Investor Event at ACR ´07 in Boston 9 November 2007

Investor event at ACR ´07 in Boston 9 November 2007

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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 www.roche.com for full information on Roche products mentioned.

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 Roche’s key therapeutic areas Current and future pillars of growth Neurology / Psychiatry Virology 6 phase I compounds Tamiflu Pegasys R1626 Polym. Inh. R7227 Protease Inh. R7128 Polym. Inh. Metabolic R3484 HPV16 R1583 GLP-1 R1658 CETP Inh. R1439 dual PPAR R1579 DPP-IV RA/Autoimmune 3 phase I compounds MabThera Actemra R1594 ocrelizumab PNP inhibitor Oncology 5 phase I compounds Xeloda MabThera Herceptin Avastin Tarceva Pertuzumab Apomab Apo2L/TRAIL ARQ 15 phase I compounds Promising Late Emerging Early On Hand Stage Mid-Term Stage 5

Roche in Inflammation/Autoimmune Diseases Building a new therapeutic franchise

MabThera/Rituxan Ocrelizumab Rheumatoid Arthritis Rheumatoid Arthritis, Multiple Sclerosis, Lupus • Launched in RA anti-TNFa inadequate • Phase II trial in RA met primary and secondary responders (IR) in U.S. and EU endpoints, presented at ACR ’06 • Filing for RA in DMARD IR in 2008 • Phase III program in RA running • Phase III in SLE to start Q4-2007 and LN in early 2008 Multiple Sclerosis (MS), Lupus, Vasculitis • Phase III in PPMS, SLE, LN and ANCA ass. • Phase II in RRMS to start H1 2008 vasculitis ongoing Phase 1 Actemra • 5 compounds for Inflammation/ Autoimmune Diseases Rheumatoid Arthritis • Filed in Japan • Broad international phase III program closing – four trials reported in 2007 10 phase III projects • Global filing Q4-2007 3 phase II projects

6 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

Endothelial cells Monocytes/ macrophages Mesenchymal cells, fibroblasts/synoviocytes IL-6

T cell activation Hepatocytes Acute-phase proteins hepcidin, CRP

Maturation of B cells megakaryocytes Osteoclast activation Bone resorption Thrombocytosis

Auto-antibodies (RF) Hyper γ-globulinaemia

Nature Nat Rev Drug Disc Firestein GS. 2003;423:356–361; Smolen JS and Steiner G. 2003;2:473–488 8 Genovese et al., Abstract L15 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

sIL-6R X X mIL-6R Cell membrane

X gp130 gp130 X

Signal transduction inhibited

9 Genovese et al., Abstract L15

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

10 Genovese et al., Abstract L15 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) Primary endpoint Proportion of patients Placebo + DMARDs (n = 415)* achieving ACR20

N = 1220

TCZ 8 mg/kg + DMARDs (n = 805)* Week 084122016 24 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) 11 Genovese et al., Abstract L15

TOWARD Study Demographics and baseline characteristics

Placebo Tocilizumab 8 mg/kg + DMARDs + DMARDs Characteristics n = 413 n = 803 Age, years (mean) 53.5 53.0 Female gender, % 84 81 Duration of disease, years (mean ± SD) 9.8±9.1 9.8±8.8 DAS28 (mean ± SD) 6.6±1.0 6.7±1.0 TJC (mean ± SD) 29.1±14.8 30.1±16.0 SJC (mean ± SD) 18.7±10.8 19.7±11.6 RF positive, % 75 78 Prior DMARDs/Anti-TNFs, n (mean ± SD) 1.6±1.6 1.6±1.6 Previous anti-TNF use, % 15 17 Methotrexate dose, mg/week (mean ± SD) 15.0±5.0 14.7±5.0

12 Genovese et al., Abstract L15 TOWARD Study Concomitant medication at baseline

Placebo Tocilizumab 8 mg/kg + DMARDs + DMARDs Co-medication use, % n = 413 n = 803 Methotrexate 73.9 75.8 Chloroquine/hydroxychloroquine 19.8 20.6 Sulfasalazine 14.3 13.1 Leflunomide 15.5 12.1 Parenteral gold 0.7 0.2 Azathioprine 2.2 2.2

