Investor science conference call from EULAR Berlin, 8 June 2012

Transcription

1 Investor science conference call from EULAR 2012 Berlin, 8 June 2012

2 This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as believes, expects, anticipates, projects, intends, should, seeks, estimates, future or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees; and 11 adverse publicity and news coverage. Any statements regarding earnings per share growth is not a profit forecast and should not be interpreted to mean that Roche s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed the historical published earnings or earnings per share of Roche. For marketed products discussed in this presentation, please see full prescribing information on our website All mentioned trademarks are legally protected 2

3 Introduction Dr. Karl Mahler, Head of Investor Relations, Roche

4 Investor events 2012 R&D and strategy updates Date / location 4 June 2012 Chicago, USA Medical Meeting / Event ASCO (American Society of Clinical Oncology) Key assets / newsflow T-DM1: EMILIA pretreated HER2+ mbc Avastin: TML treatment through multiple lines in mcrc, AURELIA platinum resistant ovarian cancer 8 June 2012 Berlin, Germany EULAR (Annual European Congress of Rheumatology ) Actemra: ADACTA RA monotherapy head to head versus adalimumab 4/5 September 2012 London, GB Investor Day / Dinner with Management R&D strategy and pipeline Growth opportunities Innovation and efficiency 4

5 Roche s Inflammation portfolio Focus on autoimmune and respiratory diseases and targeted immunotherapy RG4934 IL-17 Mab inflammatory diseas. RG7185 CRTH2 antag asthma RG7413 etrolizumab (β7) ulcerative colitis RG7258 TSLPR MAb asthma RG7415 rontalizumab SLE New Molecular Entities RG7624 CHU IL-17 MAb IL-6 MAb autoimmune diseas. RA RG7416 RG7449 LT alpha MAb M1 prime MAb RA asthma RG3637 lebrikizumab severe asthma Phase I Phase II Phase III Additional indications RG1569 Actemra systemic sclerosis RG105 MabThera ANCA assoc vascul RG1569 Actemra RA sc formulation RG1569 RG1569 Actemra Actemra early RA DMARD IR H2H RG3648 Xolair chronic idiopath. urticaria Status as of March 31, 2012 CHU Suvenyl enthesopathy 5

6 Investor conference call from EULAR 2012 Agenda 8 June :30 CET Introduction Dr. Karl Mahler, Head of Investor Relations, Roche Actemra franchise overview Dr. Karsten Jung, Global Product Strategy Head for Immunology & Ophthalmology Rheumatoid arthritis monotherapy in real-life setting: Re-evaluating need and options Prof. Paul Emery, Director of Musculoskeletal Division, Leeds Institute of Molecular Medicine, University of Leeds, UK ADACTA: A phase IV study evaluating the reduction in disease activity during monotherapy treatment with either Actemra or adalimumab Prof. Paul Emery, Director of Musculoskeletal Division, Leeds Institute of Molecular Medicine, University of Leeds, UK Q&A Moderator: Dr. Karl Mahler Total duration 1.00 hour 6

7 Actemra/RoActemra franchise overview Dr. Karsten Jung, Global Product Strategy Head for Immunology & Ophthalmology, Roche

8 Actemra / RoActemra* Rheumatoid Arthritis (RA) is the core of the franchise Expanding beyond rheumatoid arthritis Differentiation vs. other medicines in RA Three core elements of Actemra s life cycle Rheumatoid arthritis as core indication 8 *RoActemra - referred to as Actemra outside Europe & throughout the remainder of this document 8

