with chemotherapy
Approved in squamous cell carcinoma cancer of the head and neck –
SCCHN in combination with radiation therapy or chemotherapy.
Erbitux® - Product of Eli Lilly, rights to commercialize Erbitux
outside US and Canada
In 2010, sales of Erbitux® rose by 18% to 820 million €.
Strenghts :
Strong position in niche markets in Europe
High market share in metastatic colorectal cancer
Standard of care in head & neck cancer
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Oncology
Erbitux competitors - CRC
Avastin® – Bevacizumab Roche / Genentech, USA + EU
Approved for mCRC, Advanced nonsquamous NSCLC,
Metastatic kidney cancer when used with interferon alfa,
Glioblastoma.
Vectibix® – Panitumumab Amgen, USA + UE
Approved for mCRC with disease progression on or
following fluoropyrimidine-, oxaliplatin-, and irinotecancontaining chemotherapy regimens
Xeloda® – Capecitabine Roche / Genentech, USA + UE
Approved for mCRC, cancer of colon after surgery ,
breast cancer
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Oncology
Erbitux ® - in registration
Application submitted to EMA
First line therapy in NSCLC in combination with chemotherapy
NSCLC accounts for 80%–85% of all lung cancer cases.
Erbitux ® - Phase III
Gastric cancer in combinaition with chemotherapy – EXPAND
Erbitux + FUFOX : high response rate in metastatic gastric
cancer.
Adjuvant treatment in stage III colon cancer - PETACC-8
The final report with the official results of this trial is Dec.2014
Strong product in an expanding market
http://www.medscape.com/viewarticle/725271_5
http://www.ncbi.nlm.nih.gov/pubmed/20068568
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Oncology
Cilengitide
Cilengitide : the integrin inhibitors
Control tumor growth. Action : attacking the tumor cells directly in
a targeted manner and stopping angiogenesis that feed the tumor.
Phase III : Cilengitide in glioblastoma CENTRIC
Estimated Primary Completion Date : Sept.2012
Phase II : SCCHN & NSCLC
Stimuvax ®
Cancer immunotherapy that is designed to stimulate the body’s
immune system to identify and target cells expressing MUC1.
Phase III : unresectable stage III NSCLC - START & INSPIRE
Estimated Primary Completion Date : Sept. 2015
44
http://www.oncothyreon.com/pipeline/vaccines/stimuvax/collaboration.html
Oncology
Phase I
In 2010, Merck KGaA signed a worldwide research and development
agreement with Sanofi-Aventis U.S. Inc.
Two novel experimental combinations of the MEK inhibitor
AS703026/MSC1936369B with one of two compounds of sanofi-aventis.
PI3K/mTOR inhibitor SAR245409 (also known as XL765), is under the
responsibility of Merck Serono
Class I PI3K inhibitor SAR245408 (also known as XL147), is under the
responsibility of Sanofi-Aventis.
45
Therapeutic areas
CardioMetabolic
care and others
Oncology
Neuro
Endocrinology
degenerative
Diseases
Fertility
46
Neuro degenerative Diseases
Multiple sclerosis
MS is a complex, multifaceted disease of the central nervous system
(CNS) with multiple pathways. Approximately 400,000 people in the
U.S. have MS. (2.5 million worldwide)
MS interferes with the brain’s ability to control such functions as
seeing, walking & talking. It is unpredictable and every person with MS
will have his or her unique set of symptoms.
47
Neuro degenerative Diseases
Rebif ® Interferon beta-1a
Rebif is indicated for the treatment of patients with relapsing forms of multiple
sclerosis.
Rebif is a purified glycoprotein, which is produced by recombinant DNA
technology using genetically engineered Chinese Hamster Ovary cells into which
the human interferon beta-1a gene has been introduced.
Rebif decreases the frequency of clinical exacerbations and delays the
accumulation of physical disability.
Rebif was approved by the U.S. FDA on March 7, 2002 is available in over 80
countries worldwide. Blockbuster with €1.7bn sales in 2010
48
Neuro degenerative Diseases
Rebif ® Perfect Life Cycle Management Strategy
Life cycle management improves patient convenience and protects key franchises
49
Neuro degenerative Diseases
Rebif ® Ready-to-use syringes
50
Neuro degenerative Diseases
Rebiject II ® auto-injector
51
Neuro degenerative Diseases
RebiSmart® New Formulation
52
Neuro degenerative Diseases
Rebif ® Major Competitors
Avonex (interferon beta-1a) is approved by the FDA to treat
relapsing forms of MS. (Biogen Idec) It is the leading MS therapy
in the US, with around 40% of the overall market, and in Europe,
with around 30% of the overall market.
Betaferon/Betaseron is approved as monotherapy treatment
for relapsing-forms of multiple sclerosis. (Bayer)
Tysabri is approved as monotherapy treatment for relapsing forms
of multiple sclerosis. Administered by infusion (intravenous)
(Biogen Idec and Elan )
Copaxone (glatiramer acetate injection) is indicated for the
reduction of the frequency of relapses in relapsing-remitting
multiple sclerosis. (Teva Pharmaceuticals)
53
Therapeutic areas
CardioMetabolic
care and others
Oncology
Neuro
Endocrinology
degenerative
Diseases
Fertility
54
Fertility
Market position/ Strengths
Pioneer and market leader
Comprehensive portfolio of complementary products
Gonal-F® Follitropin alpha for Injection
The Gonal-f® RFF Pen is a gonadotropin hormone produced by recombinant DNA
technology (rDNA).