Oral steroids 54.6 51.2 NSAIDs 77.1 71.4 13 Genovese et al., Abstract L15

TOWARD Study Patient disposition

1220 Patients enrolled

415 Randomly assigned to 805 Randomly assigned to Tocilizumab Placebo + DMARDsa 8 mg/kg + DMARDsb

43 (10%) 53 (7%) Withdrew Withdrew 45 (11%) 19 (2%) on rescue therapy on rescue therapy

0 Withdrew 0 Withdrew

370 (89%) Completed the study 751 (93%) Completed the study Initial therapy (325) Initial therapy (732) Rescue therapy (45) Rescue therapy (19) aIncludes 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 bIncludes 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 14 Genovese et al., Abstract L15 TOWARD Study ACR responses at Week 24

Δ = 36.3* 70 60.8 60 *p < 0.0001 50 Δ = 28.6*

40 37.6 Δ = 17.6* 30 24.5 20.5 20 9.0 10 2.9 Patients withPatients an response, ACR % 0 ACR20 ACR50 ACR70

Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs 15 Genovese et al., Abstract L15

TOWARD Study ACR20 response at Week 24 by background therapy

Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs

70 65.4 65.7 65.8 63.6 59.0 60 57.7

50 46.7

40 33.3 29.4 29.3 30 25.0

20 18.0

Patients with an ACR20 response (%) 10

0.0 0.0 0 N = 224 456 50 78 16 35 17 33 4 12 82 152 15 26 e s t e ne e s D xa d zi ne rin D e mi a e i p R AR tr o al in qu io o n s u o h MA M th flu fa q r at D D e ul ro lo z 3 Me L lo h A 2 ≥ S h oc C dr 16 Genovese et al., Abstract L15 y H TOWARD Study ACR20 response over time

70

60

50

40 p < 0.0001

30

20 *

10 Patients with an ACR20 response (%) response ACR20 with an Patients

0 0 4 8 12162024 Time (weeks)

Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs

*Statistically significant vs placebo from Week 2 onwards 17 Genovese et al., Abstract L15

TOWARD Study DAS28 scores and EULAR response at Week 24

Mean change from baseline Good/moderate EULAR response* in DAS28 score* Tocilizumab Δ = 42.1 Placebo + DMARDs 8mg/kg + DMARDs 90 p<0.0001 0 79.7 80

-0.5 70

-1 60 -1.16 50 -1.5 40 37.6

score -2

Patients (%) Patients 30

-2.5 20

-3 10

0 -3.5 -3.17

Mean change from baseline in DAS28 from change Mean Δ = -2.01 Placebo + DMARDs Tocilizumab p < 0.0001 8mg/kg + DMARDs

*DAS28 was calculated based on ESR 18 Genovese et al., Abstract L15 TOWARD Study Disease activity at Week 24 Disease remission (DAS28 <2.6) Low disease activity (DAS28 ≤3.2) at Week 24* at Week 24* Δ = 39.7 50 50 45.3

40 Δ = 26.8 40 p < 0.0001 30.2 30 30

20 20 Patients (%) Patients Patients (%) Patients

10 10 5.6 3.4 0 0 Placebo + DMARDs Tocilizumab 8mg/kg Placebo + DMARDs Tocilizumab + DMARDs 8mg/kg + DMARDs

*DAS28 was calculated based on ESR 19 Genovese et al., Abstract L15

TOWARD Study Change in CRP levels over time

3

2.5

2

1.5

1 p < 0.0001 Mean CRP (mg/dL) Mean 0.5 ULN = 0.3 mg/dL 0 04812162024 Time (weeks)

Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs 20 Genovese et al., Abstract L15 TOWARD Study Increase in haemoglobin levels in patients with haemoglobin < LLN

13.5

LLN=13 mg/dL 13.0

12.5

12.0

11.5 Mean hemoglobin (mg/dL) hemoglobin Mean

11.0 0 4 8 12 16 20 24 Time (weeks)

Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs 21 Genovese et al., Abstract L15

TOWARD Study Change in HAQ-DI scores from baseline

04812162024 0

-0.1

-0.2 MCID = -0.22 -0.3 p < 0.0001 -0.4

-0.5 Mean change score in HAQ-DI -0.6 Time (weeks)

Placebo + DMARDs Tocilizumab 8 mg/kg + DMARDs 22 Genovese et al., Abstract L15 TOWARD Study Adverse events

