091208 investor science conference call ash 2009 ...4f912aca-baaa-4f85-9fff...c1 c2 c3 c4 c5 c6...

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 similarexpressions 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; and11 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 www.roche.com for full information on Roche products mentioned.

Introduction

Dr. Karl Mahler, Head of Investor Relations

4

Investor science events at major medical meetingsSeven events highlight the group’s pipeline leadership

Next week

OncologySan Antonio Breast Cancer Symposium (SABCS)

San Antonio, United States

14 December 2009

Hematology/OncologyAmerican Society of Hematology (ASH)

New Orleans, United States

8 December 2009

Berlin, Germany

Copenhagen, Denmark

New Orleans, United States

Orlando,United States

Orlando, United States

OncologyAmerican Society of Clinical Oncology (ASCO), day 2

1 June 2009

OncologyEuropean CanCer Organisation - European Society for Medical Oncology (ECCO - ESMO)

25 September 2009

Inflammation/Rheumatoid Arthritis

The European League Against Rheumatism (EULAR)

12 June 2009

Metabolism/DiabetesAmerican Diabetes Association (ADA)

8 June 2009

OncologyAmerican Society of Clinical Oncology (ASCO), day 1

31 May 2009

Steady flow of important clinical data & results

5

AgendaLeader 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 & AnswersTotal duration: Up to 1½ hour

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

Hematology pipeline overview

7

Pipeline overview

Pipeline highlights

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

9

Phase IIIPhase Ib/IIPhase I

RG3636/SGN-40(dace-tuzumab)3 Anti-CD40 DLBCL, iNHL, MM

RG3639(dulanermin)2

DR4/DR5 agonist iNHL

RG7425DR5 agonist iNHL

RG7433/ABT-2631

BH3 mimetic CLL, lymphoid malignancies

The clinical pipeline in hematology:Translating science to patient benefit

RG7159/GA101Next-gen anti-CD20 CLL, iNHL Moving to Phase III

DLBCL=Diffuse Large B-Cell Lymphoma, MM=Multiple Myeloma, iNHL=indolent Non-Hodgkin’s Lymphoma1In partnership w/Abbott 2In partnership w/Amgen 3In partnership w/Seattle Genetics

RG7422/GDC-0980PI3 kinase inhibitor NHL

AvastinAnti-angiogenic DLBCL, MM (phase II)

RG7112MDM2 antagonist Hematological tumorsN

N

N

N

O Cl

ClO

SO

O

10

Multiple hallmarks of hematological malignancies

RG7159/GA101 (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)

RG7112 (MDM2 antagonist)

Evading apoptosis

RG7433/ABT-2631 (BH3 mimetic)

The clinical pipeline in hematology:Targeting the underlying biology

Hanahan & Weinberg, The Hallmarks of Cancer, Cell, vol 100, pp 57-70, copyright Elsevier (2000)1In partnership w/Abbott 2In partnership w/Amgen 3In partnership w/Seattle Genetics

Sustained angiogenesis

Avastin(bevacizumab)

11

Pipeline overview

Pipeline highlights

12

RG7159/GA101 (Next-gen anti-CD20):First glyco-engineered type II CD20 mAb

• Increased direct cell-death induction– Unique type II epitope and elbow-

hinge modification

• Enhanced antibody-dependentcell-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; 108, abstract 229, Umaña et al, Ann Oncology 2008, 19 (suppl 4), abstract 098

CD20 peptide

Type II recognition & elbow-hinge

residues

Carbohydrateglycoengineered

(GlycoMabTM

technology)

13

B-cell depletion whole-blood assay in B-CLL patients (24 h)

CD

19+

Dep

leti

on (

%) 100

60

40

0

0

20

20 200 2000 20,000

80 GA101

Rituximab

Ab conc. (ng/mL) Time after cell transplantation (days)

n=10

Tum

or v

olum

e (m

m3 )

med

ian ±

IQR

Vehicle Rituximab30 mg/kg

GA10130 mg/kg

Rituximab1st line

2500

22 25 28 31 34 37 40 43 46 49 52 55 58 61

2000

1500

1000

500

0

SU-DHL-4NHL xenograft in mice pretreated with MabThera/Rituxan(rituximab)

Non-ADCC competent s.c. xenograft model (SCID beige)