9 Rheumatoid arthritis as core indication Actemra: substantial evidence of efficacy to support broad label in RA 9 CHF m % 1 Q1 08 Q1 09 Q1 10 Q1 11 Q1 12 Actemra global sales 184 mchf Q constant exchange rates Data across all key RA populations in mono & combination therapy Phase III clinical studies OPTION N=623 MTX IR TOWARD N=1,220 DMARD IR RADIATE AMBITION N=673 LITHE N=599 anti-tnf IR MTX naive N=1,196 MTX IR, X-ray 27.5% 30.2% 30.1% DAS28 remission at 24 wks, 8mg/kg 33.6% 33.3% DMARD IR sbla submitted to the FDA Dec ,000 patient years safety data 1 st subcutaneous RA study (SUMMACTA, qw) positive, 2 nd study (BREVACTA, q2w) expected Q Early RA data (FUNCTION) expected Q

10 Rheumatoid arthritis as core indication Actemra: stable safety profile over time 4,009 ACTEMRA patients in clinical trials Median duration was 3.6 years Total observation time was 12,293 patient-years Event rate / 100 patientyears over 12-month periods Serious adverse events Serious infections Myocardial infarction Stroke Modified from Genovese, M, et al; Long-Term Safety of Tocilizumab in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum 2011;63 Suppl 10 :

11 Differentiation versus other medicines in RA ADACTA in context what is biologic monotherapy? RA prevalence Diagnosed patient Treated by rheumatologist DMARD(s) + non-dmard therapy Cycling and DMARD combinations (no biologic) RA biologics market (after patients become DMARD-IR) Biologic combination therapy biologic use with a DMARD Biologic monotherapy biologic use without a DMARD Source: Roche analysis 11

12 Demonstrating differentiation in RA Monotherapy is a substantial portion of biologic treatment today Approximately 30% of RA biologics patients are on monotherapy 70% 30% Biologic monotherapy Biologic combination Monotherapy segment has fewer labeled medicines compared to combination segment ACTEMRA Enbrel Humira Cimzia Remicade Simponi MabThera Orencia Indicated in monotherapy * 12 Source: Multiple registries on monotherapy (see Prof. Emery presentation); Roche analysis of EU/US labels, *monotherapy label in US only 12

13 % Physicians Demonstrating differentiation in RA Actemra is already perceived as being different EU physician perception research conducted Q Physicians were asked to evaluate biologic medicine appropriateness for use with monotherapy patients Please rate each biologic on how appropriate you consider it to be for biologic monotherapy on a scale from Increasing recognition of Actemra s strength in monotherapy even before ADACTA was published % physicians = check top 3 boxes for the product 13

14 Actemra monotherapy: Differentiated efficacy profile vs. other biologic agents Clinical study Treatment arms Key endpoint Key study conclusions MTX-naïve/free patients AMBITION (N=503) 1 TCZ mono vs MTX ACR20 at Week 24 TCZ mono is superior to MTX Patients with active RA despite MTX therapy (MTX-IR) ACT-RAY (N=553) 2 TCZ mono vs TCZ + MTX DAS28 remission at Week 24 X-ray Add-on TCZ+MTX strategy was not superior to TCZ mono Patients with inadequate response to DMARDs, including TNF-inhibitors (TNF-IR) ACT-SURE (N=1681) 3 TCZ 8 mg mono / TCZ 8 mg + MTX or other DMARDs Safety at week 24 H2H in Patients with active RA despite MTX therapy (MTX-IR) TCZ mono comparable to TCZ combo ADACTA (N= 325) 4 TCZ mono vs ADA mono Change in DAS28 at Week 24 TCZ mono is superior to ADA mono 1. Jones G, et al. Ann Rheum Dis 2010; 69:88 96; 2. Dougados M, et al. Ann Rheum Dis 2011; 70(Suppl. 3):73; 3. J. Sibilia, Ann Rheum Dis 2011;70(Suppl3): Gabay et al., EULAR

15 Actemra: Expanding beyond rheumatoid arthritis Study name Indication Approved biologic therapies Status Tender Systemic juvenile idiopathic arthritis None Actemra received approval 2011 CHERISH Polyarticular course juvenile arthritis Anti-TNF inhibitors Study read out 2012, filing planned fasscinate Systemic sclerosis None Phase II FPI 2012 Additional indications under investigation 15 15

