Investor science conference call ASH 2009
New Orleans, 8 December 2009
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 www.roche.com for full information on Roche products mentioned.
2
Introduction
Dr. Karl Mahler, Head of Investor Relations
Investor science events at major medical meetings
Seven events highlight the group’s pipeline leadership
31 May 2009
Orlando,
United States
American Society of Clinical
Oncology (ASCO), day 1
Oncology
1 June 2009
Orlando,
United States
American Society of Clinical
Oncology (ASCO), day 2
Oncology
8 June 2009
New Orleans,
United States
American Diabetes Association
(ADA)
Metabolism/Diabetes
12 June 2009
Copenhagen,
Denmark
The European League Against
Rheumatism (EULAR)
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
14 December 2009
San Antonio,
United States
San Antonio Breast Cancer
Symposium (SABCS)
Oncology
9
9
9
9
9
Á
Next
week
Steady flow of important clinical data & results
4
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 1½ hour
5
Hematology pipeline overview
Dr. Sandra Horning, Sr. VP, Global Head, Clinical
Development Hematology/Oncology
Pipeline overview
Pipeline highlights
7
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
The clinical pipeline in hematology:
Translating science to patient benefit
Phase I
O
S
O
N
N
O
Cl
N
N
O
Cl
Avastin
Anti-angiogenic
DLBCL, MM (phase II)
RG7159/GA101
Next-gen anti-CD20
CLL, iNHL
RG7433/ABT-2631
BH3 mimetic
CLL, lymphoid malignancies
RG7425
DR5 agonist
iNHL
RG3639(dulanermin)2
DR4/DR5 agonist
iNHL
RG3636/SGN-40(dacetuzumab)3 Anti-CD40
DLBCL, iNHL, MM
RG7422/GDC-0980
PI3 kinase inhibitor
NHL
RG7112
MDM2 antagonist
Hematological tumors
Phase Ib/II
Phase III
Moving to Phase III
DLBCL=Diffuse Large B-Cell Lymphoma, MM=Multiple Myeloma, iNHL=indolent Non-Hodgkin’s Lymphoma
1In partnership w/Abbott 2In partnership w/Amgen 3In partnership w/Seattle Genetics
9
The clinical pipeline in hematology:
Targeting the underlying biology
Evading apoptosis
RG7433/ABT-2631 (BH3 mimetic)
Sustained angiogenesis
Avastin(bevacizumab)
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)
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
10
Pipeline overview
Pipeline highlights
11
RG7159/GA101 (Next-gen anti-CD20):
First glyco-engineered type II CD20 mAb
CD20 peptide
Type II recognition
& elbow-hinge
residues
Carbohydrate
glycoengineered
(GlycoMabTM
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; 108, abstract 229, Umaña et al, Ann Oncology 2008, 19 (suppl 4), abstract 098
12
RG7159/GA101 (Next-gen anti-CD20):
Rapid B-cell depletion and superior tumor remissions
in preclinical models
SU-DHL-4NHL xenograft in mice pretreated
with MabThera/Rituxan(rituximab)
Vehicle
100
2500
Tumor volume (mm ) median ± IQR
GA101
80
Rituximab
60
Rituximab
30 mg/kg
GA101
30 mg/kg
n=10
2000
1500
Rituximab
1st line
3
CD19+ Depletion (%)
B-cell depletion whole-blood assay in
B-CLL patients (24 h)
40
20
0
0
20
200
Ab conc. (ng/mL)
2000
20,000
1000
500
0
22 25 28 31 34 37 40 43 46 49 52 55 58 61
Time after cell transplantation (days)
Non-ADCC competent s.c. xenograft model (SCID beige)
13
RG7433/ABT-2631 (BH3 mimetic):
Acts as a BH3 mimetic to induce apoptosis
Cytotoxic Chemo
DNA damaging
agents
Anti-mitotics