RG7159/GA101 (Next-gen anti-CD20):Rapid B-cell depletion and superior tumor remissions in preclinical models

14

RG7433/ABT-2631 (BH3 mimetic):Acts as a BH3 mimetic to induce apoptosis

1In partnership w/Abbott

Bcl-xL

Apoptosis

Bim BidPuma

BikBmf

BadNoxaHrk

Bak

Bax

Caspase activation

activated

BAX / BAK

Mitochondria

Cyt CBcl-2

DNA damaging

agents

Anti-mitotics

Rituxan

TDM-1

Tarceva

GA101

Other ADC

PI3K

PI3K/mTOR

AKTMEK

Cytotoxic Chemo

Antibody-drug conjugates

Anti-CD20

EGFR targeted agents

Erbitux

ABT-263

• BCL-2 is a target for tumor biology driven over-expression in lymphoid cancers and SCLC

• BCL-2 is a target for tumor biology driven over-expression in lymphoid cancers and SCLC

15

RG7433/ABT-2631 (BH3 mimetic):Acts as a BH3 mimetic to induce apoptosis


Bcl-xL

Apoptosis

Bak

Bax

Caspase activation

activated

BAX / BAK

Mitochondria

Cyt C

Bcl-2

ABT-263

• Strongly inhibits Bcl-xL, Bcl-2

• Oral bioavailability

• Flexible dosing

16

Technology: Antibody drug conjugatesProof-of-concept in hematology; phase II in mBC HER2+

The premiseCytotoxic

Chemical linker

Antibody

Target cell

Antibody-drug conjugate (ADC)

Antibody/target Linker Drug

Expression on tumor butnot on vital tissue

Stable in circulationReleased in tumor

Highly potentNon-immunogenic

gRED=Genentech Research & Early Development, NHL=Non-Hodgkin’s Lymphoma, CLL=Chronic Lymphocytic Leukemia, MM=Multiple Myeloma

Advantages

• Greater tumor kill

• Normal tissue sparing

Preclinical gRED pipeline

• New NHL, CLL, MM targets

Proof of concept (POC)/clinical development

• ASH 2009: ADC in Hodgkin’s lymphoma

• SABCS 2009: RG3502/T-DM1(trastuzumab DM1): New phase II data in mBC 3rd line HER2+

Dr. Nancy Valente, Sr. Group Director, Clinical Development

Important clinical data at ASH 2009

18

ASH 2009: Selected clinical highlightsMabThera/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

• RG7159/GA101– 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 (BO21003) show promising

efficacy in heavily-pretreated patients with B-cell hematological malignancies

• RG7433/ABT-2631

– New data from ongoing phase I study in relapsed or refractory CLL show encouraging single-agent activity and acceptable safety


19

MabThera/Rituxan

RG7159/GA101

RG7433/ABT-263

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

Follow up

C1 C2 C3 C4 C5 C6

Updated results of the 2nd analysis at a median observation time of 37.7 months.

ASH 2009, abstract 535, Hallek et al.

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Patients: ITT population (n=817) of the CLL8 protocol

FC (n = 409) FCR (n = 408)Female 105 (26%) 105 (26%)

Male 304 (74%) 303 (74%)

Median age 61 (range 36-81) 61 (range 30-80)

Binet A 22 (5.4%) 18 (4.4%)

Binet B 259 (63.6%) 263 (64.6%)

Binet C 126 (31%) 126 (31%)

B symptoms* 197 (48%) 167 (41%)

Median cumulative illness rating scale (CIRS) 1 (range 0-8) 1 (range 0-7)

Trisomy 12 14.4% 9.6%

Del(13q) 59.7% 53.8%

Del(11q23) 22.5% 26.8%

Del(17p13) 9.5% 7.0%

*P<0,05

22

Adverse events CTC grade 3 and 4

FC FCR pTotal number of patients with≥ 1 grade 3/4 event

248 (62.9%) 309 (76.5%) < 0.0001

Hematological toxicity 39.6% 55.7 % < 0.0001

Neutropenia 21.0% 33.7% < 0.0001

Leukocytopenia 12.1% 24.0% < 0.0001

Thrombocytopenia 11.1% 7.4% 0.07

Anemia 6.8% 5.4% 0.42

Infection 21.5% 25.5% 0.18

Tumor lysis syndrome 0.5% 0.2% 0.55

Cytokine release syndrome 0.0% 0.2% 0.32


Treatment related mortality 2% for both arms.

