Transcript Biogen Idec - Moodle Lille 2

Biogen Idec
De Bouvère Fiona
Leduc Elodie
Lenoir Marie sophie
29 février 2008
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SUMMARY
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Presentation of the company
Immunology Strategy
Chronic Diseases & Immune System
Products targeting key immunologic
pathways
R&D - Extend the pipeline
Purchase of Biogen Idec ?
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I. Presentation of
the Company
Merger close Nov 12,2003
Amevive® for psoriasis (US/ROW) 2003
Avonex® Interferon β-1a for MS 1996
Initial public offering 1983
2002 Zevalin® for NHL,Schering in EU
1997 Rituxan® for NHL
1991 Initial public offering
1985 founded in San Francisco
Founded in Geneva 1978
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3 Main products
3 Areas therapeutic
Neurology
Oncology
Immunology
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Present in most major markets
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Direct commercial capabilities in 25 countries
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Large-scale pharmaceutical
manufacturing
2004
90,000-liter
Research Triangle Park, USA
2009 (expected)
90,000-liter
Hillerod, Denmark
Large cell culture facilities
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Financial Performance
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Revenue >$ 3B (2003-2007: revenue ↑ 15%, EPS ↑ 20%)
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Income = 600M$
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Financial capacity: $10 billion
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R&D budget that exceeds $750 million, 26-28% of revenue
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40% investissement in R&D
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II. Immunology
strategy
Biogen Idec’s Strategy
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Immunology strategy
The compagny has chosen to focus
on certain key areas of biology
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III. Chronic Diseases
& Immune System
MS
NHL
SI
RA
CD
Patients with high morbidity or mortality
Poor quality of life
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Non-Hodgkins Lymphoma
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Cancer affecting the lymphatic system => immune system
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B cells prolifération +++
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The most common types of B-cell lymphomas:
 diffuse large B-cell lymphoma (DLBLC)
 follicular lymphoma (FL)
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Incidence → nearly doubled over the past 30 years
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Most often in older people, rare in very young people
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Multiple Sclerosis
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Chronic disease
 Unpredictable tissue
damage in the CNS
Inflammation,
Demyelination, Loss of
nerve cells
An immunological disorder
T cells
2,500,000 people worldwide
suffer from MS
Disease-modifying
treatment delay progression
but there is NO CURE …
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Crohn’s Disease
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Chronic inflammatory
disease of the entire
gastrointestinal tract
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Periods of Remission
interrupted by relapses
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An immunological
disorder T Cells
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Currently there is no
medical or surgical cure
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American College of Gastroenterology
Rheumatoid Arthritis
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Chronic inflammatory disease
 Deformation, Swelling, Dolor
 Progressive joint destruction
 Disability, ↓ Quality and Duration of
life
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An Immunological disorder
B cells : multiple roles in initiation &
development of RA
Prevalence:
 Approximately 1% of the population
 +++ 35 – 55 years old
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+++ Anti TNF or MTX refractory patients
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IV. Products targeting
key immunologic
pathways
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RITUXIMAB for NHL & RA
Anti-CD20 Chimeric Mab => selectively ↓ CD20+ B cells
↓ or eliminate inflammatory rections & interactions with T cells
> 95% of B cells NHLs express CD20 Ag
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Rituximab for NHL
1st monoclonal antibody approved in the treatment of cancer
 Standard of care for NHL
 Extension of the indications
 One of the largest biologic blockbusters
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Rituximab for RA
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The only treatment that can reduce pain & symptoms of RA
through 6 months after 1 course of treatment (2 infusions)
Indicated in combination with MTX in Anti TNF refractory patients
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ACR : American college of Rheumatology
AVONEX®
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a recombinant form of IFN-β 1a
 The amino acid sequence of Avonex is identical to that of
natural human IFN-β
Approved to treat relapsing forms of MS
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Not all DMT are the same
AVONEX is the most prescribed MS therapy
11 years as market leader !