16 Rheumatoid arthritis monotherapy in real life setting: Re-evaluating need and options Prof. Paul Emery, Director of Musculoskeletal Division, Leeds Institute of Molecular Medicine, University of Leeds, UK

17 Patients (%) RA patients on biologics do not comply with taking DMARDs as directed, especially methotrexate Anonymous RA patient records (N=6,744) from public and private drug plans in Canada Time since first biologic prescribed: months 24 months DMARD prescription NOT filled* * Within 90 days before or 90 days after filling biologic prescription 92 randomly selected RA patients receiving biologics MTX prescription NOT filled* Choquette D et al. Ann Rheum Dis 2011; 70:

18 One third of RA patients on biologics are on monotherapy Data from biologics registries and US claims database BSRBR 2 32% RABBIT 3 34% NOR- DMARD 1 33% ARTIS 4 30% ORA 5 35% CORRONA 7 30% Healthcare insurance claims database 6 30% TNF = tumour necrosis factor; all registries/studies are anti-tnf focused, other than ORA (abatacept), AIR (rituximab) and RABBIT (anti-tnfs and anakinra) AIR 5 34% 1. Heiberg MS, et al. Arthritis Rheum 2008; 59: Soliman MM, et al. Ann Rheum Dis 2011; 70: Listing J, et al. Arthritis Res Ther 2006; 8:R Askling J, et al. Ann Rheum Dis 2007; 66: Mariette X, et al. Rheumatology 2011; 50: Yazici Y, et al. Bull NYU Hosp Jt Dis 2008; 66: Lee SJ, et al. J Rheumatol 2009; 36:

19 Methotrexate: most common adverse events in patients with RA Data from pooled analysis of 21 prospective studies of patients with RA n (range) N (range) 3,463 (24 1,155) Mean dose of MTX, mg/week (range) 8.8 (4.6 18) Mean duration of MTX, months (range) 36.5 (27 132) Adverse event n (range) % Any adverse event 2,524 (22 475) 72.9% Permanent discontinuation due to toxicity 315/3,007* 10.5% Gastrointestinal 1,065 (10 257) 30.8% Liver 640 (0 122) 18.5% Skin/hair 309 (0 111) 8.9% Central nervous system 191 (0 58) 5.5% Cytopenia 179 (0 27) 5.2% Lung - MTX pneumonitis * Total number of patients in studies with data available concerning permanent discontinuation of MTX 84 (0 28) % 0.43% Saliot C & van der Heijde D. Ann Rheum Dis 2009;68:

20 ADACTA: A phase IV study evaluating the reduction in disease activity during monotherapy treatment with either Actemra or adalimumab Prof. Paul Emery, Director of Musculoskeletal Division, Leeds Institute of Molecular Medicine, University of Leeds, UK

21 Tocilizumab monotherapy is superior to adalimumab monotherapy in reducing disease activity in patients with rheumatoid arthritis: 24-week data from the phase 4 ADACTA trial C Gabay, 1 P Emery, 2 R van Vollenhoven, 3 A Dikranian, 4 R Alten, 5 M Klearman, 6 D Musselman, 6 S Agarwal, 6 J Green, 7 A Kavanaugh 8 1 Univ Hospitals of Geneva, Geneva, Switzerland, 2 Univ Leeds, Leeds, United Kingdom, 3 Karolinska Inst, Stockholm, Sweden, 4 San Diego Arthritis Med Clin, San Diego, United States, 5 Univ Berlin, Berlin, Germany, 6 Genentech, S San Francisco, United States, 7 Roche, Welwyn, United Kingdom, 8 Univ California, San Diego, United States EULAR 2012 June 6-9, 2012; Berlin, Germany

