Biogen Idec Neurology Pipeline. Alfred Sandrock, MD, PhD SVP, Neurology Research & Development

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1 Biogen Idec Neurology Pipeline Alfred Sandrock, MD, PhD SVP, Neurology Research & Development March 25, 2009

2 Robust Neurology Pipeline Neurology Multiple Sclerosis Discovery Pre-Clinical Phase 1 Phase 2 Phase 3 Market AVONEX TYSABRI BG12 Anti-CD20 Daclizumab CDP323 PEG-IFN β-1a Anti-LINGO-1 Selective S1P agonist Current Pipeline Progress Goals Neurology Other Discovery Pre-Clinical Phase 1 Phase 2 Phase 3 Market A2a antagonist (BIIB014) Neublastin Parkinson s Neuropathic Pain 2

3 R&D Leadership in MS Working to fulfill unmet needs More convenient therapies: BG12 More effective therapies: anti-cd20 CDP323 CDP323 PEG-IFNβ Daclizumab S1P1 agonist S1P1 agonist Inhibit neurodegeneration/enhance repair: BG12 anti-lingo Silence Inflammation Protect nerve cells Repair the damage 3

4 The Two Sides of MS Pathophysiology Time since disease onset Inflammation (interferon-sensitive) conduction block, demyelination, bystander axonal injury Relapsing- Remitting Degeneration (interferon-resistant) loss of neurons/axons Secondary Progressive 4

5 BG12 Molecule Formulation Second generation fumaric acid (Dimethyl fumarate) Enteric-coated microtablet Molecular Hypothesis Anti-inflammatory effects Cytoprotective effects Note: BIIB acquired Fumapharm AG 5

6 The Nrf2 Pathway The Key to Neuroprotection in MS? Keap1 Nrf2 X Nrf2 Nrf2 Maf Jun ATF4 - Detox Enzymes - Antioxidant Enzymes - NADPH Generating Enzymes - GSH Biosynthesis Enzymes - Chaperones - Ubiquitination/Proteasome ARE Nucleus - Detoxification - Normalization of energy metabolism - Repair/degradation of damaged proteins 6

7 BG12 Activates the Nrf2 Pathway O O O O BG-12 Keap1 Nrf2 Nrf2 Maf Jun ATF4 - Detox Enzymes - Antioxidant Enzymes - NADPH Generating Enzymes - GSH Biosynthesis Enzymes - Chaperones - Ubiquitination/Proteasome Keap1 ARE Nucleus - Detoxification - Normalization of energy metabolism - Repair/degradation of damaged proteins 7

8 The Nrf2 Pathway Appears to be Important in Maintaining CNS Myelin 8

9 Nrf2 Induces a Cytoprotective Response and Inhibits Inflammatory Events Nrf2 Detoxification enzymes Antioxidant enzymes NADPH-generating enzymes GSH biosynthesis enzymes Chaperones Ubiquitination / proteasome Decreases Proinflammatory cytokines Leukocyte adhesion molecules Lymphocyte activation CYTOPROTECTION INFLAMMATION AND TISSUE DAMAGE 9

10 BG12 Phase 2b Study in RRMS 10

11 BG12 Phase 2b Study Results - Primary Endpoint 11

12 Evidence of Neuroprotection in MS? BG12 Reduced Conversion of New Gd+ Lesions to T1 Hypointense Lesions (100%) 200 OR for conversion = 0.51 (95% CI = 0.43, 0.61) P Total No. of Lesions (44%) 147 (100%) (29%) 0 Gd+ lesions (Week 4-12) T1 lesions (Week 24) Gd+ lesions (Week 4-12) T1 lesions (Week 24) Placebo 12 BG mg tid

13 BG12 Phase 2b Study Results - Safety 13

14 Excerpt from Accompanying Editorial in The Lancet The balance between efficacy, safety, and convenience will be decisive for the choice of drug. Oral formulations have advantages in convenience and will be preferred by most patients, as long as efficacy and safety are similar to that of injectable alternatives. Although comparison of drugs tested in different placebo-controlled trials is difficult and should be done cautiously, BG00012 might have a favourable benefit-to-risk profile compared with its oral competitors and the currently available first-line injectable drugs. However, we will have to await the results from the ongoing large phase III trials to establish the place of BG00012 and other oral drugs in the treatment of relapsing-remitting multiple sclerosis. Copenhagen, Denmark --- Per Soelberg Sorensen and Finn Sellebjerg, Danish Multiple Sclerosis Research Center, 14

15 BG12 Summary IFN-like efficacy on new inflammatory lesions in RRMS Mechanism of action suggests potential for additional neuroprotective effects FUMADERM : 15-year track record of long-term safety of dimethyl fumarate Two multicenter, parallel-group, randomized, placebo-controlled, dose-comparison, phase 3 clinical studies being conducted 2 doses of BG-12 (240mg bid and 240mg tid) and placebo; 1011 pts Primary endpoint: Proportion of patients relapsing over two years Fully enrolled in Q doses of BG-12, glatiramer acetate and placebo; 1232 pts Primary endpoint: Annualized relapse rate at two years Completion of enrollment expected in mid

16 PEGylated Interferon β-1a (PEG IFN) Molecule PEGylated Interferon Beta-1a Mode of Administration Subcutaneous q2 or q4 weeks Molecular Hypothesis Similar efficacy and tolerability to interferon β Reduce the frequency of administration so as to improve convenience and compliance 16

17 PEG IFN Structure PEGylated version of Inteferon β-1a delivered via liquid prefilled syringe Modified at the N-terminal α-amino group Increased half-life and systemic exposure of the protein May improve convenience and compliance for patients with MS who use Interferons PEGylated Interferon Beta-1a molecule, structural representation 17

18 PK/PD Characteristics of PEG IFN Antiviral Activity (U/mL) Median Antiviral Activity by Treatment Groups Time (h) Avonex, IM, 30 mcg BIIB017, SC, 63 mcg BIIB017, SC, 125 mcg BIIB017, SC, 188 mcg Neopterin Concentration (ng/ml) Median Neopterin Concentration by Treatment Groups Avonex, IM, 30 mcg BIIB017, SC, 63 mcg BIIB017, SC, 125 mcg BIIB017, SC, 188 mcg Time (h) Higher exposures and longer half-life than Avonex Higher and more sustained elevations in neopterin than Avonex However, flu-like symptoms and other side effects were comparable to Avonex at doses up to 125 mcg SC 18

19 PEG IFN Phase 3 Study Design Screening Year 1 Year 2 Follow-up Randomization PLACEBO BIIB mcg SC, Q2W BIIB mcg SC, Q4W N = 420 ~1260 patients (naïve to IFN) BIIB mcg SC, Q2W BIIB mcg SC, Q4W N = 420 N = 420 Titration 1 yr Superiority 2 yr Safety/ Immuno 19

20 PEG IFN Conclusions Encouraging results from Phase 1 studies Milestones to date on or ahead of schedule Positive Agency feedback on the Phase 3 plans Realistic but aggressive plan going forward to approval 20

21 Multiple Approaches to MS Therapeutics Anti-CD20 Selective S1P1 agonist BG00012 Natalizumab/ CDP 323 Daclizumab IFNβ-1a, PEG-IFN β-1a IFNβ-1a, PEG-IFN β-1a Anti-LINGO-1 21

22 Neurology Pipeline Conclusions Robust neurology pipeline Leadership in MS Targeted expansion into non-ms diseases 22

23 Biogen Idec Research & Development Day March 25, 2009