Investor science conference call ASH 2009 New Orleans, 8 December 2009

Transcription

1 Investor science conference call ASH 2009 New Orleans, 8 December 2009

2 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: 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; 0 loss of key executives or other employees; and 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

3 Introduction Dr. Karl Mahler, Head of Investor Relations

4 Investor science events at major medical meetings Seven events highlight the group s pipeline leadership 3 May 2009 June June June 2009 Orlando, United States Orlando, United States New Orleans, United States Copenhagen, Denmark American Society of Clinical Oncology (ASCO), day American Society of Clinical Oncology (ASCO), day 2 American Diabetes Association (ADA) The European League Against Rheumatism (EULAR) Oncology Oncology Metabolism/Diabetes Inflammation/Rheumatoid Arthritis 25 September 2009 Berlin, Germany European CanCer Organisation - European Society for Medical Oncology (ECCO - ESMO) Oncology 8 December 2009 New Orleans, United States American Society of Hematology (ASH) Hematology/Oncology 4 December 2009 San Antonio, United States San Antonio Breast Cancer Symposium (SABCS) Oncology Next week Steady flow of important clinical data & results 4

5 Agenda Leader in hematology Hematology pipeline overview Dr. Sandra Horning, Sr. VP, Global Head, Clinical Development Hematology/Oncology Important clinical data at ASH 2009 Dr. Nancy Valente, Sr. Group Director, Clinical Development Hematology/Oncology Leader in hematology commercial overview & opportunities Dr. Myriam Mendila, Hematology Franchise Leader Questions & Answers Total duration: Up to ½ hour 5

6 Hematology pipeline overview Dr. Sandra Horning, Sr. VP, Global Head, Clinical Development Hematology/Oncology

7 Pipeline overview Pipeline highlights 7

8 Hematology development strategy Our goal To use our science to continue developing a number of therapeutics like MabThera/Rituxan that significantly improve the lives of people with hematological malignancies Targeting the right drug to the right patient Identify the best drugs for patients based on the biologic characteristics of the tumor and the individual Integrate diagnostics and therapeutics to deliver personalised healthcare 8

9 The clinical pipeline in hematology: Translating science to patient benefit Avastin Anti-angiogenic Phase I DLBCL, MM (phase II) Phase Ib/II Phase III RG759/GA0 Next-gen anti-cd20 CLL, inhl Moving to Phase III RG7433/ABT-263 BH3 mimetic CLL, lymphoid malignancies RG7425 DR5 agonist RG3639(dulanermin) 2 DR4/DR5 agonist RG3636/SGN-40(dacetuzumab) 3 Anti-CD40 RG7422/GDC-0980 PI3 kinase inhibitor inhl inhl DLBCL, inhl, MM NHL O O S N O N O N N Cl Cl RG72 MDM2 antagonist Hematological tumors DLBCL=Diffuse Large B-Cell Lymphoma, MM=Multiple Myeloma, inhl=indolent Non-Hodgkin s Lymphoma In partnership w/abbott 2 In partnership w/amgen 3 In partnership w/seattle Genetics 9

10 The clinical pipeline in hematology: Targeting the underlying biology Evading apoptosis RG7433/ABT-263 (BH3 mimetic) Sustained angiogenesis Avastin(bevacizumab) Multiple hallmarks of hematological malignancies RG759/GA0 (Next-gen anti-cd20) RG7425 (DR5 agonist) RG3639(dulanermin) 2 (DR4/DR5 agonist) RG3636/SGN-40(dacetuzumab) 3 (Anti-CD40) RG7422/GDC-0980 (PI3 kinase inhibitor) RG72 (MDM2 antagonist) Hanahan & Weinberg, The Hallmarks of Cancer, Cell, vol 00, pp 57-70, copyright Elsevier (2000) In partnership w/abbott 2 In partnership w/amgen 3 In partnership w/seattle Genetics 0