22 Phase 4, multicentre, randomised, double-blind study of tocilizumab vs adalimumab in RA Superiority trial design Randomised Drug Treatment 8 Weeks Safety Follow-up TCZ* 8 mg/kg IV Q4 weeks + SC Placebo Q2 weeks Treated (N = 326) ADA** 40 mg SC Q2 weeks + IV Placebo Q4 weeks 1:1 randomisation Week 16+: Escape a 24 weeks; primary endpoint: Δ DAS28 a Criteria for escape: <20% improvement from baseline in SJC and TJC at week 16 or after, * TCZ tocilizumab, ** ADA adalimumab Escape therapy: Weekly SC (ADA/placebo) injections; study medication remained blinded 22

23 Key inclusion criteria RA duration of 6 months Previous/current MTX* treatment; either MTX-intolerant or continued treatment is considered inappropriate No prior treatment with a biologic agent All DMARDs** withdrawn 2 weeks prior to baseline Disease Activity Score DAS28 >5.1 at baseline *MTX methotrexate **DMARDs disease-modifying antirheumatic drugs 23

24 Study endpoints Primary endpoint Change in DAS28* from baseline to week 24 Key secondary and exploratory endpoints Efficacy at week 24: proportions of patients achieving: DAS28 remission (<2.6) and low disease activity ( 3.2) ACR20/50/70** responses ACR/EULAR (Boolean) remission Safety: Adverse events and laboratory parameters Post-hoc analyses Clinical Disease Activity Index (CDAI) responses * DAS28 Disease Activity Score (DAS)28, combined index that measures disease activity in patients with RA. It combines information from 28 tender and swollen joints (range0-28), erythrocyte sedimentation rate, and a general health assessment on a visual analog scale. The level of disease activity is interpreted as low (DAS28 3.2), moderate (3.2<DAS28 5.1) or high (DAS28>5.1). DAS28<2.6 corresponds to being in remission according to the criteria of the American College of Rheumatology. **ACR20, ACR50, ACR70 represent the percentage of reduction (20%, 50%, 70%) in certain RA symptoms and measures the number of tender and swollen joints, pain, patient s and physician s global assessments and certain laboratory markers. 24

25 Patient disposition Randomised patients N = 326 ADA 40 mg SC Q2 weeks + IV placebo Q4 weeks N = 163* TCZ 8 mg/kg IV Q4 weeks + SC placebo Q2 weeks N = 163 Completed 125 (77%) Withdrew Escaped Completed 28* (17%) 10 (6%) 132 (81%) Withdrew 24 (15%) Escaped 7 (4%) Withdrew from escape therapy 2 (1%) Withdrew from escape therapy 0 (0%) *1 ADA patient did not receive study treatment and was not included in the ITT population. Not including the 2 escape patients that withdrew. 25

26 Demographic and baseline characteristics adalimumab N = 162 tocilizumab N = 163 Age, y 53.3 (12.4) 54.4 (13.0) Female/male, % 82/18 79/21 RA duration, y 6.3 (6.9) 7.3 (8.0) No. of previous DMARDs 2.0 (1.1) 2.0 (1.1) Use of oral steroids, % Disease activity DAS (0.9) 6.7 (0.9) TJC (28 joints) 16.5 (7.0) 15.9 (6.7) SJC (28 joints) 12.4 (5.4) 11.3 (5.3) CDAI 43.1 (12.6) 40.8 (12.3) ESR, mm/h 45.5 (25.4) 50.5 (29.0) CRP, mg/dl 2.5 (3.9) 2.6 (3.1) Patient VAS, mm 73.4 (19.4) 71.2 (20.8) HAQ 1.7 (0.6) 1.6 (0.6) Data are presented as mean (SD), unless otherwise indicated. List of abbreviations used at the end 26

27 Primary endpoint Change in DAS28 from baseline to week 24 (intent-to-treat population) adalimumab 40 mg SC + IV placebo tocilizumab 8 mg/kg IV + SC placebo n Adjusted mean Difference % CI for difference -1.8 to -1.1 P-value < Analysis of variance (model included baseline value plus the stratification factors of region and duration of RA). 1 ADA patient did not receive treatment; 2 TCZ patients had no post-baseline data. LOCF was used for missing TJC, SJC, ESR, and Patient s Global VAS. If ESR=0 then ESR=1 was substituted into the DAS28 calculation to enable a non missing DAS28 27

