Investor event at ACR 07 in Boston 9 November 2007

Transcription

1 Investor event at ACR 07 in Boston 9 November 2007 Forward-looking statements 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. Please see for full information on Roche products mentioned. 2

2 Introduction Dr. Karl Mahler, Head of Investor Relations Agenda Actemra s TOWARD trial Dr. Mark Genovese, Associate Professor of Medicine, Co-Chief Division of Immunology and Rheumatology, Stanford University School of Medicine Actemra program overview Don MacLean, Actemra Lifecycle Leader Building a new franchise in Inflammation/Autoimmune Diseases Dr. Urs Schleuniger, VP, Head of Strategic Marketing Inflammation Questions & Answers 4

3 Roche s key therapeutic areas Current and future pillars of growth Oncology Xeloda MabThera Herceptin Avastin Tarceva Pertuzumab Apomab Apo2L/TRAIL ARQ 15 phase I compounds On Hand RA/Autoimmune MabThera Actemra R1594 ocrelizumab PNP inhibitor 5 phase I compounds Metabolic R1583 GLP-1 R1658 CETP Inh. R1439 dual PPAR R1579 DPP-IV 3 phase I compounds Promising Late Stage Virology Tamiflu Pegasys R1626 Polym. Inh. R7227 Protease Inh. R7128 Polym. Inh. R3484 HPV16 Emerging Mid-Term Neurology / Psychiatry 6 phase I compounds Early Stage 5 Roche in Inflammation/Autoimmune Diseases Building a new therapeutic franchise MabThera/Rituxan Rheumatoid Arthritis Launched in RA anti-tnfa inadequate responders (IR) in U.S. and EU Filing for RA in DMARD IR in 2008 Multiple Sclerosis (MS), Lupus, Vasculitis Phase III in PPMS, SLE, LN and ANCA ass. vasculitis ongoing Actemra Rheumatoid Arthritis Filed in Japan Broad international phase III program closing four trials reported in 2007 Global filing Q Ocrelizumab Rheumatoid Arthritis, Multiple Sclerosis, Lupus Phase II trial in RA met primary and secondary endpoints, presented at ACR 06 Phase III program in RA running Phase III in SLE to start Q and LN in early 2008 Phase II in RRMS to start H Phase 1 5 compounds for Inflammation/ Autoimmune Diseases 10 phase III projects 3 phase II projects 6

4 Actemra s TOWARD trial Dr. Mark Genovese, Associate Professor of Medicine, Co-Chief Division of Immunology and Rheumatology, Stanford University School of Medicine IL-6: Fundamental role in the inflammation that drives RA Monocytes/ macrophages T cell activation Thrombocytosis Maturation of megakaryocytes Endothelial cells IL-6 B cells Mesenchymal cells, fibroblasts/synoviocytes Hepatocytes Acute-phase proteins hepcidin, CRP Osteoclast activation Bone resorption Auto-antibodies (RF) Hyper γ-globulinaemia Firestein GS. Nature 2003;423: ; Smolen JS and Steiner G. Nat Rev Drug Disc 2003;2: Genovese et al., Abstract L15 8

5 Tocilizumab: Humanized anti-il-6r monoclonal antibody Tocilizumab binds to both the mil-6r and the sil-6r, preventing binding of IL-6 and association with the gp130β chain and thus IL-6-mediated signalling IL-6 X mil-6r sil-6r X Cell membrane X gp130 gp130 X Signal transduction inhibited Genovese et al., Abstract L15 9 The TOWARD Study: Tocilizumab in combination With traditional DMARD therapy Objectives To asses the efficacy and safety of tocilizumab 8 mg/kg in combination with conventional DMARD therapy Patients Moderate to severe RA 6 months duration, with an inadequate response to conventional DMARDs Excluding patients unsuccessfully treated with an anti-tnf agent Genovese et al., Abstract L15 10