11 Pipeline overview Pipeline highlights

12 RG759/GA0 (Next-gen anti-cd20): First glyco-engineered type II CD20 mab CD20 peptide Type II recognition & elbow-hinge residues Carbohydrate glycoengineered (GlycoMab TM technology) Increased direct cell-death induction Unique type II epitope and elbowhinge modification Enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) Increased affinity to the ADCC receptor FcgRIIIA Lower complement-dependent cytotoxicity (CDC) activity Due to recognition of type II epitope Umaña et al, Blood 2006; 08, abstract 229, Umaña et al, Ann Oncology 2008, 9 (suppl 4), abstract 098 2

13 RG759/GA0 (Next-gen anti-cd20): Rapid B-cell depletion and superior tumor remissions in preclinical models B-cell depletion whole-blood assay in B-CLL patients (24 h) SU-DHL-4NHL xenograft in mice pretreated with MabThera/Rituxan(rituximab) CD9+ Depletion (%) GA0 Rituximab ,000 Tumor volume (mm 3 ) median IQR Vehicle n=0 Rituximab st line Rituximab 30 mg/kg GA0 30 mg/kg Ab conc. (ng/ml) Time after cell transplantation (days) Non-ADCC competent s.c. xenograft model (SCID beige) 3

14 RG7433/ABT-263 (BH3 mimetic): Acts as a BH3 mimetic to induce apoptosis Cytotoxic Chemo DNA damaging agents Anti-mitotics Antibody-drug conjugates TDM- Other ADC Bax Anti-CD20 Rituxan GA0 Bim Bid Puma Bak Mitochondria EGFR targeted agents Tarceva Erbitux Bad Bik Hrk Noxa Bmf Bcl-2 ABT-263 Cyt C activated BAX / BAK PI3K Bcl-xL Caspase activation MEK PI3K/mTOR AKT BCL-2 is a target for tumor biology driven over-expression in lymphoid cancers and SCLC Apoptosis In partnership w/abbott 4

15 RG7433/ABT-263 (BH3 mimetic): Acts as a BH3 mimetic to induce apoptosis Bax Bak Mitochondria Bcl-2 Bcl-xL ABT-263 activated BAX / BAK Cyt C Caspase activation Strongly inhibits Bcl-xL, Bcl-2 Oral bioavailability Flexible dosing Apoptosis In partnership w/abbott 5

16 Technology: Antibody drug conjugates Proof-of-concept in hematology; phase II in mbc HER2+ The premise Antibody Cytotoxic Advantages Greater tumor kill Chemical linker Normal tissue sparing Preclinical gred pipeline New NHL, CLL, MM targets Target cell Antibody-drug conjugate (ADC) Antibody/target Linker Drug Expression on tumor but not on vital tissue Stable in circulation Released in tumor Highly potent Non-immunogenic Proof of concept (POC)/clinical development ASH 2009: ADC in Hodgkin s lymphoma SABCS 2009: RG3502/T-DM (trastuzumab DM): New phase II data in mbc 3rd line HER2+ gred=genentech Research & Early Development, NHL=Non-Hodgkin s Lymphoma, CLL=Chronic Lymphocytic Leukemia, MM=Multiple Myeloma 6

17 Important clinical data at ASH 2009 Dr. Nancy Valente, Sr. Group Director, Clinical Development

18 ASH 2009: Selected clinical highlights MabThera/Rituxan consolidating its position in CLL; early-mid stage pipeline moving ahead MabThera/Rituxan New data from the phase III study CLL-8 (ASH 2008) are the first to show that a specific first-line treatment for CLL results in an improved overall survival New data with chemotherapies other than those used in the CLL-8 study (FC) show encouraging efficacy and acceptable safety for patients with untreated CLL RG759/GA0 New findings from the first phase I/II study GAUGUIN (BO20999, ASH 2008) demonstrate safety and efficacy in the CLL cohort New data from the second phase I/II study GAUSS (BO2003) show promising efficacy in heavily-pretreated patients with B-cell hematological malignancies RG7433/ABT-263 New data from ongoing phase I study in relapsed or refractory CLL show encouraging single-agent activity and acceptable safety In partnership w/abbott 8