Antibody-drug conjugates
Other ADC
TDM-1
Bax
Bak
Anti-CD20
Rituxan
Bad
Bik
Hrk Noxa Bmf
EGFR targeted agents
Tarceva
Mitochondria
Bim
Bid
Puma
GA101
activated
ABT-263
Erbitux
Cyt C
BAX / BAK
Bcl-2
PI3K
MEK
AKT
PI3K/mTOR
1In
partnership w/Abbott
Bcl-xL
Caspase activation
•• BCL-2
BCL-2 is
is aa target
target for
for tumor
tumor
biology
biology driven
driven over-expression
over-expression
in
lymphoid
cancers
in lymphoid cancers and
and SCLC
SCLC
Apoptosis
14
RG7433/ABT-2631 (BH3 mimetic):
Acts as a BH3 mimetic to induce apoptosis
Bax
Bak
Mitochondria
activated
ABT-263
Cyt C
BAX / BAK
Bcl-2
Bcl-xL
• Strongly inhibits Bcl-xL,
Bcl-2
• Oral bioavailability
• Flexible dosing
Caspase activation
Apoptosis
1In
partnership w/Abbott
15
Technology: Antibody drug conjugates
Proof-of-concept in hematology; phase II in mBC HER2+
The premise
Advantages
Antibody
Cytotoxic
Chemical linker
• Greater tumor kill
• Normal tissue sparing
Preclinical gRED pipeline
• New NHL, CLL, MM targets
Proof of concept (POC)/clinical
development
Target cell
• ASH 2009: ADC in Hodgkin’s
lymphoma
Antibody-drug conjugate (ADC)
Antibody/target
Expression on tumor but
not on vital tissue
Linker
Stable in circulation
Released in tumor
Drug
• SABCS 2009: RG3502/T-DM1
(trastuzumab DM1): New phase II
data in mBC 3rd line HER2+
Highly potent
Non-immunogenic
gRED=Genentech Research & Early Development, NHL=Non-Hodgkin’s Lymphoma, CLL=Chronic Lymphocytic Leukemia, MM=Multiple Myeloma
16
Important clinical data at ASH 2009
Dr. Nancy Valente, Sr. Group Director,
Clinical Development
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
• 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
1In
partnership w/Abbott
18
MabThera/Rituxan
RG7159/GA101
RG7433/ABT-263
19
CLL8 Study Design
Patients with
untreated, active
CLL and
good physical
fitness
(CIRS ≤ 6, creatinine
clearance ≥ 70
ml/min)
6 courses
FCR
Follow
up
R
FC
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.
20
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%)
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%)
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%
Median age
Median cumulative illness
rating scale (CIRS)
*P<0,05
21
Adverse events CTC grade 3 and 4
FC
FCR
p
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
Total number of patients with
≥ 1 grade 3/4 event
Treatment related mortality 2% for both arms.
ASH 2009, abstract 535, Hallek et al.
22
Best response to treatment
FC
FCR
CR*
PR
21.8%
66.6%
44.1%
51.0%
Overall response rate
88.4%
95.1%
**CRu
All included
**CRi
in PR
nPR
SD
PD
4.6%
1.9%
5.7%
7.8%
3.8%
3.6%
2.3%
3.4%
3.9%
1.0%
*According NCI WG Criteria, confirmatory BM assessment performed up to 6 months after final restaging
ASH 2009, abstract 535, Hallek et al.
P < 0.01
23
Progression free survival: FCR versus FC
ASH 2008
ASH 2009
p=0.000007
Median PFS: 32.3 months for FC vs 42.8 months for FCR
ASH 2009, abstract 535, Hallek et al.
p<0.001
Median PFS: 32.8 months for FC vs 51.8 months for FCR,
n=790, HR 0.563, ranges 0.460-0.689
24
PFS rate 3 yrs post randomization:
FC: 44.7%, FCR: 64.9%
Overall survival
Overall survival 3
years post
randomization:
FCR: 87.2%
FC: 82.5%
n=817, HR 0.664,
p=0.012
ASH 2009, abstract 535, Hallek et al.