6 TOWARD Study Study design Phase III, double-blind, placebo-controlled, international, multicenter study 50% of the study sites located in USA, which enrolled 41% of patients Randomization (1:2) Placebo + DMARDs (n = 415)* Primary endpoint Proportion of patients achieving ACR20 N = 1220 TCZ 8 mg/kg + DMARDs (n = 805)* Week iv Infusion *2 patients did not receive study medication and were subsequently excluded Patients who did not achieve a 20% improvement from baseline in both SJC and TJC at week 16 were offered rescue therapy (adjustment of the background DMARD dose and/or treatment with a different conventional DMARD) Genovese et al., Abstract L15 11 TOWARD Study Demographics and baseline characteristics Characteristics Age, years (mean) Female gender, % Duration of disease, years (mean ± SD) DAS28 (mean ± SD) TJC (mean ± SD) SJC (mean ± SD) RF positive, % Prior DMARDs/Anti-TNFs, n (mean ± SD) Previous anti-tnf use, % Methotrexate dose, mg/week (mean ± SD) Placebo + DMARDs n = ± ± ± ± ± ±5.0 Tocilizumab 8 mg/kg + DMARDs n = ± ± ± ± ± ±5.0 Genovese et al., Abstract L15 12

7 TOWARD Study Concomitant medication at baseline Co-medication use, % Methotrexate Chloroquine/hydroxychloroquine Sulfasalazine Leflunomide Parenteral gold Azathioprine Placebo + DMARDs n = Tocilizumab 8 mg/kg + DMARDs n = Oral steroids NSAIDs Genovese et al., Abstract L15 13 TOWARD Study Patient disposition 1220 Patients enrolled 415 Randomly assigned to Placebo + DMARDs a 805 Randomly assigned to Tocilizumab 8 mg/kg + DMARDs b 43 (10%) Withdrew 45 (11%) on rescue therapy 53 (7%) Withdrew 19 (2%) on rescue therapy 0 Withdrew 0 Withdrew 370 (89%) Completed the study Initial therapy (325) Rescue therapy (45) 751 (93%) Completed the study Initial therapy (732) Rescue therapy (19) a Includes 2 patients randomized to placebo who were not dosed and 2 patients who were randomized to placebo but received tocilizumab 8 mg/kg throughout the study b Includes 2 patients randomized to tocilizumab 8 mg/kg who were not dosed and 3 patients who were randomized to tocilizumab 8 mg/kg but received placebo throughout the study Genovese et al., Abstract L15 14

8 TOWARD Study Patients with an ACR response, % ACR responses at Week 24 Δ = 36.3* 60.8 *p < Δ = 28.6* 37.6 Δ = 17.6* ACR20 ACR50 ACR70 Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs Genovese et al., Abstract L15 15 TOWARD Study ACR20 response at Week 24 by background therapy Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs Patients with an ACR20 response (%) N = Methotrexate Leflunomide Sulfasalazine Chloroquine Hydrochloroquine Azathioprine 2 DMARDs 3 DMARDs Genovese et al., Abstract L15 16

9 TOWARD Study ACR20 response over time 70 Patients with an ACR20 response (%) * p < Time (weeks) Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs *Statistically significant vs placebo from Week 2 onwards Genovese et al., Abstract L15 17 TOWARD Study DAS28 scores and EULAR response at Week 24 Mean change from baseline in DAS28 score Mean change from baseline in DAS28 score* Placebo + DMARDs Δ = p < Tocilizumab 8mg/kg + DMARDs Patients (%) Good/moderate EULAR response* Δ = 42.1 p< Placebo + DMARDs 79.7 Tocilizumab 8mg/kg + DMARDs *DAS28 was calculated based on ESR Genovese et al., Abstract L15 18

10 TOWARD Study 50 Disease activity at Week 24 Disease remission (DAS28 <2.6) at Week 24* Low disease activity (DAS28 3.2) at Week 24* 50 Δ = Patients (%) Δ = 26.8 p < Patients (%) Placebo + DMARDs Tocilizumab 8mg/kg + DMARDs 0 Placebo + DMARDs Tocilizumab 8mg/kg + DMARDs *DAS28 was calculated based on ESR Genovese et al., Abstract L15 19 TOWARD Study Change in CRP levels over time 3 Mean CRP (mg/dl) p < ULN = 0.3 mg/dl Time (weeks) Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs Genovese et al., Abstract L15 20

11 TOWARD Study Increase in haemoglobin levels in patients with haemoglobin < LLN 13.5 Mean hemoglobin (mg/dl) LLN=13 mg/dl Time (weeks) Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs Genovese et al., Abstract L15 21 TOWARD Study Change in HAQ-DI scores from baseline Mean change in HAQ-DI score MCID = p < Time (weeks) Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs Genovese et al., Abstract L15 22