19 MabThera/Rituxan RG759/GA0 RG7433/ABT-263 9

20 CLL8 Study Design Patients with untreated, active CLL and good physical fitness (CIRS 6, creatinine clearance 70 ml/min) R FCR FC 6 courses C C2 C3 C4 C5 C6 Follow up Updated results of the 2nd analysis at a median observation time of 37.7 months. ASH 2009, abstract 535, Hallek et al. 20

21 Patients: ITT population (n=87) of the CLL8 protocol FC (n = 409) FCR (n = 408) Female 05 (26%) 05 (26%) Male 304 (74%) 303 (74%) Median age 6 (range 36-8) 6 (range 30-80) Binet A 22 (5.4%) 8 (4.4%) Binet B 259 (63.6%) 263 (64.6%) Binet C 26 (3%) 26 (3%) B symptoms* 97 (48%) 67 (4%) Median cumulative illness rating scale (CIRS) (range 0-8) (range 0-7) Trisomy 2 4.4% 9.6% Del(3q) 59.7% 53.8% Del(q23) 22.5% 26.8% Del(7p3) 9.5% 7.0% *P<0,05 2

22 Adverse events CTC grade 3 and 4 FC FCR p Total number of patients with 248 (62.9%) 309 (76.5%) < grade 3/4 event Hematological toxicity 39.6% 55.7 % < Neutropenia 2.0% 33.7% < Leukocytopenia 2.% 24.0% < Thrombocytopenia.% 7.4% 0.07 Anemia 6.8% 5.4% 0.42 Infection 2.5% 25.5% 0.8 Tumor lysis syndrome 0.5% 0.2% 0.55 Cytokine release syndrome 0.0% 0.2% 0.32 ASH 2009, abstract 535, Hallek et al. Treatment related mortality 2% for both arms. 22

23 Best response to treatment FC FCR CR* 2.8% 44.% PR 66.6% 5.0% Overall response rate 88.4% 95.% **CR u 4.6% 3.6% All included **CR in PR i.9% 2.3% npr 5.7% 3.4% SD 7.8% 3.9% PD 3.8%.0% *According NCI WG Criteria, confirmatory BM assessment performed up to 6 months after final restaging ASH 2009, abstract 535, Hallek et al. P <

24 Progression free survival: FCR versus FC ASH 2008 ASH 2009 Median PFS: 32.3 months for FC vs 42.8 months for FCR ASH 2009, abstract 535, Hallek et al. p= p<0.00 Median PFS: 32.8 months for FC vs 5.8 months for FCR, n=790, HR 0.563, ranges PFS rate 3 yrs post randomization: 24 FC: 44.7%, FCR: 64.9%

25 Overall survival Overall survival 3 years post randomization: FCR: 87.2% FC: 82.5% n=87, HR 0.664, p=0.02 ASH 2009, abstract 535, Hallek et al. 25

26 Summary: FCR improves outcome The addition of rituximab to FC first line therapy improves the outcome of patients with advanced, symptomatic CLL with regard to Response rates (CR, ORR, MRD) Progression-free survival Overall survival Acheiving a CR produces a longer survival First randomized trial to demonstrate that the choice of first line therapy improves the natural course of CLL. ASH 2009, abstract 535, Hallek et al. 26

27 MabThera/Rituxan: Encouraging safety and efficacy with multiple chemotherapies Study Pts evaluated Median age/upper ORR Safety Bendamustine + MabThera/Rituxan 7 64 yrs / NR 9% Myelosuppression/ infections Chlorambucil + MabThera/Rituxan yrs / up to 86 yrs 84% GI disorders, infections Fludarabine + MabThera/Rituxan yrs / up to 86 yrs 84% NR MabThera/Rituxan has encouraging efficacy and acceptable safety in a variety of chemotherapy combinations for patients with untreated CLL ASH 2009, abstract 205, Fischer et al 2 ASH 2009, abstract 3428, Hillmen et al 3 ASH 2009, abstract 539, Woyach et al 27