Placebo Tocilizumab 8mg/kg + DMARDs + DMARDs Patients, n (%) (n = 414) (n = 802) Any adverse event 61.1% (253) 72.8% (584) Severe adverse event 8.5% (35) 7.7% (62) Related adverse event 31.4% (130) 46.5% (373) Serious adverse event 4.3% (18) 6.7% (54) Adverse event leading to 1.9% (8) 3.9% (31) discontinuation Adverse event leading to dose 7.2% (30) 13.8% (111) modification Death <1% (2) <1% (2)

23 Genovese et al., Abstract L15

TOWARD Study Serious adverse events (System organ classes)

Placebo + DMARDs TCZ 8mg/kg + DMARDs Patients, % (n) (n = 414) (n = 802) Patients with at least 1 SAE 4.3% (18) 6.7% (54) Total number SAEs 20 67 Infections and infestations 1.9% (8) 2.7% (22) Musculoskeletal 0.7% (3) 0.2% (2) Gastrointestinal 0.2% (1) 1.1% (9) Nervous system 0.5% (2) 0.7% (6) Blood and lymphatics – 0.2% (2) Cardiac 0.2% (1) 0.4% (3) Injuries, poisoning – 0.9% (7) Neoplasms, etc – 0.1% (1) Renal and urinary – 0.4% (3) Respiratory 0.2% (1) 0.2% (2) Vascular 0.5% (2) 0.2% (2) Hepatobiliary – 0.2% (2) 24 Genovese et al., Abstract L15 TOWARD Study Serious infections

Tocilizumab 8mg/kg + Placebo + DMARDs DMARDs Patients, % (n) (n = 414) (n = 802) Patients with at least one serious 1.9% (8) 2.7% (22) infection Total number of events 8 23 Cellulitis - 0.6% (5) Pneumonia 0.5% (2) 0.4% (3) Herpes Zoster - 0.4% (3) Bronchitis 0.2% (1) 0.1% (1) Pyelonephritis 0.2% (1) 0.1% (1) Abscess limb 0.2% (1) - Arthritis bacterial - 0.1% (1) Cellulitis staphylococcal - 0.1% (1) Endocarditis enterococcal - 0.1% (1) 25 Genovese et al., Abstract L15

TOWARD Study Changes in neutrophil counts (CTC grade)*

Placebo Tocilizumab 8 mg/kg CTC grade + DMARDs + DMARDs n = 414 n = 802

Normal 94.9% 65.6%

Grade 1 (

Grade 2 (<1.5 – 1.0 x 109/L) <1% 11.6%

Grade 3 (<1.0 – 0.5 x 109/L) - 3.7%

Grade 4 (<0.5 x 109/L) - -

*Neutrophil count decreases were transient 26 Genovese et al., Abstract L15 TOWARD Study Shifts in ALT and AST from baseline to highest value

Highest Value ALT (ULN = 55 U/L) Normal range ULN-3xULN >3xULN Total Placebo + DMARDs Normal range (n=380) 83.9% 15.3% <1% 100% ULN-3xULN (n=33) 27.3% 72.7% - 100% TCZ 8 mg/kg + DMARDs Normal range (n=737) 50.5% 45.0% 4.5% 100% ULN-3xULN (n=62) 6.5% 77.4% 16.1% 100% AST (ULN = 40 U/L)

Baseline Placebo + DMARDs Normal range (n=396) 87.1% 12.4% <1% 100% ULN-3xULN (n=17) 23.5% 76.5% - 100% TCZ 8 mg/kg + DMARDs Normal range (n=747) 60.5% 38.3% 1.2% 100% ULN-3xULN (n=53) 13.3% 80.3% 7.5% 100%

27 Genovese et al., Abstract L15

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 infliximab1 • 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 TOWARD Study Changes in lipid levels

80 Total cholesterol HDL LDL 67.4 70 65.0 64.5 65.5 60 56.6 48.6 50 40

30 23.0 Patients (%) Patients 20 15.0 16.1 6.0 10 5.5 3.4 0 No Change to No Change to No Change to change ≥240 change ≥60 mg/dL change ≥160 mg/dL mg/dL