12 TOWARD Study Adverse events Patients, n (%) Any adverse event Severe adverse event Related adverse event Serious adverse event Adverse event leading to discontinuation Adverse event leading to dose modification Death Placebo + DMARDs (n = 414) 61.1% (253) 8.5% (35) 31.4% (130) 4.3% (18) 1.9% (8) 7.2% (30) <1% (2) Tocilizumab 8mg/kg + DMARDs (n = 802) 72.8% (584) 7.7% (62) 46.5% (373) 6.7% (54) 3.9% (31) 13.8% (111) <1% (2) Genovese et al., Abstract L15 23 TOWARD Study Serious adverse events (System organ classes) Patients, % (n) Patients with at least 1 SAE Total number SAEs Infections and infestations Musculoskeletal Gastrointestinal Nervous system Blood and lymphatics Cardiac Injuries, poisoning Neoplasms, etc Renal and urinary Respiratory Vascular Placebo + DMARDs (n = 414) 4.3% (18) 0.2% (1) 0.5% (2) 0.2% (1) 0.5% (2) 0.7% (6) 0.2% (2) 0.4% (3) 0.9% (7) 0.1% (1) 0.4% (3) 0.2% (2) 0.2% (2) Hepatobiliary 0.2% (2) Genovese et al., Abstract L % (8) 0.7% (3) 0.2% (1) TCZ 8mg/kg + DMARDs (n = 802) 6.7% (54) % (22) 0.2% (2) 1.1% (9)

13 TOWARD Study Patients, % (n) Patients with at least one serious infection Total number of events Cellulitis Pneumonia Herpes Zoster Bronchitis Pyelonephritis Abscess limb Arthritis bacterial Cellulitis staphylococcal Endocarditis enterococcal Serious infections Placebo + DMARDs (n = 414) 1.9% (8) 0.2% (1) 0.1% (1) 0.1% (1) Genovese et al., Abstract L % (2) - 0.2% (1) 0.2% (1) Tocilizumab 8mg/kg + DMARDs (n = 802) 2.7% (22) % (5) 0.4% (3) 0.4% (3) 0.1% (1) - 0.1% (1) 0.1% (1) TOWARD Study Changes in neutrophil counts (CTC grade)* CTC grade Normal Grade 1 (<LLN 1.5 x 10 9 /L) Grade 2 (< x 10 9 /L) Grade 3 (< x 10 9 /L) Grade 4 (<0.5 x 10 9 /L) *Neutrophil count decreases were transient Placebo + DMARDs n = % 4.3% <1% - - Tocilizumab 8 mg/kg + DMARDs n = % 18.8% 11.6% 3.7% - Genovese et al., Abstract L15 26

14 TOWARD Study Shifts in ALT and AST from baseline to highest value Highest Value Baseline ALT (ULN = 55 U/L) Placebo + DMARDs Normal range (n=380) ULN-3xULN (n=33) TCZ 8 mg/kg + DMARDs Normal range (n=737) ULN-3xULN (n=62) AST (ULN = 40 U/L) Placebo + DMARDs Normal range (n=396) ULN-3xULN (n=17) TCZ 8 mg/kg + DMARDs Normal range (n=747) ULN-3xULN (n=53) Normal range 83.9% 27.3% 50.5% 6.5% 87.1% 23.5% 60.5% 13.3% ULN-3xULN 15.3% 72.7% 45.0% 77.4% 12.4% 76.5% 38.3% 80.3% >3xULN <1% - 4.5% 16.1% <1% - 1.2% 7.5% Total 100% 100% 100% 100% 100% 100% 100% 100% Genovese et al., Abstract L15 27 TOWARD Study Clinical implications of ALT/AST changes Around 5% in tocilizumab + DMARD arm showed transient ALT elevations greater than 3x the upper limit of normal In the same range as infliximab 1 Elevations in liver enzymes transient No concomitant bilirubin elevations No clinical findings such as hepatitis or liver failure Consistent with previous tocilizumab studies 1 Source: Remicade USPI, Infliximab + methotrexate 28

15 TOWARD Study Changes in lipid levels Patients (%) Total cholesterol HDL LDL No change Change to 240 mg/dl No change Change to 60 mg/dl No change Change to 160 mg/dl Placebo + DMARDs TCZ 8 mg/kg + DMARDs Genovese et al., Abstract L15 29 TOWARD Study Summary of changes in atherogenic index (apob /apoa) baseline to last (% of Patients) (Improved) (Worsened) <-30% -30 to <-15% -15 to 15% >15 to 30% >30% Missing Placebo (%) (n=414) mg/kg + MTX (%) (n=802) Genovese et al., Abstract L15 30