23

Best response to treatment

FC FCR

CR* 21.8% 44.1%PR 66.6% 51.0%

Overall response rate 88.4% 95.1%

All includedin PR

**CRu 4.6% 3.6%**CRi 1.9% 2.3%nPR 5.7% 3.4%

SD 7.8% 3.9%PD 3.8% 1.0%

*According NCI WG Criteria, confirmatory BM assessment performed up to 6 months after final restagingP < 0.01ASH 2009, abstract 535, Hallek et al.

24

Progression free survival: FCR versus FC


Median PFS: 32.3 months for FC vs 42.8 months for FCR

ASH 2008

p=0.000007

Median PFS: 32.8 months for FC vs 51.8 months for FCR, n=790, HR 0.563, ranges 0.460-0.689PFS rate 3 yrs post randomization: FC: 44.7%, FCR: 64.9%

p<0.001

ASH 2009

25

Overall survival

Overall survival 3 years post randomization:FCR: 87.2%FC: 82.5%

n=817, HR 0.664, p=0.012


26

Summary: FCR improves outcome

• The addition of rituximab to FC first line therapy improves theoutcome of patients with advanced, symptomatic CLL withregard 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 firstline therapy improves the natural course of CLL.


27

MabThera/Rituxan: Encouraging safety and efficacy with multiple chemotherapies

Myelo-suppression/ infections

91%64 yrs / NR117Bendamustine + MabThera/Rituxan1

NR84%63 yrs / up to 86 yrs

104Fludarabine + MabThera/Rituxan3

GI disorders, infections

84%70.5 yrs / up to 86 yrs

50Chlorambucil + MabThera/Rituxan2

SafetyORRMedian age/upper

PtsevaluatedStudy

MabThera/Rituxan has encouraging efficacy and acceptable safety in a variety of chemotherapy combinations for patients with untreated CLL

1ASH 2009, abstract 205, Fischer et al 2ASH 2009, abstract 3428, Hillmen et al 3ASH 2009, abstract 539, Woyach et al

28

MabThera/Rituxan

RG7159/GA101

RG7433/ABT-263

29

RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:Phase I dose-escalation (3+3 design)

• CD20+ CLL for whom “no therapy of higher priority was available”

• n = 3 per cohort– Successive cohorts initiated

if no DLT

• Enrolment from July to November 2008 at 7 sites in France

Cohort group

GA101 doseDose 1/Doses 2–9

1 400/800 mg

2 800/1200 mg

31 1200/2000 mg

4 1000/1000 mg

3 6 9 12 15 18 21 weeks

Tumor assessment

25

GA101 single agent (total 9 doses)

1 33

GA101 administered as per rituximab administration guidelines; 14 patients enrolled in cohort at 1200/2000 mg dose levelASH 2009, abstract 884, Morschhauser et al

30

RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:Patient characteristics

ASH 2009, abstract 884, Morschhauser et al

2124 mm2 (1068–26732)Baseline SPD, median (range)

50.5 x 109/L (5.0–153)Lymphocytes, median (range)

190 x 109/L (93–358)Platelets, median (range)

B-CLL patients (n=13)

Age, median (range) 64 yr (46–81)

Male/female 9/4

Duration of CLL, median (range) 7.6 yr (2.8–15.7)

Time from last treatment, median (range)Prior therapies, median (range)

25 mo (7–68)3 (1–8)

Prior rituximab 62%

Prior fludarabine 100%

Prognostic factors (n = 9)

Cytogenetics 17p– (n = 2), 11q– (n = 1), 13q– (n = 1),tri 12 (n = 2), normal karyotype (n = 3)

IgVH status

p53 status (n = 8)

Mutated (n = 2) (VH3-21 [n = 1]),unmutated (n = 7)

Mutated (n = 1) Unmutated (n = 7)

31

RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:Grade 3 & 4 adverse events during treatment period


2IRR*

1Bronchitis*

1Oral herpes

1Gingivitis*

1Tumor lysis syndrome*

10Total Pts with at least 1 AE

Adverse event (n=13)