It is used in ovulation induction (OI) and in vitro fertilization (IVF)
55
Fertility
Luveris® lutropin alfa for injection
The first and only recombinant human luteinizing
hormone (r-hLH) approved in the world
Cetrotide® cetrorelix acetate
Gonadotropin releasing hormone antagonist
Crinone® progesterone gel
Indicated for progesterone supplementation as part
of an Assisted Reproductive Technology (ART)
Ovidrel® hCG
The first and only recombinant human chorionic
gonadotropin (r-hCG)
56
Therapeutic areas
CardioMetabolic
care and others
Oncology
Neuro
Endocrinology
degenerative
Diseases
Fertility
57
Endocrinology
Market position/ Strengths
Among Top 5 in growth hormones
“only in class”products for selected niche indications
Saizen® somatropin for injection
Recombinant human growth hormone made by DNA technology.
Endocrinology
Serostim® somatropin for injection
Indicated for the treatment of HIV wasting in patients
receiving antiretroviral therapy
Egrifta® tesamorelin for injection
First treatment indicated to reduce excess abdominal
fast in HIV-infected patients with lipodystrophy
Kuvan® sapropterin dihydrochloride
First treatment indicated in Europe for the treatment
of hyperphenylalaninemia
59
Therapeutic areas
CardioMetabolic
care and others
Oncology
Neuro
Endocrinology
degenerative
Diseases
Fertility
60
CardioMetabolic care and others
CardioMetabolic Care
Market position/
DiabetesStrengths
246 million
people
with type
diabetes
around
the world
Leading
market
positions
with2 gold
standard
products
that have high
Glucophage
brand
equity : 1st first-line treatment for type 2 diabetes
Glucovance
Excellent track record in life cycle management (i. e. formulations)
Metformine : was the Molecule of Merck
Strong position in Emerging Markets
Cardiovascular diseases
CV diseases are responsible for one in every three deaths which
translates into 17 million people worldwide each year
Bisoprolol : 1st-line treatment of hypertension
Thyroid disease
200 million people worldwide suffer from hypothyroidism
20% of this population is currently receiving treatment
Levothyroxine sodium
61
CardioMetabolic care and others
Rheumatology
Atacicept - anti-BLyS/anti-APRIL fusion protein
Phase II : Systemic lupus erythematosus (SLE)
Phase I : Lupus nephritis
Fibroblast growth factor 18
Phase II : Cartilage injury
Phase I : Osteoarthritis
Partnership with BMS
Exclusive worldwide license to Merck Serono to develop and commercialize
Fibroblast Growth Factor 18, and the genetic fusion molecule Atacicept.
62
Merck Serono’s future
63
Merck Serono’s future
Strategy focus
Expand their fast growing presence in China and other Emerging
Markets
Grow their U.S. business with specialist-focused therapies
Expand their ongoing presence in the Japanese market
64
Development programs discontinued
Neuro- degenerative Diseases
Cladribine tablets for use in Multiple Sclerosis (Phase III)
Safinamide for treatment of Parkinson indications (Phase III)
New Formulation of Rebif in the U.S.
Oncology
Erbitux for use in metastatic triple-negative breast cancer (Phase II)
Clinical development for IMO-2055, currently in development for
squamous cell carcinoma of the head and neck (Phase II)
Endocrinology
ARX-201 for use in growth hormone deficiencies (Phase II)
65
Redefining the R&D organization
New R&D Organization
One executive for separated R and D functions
Leaner organization with clear responsibilities on individuals rather than on
committees.
66
Merck Serono’s future
February 2012
Mendor signed a distribution agreement with Merck Serono for the meter
Mendor Discreet ™
Merck Serono + Threshold = global agreement to co-develop and
commercialize phase III Hypoxia-Targeted Drug TH-302
67
Merck Serono’s future
April 2012
To return all rights to Safinamide at Newron Pharmaceuticals SpA
But continue co develepment for Pruvanserine & Sarizotan
2012
Merck Serono will increase tenfold its annual donation of praziquantel
tablets which will increase from 25 to 250 million units - schistosomia
68
Strategy for the future
Future growth trends
2006-2011
Neurodegenerative Disease
7.9%
Oncology
24.2%
Fertility
5.9%
Endocrinology
8.9%
Cardiometabolic
Care/Others
5.5%
Future growth trend
They want to become the leader in oncology by 2015
69
Merck Serono’s SWOT
STRENGTHS
WEAKNESSES
Erbitux ® standard of care
Rebif® performance benefiting from
volume growth and price/Life cycle
management
New R&D hub in Beijing
Efficient patent cliff
Leader in fertility
Great reputation
50% of sales held by Rebif® et Erbitux®
Failure in gaining regulatory approvals for
cladribine tablets
Lack of new products in the portfolio
Licence for Erbitux®
OPPORTUNITIES
THREATS
Expand Merck Serono’s oncology pipeline
and product portfolio
Increasing competition from biosimilar
Several patenerships (BMS-Sanofi)
Possible expansion in Asia
Increasing competition in multiple sclerosisoncology market
Competitors=Avastin® for Erbitux® and
Avonex®-Tysabri® for Rebif®
Generics²
Thank you for your attention
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