16 The TOWARD study conclusions (1) Tocilizumab 8 mg/kg + DMARD significantly decreased disease activity over 24 weeks compared with placebo + DMARDs Higher proportion of patients in tocilizumab group achieved ACR20, ACR50, ACR70 and EULAR good/moderate response Higher mean reduction in DAS28 and HAQ-DI Rapid reduction in inflammation with normalization of CRP and hemoglobin levels Genovese et al., Abstract L15 31 The TOWARD study conclusions (2) Tocilizumab 8 mg/kg + DMARD was well tolerated in this patient population Incidence of serious infections 2.7% Transient neutropenia grade 3, but no association with febrile or infectious events Transient elevations in liver enzymes, but no clinical hepatitis Increases in cholesterol in some patients without change in atherogenic index Tocilizumab 8 mg/kg appears effective and safe when combined with a wide range of DMARDs in patients inadequately responding to a range of conventional DMARDs Genovese et al., Abstract L15 32

17 Actemra program overview Don MacLean, Actemra Lifecycle Leader Actemra Potential to become a significant new RA treatment First-in-class agent Humanized monoclonal antibody blocking the activity of IL-6 via inhibition of the IL-6 receptor Conclusions from Japanese phase III trials Impressive efficacy in DMARD inadequate responders Effective as monotherapy Well tolerated Large international phase III program 5 registration trials (>4 000 patients) Mono and combo therapy Patient populations studied: MTX inadequate responders DMARD inadequate responders Anti-TNFα inadequate responders MTX naïve patients First 4 trials all met primary endpoint Filed in Japan in April 2006 Global filing Q

18 Actemra: Filing & expected launches in RA USA Q U.S. filing U.S. launch U.S. launch *label extension EU Q EU filing EU launch EU launch *label extension * 1 and 2 year data from the LITHE trial 35 Actemra s international phase III program in RA OPTION TOWARD RADIATE AMBITION LITHE Reducing S&S Primary endpoint Reducing S&S Reducing S&S Reducing S&S Reducing S&S Inhibiting PJD PF improvements Population MTX IRs DMARD IRs Anti-TNF IRs MTX naive MTX IRs Treatment Actemra + MTX Actemra + DMARDS Actemra + MTX Actemra monotherapy Actemra + MTX 2 year Duration 6 months 6 months 6 months 6 months (6 month/ 1 yr interim analysis) 36

19 Actemra: Roche's international phase III studies in RA Study type Treatment in study Patient population type Actemra dose Study N Design Dosing regimen WA17822 OPTION month signs & symptoms study in combination with MTX in MTX-IR patients Actemra: 4 or 8 mg/kg + MTX vs continued MTX WA18063 TOWARD month signs & symptoms study in combination with DMARDs in DMARD-IR patients Actemra: 8 mg/kg + DMARDs vs continued DMARD WA18062 RADIATE month signs & symptoms study in combination with MTX in anti-tnf failure patients Actemra: 4 or 8 mg/kg + MTX vs continued MTX WA17824 AMBITION month signs & symptoms monotherapy study in MTX-naïve patients Actemra: 8 mg/kg vs MTX (escalating dose from 7.5 mg to 20 mg/week) WA17823 LITHE year signs & symptoms, joint damage and physical function study in combination with MTX in MTX-IR patients ongoing 6 month interim signs and symptoms in MAA 1 year S+S and x-ray data May 2008 Actemra: 4 or 8 mg/kg + MTX vs continued MTX WA18695 WA Open-label LTE studies with patients from WA17822 Open-label LTE studies with patients from WA17824, WA18062 and WA18063 Actemra: 8 mg/kg + standard anti-rheumatic therapy Actemra: 8 mg/kg alone or + standard anti-rheumatic therapy 37 Actemra: Summary of efficacy results from core studies Consistent and robust effects on all primary and secondary endpoints in all patients studied In MTX naïve - Actemra monotherapy demonstrated relief of signs and symptoms of RA superior to MTX For higher hurdles of efficacy (e.g. ACR50, ACR70, DAS28 remission, and EULAR good response) significant improvements seen in many patients Improvement in patients quality of life shown by HAQ-DI, SF-36 and FACITfatigue Normalisation of haemoglobin levels in patients who were anaemic at baseline Rapid onset of response shown by: normalization of markers of acute inflammation (C-reactive protein and ESR) first evidence of clinically important response (ACR and DAS/EULAR) as early as week 2 Efficacy is most apparent and reliable for the 8 mg/kg every 4 weeks regimen 38