28 MabThera/Rituxan RG759/GA0 RG7433/ABT

29 RG759/GA0 (Next-gen anti-cd20) GAUGUIN study: Phase I dose-escalation (3+3 design) GA0 single agent (total 9 doses) Tumor assessment weeks CD20+ CLL for whom no therapy of higher priority was available Cohort group GA0 dose Dose /Doses 2 9 n = 3 per cohort Successive cohorts initiated if no DLT Enrolment from July to November 2008 at 7 sites in France 400/800 mg 2 800/200 mg 3 200/2000 mg 4 000/000 mg GA0 administered as per rituximab administration guidelines; 4 patients enrolled in cohort at 200/2000 mg dose level ASH 2009, abstract 884, Morschhauser et al 29

30 RG759/GA0 (Next-gen anti-cd20) GAUGUIN study: Patient characteristics B-CLL patients (n=3) Age, median (range) 64 yr (46 8) Male/female 9/4 Baseline SPD, median (range) Lymphocytes, median (range) Platelets, median (range) 224 mm 2 ( ) 50.5 x 0 9 /L (5.0 53) 90 x 0 9 /L (93 358) Duration of CLL, median (range) 7.6 yr ( ) Time from last treatment, median (range) Prior therapies, median (range) 25 mo (7 68) 3 ( 8) Prior rituximab 62% Prior fludarabine 00% Prognostic factors (n = 9) Cytogenetics 7p (n = 2), q (n = ), 3q (n = ), tri 2 (n = 2), normal karyotype (n = 3) IgV H status p53 status (n = 8) Mutated (n = 2) (V H 3-2 [n = ]), unmutated (n = 7) Mutated (n = ) Unmutated (n = 7) ASH 2009, abstract 884, Morschhauser et al 30

31 RG759/GA0 (Next-gen anti-cd20) GAUGUIN study: Grade 3 & 4 adverse events during treatment period Adverse event (n=3) Neutropenia* 7 Thrombocytopenia* 2 Febrile neutropenia* IRR* 2 Bronchitis* Oral herpes Gingivitis* Tumor lysis syndrome* Total Pts with at least AE *Includes SAE (4 patients in total) ASH 2009, abstract 884, Morschhauser et al 0 3

32 RG759/GA0 (Next-gen anti-cd20) GAUGUIN study: Grade 3 & 4 neutropenia 2 CTC Grade 3 & 4 neutropenic episodes in 9 patients During treatment, 8 transient neutropenic episodes 3 occurred during Cycle patient experienced febrile neutropenia All patients completed treatment phase, receiving all 9 scheduled infusions No dose reductions 4 episodes after treatment Median duration: 0 days (range 28); 7 patients received G-CSF No clear dose relationship ASH 2009, abstract 884, Morschhauser et al 32

33 RG759/GA0 (Next-gen anti-cd20) GAUGUIN study: Best overall response 62% Cohort CR PR SD PD 400/800 mg x x x 800/200mg x x x 200/2000 mg x x x x 000/000 mg x x x Total (n=3) Median duration of response 8+ months [range months] 6 responding patients currently ongoing [ CR, 5 PR], 2 patients SD in follow-up; 5 patients PD ASH 2009, abstract 884, Morschhauser et al Response assessment based on revised CLL criteria, Hallek et al, Blood 2008; :

34 RG759/GA0 (Next-gen anti-cd20) GAUGUIN study: All 3 patients achieve tumour shrinkage 0 Patients (n=3) -20 Tumor burden decrease (%) ASH 2009, abstract 884, Morschhauser et al Response assessment based on revised CLL criteria, Hallek et al, Blood 2008; :

35 RG759/GA0 (Next-gen anti-cd20) GAUGUIN study: Conclusions Safety profile GA0 is well tolerated in CLL with no DLTs Similar to GA0 phase I safety profile in NHL except neutropenia Higher rate of reversible grade 3 & 4 neutropenia in CLL Very encouraging efficacy observed as single agent in relapsed/ refractory CLL ORR: 62% (8/3) Rapid and sustained hematologic response in all patients (including two patients with 7p ) All patients demonstrate reduction in lymph nodes ASH 2009, abstract 884, Morschhauser et al 35

