Urs Schleuniger, PhD - Roche

Therapies that promise to make a difference
Urs Schleuniger, PhD

Today, significant unmet medical need remains
Need exists for novel treatments
Remission
claim for the future
Major Clinical Response
(ACR70 maintained for 6 months)
Emerging claim < 20%
Reduction in Signs and Symptoms of RA (ACR20)
“Partial Clinical Response” ~65%
Traditional claim
Pyramid of response

Rheumatoid Arthritis
Current treatment options
RA patients
RA diagnosed
NSAID or Cox-2
Non-MTX DMARDs
Methotrexate
(MTX)
Methotrexate
Methotrexate
+
+
Other DMARDs
(Combination therapy)
Biologic
(Switching between
different Anti-TNFs)
DMARD: Disease modifying anti rheumatic drugs, NSAIDs: Non-steroidal antiinflammatory drugs

Major players are active in this area
Opportunities remain for novel therapies
Phase I/II
Denosumab
Amgen
Ocrelizumab
Roche
Orals
e.g. p38
HuMax 20
GenMab
Belimumab
HGS/CAT/GSK
Tru015
Trubion/Wyeth
Phase III
Actemra
Roche
Cimzia
Celltech/UCB
Golimumab
J&J
Launched
Enbrel
Amgen
Remicade
J&J
Humira
Abbott
MabThera
Roche
Orencia
BMS
1998 1999 2000 2001 2002 2003 2004 2005
2006
2008 2010 2012
Anti-TNF Other MoA Costimulation modulator B-Cell Targeted Therapy Roche

Roche’s first step
in providing novel rheumatoid arthritis treatments

MabThera/Rituxan
Innovative and effective
• The first and only B cell therapy in RA
• A monoclonal antibody that selectively targets
a subset of B cells, leaving the immune system intact
• REFLEX, a Phase III trial in patients with long-standing,
severe disease who had failed to respond, or were
intolerant to, TNF inhibitor therapy confirmed MabThera’s
efficacy
REFLEX - Randomised Evaluation oF Long-term Efficacy of
RituXimab in RA

MabThera/Rituxan
Effective and lasting with proven safety
• Repeat courses of MabThera provided improved efficacy
• Remission rates doubled (6% to 13%)
• ACR70 doubled (12% to 21%) - signs and symptoms of disease improved by
70% in patients treated with MabThera
• Repeated courses of only 2 infusions every 6 to 12 months lead to improved
mobility and reduced pain
• MabThera’s safety profile is established with more than 960,000 patient exposures
in oncology and autoimmune disease

MabThera/Rituxan
Inhibition of joint damage
• Unique data in patients with an inadequate response to one
or more TNF inhibitors showed significant inhibition of joint
structural damage at 12 months:
• More than 50% reduction in joint space narrowing
and bone erosions compared to MTX alone
X-ray changes that MabThera aims to inhibit

MabThera/Rituxan
Summary
• Innovative: first and only selective B cell therapy
• Effective: provides lasting treatment success with repeated courses of only
2 infusions every 6 to 12 months
• Safety: selectively targets CD20-positive B cells, leaving the other
important cells in the immune system intact
• Cost-effective: lower average annual treatment cost when compared to
other available biologics

Another opportunity to make a difference
Actemra

Actemra
First-in-class biologic agent
• Blocks interleukin-6 (IL-6), an important protein involved in the
inflammation associated with RA
• This unique IL-6 inhibition is thought to impact both joints and the entire
body
• Actemra is being developed in collaboration with Chugai in Japan
• Chugai have filed in Japan for RA in adults and systemic onset juvenile
idiopathic arthritis (sJIA) in children
• Planned filing in US and EU is late 2007

Actemra
Showing impressive results
Rheumatoid arthritis
In two Japanese monotherapy trials results showed:
• Best ever reported symptom control
• Significantly less radiographic joint destruction after one year
A large Phase III programme in RA is currently being
conducted with more than 4000 patients in 41 countries in
different patient groups

Actemra
Showing impressive results
Systemic juvenile idiopathic arthritis (sJIA)
A Japanese study confirmed significant improvements amongst
children not adequately responding to conventional therapies:
• More than two thirds of patients achieved 70% improvement of symptoms
• More than three quarters of patients had 50% reduction in signs and
symptoms of disease

How does Roche hope to make a difference
in the future?
Ocrelizumab R1594

Ocrelizumab R1594
• Humanised antibody (anti-CD20) that also targets B cells
• Potential for improved administation
• Less immunogenicity potentially improving tolerability
• Development programme will move into Phase III in early 2007 for RA
• Ocrelizumab provides an opportunity to treat other debilitating autoimmune
diseases e.g. lupus and multiple sclerosis

R1503
• R1503 offers selective inhibition of p38α
• p38 regulates the production of the cytokines TNF, IL-1 and IL-6, which are
inflammatory mediators that are overactive in RA
• Oral biologic
• Currently in Phase II

Roche in RA and Autoimmune Diseases
Depth of portfolio and breadth of indications
Phase I
Phase II
Phase III
Launched
Other AI diseases RA
Oral DMARDs
Improved
Biologics
R1295 R1295
Phase I
R1541 (IBD)
R3421 (AI)
BR3-FC (RA) GNE
R1503 R1503 p38 p38 inh inh
R1594 R1594
Ocrelizumab
Phase II
MabThera
(RRMS) GNE
MabThera
DMARD IR IR
Actemra
Actemra (sJIA)
CellCept (LN)
CellCept (MG)
Phase III
MabThera
TNF TNF inhib inhibIRIR
MabThera
(PPMS) GNE
MabThera
(ANCA av) GNE
MabThera
(SLE) GNE
MabThera
(LN) GNE

Summary
Roche in RA and autoimmune diseases
• Innovative pipeline with 2 first-in-class drugs in phase III/launch
• Large investment in development program (second only to oncology)
• Scientific and commercial collaboration with co-marketing partners
Genentech and Chugai
• Strong corporate commitment to build up RA/Autoimmune franchise
Roche poised to become a leader in RA

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