Neutropenia* 7

Thrombocytopenia* 2

Febrile neutropenia* 1

*Includes 1 SAE (4 patients in total)

32

RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:Grade 3 & 4 neutropenia

• 12 CTC Grade 3 & 4 neutropenic episodes in 9 patients

• During treatment, 8 transient neutropenic episodes

– 3 occurred during Cycle 1

– 1 patient experienced febrile neutropenia

– All patients completed treatment phase, receiving all 9 scheduled infusions

– No dose reductions

• 4 episodes after treatment

• Median duration: 10 days (range 1–28); 7 patients received G-CSF

• No clear dose relationship


33

RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:Best overall response 62%1

Cohort CR PR SD PD

400/800 mg x x x

800/1200mg x x x

1200/2000 mg x x x x

1000/1000 mg x x x

Total (n=13) 1 7 5 0

• Median duration of response 8+ months [range 2.2-10.4 months]

• 6 responding patients currently ongoing [1 CR, 5 PR], 2 patients SD in follow-up; 5 patients PD

ASH 2009, abstract 884, Morschhauser et al1Response assessment based on revised CLL criteria, Hallek et al, Blood 2008; 111:5446–5456

34

RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study: All 13 patients achieve tumour shrinkage1

-100

-80

-60

-40

-20

0

Tum

or b

urde

n de

crea

se (

%)

Patients (n=13)

ASH 2009, abstract 884, Morschhauser et al1Response assessment based on revised CLL criteria, Hallek et al, Blood 2008; 111:5446–5456

35

RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:Conclusions

• Safety profile

– GA101 is well tolerated in CLL with no DLTs

– Similar to GA101 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% (8/13)

– Rapid and sustained hematologic response in all patients (including two patients with 17p–)

– All patients demonstrate reduction in lymph nodes


36

• 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

GA101 administered as per Rituximab administration guidelines

2 3 4 weeks

Response assessment

13

GA101 single-agent (total 4 doses)

1

RG7159/GA101 (Next-gen anti-CD20) GAUSS study:Phase I dose escalation (3+3 design), induction dosing

ASH 2009, abstract 934, Sehn et al

1000 / 1000 mg61200 / 2000 mg5

Cohort group

GA101 doseDose 1/doses 2–4

1 100 / 200 mg2 200 / 400 mg3 400 / 800 mg4 800 / 1200 mg

37

RG7159/GA101 (Next-gen anti-CD20) GAUSS study:Patient demographics and disease characteristics


1High-Risk (III and IV)4Intermediate (I and II)

Rai StageCLL Patients (n=5)

4 (40)High risk: 3-5 risk factors3 (30)Intermediate risk: 2 risk factors3 (30)Low risk: 0-1 risk factor

Follicular lymphoma prognostic index (n=10)15 (89)III / IV2 (11)I / II

Clinical Stage (Ann Arbor)NHL Patients (n=17)

Characteristic (n=22) No. of patients (%)Median age [range] 60 [47-77]Male / female 13 / 9Histological subtype (n=22)

Diffuse large B-Cell lymphoma 3 (14)Other aggressive pathologies (MCL + transformed MZL) 2 (9)Follicular lymphoma 10 (45)Small lymphocytic lymphoma 2 (9)Chronic lymphocytic leukaemia 5 (23)

38

RG7159/GA101 (Next-gen anti-CD20) GAUSS study:Prior treatment regimens and response

Chronic Lymphocytic Leukemia (n=5)

Non-Hodgkin’s Lymphoma (n=17)

Variable No of patients (%)

No. of prior therapies, median (range) 4 (1–7)

Types of previous therapy

Percentage receiving prior rituximab-containing regimens (n=22) 19 (86)

No. of prior rituximab-containing regimens, median (range) 2 (1-4)

No. of rituximab-refractory patients (n=22) 11 (50)

NHL patients with prior anthracycline 11 (65)

NHL patients with prior ASCT 3 (18)

CLL patients refractory to fludarabine 5 (100)


39

RG7159/GA101 (Next-gen anti-CD20) GAUSS study:Most common adverse events by severity during induction

Adverse event (AE)

No. of patients (%)

Induction (n=22)