36 RG759/GA0 (Next-gen anti-cd20) GAUSS study: Phase I dose escalation (3+3 design), induction dosing GA0 single-agent (total 4 doses) Response assessment weeks GA0 administered as per Rituximab administration guidelines CD20+ malignant disease for which no therapy of higher priority was available N = 3 per cohort Successive cohorts initiated if no DLT Enrolment from January 2008 to January 2009 at 5 sites in Canada ASH 2009, abstract 934, Sehn et al Cohort group GA0 dose Dose /doses / 200 mg / 400 mg / 800 mg / 200 mg / 2000 mg / 000 mg 36

37 RG759/GA0 (Next-gen anti-cd20) GAUSS study: Patient demographics and disease characteristics Characteristic (n=22) No. of patients (%) Median age [range] 60 [47-77] Male / female 3 / 9 Histological subtype (n=22) Diffuse large B-Cell lymphoma 3 (4) Other aggressive pathologies (MCL + transformed MZL) 2 (9) Follicular lymphoma 0 (45) Small lymphocytic lymphoma 2 (9) Chronic lymphocytic leukaemia 5 (23) NHL Patients (n=7) Clinical Stage (Ann Arbor) I / II 2 () III / IV 5 (89) Follicular lymphoma prognostic index (n=0) Low risk: 0- risk factor 3 (30) Intermediate risk: 2 risk factors 3 (30) High risk: 3-5 risk factors 4 (40) CLL Patients (n=5) Rai Stage Intermediate (I and II) 4 High-Risk (III and IV) ASH 2009, abstract 934, Sehn et al 37

38 RG759/GA0 (Next-gen anti-cd20) GAUSS study: Prior treatment regimens and response Variable No of patients (%) No. of prior therapies, median (range) 4 ( 7) Types of previous therapy Percentage receiving prior rituximab-containing regimens (n=22) 9 (86) No. of prior rituximab-containing regimens, median (range) 2 (-4) No. of rituximab-refractory patients (n=22) (50) Non-Hodgkin s Lymphoma (n=7) NHL patients with prior anthracycline (65) NHL patients with prior ASCT 3 (8) Chronic Lymphocytic Leukemia (n=5) CLL patients refractory to fludarabine 5 (00) ASH 2009, abstract 934, Sehn et al 38

39 RG759/GA0 (Next-gen anti-cd20) GAUSS study: Most common adverse events by severity during induction No. of patients (%) Induction (n=22) Adverse event (AE) All grades Grade 3 & 4 Non-hematologic AEs Infusion-related reactions 6 (73) 4 Infections 6 (27) - Headache 4 (8) Nausea 4 (8) - Pyrexia 4 (8) - Diarrhea 3 (4) - Fatigue 3 (4) - Hematologic AEs Neutropenia 4 (8) 4 Febrile neutropenia (5) Thrombocytopenia (5) ASH 2009, abstract 934, Sehn et al 39

40 RG759/GA0 (Next-gen anti-cd20) GAUSS study: Overall response following induction, by dose, 3 wks Dose No. of patients CR PR SD PD Non evaluable 00/200 mg /400 mg /800 mg /200 mg /2000 mg /000 mg Total Percent 24% 62% 4% ASH 2009, abstract 934, Sehn et al 40

41 RG759/GA0 (Next-gen anti-cd20) GAUSS study: Overall response following induction, by histology, 3 wks Histology No. of patients CR PR SD PD Non evaluable Diffuse large B-Cell lymphoma 3 Other aggressive histologies (MCL + transformed MZL) 2 Follicular lymphoma Small lymphocytic lymphoma 2 Chronic lymphocytic leukemia 5 4 ASH 2009, abstract 934, Sehn et al 4