20 Actemra: Summary of safety findings from core studies Over 2600 patients were exposed to Actemra for 6 months in the pivotal phase III studies In the long term safety population approximately 1400 patients were exposed for 12 months and approximately 600 patients were exposed for 18 months The safety profile of Actemra is consistent across all studies. The drug is well tolerated and the majority of adverse event were of mild or moderate intensity The safety profile of the two dose regimens was similar 39 Actemra: Long-term RA data from the Japanese program ACR20 (%) ACR50 (%) Year Efficacy assessment Year Year Year Year Median duration of treatment with Actemra was 62.8 months SAE rate 0.3 per patient-year with 0.06 serious infections per patientyear (588 patient-years) Cholesterol increase after treatment initiation and stabilized at a mean value of ~210 mg/dl ACR70 (%) Actemra: DAS28 Remission rate (%) Excellent long-term efficacy and a very good safety profile * Nishimoto et al., poster session ,

21 Actemra: Next steps in development Continued investment & lifecycle management Systemic Juvenile Idiopathic Arthritis (sjia) Phase III to start early 2008 Subcutaneous dose form Formulation and pre-clinical work ongoing Global Phase IIIB/IV Will generate further data for publications and broaden the clinical experience base Cardiovascular/Inflammation ROSE study in U.S. 41 Building a new franchise in Inflammation/Autoimmune Diseases Dr. Urs Schleuniger, VP, Head of Strategic Marketing Inflammation

22 Roche s key therapeutic areas Current and future pillars of growth Oncology Xeloda MabThera Herceptin Avastin Tarceva Pertuzumab Apomab Apo2L/TRAIL ARQ 15 phase I compounds On Hand RA/Autoimmune MabThera Actemra R1594 ocrelizumab PNP inhibitor 5 phase I compounds Metabolic R1583 GLP-1 R1658 CETP Inh. R1439 dual PPAR R1579 DPP-IV 3 phase I compounds Promising Late Stage Virology Tamiflu Pegasys R1626 Polym. Inh. R7227 Protease Inh. R7128 Polym. Inh. R3484 HPV16 Emerging Mid-Term Neurology / Psychiatry 6 phase I compounds Early Stage 43 Roche s focus in Inflammation/Autoimmune Diseases INDICATION PRIMARY PATHOLOGY HIGH NEED? PREVALENCE PATIENTS DISEASE PROGRESSION Rheumatoid Arthritis Joint/bone degeneration Yes 1% global +60 mln WW Mild, moderate, severe Multiple Sclerosis Destruction of CNS myelin Yes <<1% global mln WW RRMS; SPMS; PPMS; PRMS * Systemic Lupus Erythematpsus Tissue damage from autoantibodies Yes <0.5% global 0.5 mln U.S. Mild, intermittent, persistent, fulminant Lupus Nephritis Renal involvement in SLE Yes 40 85% SLE patients mln U.S. Class I - VI Psoriasis Autoimmune infiltration into skin Yes 1 2% global 125 mln WW Plaque-type: Mild, moderate, severe Inflammatory Bowel Disease Chronic intestinal inflammation Yes 0.2% - 0.5% global > 5 mln Mild, moderate, severe * RRMS: Relapsing-Remitting Multiple Sclerosis; SPMS: Secondary-Progressive MS; PPMS: Primary Progressive MS; PRMS: Progressive Relapsing MS 44

