Slide 1: Reaccelerating TYSABRI
Reaccelerating TYSABRI • William Sibold, SVP US Commercial • Dr. Alfred Sandrock, SVP Neurology 18 March 2009
Slide 2: Forward Looking Statements and Important Information
Forward Looking Statements and Important Information This presentation includes forward-looking statements about regulatory actions and the sales potential and the benefit-risk profile of TYSABRI(r) Each forward-looking statement is subject to risks and uncertainties that could cause actual results
Slide 3: Agenda
Agenda TYSABRI Commercial Plan & Execution TYSABRI R&D Initiatives
Slide 4: MS drug monthly patient uptake: ENBREL, REMICADE, HUMIRA, TYSABRI
Month ENBREL REMICADE HUMIRA TYSABRI US Intl 1 2343 656 5 1350 802 548 2 10261 3705 29 2614 1337 1277 3 16220 5508 61 4128 3209 920 4 19597 6692 1832 8319 6525 1794 5 29915 4066 6814 9800 7562 2239 6 26675 4647 12274 11333 8143 3189 7 27864 6098 13182 15787 12231 3556 8 34678 4092 15622 15033 11155
Slide 5: Evolution to Product Leadership
Evolution to Product Leadership Acknowledge the Objection: Fear of PML Overcome the Objection: TYSABRI Benefit vs. PML Risk Change the Behavior: Focus on Unique Selling Point
Slide 6: Physician Confidence Returning
Physician Confidence Returning Jan, 06 Feb, 06 Mar, 06 Q1 '06 Rolling Average Apr, 06 May, 06 June, 06 Q2 '06 Rolling Average H1 2006 July, 06** Aug., 06 Q3 '06 Rolling Average Oct., 06 Nov., 06 Dec., 06 Q4 '06 Rolling Average H2 2006 Jan., 07 Feb., 07 Mar., 07 Q1 '07 Apr., 07 May., 07 June., 07 Q2
Slide 7: Evolution to Product Leadership
Evolution to Product Leadership "Effective Drug with Fatal Side Effect" "Unprecedented effect, with manageable side effect"
Slide 8: TYSABRI: A Drug That Improves MS
TYSABRI(r): A Drug That Improves MS Reduction of disease progression Reduction in relapse rate Free of disease activity 54%2 68%2 37%1 Improvement Failure-based paradigm Improvement paradigm Intermediate 69%3 1.Havrdova, et al. Lancet.neurology February 9, 2009 S1474-4422(09)70021-3 ; Effect of nata
Slide 9: Freedom From Disease Activity
Free of progression Free of relapses Free of new T2 lesions Free of Gd+ lesions MRI activity Clinical activity 37% free of disease activity Havrdova E, et al. Presented at: WCTRIMS, September 2008, Montreal Canada Freedom From Disease Activity Patients with no disease activity Patients with no disea
Slide 10: Beyond Slowing the Disease: Sustained Improvement
Beyond Slowing the Disease Sustained Improvement Note: Tysabri data presented at 2008 ECTRIMS meeting, Munschauer et al. P474. Physician perception based on October 2008 Biogen Idec market research. "I can go out on my own. I can return to my role as a mother with my daughter. I can do the shopping,
Slide 11: Improved Walking, Dexterity, and Thinking
Beyond Slowing the Disease Improved Walking, Dexterity, and Thinking Placebo n=264 Natalizumab n=536 P=0.003 P=0.011 - -2.0 - -1.5 - -1.0 - -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 SF-36 PCS SF-36 MCS Mean Change From Baseline at 2 Years ? SE Note: PCS = Physical Component Summary; MSC = Mental Component Su
Slide 12: Comprehensive Dialogue with Our Customers
Comprehensive Dialogue with Our Customers Thousands of Interactions With Each of Our Audiences Patient Services Direct Mail Live Programming Congresses Sales Details Doctors Nurses Nurse Practitioners Patients Patient Associations Pharmacists Regulators Payers PE Specialists Webcasts Websites Med In
Slide 13: Most Neurologists Expect to Increase Use of TYSABRI
Most Neurologists Expect to Increase Use of TYSABRI ZS PhysPulse: Q243a. Please indicate how you expect your usage of each of the available MS drug therapies to change over the next six months. *Expected change in usage over six months following fielding. +Countries included: Belgium, France, German
Slide 14: High Hopes
HIGH HOPES AND FOR MAI ot TYSABRIL (natalizumab}
Slide 15: Agenda
Agenda TYSABRI Commercial Plan & Execution TYSABRI R&D Initiatives
Slide 16: Biogen Idec Neurology R&D
Biogen Idec Neurology R&D TYSABRI Leading the way on science of TYSABRI Delivering tools and information to neurologists to improve patient outcomes Doing it Quickly
Slide 17: Putting PML in Perspective
Putting PML in Perspective PML is difficult to diagnose 5HT2A may be helpful PML can't be treated or cured PML is most often fatal Clinical vigilance appears to be effective at identifying patients early Original results not replicated In vitro evidence for mefloquine Rapid intervention appears to i
Slide 18: Re-defining the TYSABRI PML Experience