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Natalizumab for CD & MS
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A humanized IgG4 Mab
the first anti-α4 integrin in the new class
of selective adhesion molecule inhibitors
CD
MS
Vascular endothelial cells
of the gastrointestinal tract
Blood brain barrier
MadCAM-1
bloodstream
VCAM-1
47
Natalizumab
LT
41
LT
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Areas of inflammation
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Natalizumab nature 2005
Tysabri for highly active RRMS
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Tysabri for patients who need more efficacy
 Slow disability progression by 42 %
 68% reduction over 2 years as opposed to
 33 % reduction from the ABCR therapies (β-interferon & Copaxone)
Tysabri improved health-related quality of life and reduced vision loss 27
N Engl J Med 2006;354:899-910.
Tysabri for CD : ENACT-2 Trial
Percentage of Patients with
a Response or Remission at Weeks 36 and 60
Among the patients that had previously failed TNF-inhibitors
→ response and remission was also sustained
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NEJM, 2006, Sandborn et al.
Durable maintenance of
remission
Percentage of Patients with
• Immunogenicity and tolerability are comparable to anti-TNFs
• Risk of PML
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Tysabri & PML
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3 cases of Progressive Multifocal Leukoencephalopathy
 2 of 3 died
 1 has survived but with neurological impairment
3 months later tysabri was voluntary pulled from the market
PML, an opportunistic infection
 a rare nervous system disorder caused by JC virus
 normally latent in > 80% of healthy individuals
 incidence is highest in patients with underlying immunodeficiency (HIV)
 immunosuppressant drugs are linked with PML
Risk of PML 1/1000 in the clinical trials population who had taken ~ 18
doses of Tysabri
 unknown with longer treatment
It is currently impossible to identify patients at risk
The discontinuation of natalizumab may not be sufficient to provide a
favorable clinical outcome
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Arch Neurol. 2007;64:169-176
Natalizumab is an important
consideration for patients
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Tysabri® ≠ other MS medicines
 convenient once-monthly dosing
 a favorable tolerability profile without
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the flu-like symptoms of the INF
disfiguration from Copaxone
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Patients go along with the risk of PML
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In response to the safety concerns a risk management plan was
developed
 All prescribers, infusion sites, and patients receiving natalizumab are
required to enroll the TOUCH™ (TYSABRI Outreach: Unified
Commitment to Health) Prescribing Program
 TYGRIS : (TYSABRI Global obseRvation program In Safety)
FDA Advisory Committee
Meeting on Tysabri
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A potential blockbuster
Tysabri® exposure worldwide
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June 2006 Tysabri® was reintroduced in the US and approved in the EU
Tysabri’s global sales have grown rapidly
a "wait and see" approach by the medical community
no new cases of PML, doctors could consider using it in a year
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By 2010: a goal of 100,000 patients and ~ $2.4 billion in total revenue
Biogen Idec’s misfortune …
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Tysabri® pulled off the
market in February 2005
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Biogen and Elan lost $18
billion in market value
For sale?!
Oceanside plant, California
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The state-of-the-art
biologics manufacturing
facility had been marked
to make Tysabri® …
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High cost of operating the
plant - estimated at $80M $100 M/year
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NATURE REVIEWS | DRUG DISCOVERY VOLUME 4 | JULY 2005 |
… has become Genentech’s
gain
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June 2005 : Genentech is buying Biogen Idec’s Oceanside
biologics manufacturing site for US$ 408 million …
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90,000 L of bioreactor capacity + purification train +
extensive laboratory facilities for quality control ~
240 000 m²
Difficult to fit production to the market
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June 2006 : Tysabri® return on the market
2009 : Hillerod, Denmark
One of the first drugs to be produced there will be Tysabri®, for
European distribution
The plant is designed to be flexible and able to incorporate
changes in production strategy very rapidly
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V. R&D
Extend the pipeline
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Expand the Core
Enhance the pipeline
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RITUXAN Expand the Core : MS
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A rational : B-cells involvement in MS
Pathological analysis of tissue from MS patients
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In a subgroup : process associated with Ab & complement
deposits contributes to myelin damage
Early antibody mediated step may occur in the initial stage
of lesion development, before noticeable demyelination
occurs
A reduction in clinical disease activity after administration
of B-cell-depleting therapy could be interpreted as
confirming the role of antibodies in acute disease
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Phase 2 trial
Gadolinum-Enhancing
lesions (GEL) in each
study grp from baseline
to week 48
A shows the mean total
number of GEL by week
B shows the mean number
of new GEL by week
It is now evident that
B cells play key roles
in RRMS !!