25
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
MabThera/Rituxan: Encouraging safety and efficacy
with multiple chemotherapies
Study
Pts
evaluated
Median
ORR
age/upper
Safety
Bendamustine +
MabThera/Rituxan1
117
64 yrs / NR
91%
Myelosuppression/
infections
Chlorambucil +
MabThera/Rituxan2
50
70.5 yrs / up
to 86 yrs
84%
GI disorders,
infections
Fludarabine +
MabThera/Rituxan3
104
63 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
1ASH
2009, abstract 205, Fischer et al
2ASH
2009, abstract 3428, Hillmen et al
3ASH
2009, abstract 539, Woyach et al
27
MabThera/Rituxan
RG7159/GA101
RG7433/ABT-263
28
RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:
Phase I dose-escalation (3+3 design)
Tumor assessment
GA101 single agent (total 9 doses)
1
3
6
9
12
15
18
21
25
33
weeks
• CD20+ CLL for whom “no therapy of
higher priority was available”
Cohort
group
GA101 dose
Dose 1/Doses 2–9
• n = 3 per cohort
– Successive cohorts initiated
if no DLT
1
400/800 mg
2
800/1200 mg
31
1200/2000 mg
4
1000/1000 mg
• Enrolment from July to November 2008
at 7 sites in France
GA101 administered as per rituximab administration guidelines; 14 patients enrolled in cohort at 1200/2000 mg dose level
ASH 2009, abstract 884, Morschhauser et al
29
RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:
Patient characteristics
B-CLL patients
Age, median (range)
Male/female
(n=13)
64 yr (46–81)
9/4
Baseline SPD, median (range)
2124 mm2 (1068–26732)
Lymphocytes, median (range)
50.5 x 109/L (5.0–153)
Platelets, median (range)
190 x 109/L (93–358)
Duration of CLL, median (range)
Time from last treatment, median (range)
Prior therapies, median (range)
7.6 yr (2.8–15.7)
25 mo (7–68)
3 (1–8)
Prior rituximab
62%
Prior fludarabine
100%
Prognostic factors (n = 9)
Cytogenetics
IgVH status
p53 status (n = 8)
ASH 2009, abstract 884, Morschhauser et al
17p– (n = 2), 11q– (n = 1), 13q– (n = 1),
tri 12 (n = 2), normal karyotype (n = 3)
Mutated (n = 2) (VH3-21 [n = 1]),
unmutated (n = 7)
Mutated (n = 1) Unmutated (n = 7)
30
RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:
Grade 3 & 4 adverse events during treatment period
Adverse event
(n=13)
Neutropenia*
7
Thrombocytopenia*
2
Febrile neutropenia*
1
IRR*
2
Bronchitis*
1
Oral herpes
1
Gingivitis*
1
Tumor lysis syndrome*
1
Total Pts with at least 1 AE
10
*Includes 1 SAE (4 patients in total)
ASH 2009, abstract 884, Morschhauser et al
31
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
ASH 2009, abstract 884, Morschhauser et al
32
RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:
Best overall response 62%1
Cohort
CR
400/800 mg
800/1200mg
x
PR
SD
x
xx
x
x
1200/2000 mg
xxxx
1000/1000 mg
x
xx
7
5
Total (n=13)
1
PD
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 al
1Response assessment based on revised CLL criteria, Hallek et al, Blood 2008; 111:5446–5456
33
RG7159/GA101 (Next-gen anti-CD20) GAUGUIN study:
All 13 patients achieve tumour shrinkage1
Patients (n=13)
0
Tumor burden decrease (%)
-20
-40
-60
-80
-100
ASH 2009, abstract 884, Morschhauser et al
1Response assessment based on revised CLL criteria, Hallek et al, Blood 2008; 111:5446–5456
34
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
ASH 2009, abstract 884, Morschhauser et al
35
RG7159/GA101 (Next-gen anti-CD20) GAUSS study:
Phase I dose escalation (3+3 design), induction dosing
Response assessment
GA101 single-agent (total 4 doses)
1
2
3
13
4
weeks
GA101 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
GA101 dose
Dose 1/doses 2–4
1
2
3
4
5
6
100 / 200 mg