All grades Grade 3 & 4

Non-hematologic AEs

Infusion-related reactions 16 (73) 4

Infections 6 (27) -

Headache 4 (18) 1

Nausea 4 (18) -

Pyrexia 4 (18) -

Diarrhea 3 (14) -

Fatigue 3 (14) -

Hematologic AEs

Neutropenia 4 (18) 4

Febrile neutropenia 1 (5) 1

Thrombocytopenia 1 (5) 1


40

RG7159/GA101 (Next-gen anti-CD20) GAUSS study:Overall response following induction, by dose, 13 wks

Dose No. of patients CR PR SD PD Non evaluable

100/200 mg 3 1 2

200/400 mg 3 2 1

400/800 mg 3 2 1

800/1200 mg 3 3

1200/2000 mg 3 3

1000/1000 mg 7 4 2 1

Total 22 5 13 3 1

Percent 24% 62% 14%


41

RG7159/GA101 (Next-gen anti-CD20) GAUSS study:Overall response following induction, by histology, 13 wks

1113 Diffuse large B-Cell lymphoma

112Other aggressive histologies (MCL + transformed MZL)

17210 Follicular lymphoma

112Small lymphocytic lymphoma

145Chronic lymphocytic leukemia

Histology No. of patients CR PR SD PD Non

evaluable


42

Dose Cohort (mg) Diagnosis

End of induction response

Duration of GA-101 treatment to date Best Response

Progression (Y/N)

100/ 200 MZL PR 9 months PR Y

200/ 400 DLBCL PR 4 month PR Y

FL SD 17 months PR* N

FL PR 17 months PR N

400/ 800 SLL PR 14 months PR N

FL PR 17 months PR N

1200/ 2000 CLL SD 3 months SD Y

FL SD 9 months SD N

RG7159/GA101 (Next-gen anti-CD20) GAUSS study: Treatment response in patients receiving extended therapy


43

RG7159/GA101 (Next-gen anti-CD20) GAUSS study:Conclusions

• GA101 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


44

RG7159/GA101 (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=180)

GA101

1000 mg

Weekly x 4

Rituximab375mg/m2

Weekly x 4

CR PR SD

GA101 extended treatment (1000mg

once every 2 months, up to 2 years)

Rituximab extended treatment (375 mg/m2 once

every 2 months, up to 2 years)

Randomization


45

RG7159/GA101 (Next-gen anti-CD20):Clinical development; beyond MabThera/Rituxan

Phase I/II studies

– BO21000 iNHL, n=56, RG7159/GA101 + FC or RG7159/GA101 + CHOP

– GUIGUIN (BO20999) aNHL, iNHL as well as CLL cohort, total n=133

– GAUSS (BO21003) 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 +/- RG7159/GA101• FPI Q2 2010; filing expected post 2012

– BO21004 CLL 1st line (n=780)• Chlorambucil +/- RG7159/GA101 or chlorambucil + MabThera/Rituxan• FPI Q4 2009; filing expected 2012

RG7159/GA101: Extensive clinical program well underway

46

MabThera/Rituxan

RG7159/GA101

RG7433/ABT-263

47

n = 3250 mg n = 3200 mgn = 6110 mgn = 310 mg

Dose levels

RG7433/ABT-2631: Phase I in relapsed/refractory CLLM06-873 study design

Screening 14d on/7d off

15 Patients

Safety

PK

MTD

21d on / 0d offSafety

PK

MTD14 Patients

Intermittent

Continuous with lead in

Screening

7d 100mg

ASH 2009, abstract 883, Roberts et al1In partnership w/Abbott

n = 4300 mg n = 3250 mgn = 4200 mgn = 3125 mg

Dose levels

48

RG7433/ABT-2631: Phase I in relapsed/refractory CLLPatient characteristics

17p13.2 del11q22.3 del

MedianRange

MedianRange

Male Female

MedianRange

8 / 21 pts 5 / 21 pts

Unfavorable FISH

8 ptsFludarabine-refractory

4.51-11

Number of prior therapies

12 ptsBulky nodes >5 cm

15.5 x 109/L 0.8-284.3

Lymphocyte count

1910

Gender

67 years 50-79 years

Age

Patient characteristics (n=29)


49

RG7433/ABT-2631: Phase I in relapsed/refractory CLLPromising results in CLL

Efficacy

• Overall response rate (ORR): 29% (7/24)