28 DAS28 DAS28 Mean (± SE*) over time ADA 40 mg + placebo (IV) (N = 162) TCZ 8 mg/kg + placebo (SC) (N = 163) Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24 LOCF used for tender and swollen joint counts, ESR and Patient's Global Assessment of Disease Activity VAS If ESR = 0 then ESR = 1 is substituted into the DAS28 calculation to enable a non-missing DAS28. *SE standard error 28

29 Patients Secondary endpoints Proportions of patients with DAS28 remission/ low disease activity at week 24 (intent-to-treat population) ADA (N = 162) TCZ (N = 163) 60% 50% 40% 51.5% * 39.9% * 30% 20% 10% 19.8% 10.5% 0% DAS28 low disease activity ( 3.2) DAS28 remission (<2.6) *P <.0001 (vs ADA); significance was determined using a logistic regression analysis (covariates included treatment, region, and duration of RA). LOCF was used for missing TJC, SJC, no imputation was used for ESR and Patient s Global VAS. Non-responder imputation was used for missing data. If ESR=0 then ESR=1 was substituted into the DAS28 calculation to enable a non missing DAS28. 29

30 Patients Secondary endpoints Proportions of patients with ACR20/50/70 response at week 24 (intent-to-treat population) 70% 65.0% * ADA (N = 162) TCZ (N = 163) 60% 50% 49.4% 47.2% 40% 30% 27.8% 32.5% * 20% 17.9% 10% 0% ACR 20 ACR 50 ACR70 *P <.005 (vs ADA). P <.0005 (vs ADA). Significance was determined using a logistic regression analysis (covariates included treatment, region, and duration of RA). LOCF was used for missing TJC, SJC. If CRP was missing ESR was substituted. Non-responder imputation was used for missing data. 30

31 Patients Post-hoc analysis: Clinical Disease Activity Index (CDAI) analysis at week 24 (intent-to-treat population) ADA (N = 162) TCZ (N = 163) 50% 47.9% 40% 30% 29.0% 30.7% 20% 19.8% 10% 0% 9.3% 17.2%* Remission Remission + Low Disease Activity ( 0 (>0 to to 2.8) <10) *P = , remission (unadjusted, no control for multiple testing). P = , remission + low disease activity (unadjusted, no control for multiple testing). Proportions of patients were compared using CMH analysis stratified by region and duration of RA. Data collected after withdrawal/initiation of escape therapy was set to missing. LOCF was used for missing data. 31

32 Absolute Mean SJC Count Swollen Joint Counts 28 (intent-to-treat population) 14 ADA (N = 162) TCZ (N = 163) ADA N = 162; TCZ N = 163 LOCF used for Missing Data N = 156; N = 159 N = 162; N = 161 N = 162; N = 161 Baseline Wk 4 Wk 8 Wk 12 Wk 16 Wk 20 Wk 24 Visit N = 162; N = 161 N = 162; N = 161 N = 162; N =

33 Safety Adverse events (safety population) adalimumab (N=162) tocilizumab (N=162) AEs Patients with at least one AE, n (%) 134 (83) 133 (82) SAEs Patients with at least one SAE, n (%) 16 (10) 19 (12) Infection AEs Patients with at least one infection AE, n (%) 68 (42) 77 (48) Infection SAEs 7 6 Patients with at least one infection SAE, n (%) 5 (3) 5 (3) Deaths, n (%) 0 (0) 2 (1) Multiple occurrences of the same AE in 1 individual were counted only once. 33

34 Safety Overall, 2 deaths were reported, both in the TCZ arm The death of a 49-year old female on study day 2 was considered unrelated to study drug Cause of death: Illicit drug overdose (marijuana, benzodiazepines, methadone in urine) The sudden death of a 56-year old male on study day 93 was considered possibly related to study drug Comorbidities: Interstitial lung disease, peripheral vascular disease (stent placement), hypertension, overweight (BMI 28), smoking (for 30 years) Cause of death: Unknown (no autopsy was performed) 34

