r
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; 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.
For marketed products discussed in this presentation, please see full prescribing information on our website –www.roche.com
All mentioned trademarks are legally protected
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Burkhard Piper, Head Roche Diabetes CareCopenhagen, September 15, 2006
Roche Diabetes Care Renewed portfolio for growth
Roche Diagnostics: a significant businessDiabetes Care: a third of sales
78 %
22 %
Pharma
Diagnostics
Roche GroupH1 ’06 Sales CHF 19.8 bn
67 %
33 %
Diabetes Care
Roche DiagnosticsH1 ’06 Sales CHF 4.3 bn
Accu-Chek: 4th largest brand in Roche
Roche: unique, risk diversified profile
CellCeptCellCeptPegasysPegasys
NeoRecormonNeoRecormon
HerceptinHerceptin
XelodaXeloda
MabTheraMabThera
AvastinAvastin
Future pillars
BonivaBoniva
Diabetes CareDiabetes Care
Molecular DiagnosticsMolecular
DiagnosticsCentralizedDiagnosticsCentralizedDiagnostics
USAUSA (Greater)Europe
(Greater)Europe JapanJapan Asia ChinaAsia China Latin
AmericaLatin
America
TarcevaTarceva
Geographic Diversification
“Pillars of Value” diversification
TamifluTamiflu
Assets on hand
Autoimmunity
Metabolism
Neurology
Rheumatoid Arthritis
Metabolism: focus for Pharma and DiagnosticsBiomarker program across healthcare spectrum
Early Detection Diagnosis
Treatment Selection Monitoring
Screening → Monitoring tests• Genetic disposition/ Early detection• Impairment in insulin resistance• Beta cell function
Treatment• Early validation mechanism of action• Patient stratification/ Response to tx• Drug differentiation
Prognosis
Marker candidates:
• Metabolic disease– Beta cell failure and drug-related
mechanisms of action– Adipose tissue signalling – Lipid profile
• Cardiovascular diseases– Cardiac functionality and
Nephropathy– Plaque vulnerability
Diabetes Care Market
Roche Diabetes Care
Strategy for Future Growth
Diabetes Care Fast growing, highly attractive market
Type 1
170
210
Number people with diabetes
Type 2
2005 2014E
• Epidemic growth of People with Diabetes
• Blood glucose monitoring growth driven by Type 2’s starting insulin therapy
• Increased rivalry with all competitors investing in growth
• Pricing pressure from healthcare cost containment & public tenders
• Convergence of insulin delivery, blood glucose monitoring, andlifestyle/ therapeutic advice
Key Trends
Source: WHO 2005
Millions
0
1
2
2004 2005 2010
Glucose Monitoring Products Insulin Infusion Products
Combined category growth projected to exceed 8 % Yielding CHF ~14 billion market by 2010
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
2004 2005 2010
CHF bn CHF bn
Source: Roche analysis, Boston Biomedical Consultants, HSBC
10 %
7-8 %
12 %
11-12 %
52 %48 %
pumps disposables
Blood glucose strips provide majority of sales Insulin delivery balanced growth
6 %6 %
88 %
strips meters lancets
Source: Roche analysis, company reports, Boston Biomedical Consultants, HSBC
Glucose monitoringCHF 8.5 bn 2005
Insulin InfusionCHF 1 bn 2005
Diabetes Care Market
Roche Diabetes Care
Strategy for Future Growth
Roche Diabetes Care: Market leadership built on 30 years of experience
* includes blood glucose strips & meters, devices & lancets; excludes urine glucose stripssource: Boston Biomedical Consultants, Company reports, Roche analysis
Blood Glucose Monitoring 2005* Insulin Infusion Systems 2005
8 %
12 %
15 %
65 %
# 2 market position
10 %
14 %
15 %
34 %
27 %
# 1 market position
Roche
Roche
Lifescan
Lifescan
Bayer
Abbott
other
other
Medtronic
- launched 1994
- 8 LCM improvements over 11 yrs
- #1 product globally until 2003
• 4 µl, 26 seconds
Accu-Chek Aviva
• 5 sec test
• 0.6 µl sample
• launched 2005
Accu-Chek Compact Plus
• Integrated 17 test drum and lancet
• 5 sec
• launched ‘05-’06
Our leadership is being challenged while we replace our flagship Accu-Chek Advantage platform