Re-defining the TYSABRI(r) PML Experience Rate Outcome 1 / 1000 Less Frequent Less Severe Outcome Available Data at Launch Death or Severe Disability *As of Feb 09. Based on 5 postmarket cases with approx 20,000 patients on treatment for >12 months. ZS PhysPulse data - US Neurologists October 2008;
Slide 19: Plasma Exchange Facilitates Removal of Natalizumab
Plasma Exchange Facilitates Removal of Natalizumab
Slide 20: Establishing PLEX as Standard of Care in PML Cases
Could we rapidly reconstitute immune system of TYSABRI patient to improve PML prognosis? Ad Board 1Q08 Investigator Mtings MS Congress 3Q07 & 1Q/3Q08 BIIB PML Intervention Support Used successfully in 1st PML Case July 08 Example: Establishing PLEX as Standard of Care in TYSABRI PML Cases 1 (800) 45
Slide 21: Last Year's Presentation: Promise of 5HT2a Blockers
Last Year's Presentation: The Promise of 5HT2a Blockers as anti-JCV Therapy O'Connor, K.A. & Roth, B.L. Nat. Rev. Drug Discov. (2005) 5HT2a blocker
Slide 22: JCV Infectivity Assay
JCV Infectivity Assay 400 (Cell Count 10000 = #JCV+ cells S300 ~ 8000 z os 2 60008 3 $200 z= £ 40002 8 6 2a 2100 - ~ te 2000 0 0 400 200 100 50 25 JCV 1/dilution _{ biogen idec |
Slide 23: 5HT2a Blockers Proved Ineffective at Inhibiting JCV Infectivity
5HT2a Blockers Proved Ineffective at Inhibiting JCV Infectivity 5HT2a's Effect Controls No inhibitive effect
Slide 24: Exhaustive Screen For Potential Inhibitive Compounds
Exhaustive Screen For Potential Inhibitive Compounds 2000 compounds Spectrum collection Screened at 10 mM 67 inhibitors: % JCV inhibition ^20% total cell # inhibition ^ 20% 14 potent inhibitors: IC50 ^ 20 mM Therapeutic index (IC50/TC50*)>2 Brain Penetration (lit search) Mefloquine: IC50 = 3.2 +- 0.
Slide 25: Re-defining the TYSABRI PML Experience
Rate Outcome 1 / 1000 Less Frequent Less Severe Outcome Available Data at Launch Death or Severe Disability Re-defining the TYSABRI(r) PML Experience * As of Feb 09. Based on 5 postmarket cases with approx 20,000 patients on treatment for >12 months ? 1/4000 over 12 months exposure* Patient Selectio
Slide 26: Emerging Consensus: Drug Holidays Not Recommended
Emerging Consensus: Drug Holidays Not Recommended Drug holiday likely decreases benefit/risk profile of natalizumab In the majority of patients disease activity returns rapidly on cessation of natalizumab No evidence that a drug holiday reduces PML risk - and impractical to test To prove or disprove
Slide 27: Clinical Disease Activity Returns to Placebo Levels within 5-6 Months
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 1 2 3 4 5 6 Months Post Natalizumab Cessation Unadjusted Annualized Relapse Rate AFFIRM (N=480) SENTINEL (N=268) On-study Placebo ARR (AFFIRM 0.73; SENTINEL 0.75) Clinical Disease Activity Returns to Placebo Levels within 5 - 6 Months AFFIRM; SENTINEL
Slide 28: Highly Active Patients Return to High Relapse Rates
Months Post Natalizumab Cessation Unadjusted Annualized Relapse Rate 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 1 2 3 4 5 6 Highly Active (n=154) All Patients (n=798) Patients Who Were Highly-Active before Starting TYSABRI, Return to High Relapse Rates AFFIRM; SENTINEL
Slide 29: DMTs Don't Prevent Return of Clinical Disease Activity
1 2 3 4 5 6 Months Post Natalizumab Cessation Unadjusted Annualized Relapse Rate On-study Placebo ARR (AFFIRM 0.73; SENTINEL 0.75) DMT (n=298) No DMT (n=500) 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 AFFIRM; SENTINEL DMT's Don't Prevent Return of Clinical Disease Activity After Stopping TYSABRI
Slide 30: Further Reducing Risk?
Further Reducing Risk? Basic Science On Potential Risk Factors Immune Function JC Virus Other Host Genetics Viral Genetics Unknown? PML Is an Extremely Rare Event - Likely Results from the Interplay of Multiple Factors Immune Function JC Virus Other Host Genetics Viral Genetics Unknown?
Slide 31: TYSABRI Raised Awareness of PML, but It Is Increasingly Linked to Many Drugs
TYSABRI Raised Awareness of PML, but It Is Increasingly Linked to Many Drugs PML included in label Commonly used by neurologists
Slide 32: TYSABRI: Unprecedented Efficacy
ITT Population N=627 Evaluable* Population N=518 Relapse rate 0.23 0.21 Proportion with disability progression 17% 15% Number of new or enlarging T2 lesions over 2 years 1.9 1.0 Proportion with no Gd-enhancing lesions at 2 years 97% 99% *On study for 2 years, missed <4 doses and <2 consecutive doses
Slide 33: TYSABRI: A Drug That Improves MS
TYSABRI: A Drug That Improves MS Reduction of disease progression Reduction in relapse rate Free of disease activity 54%2 68%2 37%1 Improvement Failure-based paradigm Improvement paradigm Intermediate 69%3 1.Havrdova, et al. Lancet.neurology February 9, 2009 S1474-4422(09)70021-3 ; Effect of nataliz