42 RG759/GA0 (Next-gen anti-cd20) GAUSS study: Treatment response in patients receiving extended therapy Dose Cohort (mg) Diagnosis End of induction response Duration of GA-0 treatment to date Best Response Progression (Y/N) 00/ 200 MZL PR 9 months PR Y 200/ 400 DLBCL PR 4 month PR Y FL SD 7 months PR* N FL PR 7 months PR N 400/ 800 SLL PR 4 months PR N FL PR 7 months PR N 200/ 2000 CLL SD 3 months SD Y FL SD 9 months SD N ASH 2009, abstract 934, Sehn et al 42

43 RG759/GA0 (Next-gen anti-cd20) GAUSS study: Conclusions GA0 safety profile Well tolerated No dose-limiting toxicities Infusion reactions primarily limited to first cycle Safety profile similar to that of rituximab Efficacy observed in highly pre-treated patients Phase II study now going head to head in indolent lymphoma Extended therapy is safe and may improve efficacy ASH 2009, abstract 934, Sehn et al 43

44 RG759/GA0 (Next-gen anti-cd20) GAUSS study: Study being expanded by large phase II cohort in inhl First head to head trial against rituximab monotherapy Relapsed CD20+ indolent NHL (N=80) GA0 000 mg Weekly x 4 Rituximab 375mg/m 2 Weekly x 4 CR PR SD GA0 extended treatment (000mg once every 2 months, up to 2 years) Rituximab extended treatment (375 mg/m2 once every 2 months, up to 2 years) Randomization ASH 2009, abstract 934, Sehn et al 44

45 RG759/GA0 (Next-gen anti-cd20): Clinical development; beyond MabThera/Rituxan Phase I/II studies BO2000 inhl, n=56, RG759/GA0 + FC or RG759/GA0 + CHOP GUIGUIN (BO20999) anhl, inhl as well as CLL cohort, total n=33 GAUSS (BO2003) inhl, total n= approx 200 Data flow to continue at upcoming medical meetings Phase III program (initial studies only) GAO4753g inhl refractory (n=360) Bendamustine +/- RG759/GA0 FPI Q2 200; filing expected post 202 BO2004 CLL st line (n=780) Chlorambucil +/- RG759/GA0 or chlorambucil + MabThera/Rituxan FPI Q4 2009; filing expected 202 RG759/GA0: Extensive clinical program well underway 45

46 MabThera/Rituxan RG759/GA0 RG7433/ABT

47 RG7433/ABT-263 : Phase I in relapsed/refractory CLL M study design Intermittent Screening 4d on/7d off 5 Patients Safety PK MTD Dose levels 0 mg n = 3 0 mg n = mg n = mg n = 3 Continuous with lead in Screening 7d 00mg 4 Patients 2d on / 0d off Safety PK MTD Dose levels 25 mg n = mg n = mg n = mg n = 4 ASH 2009, abstract 883, Roberts et al In partnership w/abbott 47

48 RG7433/ABT-263 : Phase I in relapsed/refractory CLL Patient characteristics Patient characteristics (n=29) Age Gender Lymphocyte count Bulky nodes >5 cm Number of prior therapies Fludarabine-refractory Unfavorable FISH Median Range Male Female Median Range Median Range 7p3.2 del q22.3 del 67 years years x 0 9 /L pts pts 8 / 2 pts 5 / 2 pts ASH 2009, abstract 883, Roberts et al In partnership w/abbott 48

49 RG7433/ABT-263 : Phase I in relapsed/refractory CLL Promising results in CLL Efficacy Overall response rate (ORR): 29% (7/24) ORR excluding 3 pts treated at doses <0 mg: 33% (7/2) Response type Partial response (PR) Stable disease (SD) with >50% peripheral lymphocyte reductions >2mths Stable disease (SD) Progressive disease (PD) n Median progression-free survival not reached Median time on study 9 months (range -6 months) 72-yr male, 7 prior txs, fludarabine-refractory, 7p del Fludarabine-refractory pts (5/6 evaluable treated at >00mg) 2 partial responses (PR) 2 nodal reductions 49% and 47%, respectively ASH 2009, abstract 883, Roberts et al In partnership w/abbott Pre-treatment After 7 cycles 49