23 Roche s Inflammation/Autoimmune Diseases portfolio Expanding breadth of indications Phase I Phase II Phase III Approved RA R7277 (RA) Toyama Ocrelizumab (RA) MabThera/Rituxan (RA) DMARD IR MabThera/Rituxan (RA TNF IR) Actemra (RA) R7277 (RA) Toyama Ocrelizumab (SLE) moving to ph. 3 Ocrelizumab (RA) MabThera/Rituxan (RA) DMARD IR MabThera/Rituxan (RA TNF IR) All Autoimmune R3477 (MS) Actelion R1295 (MS) IFN-alpha Ab (SLE) GNE Ocrelizumab (LN) moving to ph. 3 Ocrelizumab (RRMS) MabThera/Rituxan (RRMS) GNE MabThera/Rituxan (PPMS) GNE MabThera/Rituxan ANCA avasc. GNE MabThera/Rituxan (SLE) GNE Actemra (RA) Actemra (sjia) CellCept (PV) R3421 (AI) Biocryst MabThera/Rituxan (LN) GNE 45 Roche s RA portfolio with first in class novel therapies Addressing unmet medical need Roche MabThera/ Rituxan Actemra Orals e.g. AP-1 Ocrelizumab Launched Phase III Phase I/II and later Launched Phase III Phase I/II Competitors Enbrel Amgen Remicade J&J Anti-TNF Other MoA Humira Abbott Co-stimulation modulator B-Cell Targeted Therapy Cimzia UCB Golimumab J&J Denosumab Amgen Orencia BMS HuMax 20 GenMab Belimumab HGS/CAT/GSK Tru015 Trubion/Wyeth 46

24 MabThera/Rituxan: Advancing in RA Feb 2006 Initial approvals in RA U.S. approval: TNF IRs July 2006 Feb 2007 April 2007 EU approval: TNF IRs Regulatory progress U.S. filing: X-Ray in TNF IRs EU SmPC: X-Ray in TNF IRs 2008 and beyond Global filing: DMARD-IRs SCORE Trial: MRI data in DMARD-IRs Global filing: MTX-Naive / X-Ray (IMAGE) 47 Inhibition of radiographic progression First evidence in patients with inadequate response to TNF inhibitors Mean change at Week p= Total Genant-modified Sharp score p= Joint space narrowing Placebo (n=184) RTX (n=273) p= Erosion score Primary analysis: Radiographs within time window, linear extrapolation from Week 24 for missing values Keystone et al. EULAR 2007 (Abstract no. SAT0011) 48

25 ACR scores are sustained Repeated courses in patients with prior IR to TNF inhibitors Patients (%) ACR20 ACR50 ACR70 Course 1 (n=96) Course 2 (n=96) Course 3 (n=96) Keystone et al, EULAR 2007 (Abstract no. SAT0012) Week 24, n=96 49 MabThera/Rituxan potentially offers larger DAS improvement than alternative TNF inhibitor Source: Finckh et al, A&R, May

26 MabThera: Increased experience and use among prescribers More and more rheumatologists get experience with MabThera More and more prescribers use MabThera after 1 TNF 70% 60% 56% 61% 70% 60% 50% 50% 40% 30% 39% 40% 30% 32% 38% 20% 20% 10% 10% 0% Q4'06 Q1'07 Q2'07 Q3'07 Q4'07 0% Q1'07 Q2'07 Q3'07 Q4'07 Source: Quarterly performance research 51 MabThera/Rituxan: Roche s ongoing phase III program Trial Data timing Treatment Sample size Endpoints MTX-IR SERENE 2008 MTX + placebo vs. MTX + MT/R 1g vs. MTX + MT/R 2g 495 Reduction in signs and symptoms MTX-IR Dose escalation MIRROR 2008 MT/R 1g retx 1g vs. MT/R 1g retx 2g vs. MT/R 2g retx 2g 375 Effect of further courses and dose escalation DMARD-IR SCORE 2009 MTX + placebo vs. MTX + MT/R 1g vs. MTX + MT/R 2g 180 MRI changes at 6 months MTX naïve (X-ray study) IMAGE 2010 MTX vs. MTX + MT/R 1g vs. MTX + MT/R 2g 852 Reduction in signs and symptoms Inhibition of structural joint damage Improvement in physical function EU filing

27 MabThera/Rituxan: Conclusions Sustained or improved efficacy with repeat treatment Benefits of MabThera/Rituxan are sustained with repeated courses Stopping joint damage progression remains a priority in inadequate responders to TNF inhibitors REFLEX study provides first and only evidence of inhibition of structural joint damage in this patient population This is independent of achieving a clinical response with MabThera/Rituxan Overall safety profile consistent with prior studies Similar serious infection rates with repeat treatment courses no opportunistic infections, viral reactivations or tuberculosis reported No lymphoproliferative malignancies and no increased risk of malignancy with additional courses of treatment were observed Long-term follow-up of RA patients receiving MabThera/Rituxan showed safety profile similar with each course 53 Ocrelizumab in Inflammation/Autoimmune Diseases Humanized anti-cd 20 antibody Shows Roche and Genentech s commitment to study B-cell therapy in a wider range of autoimmune diseases Rheumatoid Arthritis Global Phase III program with first study started in December 2006 Lupus (SLE/LN) Two global Phase III trials are in starting phase with enrollment expected in 4Q 2007 (SLE) and early 2008 (LN) Relapsing-Remitting MS (RRMS) Phase II expected to start 1H