35 mg/dl mmol/l LDL-cholesterol LDL-cholesterol by visit (safety population) ADA TCZ ADA n = 144 TCZ n = 146 ADA n = 138 TCZ n = 143 ADA n = 137 TCZ n = 138 ADA n = 127 TCZ n = 128 Baseline Wk 8 Wk 16 Wk 24 Visit Patients on LLA at baseline & no change in LLA post BL = 20 patients in each arm Patients started on LLA after week 4 = 6 ADA patients; 10 TCZ patients 35

36 Patients, % ALT levels by CTC* grade (worst value) (safety population) 80% 70% 60% 72.2% 62.3% ADA (N=162) TCZ (N=162) 50% 40% 30% 20% 10% 0% 30.9% 24.7% 5.6% 1.9% 1.2% 1.2% Normal >ULN-2.5xULN >2.5x-5xULN >5x-20xULN ALT levels *CTC Common Toxicity Criteria: Grade 1, >ULN to 2.5xULN; Grade 2, >2.5xULN to 5xULN; Grade 3, >5xULN to 20xULN. 36

37 Conclusions Efficacy Tocilizumab (TCZ) monotherapy was superior to adalimumab (ADA) monotherapy in reducing signs and symptoms of RA Safety The overall adverse event profile was comparable between the two treatment arms The safety observed in the TCZ arm of this study is consistent with the known safety profile of TCZ and no new or unexpected adverse events were observed 37

38 Investigators (82 centres from 15 countries) Australia: Nash Youssef Belgium: Malaise Margaux Brazil: Radominski Ximenes Zerbini Czech Republic: Pavelka Finland: Hannonen Leirisalo-Repo Germany: Alten Braun Fiehn Gauler Heilig Rubbert-Roth Specker Tony Wassenberg von Hinuber Greece: Aslanidis Boumpas Sfikakis Mexico: Elizonda Irazoque Zazueta Portugal: Bernardes Canas Da Silva Fonseca Spain: Alvaro Gracia Blanco Juan Navarro-Sarabia Sanmarti Sweden: Baecklund van Vollenhoven Switzerland: Dudler Gabay Hasler Kyburz Muller Turkey: Bilgen Hamuryudan Karaaslan Terzioglu UK: Emery Hakim Isaacs Sheeran Thompson USA: Borofsky Bushan Chindalore Churchill Curtis Dikranian Ettlinger Forstot Fung Gladstein Halter Hensarling Huffstutter Hsu Jerdan Kenney King Ii Kivitz Klein Kohen Lawson Lee Logan Lue Payne Rizzo Samuels Sayers Scoville Sherrer Singhal Trapp Waller Wolfe 38

39 Disclosures The authors disclose the following financial relationships: Cem Gabay Consultant for: Roche 2,4, Abbott 2,4, Merck 2,4, UCB 2,4, Pfizer, 2,4 BMS 2,4, Merckserono 2,4, Novartis 2,4, Amgen 2,4 Paul Emery: Merck 4, Abbott 4, Pfizer 4, Roche 4, UCB 4, BMS 4 Ronald van Vollenhoven: Abbott 1,4, GSK 1,4, MSD 1,4, Pfizer 1,4, Roche 1,4, UCB 1,4 Alten Dikranian: Genentech 2, UCB 2, Abbott 2, BMS 2 Rieke Alten: BMS 1,2,4, Novartis 1,2,4, Pfizer 1,2,4, Roche 1,2,4, UCB 1,2,4, Abbott 2,4 Micki Klearman: Genentech 3 David Musselman: Genentech 3 Sunil Agarwal: Genentech 3 Jennifer Green: Roche 3 Arthur Kavanaugh: Roche 1, Amgen 1, Abbott 1, BMS 1, Janssen 1, UCB 1, Pfizer 1 1 Research Grants; 2 Speakers Bureau; 3 Employment; 4 Consulting Fees 39