50 RG7433/ABT-263 : Phase I in relapsed/refractory CLL Response in patients with poor prognosis Response to treatment Time to progression 6 pts with cytogenetic data and dose >00mg / day FISH abnormality n Response a Del 7p 6 5 Del q b 5 4 Neither 5 5 a Response includes PR, >50% in lymphocytes, or both b Del q, without Del 7p (Döhner) Progression Free (%) ASH 2009, abstract 883, Roberts et al In partnership w/abbott 50

51 RG7433/ABT-263 : Phase I in relapsed/refractory CLL Conclusions Acceptable safety profile with thrombocytopenia as the dose limiting toxicity (due to Bcl-xL inhibition) Single-agent activity observed in relapsed, refractory CLL Preliminary evidence of sustained clinical activity with ongoing dosing In some fludarabine-refractory patients In some patients with 7p del CLL and q del CLL ASH 2009, abstract 883, Roberts et al In partnership w/abbott RG7433/ABT-263: Promising data in CLL 5

52 Leader in hematology commercial overview & opportunities Dr. Myriam Mendila, Hematology Franchise Leader

53 MabThera/Rituxan: Leading hematology product Top products commonly used to treat hematological malignancies Global sales Source: IMS MIDAS in PADDS as of Q Q3-97 Q-98 Q3-98 Q-99 Q3-99 Q-00 Q3-00 Q-0 Q3-0 Q-02 Q3-02 Q-03 Q3-03 Q-04 Q3-04 Q-05 Q3-05 Q-06 Q3-06 Q-07 Q3-07 Q-08 Q3-08 Q-09 MabThera/Rituxan Imatinib Bortezomib Lenalidomide Doxorubicin Dasatinib Dexamethasone Thalidomide Topotecan Bendamustine Prednisone Nilotinib Fludarabine Melphalan Cyclophosphamide Alemtuzumab Vincristine Bleomycin Cladribine Ibritumomab tiuxetan Chlorambucil 53

54 MabThera/Rituxan: The success continues Continued sales growth, in particular Europe/RoW Key facts Outstanding clinical benefit combined with excellent tolerability Recent approvals and/or phase III results to support further growth: CLL st line, now OS benefit CLL relapsed inhl st line maintenance 2 Over.7 million patients treated 3 Group sales, CHF bn M M 2009 Outstanding clinical benefit Europe/RoW US Japan Approved EU, final label discussion U.S. 2 Filing Including the use of MabThera/Rituxan in autoimmune diseases, the number is over.9 million 54

55 MabThera/Rituxan: Growth opportunities in EU/RoW PRIMA and OS benefit in CLL to drive further uptake Growth opportunities Thousand patients treated No MabThera/Rituxan MabThera/Rituxan inhl inhlmaint anhl CLL inhl inhlmaint anhl CLL inhl inhlmaint U.S. 2 Top-5 EU E7 3 PRIMA study in inhl st line maintenance (filing 200) 2 CLLfinal label discussion U.S. 3 E7: Brazil, Russia, China, Mexico, Turkey, South Korea, India anhl CLL 55

56 MabThera/Rituxan: S.c. formulation in development Phase I study has enrolled its first patient New formulation will have all the current benefits of MabThera/Rituxan Additional benefits for patients, payers and prescribers: Possibility of non-hospital/self administration Improved patient convenience and preference provide for greater independence Potential for less infusion-related reactions Less resource-intensive and much faster than current i.v. administration Reduced medical resource utilization (address capacity issues) Proprietary Roche Diagnostics-developed injection device First-patient-in in phase I trial in Q Maximizing the overall hematology franchise 56

57 Leader in hematology Leadership in hematology Avastin & pipeline molecules in hematological malignancies Avastin & pipeline molecules in hematological malignancies in combo with MabThera/Rituxan MabThera/Rituxan Standard of care inhl, anhl, CLL MabThera/Rituxan s.c. formulation RG759/GA0 New-gen anti-cd20 w/improved properties Anti-CD20 lifecycle management 57

58 Questions & Answers Moderator: Dr. Karl Mahler, Head of Investor Relations

59 We Innovate Healthcare 59