28 Multiple sclerosis An emerging therapeutic area for Roche MS is a common neurological disease affecting more than 1 million people worldwide Multifocal inflammatory disease that damages the myelin of CNS and causes neurological impairment and, frequently, severe disability Commonest cause of neurological disability in young and middle-aged adults Prevalence of MS varies by geographical areas high prevalence: Europe, Northern U.S., Canada, AUS low prevalence: Japan and Africa More common in women (2:1), Caucasians MRI allows clinicians to detect and follow pathological progression of disease & response to treatment 55 Prevalence of MS in Europe ~260,000 patients total SPMS 25% PPMS 10% RRMS 65% patients Diagnosed (81%) patients Treated (~66%) patients Source: Data Monitor

29 Multiple sclerosis therapies and treatment trends Diagnosis and treatment rates for MS in major pharma markets 300 Prevalent population (thousands) United States France Germany Italy Spain United Kingdom Japan Undiagnosed Diagnosed, not drug-treated Diagnosed, drug-treated Source: Decision Resources 57 Multiple sclerosis therapy breakdown Role of biologics forecasted to grow substantially Altered peptide ligands Chemo. 1% MAbs. 1% 25% Other a < 1% Oral immunomodulators Oral immunosuppressants 6% 19% Other b < 1% 45% Recombinant interferons 72% MAbs 13% Recombinant interferons Other includes corticosteroids, azathioprine and mycophenolate mofetil Other includes corticosteroids and chemotherapeutics Source: Decision Resources 16% Altered peptide ligands 58

30 Development hurdles & treatment challenges Unmet need: Remaining opportunity in MS Reversing neuronal damage Area of highest medical need Importance Preventing disease progression Improved therapy for chronic-progressive multiple sclerosis More-convenient drug delivery Improved diagnostic criteria Improved animal models Level of attainment Source: Decision Resources Low attainment/ high opportunity Medium attainment/ medium opportunity High attainment/ low opportunity 59 Proof-of-concept for anti-cd20 in RRMS Ocrelizumab prioritized for further development Genentech s/biogen Idec s Proof of Concept (Phase 2) placebo-controlled trial of MabThera/Rituxan was presented at the 2007 American Academy of Neurology Treatment with MabThera/Rituxan led to significantly fewer inflammatory brain lesions and relapses over a 6 month period Preliminary evidence supports the involvement of B cells in RRMS pathophysiology Roche and Genentech will develop ocrelizumab (humanized anti-cd20) for RRMS: Global Phase 2 planned to start 1 st half 2008 Anti-CD20 therapy may become an option in the future treatment of MS 60

31 Roche s emerging multiple sclerosis portfolio New approaches to MS therapy multiple opportunities MabThera/Rituxan (anti CD-20) Phase II (HERMES) in RRMS met primary endpoints Data presented at AAN 07 Phase II/III in PPMS (OLYMPUS) results in 1H-2008 Ocrelizumab (hum. anti CD-20) Phase II in RRMS to start 1H-2008 S1P1 selective receptor agonist Phase I - joint development with Actelion Inhibits migration and recirculation of lymphocytes from lymph nodes Orally active In development for multiple autoimmune disorders, including MS Go/no-go decision in Q phase III project 1 phase II project 1 phase I project 61 Roche in autoimmune disorders Roche is well placed to address high unmet need and capitalize from large growth opportunity Innovative pipeline with 2 first-in-class RA drugs in launch / pre-launch Large investment in development program (second only to oncology) Scientific and commercial collaboration with co-marketing partners Genentech and Chugai as well as other 3rd parties Strong corporate commitment to build up Autoimmune franchise RA MS Lupus Vasculitis Roche poised to become a leader in Inflammation/Autoimmune Diseases 62

32 Questions & Answers We Innovate Healthcare 64