Placebo + DMARDs TCZ 8 mg/kg + DMARDs 29 Genovese et al., Abstract L15

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 (%) 5.2 16 57.6 13.1 8.4 1.9 (n=414)

8 mg/kg + MTX (%) 7.0 16 54.8 11.9 10.3 1.6 (n=802)

30 Genovese et al., Abstract L15 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

31 Genovese et al., Abstract L15

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

32 Genovese et al., Abstract L15 Actemra program overview

Don MacLean, Actemra Lifecycle Leader

Actemra Potential to become a significant new RA treatment

First-in-class agent Large international phase III program • Humanized monoclonal antibody • 5 registration trials (>4‘000 patients) blocking the activity of IL-6 via • Mono and combo therapy inhibition of the IL-6 receptor • Patient populations studied: • Conclusions from Japanese phase III trials – MTX inadequate responders – Impressive efficacy in DMARD – DMARD inadequate responders – Anti-TNF inadequate responders inadequate responders α – Effective as monotherapy – MTX naïve patients – Well tolerated • First 4 trials all met primary endpoint

Filed in Japan in April 2006 Global filing Q4-2007 34 Actemra: Filing & expected launches in RA

USA Q4-2007 U.S. launch U.S. launch U.S. filing *label extension

2005 2006 2007 2008 2009 2010

EU

Q4-2007 EU launch EU launch EU filing *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 Inhibiting PJD Reducing S&S Reducing S&S Reducing S&S Reducing S&S endpoint PF improve- ments

Population MTX IRs DMARD IRs Anti-TNF IRs MTX naive MTX IRs

Actemra + Actemra + Actemra + Actemra Actemra + Treatment MTX DMARDS MTX monotherapy MTX

2 year (6 month/ Duration 6 months 6 months 6 months 6 months 1 yr interim analysis)

36 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 623 6-month signs & symptoms study in combination Actemra: 4 or 8 mg/kg + MTX vs OPTION with MTX in MTX-IR patients continued MTX

WA18063 1220 6-month signs & symptoms study in combination Actemra: 8 mg/kg + DMARDs vs TOWARD with DMARDs in DMARD-IR patients continued DMARD

WA18062 499 6-month signs & symptoms study in combination Actemra: 4 or 8 mg/kg + MTX vs RADIATE with MTX in anti-TNF failure patients continued MTX

WA17824 673 6-month signs & symptoms monotherapy study in Actemra: 8 mg/kg vs MTX AMBITION “MTX-naïve” patients (escalating dose from 7.5 mg to 20 mg/week)

WA17823 1196 2-year signs & symptoms, joint damage and Actemra: 4 or 8 mg/kg + MTX vs LITHE physical function study in combination with MTX continued MTX in MTX-IR patients – ongoing 6 month interim signs and symptoms in MAA 1 year S+S and x-ray data May 2008

WA18695 537 Open-label LTE studies with patients from WA17822 Actemra: 8 mg/kg + standard anti-rheumatic therapy Open-label LTE studies with patients from 1902 WA17824, WA18062 and WA18063 WA18696 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 FACIT- fatigue • 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 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

Efficacy assessment • Median duration of treatment with Year Year Year Year Year Actemra was 62.8 months 1 2 3 4 5 • SAE rate 0.3 per patient-year with 0.06 serious infections per patient- 75.6 81.5 84.1 80.8 84.2 ACR20 (%) year (588 patient-years) • Cholesterol increase after treatment 55.0 59.7 64.5 63.6 68.4 initiation and stabilized at a mean ACR50 (%) value of ~210 mg/dL

28.2 37.0 39.3 42.4 44.7 ACR70 (%) Actemra:

DAS28 Excellent long-term efficacy 34.1 44.7 47.7 38.2 48.4 Remission and a very good safety profile rate (%)

* Nishimoto et al., poster session 117-01, 296 40 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 Roche’s key therapeutic areas Current and future pillars of growth Neurology / Psychiatry Virology 6 phase I compounds Tamiflu Pegasys R1626 Polym. Inh. R7227 Protease Inh. R7128 Polym. Inh. Metabolic R3484 HPV16 R1583 GLP-1 R1658 CETP Inh. R1439 dual PPAR R1579 DPP-IV RA/Autoimmune 3 phase I compounds MabThera Actemra R1594 ocrelizumab PNP inhibitor Oncology 5 phase I compounds Xeloda MabThera Herceptin Avastin Tarceva Pertuzumab Apomab Apo2L/TRAIL ARQ 15 phase I compounds Promising Late Emerging Early On Hand Stage Mid-Term Stage 43