200 / 400 mg
400 / 800 mg
800 / 1200 mg
1200 / 2000 mg
1000 / 1000 mg
36
RG7159/GA101 (Next-gen anti-CD20) GAUSS study:
Patient demographics and disease characteristics
Characteristic (n=22)
Median age [range]
Male / female
Histological subtype (n=22)
Diffuse large B-Cell lymphoma
Other aggressive pathologies (MCL + transformed MZL)
Follicular lymphoma
Small lymphocytic lymphoma
Chronic lymphocytic leukaemia
NHL Patients (n=17)
Clinical Stage (Ann Arbor)
I / II
III / IV
Follicular lymphoma prognostic index (n=10)
Low risk: 0-1 risk factor
Intermediate risk: 2 risk factors
High risk: 3-5 risk factors
CLL Patients (n=5)
Rai Stage
Intermediate (I and II)
High-Risk (III and IV)
ASH 2009, abstract 934, Sehn et al
No. of patients (%)
60 [47-77]
13 / 9
3 (14)
2 (9)
10 (45)
2 (9)
5 (23)
2 (11)
15 (89)
3 (30)
3 (30)
4 (40)
4
1
37
RG7159/GA101 (Next-gen anti-CD20) GAUSS study:
Prior treatment regimens and response
Variable
No. of prior therapies, median (range)
No of patients (%)
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)
Non-Hodgkin’s Lymphoma (n=17)
NHL patients with prior anthracycline
11 (65)
NHL patients with prior ASCT
3 (18)
Chronic Lymphocytic Leukemia (n=5)
CLL patients refractory to fludarabine
ASH 2009, abstract 934, Sehn et al
5 (100)
38
RG7159/GA101 (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
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)
-
Neutropenia
4 (18)
4
Febrile neutropenia
1 (5)
1
Thrombocytopenia
1 (5)
1
Non-hematologic AEs
Hematologic AEs
ASH 2009, abstract 934, Sehn et al
39
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
800/1200 mg
3
3
1200/2000 mg
3
3
1000/1000 mg
7
4
2
1
5
13
3
1
24%
62%
14%
Total
Percent
ASH 2009, abstract 934, Sehn et al
22
1
40
RG7159/GA101 (Next-gen anti-CD20) GAUSS study:
Overall response following induction, by histology, 13 wks
Histology
No. of
patients
CR
PR
SD
PD
1
1
Diffuse large B-Cell lymphoma
3
1
Other aggressive histologies
(MCL + transformed MZL)
2
1
Follicular lymphoma
10
2
7
Small lymphocytic lymphoma
2
1
1
Chronic lymphocytic leukemia
5
ASH 2009, abstract 934, Sehn et al
Non
evaluable
1
4
1
1
41
RG7159/GA101 (Next-gen anti-CD20) GAUSS study:
Treatment response in patients receiving extended therapy
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
SLL
PR
14 months
PR
N
FL
PR
17 months
PR
N
CLL
SD
3 months
SD
Y
FL
SD
9 months
SD
N
400/ 800
1200/ 2000
ASH 2009, abstract 934, Sehn et al
42
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
ASH 2009, abstract 934, Sehn et al
43
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
GA101
Relapsed CD20+
indolent NHL
(N=180)
1000 mg
Weekly x 4
Rituximab
375mg/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
ASH 2009, abstract 934, Sehn et al
44
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
45
MabThera/Rituxan
RG7159/GA101
RG7433/ABT-263
46
RG7433/ABT-2631: Phase I in relapsed/refractory CLL
M06-873 study design
Intermittent
Screening
14d on/7d off
15 Patients
Dose levels
10 mg
n=3
110 mg
n=6
200 mg n = 3
250 mg
n=3
Safety
PK
MTD
Continuous with lead in
7d 100mg
Screening
Safety
21d on / 0d off
14 Patients
ASH 2009, abstract 883, Roberts et al
1In partnership w/Abbott
PK
Dose levels
125 mg
n=3
200 mg
n=4
250 mg n = 3
300 mg
n=4
MTD
47
RG7433/ABT-2631: Phase I in relapsed/refractory CLL
Patient characteristics
Patient characteristics (n=29)
Age
Median
Range
67 years
50-79 years
Gender
Male
Female
19
10
Lymphocyte count
Median
Range
15.5 x 109/L
0.8-284.3
Bulky nodes >5 cm
Number of prior therapies
12 pts
