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Biogen Idec De Bouvère Fiona Leduc Elodie Lenoir Marie sophie 29 février 2008 1 SUMMARY Presentation of the company Immunology Strategy Chronic Diseases & Immune System Products targeting key immunologic pathways R&D - Extend the pipeline Purchase of Biogen Idec ? 3 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 5 3 Main products 3 Areas therapeutic Neurology Oncology Immunology 6 Present in most major markets Direct commercial capabilities in 25 countries 7 Large-scale pharmaceutical manufacturing 2004 90,000-liter Research Triangle Park, USA 2009 (expected) 90,000-liter Hillerod, Denmark Large cell culture facilities 8 Financial Performance Revenue >$ 3B (2003-2007: revenue ↑ 15%, EPS ↑ 20%) Income = 600M$ Financial capacity: $10 billion R&D budget that exceeds $750 million, 26-28% of revenue 40% investissement in R&D 9 II. Immunology strategy Biogen Idec’s Strategy 11 Immunology strategy The compagny has chosen to focus on certain key areas of biology 12 III. Chronic Diseases & Immune System MS NHL SI RA CD Patients with high morbidity or mortality Poor quality of life 14 Non-Hodgkins Lymphoma Cancer affecting the lymphatic system => immune system B cells prolifération +++ The most common types of B-cell lymphomas: diffuse large B-cell lymphoma (DLBLC) follicular lymphoma (FL) Incidence → nearly doubled over the past 30 years Most often in older people, rare in very young people 15 Multiple Sclerosis 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 … 16 Crohn’s Disease Chronic inflammatory disease of the entire gastrointestinal tract Periods of Remission interrupted by relapses An immunological disorder T Cells Currently there is no medical or surgical cure 17 American College of Gastroenterology Rheumatoid Arthritis Chronic inflammatory disease Deformation, Swelling, Dolor Progressive joint destruction Disability, ↓ Quality and Duration of life An Immunological disorder B cells : multiple roles in initiation & development of RA Prevalence: Approximately 1% of the population +++ 35 – 55 years old +++ Anti TNF or MTX refractory patients 18 IV. Products targeting key immunologic pathways 19 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 20 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 21 Rituximab for RA 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 22 ACR : American college of Rheumatology AVONEX® 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 23 Not all DMT are the same AVONEX is the most prescribed MS therapy 11 years as market leader ! 24 Natalizumab for CD & MS 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 47 Natalizumab LT 41 LT 25 Areas of inflammation 26 Natalizumab nature 2005 Tysabri for highly active RRMS 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 28 NEJM, 2006, Sandborn et al. Durable maintenance of remission Percentage of Patients with • Immunogenicity and tolerability are comparable to anti-TNFs • Risk of PML 29 Tysabri & PML 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 30 Arch Neurol. 2007;64:169-176 Natalizumab is an important consideration for patients Tysabri® ≠ other MS medicines convenient once-monthly dosing a favorable tolerability profile without the flu-like symptoms of the INF disfiguration from Copaxone Patients go along with the risk of PML 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 31 A potential blockbuster Tysabri® exposure worldwide 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 32 By 2010: a goal of 100,000 patients and ~ $2.4 billion in total revenue Biogen Idec’s misfortune … Tysabri® pulled off the market in February 2005 Biogen and Elan lost $18 billion in market value For sale?! Oceanside plant, California The state-of-the-art biologics manufacturing facility had been marked to make Tysabri® … High cost of operating the plant - estimated at $80M $100 M/year 33 NATURE REVIEWS | DRUG DISCOVERY VOLUME 4 | JULY 2005 | … has become Genentech’s gain June 2005 : Genentech is buying Biogen Idec’s Oceanside biologics manufacturing site for US$ 408 million … 90,000 L of bioreactor capacity + purification train + extensive laboratory facilities for quality control ~ 240 000 m² Difficult to fit production to the market 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 34 V. R&D Extend the pipeline 35 Expand the Core Enhance the pipeline 36 RITUXAN Expand the Core : MS A rational : B-cells involvement in MS Pathological analysis of tissue from MS patients 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 37 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 !! 38 Possible therapeutic targets involving B-cells in MS B cells mediating process that may explain the effect of Rituximab on Disease Activity in MS : Antigen presentation Cytokine production T-cell regulation APC : antigen-presenting cell, BCR : B-cell receptor MHC : major histocompatibility complex TCR : T-cell receptor 39 BG12 Enhance the pipeline Proof of concept efficiency : FUMADERM® 1st generation Fumaric Acid and Esters (FAE) oral systemic therapy for Psoriasis : AUTOIMMUNE DISEASE FAE : immunomodulatory + potential neuroprotective effects 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 ? 40 EFFECTIVE 41 BG 12 Is vying to be the first oral pill against MS (ABCR = Avonex, Betaseron, Copaxone, Rebif) 42 VI. Purchase of Biogen Idec ? 43 Biogen Idec goes on the auction block Speculations on buyers candidates 44 Biogen Idec should be sold or remain as a stand-alone company ? Pharma buyers Logical candidates 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 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 Roche Holding AG: Only 3 new chemical entity Collaboration with Biogen on cancer drug Rituximab Acquisition estimated to 29.2 B$ has already Genentech Sanofi-Aventis was looking for acquisitions in biotechnology J&J may be looking to expand into the neuroscience realm Novartis AG a possible buyer GSK focuses on other priorities has no real expertise in neuroscience has similar products Officials at all the firms declined to comment… 46 Skepticism about the firm’s acquisition chances … 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… 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 Tysabri® : Elan has financial problems Genentech has the resources to gain full control over Rituxan® → the loss of rights would diminish Biogen's value to a potential acquirer Genentech / Biogen → 2nd & 3rd generation versions of Rituxan® Biogen would receive lower royalty payments on the newer drugs Roche’s obligation to pay royalties ends in 2009 for sales in most European countries everywhere by 2012 48 Disappointing sales of its mature products… BIID revenues 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 49 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 50 Merci de votre attention 51