• ORR excluding 3 pts treated at doses <110 mg: 33% (7/21)

• Median progression-free survival not reached

– Median time on study 9 months (range 1-16 months)

• Fludarabine-refractory pts (5/6 evaluable treated at >100mg)

– 2 partial responses (PR)

– 2 nodal reductions 49% and 47%, respectively

7Stable disease (SD) with >50% peripheral lymphocyte reductions >2mths

2Progressive disease (PD)8Stable disease (SD)

7Partial response (PR)

nResponse type

Pre-treatment After 7 cycles

72-yr male, 7 prior txs, fludarabine-refractory, 17p del


50

Prog

ress

ion

Free

(%

)

Time to progression

RG7433/ABT-2631: Phase I in relapsed/refractory CLLResponse in patients with poor prognosis

Response to treatment

FISH abnormality

n Responsea

Del 17p 6 5

Del 11qb 5 4

Neither 5 5

• 16 pts with cytogenetic data and dose >100mg / day


a Response includes PR, >50% in lymphocytes, or both

b Del 11q, without Del 17p (Döhner)

51

RG7433/ABT-2631: Phase I in relapsed/refractory CLLConclusions

• 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 17p del CLL and 11q del CLL

RG7433/ABT-263: Promising data in CLLASH 2009, abstract 883, Roberts et al1In partnership w/Abbott

Dr. Myriam Mendila, Hematology Franchise Leader

Leader in hematology — commercial overview & opportunities

53

MabThera/Rituxan: Leading hematology productTop products commonly used to treat hematological malignancies

Q3-97

Q1-98

Q3-98

Q1-99

Q3-99

Q1-00

Q3-00

Q1-01

Q3-01

Q1-02

Q3-02

Q1-03

Q3-03

Q1-04

Q3-04

Q1-05

Q3-05

Q1-06

Q3-06

Q1-07

Q3-07

Q1-08

Q3-08

Q1-09

MabThera/RituxanImatinibBortezomibLenalidomideDoxorubicinDasatinibDexamethasoneThalidomideTopotecanBendamustinePrednisoneNilotinibFludarabineMelphalanCyclophosphamideAlemtuzumabVincristineBleomycinCladribineIbritumomab tiuxetanChlorambucil

Global sales1

1Source: IMS MIDAS in PADDS as of Q2 2009

54

MabThera/Rituxan: The success continuesContinued 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 1st line1, now OS benefit

– CLL relapsed1

– iNHL 1st line maintenance2

• Over 1.7 million patients treated3

01234567

2001

2002

2003

2004

2005

2006

2007

2008

9M 20

089M

2009

Europe/RoW US Japan

Group sales, CHF bn

1Approved EU, final label discussion U.S. 2Filing 2010 3Including the use of MabThera/Rituxan in autoimmune diseases, the number is over 1.9 million

Outstanding clinical benefit

55

0

10

20

30

40

50

60

70

iNHL

iNHLm

aint

aNHL

CLL

iNHL

iNHLm

aint

aNHL

CLL

iNHL

iNHLm

aint

aNHL

CLL

MabThera/Rituxan: Growth opportunities in EU/RoWPRIMA1 and OS benefit in CLL to drive further uptake

U.S.2 Top-5 EU E73

Growth opportunities

Thou

sand

pat

ient

s tr

eate

d

No MabThera/Rituxan

MabThera/Rituxan1PRIMA study in iNHL 1st line maintenance (filing 2010) 2CLLfinal label discussion U.S. 3E7: Brazil, Russia, China, Mexico, Turkey, South Korea, India

56

MabThera/Rituxan: S.c. formulation in developmentPhase 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 Q3-2009

Maximizing the overall hematology franchise

57

Leader in hematology

MabThera/RituxanStandard of care

iNHL, aNHL, CLL

MabThera/Rituxans.c. formulation

RG7159/GA101New-gen anti-CD20

w/improved properties

Avastin & pipeline molecules in hematological malignancies

Avastin & pipeline molecules in hematological malignancies

in combo with MabThera/Rituxan

Anti-CD20 lifecycle management

Lead

ersh

ip in

hem

atol

ogy

Moderator: Dr. Karl Mahler, Head of Investor Relations

Questions & Answers

59

We Innovate Healthcare

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