Median
Range
Fludarabine-refractory
Unfavorable FISH
ASH 2009, abstract 883, Roberts et al
1In partnership w/Abbott
4.5
1-11
8 pts
17p13.2 del
11q22.3 del
8 / 21 pts
5 / 21 pts
48
RG7433/ABT-2631: 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
<110 mg: 33% (7/21)
•
Median progression-free survival
not reached
Response type
n
Partial response (PR)
Stable disease (SD) with >50% peripheral
lymphocyte reductions >2mths
Stable disease (SD)
Progressive disease (PD)
7
7
8
2
72-yr male, 7 prior txs, fludarabine-refractory, 17p del
– 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
ASH 2009, abstract 883, Roberts et al
1In partnership w/Abbott
Pre-treatment
After 7 cycles
49
RG7433/ABT-2631: Phase I in relapsed/refractory CLL
Response in patients with poor prognosis
Response to treatment
Time to progression
FISH
abnormality
n
Responsea
Del 17p
6
5
Del 11qb
5
4
Neither
5
5
a
Response includes PR, >50% in
lymphocytes, or both
b Del 11q, without Del 17p
(Döhner)
ASH 2009, abstract 883, Roberts et al
1In partnership w/Abbott
Progression Free (%)
• 16 pts with cytogenetic data and
dose >100mg / day
50
RG7433/ABT-2631: 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 17p del CLL and 11q del CLL
RG7433/ABT-263: Promising data in CLL
ASH 2009, abstract 883, Roberts et al
1In partnership w/Abbott
51
Leader in hematology — commercial overview &
opportunities
Dr. Myriam Mendila, Hematology Franchise
Leader
MabThera/Rituxan: Leading hematology product
Top products commonly used to treat hematological
malignancies
Q3
Q 97
1Q 3 98
Q 98
1Q 99
3Q 99
1Q 00
3Q 00
1Q 01
3Q 1 01
Q 02
3Q 1 02
Q 3 03
Q 1 03
Q 3 04
Q 1 04
Q 3 05
Q 05
1Q 3 06
Q 06
1Q 07
3Q 07
1Q 08
3Q 08
109
Global sales1
1Source:
IMS MIDAS in PADDS as of Q2 2009
MabThera/Rituxan
Imatinib
Bortezomib
Lenalidomide
Doxorubicin
Dasatinib
Dexamethasone
Thalidomide
Topotecan
Bendamustine
Prednisone
Nilotinib
Fludarabine
Melphalan
Cyclophosphamide
Alemtuzumab
Vincristine
Bleomycin
Cladribine
Ibritumomab tiuxetan
Chlorambucil
53
MabThera/Rituxan: The success continues
Continued sales growth, in particular Europe/RoW
9 M 08
20
09
9M
20
08
20
07
20
06
20
05
20
04
20
03
– iNHL 1st line maintenance2
20
– CLL relapsed1
02
– CLL 1st line1, now OS benefit
20
• Recent approvals and/or phase III results
to support further growth:
7
6
5
4
3
2
1
0
01
• Outstanding clinical benefit combined with
excellent tolerability
Group sales, CHF bn
20
Key facts
• Over 1.7 million patients treated3
Outstanding clinical benefit
1Approved
Europe/RoW
US
Japan
EU, final label discussion U.S. 2Filing 2010 3Including the use of MabThera/Rituxan in autoimmune diseases, the number is over 1.9 million
54
MabThera/Rituxan: Growth opportunities in EU/RoW
PRIMA1 and OS benefit in CLL to drive further uptake
Growth opportunities
Thousand patients treated
70
60
50
40
30
20
10
MabThera/Rituxan
1PRIMA
Top-5 EU
CL
L
aN
HL
t
m
ain
iN
HL
iN
HL
CL
L
aN
HL
t
m
ain
iN
HL
CL
L
t
m
ain
aN
HL
U.S.2
iN
HL
No MabThera/Rituxan
iN
HL
iN
HL
0
E73
study in iNHL 1st line maintenance (filing 2010) 2CLLfinal label discussion U.S. 3E7: Brazil, Russia, China, Mexico, Turkey, South Korea, India
55
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 Q3-2009
Maximizing the overall hematology franchise
56
Leadership in hematology
Leader 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
RG7159/GA101
New-gen anti-CD20
w/improved properties
Anti-CD20 lifecycle management
57
Questions & Answers
Moderator:
Dr. Karl Mahler, Head of Investor Relations
We Innovate Healthcare
59