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Possible therapeutic targets
involving B-cells in MS
B cells mediating process that may explain the effect of
Rituximab on Disease Activity in MS :
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Antigen presentation
Cytokine production
T-cell regulation
APC : antigen-presenting cell,
BCR : B-cell receptor
MHC : major histocompatibility complex
TCR : T-cell receptor
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BG12 Enhance the pipeline
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Proof of concept efficiency : FUMADERM®
 1st generation Fumaric Acid and Esters (FAE)
 oral systemic therapy for Psoriasis : AUTOIMMUNE DISEASE
 FAE : immunomodulatory + potential neuroprotective effects
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BG 12 = Dimethyl Fumarate - oral 2nd generation FAE
 immunomodulator with novel mechanism of action
 cytoprotective + anti-inflammatory + Antioxidant properties
 Neuroprotective => a candidate for primary progressive MS ?
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EFFECTIVE
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BG 12 Is vying to be the
first oral pill against MS
(ABCR = Avonex, Betaseron, Copaxone, Rebif)
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VI. Purchase of
Biogen Idec ?
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Biogen Idec goes on the
auction block
Speculations on buyers candidates
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Biogen Idec should be sold or remain as a stand-alone company ?
Pharma buyers
Logical candidates
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How valuable BIID would be to a pharma buyer ?
 to replenish the pipeline → emerge as a worldwide leader in MS
 to boost their ability to produce biologic drugs
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Pfizer : buyer candidate most often mentioned
 big wave of patent expirations → pressure from generics
 After the acquisition of Warner Lambert and Pharmacia in the 1990s :
Pfizer is just too big and has spent the last 5 years trying to figure out 45
how to reorganize its pipeline and what to do with all of the employees
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Roche Holding AG:
 Only 3 new chemical entity
 Collaboration with Biogen on cancer drug Rituximab
 Acquisition estimated to 29.2 B$
 has already Genentech
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Sanofi-Aventis was looking for acquisitions in biotechnology
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J&J may be looking to expand into the neuroscience realm
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Novartis AG a possible buyer
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GSK focuses on other priorities
 has no real expertise in neuroscience
 has similar products
Officials at all the firms declined to comment…
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Skepticism about the firm’s
acquisition chances …
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A bidding war will inevitably result in an overpriced Biogen
 A shorter-than-expected list of bidders
 Tysabri® has done much better than anybody anticipated this year but
does not justifies $23 billion…
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Tysabri® wild card
 Neurological drug to watch
 PML in 1/1 000 patients → could climb as high as 5/1 000
 It took at least 28 months for PML to be diagnosed → Nov. 2008
 Questions about appropriate usage, monitoring and tight prescribing
restrictions → limit the drug’s market
 BIID is not alone in its MS efforts :
At least 27 new therapies are being developed by 20 companies
 FDA approval for CD
 Market already sealed up by Remicade®, Humira®
 EMeA : CHMP → adopted a negative opinion → EC Q1 2008 47
Buying two partial products
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Tysabri® : Elan has financial problems
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Genentech has the resources to gain full control over Rituxan®
→ the loss of rights would diminish Biogen's value to a potential
acquirer
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Genentech / Biogen → 2nd & 3rd generation versions of Rituxan®
 Biogen would receive lower royalty payments on the newer drugs
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Roche’s obligation to pay royalties ends
 in 2009 for sales in most European countries
 everywhere by 2012
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Disappointing sales of its
mature products…
BIID revenues
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Avonex® the most valuable asset ? Buying a sinking product !
 Threats : 2010–2011 competitors coming
Risk of biogeneric competition
 Avonex® coming off patent in 2013
 Patents for Rituxan® ( RA and NHL) expiring between 2013
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and 2018
Potential buyout
BIID abandoned its search
for a buyer
BIID loses $6 billion in value
Safety data for
Tysabri
US approval
Tysabri® for CD
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Merci de votre attention
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