Roche’s focus in Inflammation/Autoimmune Diseases

PRIMARY HIGH DISEASE INDICATION PREVALENCE PATIENTS PATHOLOGY NEED? PROGRESSION

Joint/bone Mild, moderate, Yes 1% global +60 mln WW Rheumatoid Arthritis degeneration severe

Destruction of RRMS; SPMS; Yes <<1% global 0.6 - 1.1 mln WW Multiple Sclerosis CNS myelin PPMS; PRMS *

Tissue damage Systemic Lupus Mild, intermittent, from Yes <0.5% global 0.5 mln U.S. persistent, fulminant Erythematpsus autoantibodies

Renal 40 – 85% SLE involvement in Yes 0.2 – 0.4 mln U.S. Class I - VI Lupus Nephritis patients SLE

Autoimmune Plaque-type: Mild, infiltration into Yes 1 – 2% global 125 mln WW Psoriasis moderate, severe skin

Inflammatory Bowel Chronic intestinal Yes 0.2% - 0.5% global > 5 mln Mild, moderate, severe Disease inflammation

* RRMS: Relapsing-Remitting Multiple Sclerosis; SPMS: Secondary-Progressive MS; PPMS: Primary Progressive MS; PRMS: Progressive Relapsing MS 44 Roche’s Inflammation/Autoimmune Diseases portfolio Expanding breadth of indications

Phase I Phase II Phase III Approved

MabThera/Rituxan R7277 (RA) Ocrelizumab (RA) MabThera/Rituxan Toyama (RA) DMARD IR (RA TNF IR) RA

Actemra (RA)

moving to ph. 3 MabThera/Rituxan MabThera/Rituxan R7277 (RA) Ocrelizumab Ocrelizumab (RA) Toyama (SLE) (RA) DMARD IR (RA TNF IR)

Ocrelizumab moving to ph. 3 MabThera/Rituxan R3477 (MS) (PPMS) Actemra Actelion (LN) GNE (RA)

MabThera/Rituxan Ocrelizumab Actemra R1295 (MS) (RRMS) ANCA aVasc. GNE (sJIA)

Autoimmune IFN-alpha Ab MabThera/Rituxan MabThera/Rituxan (SLE) (RRMS) (SLE) CellCept GNE GNE GNE (PV) All

R3421 (AI) MabThera/Rituxan Biocryst (LN) GNE

45

Roche’s RA portfolio with first in class novel therapies Addressing unmet medical need

Roche Orals e.g. AP-1 MabThera/ Actemra Ocrelizumab Rituxan

Launched Phase III Phase I/II 1998 1999 2000 2001 2002 2003 2004 2005 20062007 2008 and later Launched Phase III Phase I/II Competitors Enbrel Cimzia Denosumab Amgen UCB Amgen Remicade Humira Golimumab Orencia J&J Abbott J&J BMS HuMax 20 GenMab Belimumab Anti-TNF Co-stimulation modulator HGS/CAT/GSK Tru015 Other MoA B-Cell Targeted Therapy 46 Trubion/Wyeth MabThera/Rituxan: Advancing in RA

Initial approvals in RA Feb 2006 U.S. approval: TNF IRs

July 2006 EU approval: TNF IRs

Regulatory progress Feb 2007 U.S. filing: X-Ray in TNF IRs April EU SmPC: 2007 X-Ray in TNF IRs

Global filing: Global filing: 2008 and DMARD-IRs MTX-Naive / X-Ray (IMAGE) beyond SCORE Trial: MRI data in DMARD-IRs

47

Inhibition of radiographic progression First evidence in patients with inadequate response to TNF inhibitors

p=0.0046 Placebo (n=184) RTX (n=273) 2.5 2.31

2.0 p=0.0114 p=0.0006 1.5 1.32 1 0.99 1.0 0.59 0.5 0.41

Mean change at Week 56 0.0 Total Genant-modified Joint space narrowing Erosion score Sharp score

Primary analysis: Radiographs within time window, linear extrapolation from Week 24 for missing values