40 Actemra/RoActemra summary Dr. Karsten Jung, Global Product Strategy Head for Immunology & Ophthalmology, Roche

41 Actemra clearly demonstrates differentiation in RA Actemra has now a strong foundation of clinical data in RA ADACTA provides solid H2H data to inform treatment decisions in RA monotherapy Upcoming clinical and regulatory newsflow will advance the franchise Timeline Indication Milestone 2012 RA DMARD IR 1 st line biologic label in US RA DMARD IR monotherapy RA, moderate to severe; subcutaneous application Expect FDA approval Ph III ADACTA H2H vs. Humira Application to EMA for label update Ph III SUMMACTA Ph III BREVACTA Application to FDA and EMA RA, early moderate to severe Polyarticular-course juvenile idiopathic arthritis Ph III FUNCTION Ph III CHERISH Application to FDA and EMA 2013 Systemic sclerosis Ph II readout 41

42 Questions & Answers 42

43 List of abbreviations ACR20/50/70 ADA AE ALT Anti-TNF inh CDAI CTC DAS28 DMARD DMARD-naive ESR FPI Percentage of reduction (20%, 50%, 70%) in certain RA symptoms; also measures the number of tender and swollen joints, pain, patient s and physician s global assessments and certain laboratory markers Adalimumab Adverse event Alanin transaminase; liver enzyme used for diagnostic evaluation of hepatic injury Anti-tumor necrosis factor inhibitor Clinical disease activity index; score for routine assessment of disease activity in rheumatoid arthritis patients Common toxicity criteria Disease activity Score 28; index combines information from 28 tender and swollen joints (range0-28), erythrocyte sedimentation rate, and a general health assessment on a visual analog scale. The level of disease activity is interpreted as low (DAS28 3.2), moderate (3.2<DAS28 5.1) or high (DAS28>5.1). DAS28<2.6 corresponds to being in remission according to the criteria of the American College of Rheumatology Disease-modifying antirheumatic drug No previous administration of DMARD Erythrocyte sedimentation rate First-patient-in H2H HAQ IR ITT IV LDL LLA LOCF MTX MTX-naive RA SAE SC SE Head-to-head Health assessment questionnaire Inadequate responder Intent-to-treat Intravenous Low-density lipoprotein Lipid-lowering agent Last observation carried forward: analysis method in rheumatoid arthritis Methotrexate No previous administration of methotrexate Rheumatoid arthritis Serious adverse event Subcutaneous Standard error SJC 28 Swollen joint count 28 TJC 28 Tender joint count 28 TCZ ULN VAS Tocilizumab Upper limit of normal Visual analogue scale, measurement instrument for subjective characteristics 43

44 We Innovate Healthcare 44

45 Appendix 45

46 Actemra clinical safety Rates of SAEs, serious infections and cardiovascular events remained stable over time Event rate / 100 patient-years over 12-month periods Serious adverse events Serious infections Myocardial infarction Stroke ,009 ACTEMRA patients in clinical trials, median duration was 3.6 years, total observation time was 12,293 patient-years* Mortality rates of patients treated with Actemra are no greater than those observed with TNF antagonists Actemra Epidemiology data for TNF- 6 month pooled controlled data LTE studies antagonists Placebo/DMARD All TCZ Data cut Feb 2010 PY exposure a Rate of deaths (95% CI) Number of events (0.26, 1.86) 5 (0.14, 1.03) 5 (0.44, 0.71) 69 (0.38, 0.91) a 23 Rate of Deaths per 100 Patient Years a Unadjusted mortality rate for RA patients treated with TNF antagonists; calculated based on meta-analysis data of 17 trials; 4097 patients Leombruno et al. Ann Rheum Dis 2009;68: *Modified from Genovese, M, et al; Long-Term Safety of Tocilizumab in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum 2011;63 Suppl 10 :