Keystone et al. EULAR 2007 (Abstract no. SAT0011) 48 ACR scores are sustained Repeated courses in patients with prior IR to TNF inhibitors

90 76 77 80 69 70

60 48 48 50 36 40 Patients (%) 25 30 19 20 11 10 0 ACR20 ACR50 ACR70 Course 1 (n=96) Course 2 (n=96) Course 3 (n=96)

Week 24, n=96 Keystone et al, EULAR 2007 (Abstract no. SAT0012) 49

MabThera/Rituxan potentially offers larger DAS improvement than alternative TNF inhibitor

Source: Finckh et al, A&R, May 2007 50 MabThera: Increased experience and use among prescribers

More and more rheumatologists get More and more prescribers use experience with MabThera MabThera after 1 TNF

70% 70% 61% 60% 56% 60%

50% 50% 39% 40% 40% 38% 32% 30% 30%

20% 20%

10% 10%

0% 0% Q4'06 Q1'07 Q2'07 Q3'07 Q4'07 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 + placebo vs. Reduction in signs and MTX-IR 2008 MTX + MT/R 1g vs. 495 symptoms SERENE MTX + MT/R 2g

MT/R 1g retx 1g vs. MTX-IR 2008 MT/R 1g retx 2g vs. 375 Effect of further courses Dose escalation and dose escalation MIRROR MT/R 2g retx 2g MTX + placebo vs. DMARD-IR 2009 MTX + MT/R 1g vs. 180 MRI changes at 6 months SCORE MTX + MT/R 2g Reduction in signs and MTX vs. symptoms MTX naïve 2010 MTX + MT/R 1g vs. 852 Inhibition of structural (X-ray study) joint damage IMAGE MTX + MT/R 2g Improvement in physical function EU filing 2008

52 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-2008

54 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 MRI allows clinicians to detect and – low prevalence: Japan and Africa follow pathological progression of disease & response to treatment • More common in women (2:1), Caucasians

55

Prevalence of MS in Europe

~260,000 patients total

PPMS SPMS 10% RRMS 25% 65%

169’000 patients

Diagnosed (81%) 137’000 patients

Treated (~66%) 90’000 patients

Source: Data Monitor 2007 56 Multiple sclerosis therapies and treatment trends Diagnosis and treatment rates for MS in major pharma markets

300

250

200

150

(thousands) 100 Prevalent population 50

0 United States France Germany Italy Spain United Japan Kingdom Undiagnosed Diagnosed, not drug-treated Diagnosed, drug-treated

Source: Decision Resources 57

Multiple sclerosis therapy breakdown Role of biologics forecasted to grow substantially

2005 2020

Chemo. 1% Otherb < 1% MAbs. 1% Othera < 1% Oral Altered immunomodulators Recombinant peptide interferons Oral ligands 19% 25% immunosuppressants

6% 45%

72% MAbs 13%

16% Recombinant interferons Altered peptide “Other” includes corticosteroids, azathioprine and mycophenolate mofetil ligands “Other” includes corticosteroids and chemotherapeutics Source: Decision Resources 58 Development hurdles & treatment challenges Unmet need: Remaining opportunity in MS

Reversing neuronal Area of highest medical need… damage

Preventing disease progression

Improved therapy for chronic-progressive multiple sclerosis Importance More-convenient drug delivery

Improved diagnostic criteria

Improved animal models

Level of attainment Low attainment/ Medium attainment/ High attainment/ high opportunity medium opportunity low opportunity Source: Decision Resources 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 1st half 2008

Anti-CD20 therapy may become an option in the future treatment of MS

60 Roche’s emerging multiple sclerosis portfolio New approaches to MS therapy – multiple opportunities

MabThera/Rituxan (anti CD-20) S1P1 selective receptor agonist • Phase II (HERMES) in RRMS met • Phase I - joint development with primary endpoints Actelion • Data presented at AAN ‘07 • Inhibits migration and recirculation of • Phase II/III in PPMS (OLYMPUS) – lymphocytes from lymph nodes results in 1H-2008 • Orally active • In development for multiple autoimmune disorders, including MS Ocrelizumab (hum. anti CD-20) • Phase II in RRMS to start 1H-2008 • Go/no-go decision in Q1 2008

1 phase III project 1 phase II project 1 phase I project

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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 Questions & Answers

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