CompetitorsOne Touch Ultra• 1 µl, 5 secs• launched 2003
Freestyle• 0.3 µl, 15 secs• launched 2000
Ascencia Contour• 0.6 µl, 15 secs• launched 2003
Accu-Chek Advantage
H1 ’06: Roche Diabetes Care sales Positive trends in Europe & emerging markets
ROW
EMEA
Total1%
-9%
7%
5%
North America
EMEA
ROW16%
28%
56%
North America
H1 ‘06 growth drivers: Italy, France, UK & Russia, Latin America, China and India
CHF 1,428 m local sales growth
Accu-ChekD-Tron
D-Tron
New product portfolio positively impacting sales
2005 2006
Accu-Chek Aviva
Accu-Chek Compact Plus
Accu-Chek Advantage
Market Growth ~7 %
7 %
-5 %
6 %
-1 %
Q3 05 Q4 05 Q1 06 Q2 06
Local Sales Growth %
Accu-Chek Spirit
63% 51%35%
19%46%
Accu-Chek Competitor1
Competitor2
Competitor3
Competitor4
Italy(n= 165)Italy(n= 165)
77% 80%
27%54% 46%
Accu-Chek Competitor1
Competitor2
Competitor3
Competitor4
France(n= 203)France(n= 203)
81% 76%50%
37%16%
Accu-Chek Competitor1
Competitor2
Competitor3
Competitor4
Increasing value of the Accu-Chek brand Consumer awareness ahead of leading competitors
USA(n= 201)USA(n= 201) 92%
61%32%
59%40%
Accu-Chek Competitor1
Competitor2
Competitor3
Competitor4
Germany(n= 203)Germany(n= 203)
Source: 2005 consumer awareness study - prompted awareness
Diabetes Care Market
Roche Diabetes Care
Strategy for Future Growth
How do we differentiate Accu-Chek?
BayerBayerLifeScanLifeScan
AbbottAbbott
HypoguardHypoguard
BDBD
HDIHDI
MenariniMenarini
AccuAccu--ChekChek
Differentiation from a customer’s viewUnderstanding unique customer needs
• Management requires behavior changes & many daily self-care activities
strong need for products that improve compliance
• Tight blood glucose control can prevent or delay onsetand progression of complications
strong need for easier to use products
• Diabetes related data are overwhelming
strong need for tools that provide practical advice
Roche’s innovation response to people with diabetesInvestment in 5 highly attractive “connected” business segments
Blood Glucose Monitoring Systems• Single Strip Systems • Integrated Strip Systems
Continuous GlucoseMonitoring Systems
mmol/L
Time
Insulin Pump Systems
Connectivitysolutions
& Information
management
AdvisingSystems
Auto blood sampling
2000 2004 2008 2012
Accu-ChekCompact
Accu-ChekCompact Plus
Strip Integration
Lancing Integration
Waste free
Key Integration Features
Add
ed c
usto
mer
ben
efit
Next Gen
Next Gen
Further expand integrated systems leadership Fewer handling steps and fewer parts to carry
Fewer Handling steps
• With each successive integration step, less user intervention needed – better compliance
Less parts to carry
• With integrated lancing device, less need to carry many supplies – better compliance
Waste-free operation
• A clearly articulated customer need which currently remains unaddressed - we are working to solve
Technological approaches Benefits - improved compliance and outcomes
“Lancing Strip” “Measuring Needle”“Continuous Strip”
- No waste handling - Improved hygiene
- Less pain, no blood seen - Small, fully integrated devices
- No waste handling - Improved hygiene
- Less pain, no blood seen - Small, fully integrated devices
Completingthe
Circle of Care
Insulin Pump Users
Circle of Care SolutionsCombining our areas of expertise
Non Insulin Dependent
Insulin Dependent
Collect
Analyze
Act
Enable People with Diabetes to live the life they want…
Circle of Care solutions position Accu-Chek uniquely as a trusted partner in diabetes management
5
Renewed portfolio launched and driving growth2
Innovation driven by on-going investment in technologies for next generation products
3 Integrated strip systems offer clear differentiation
4
bG monitoring and insulin delivery markets remains highly attractive with high growth
1
In Summary: well positioned to further drive value of the Accu-Chek brand
Diabetes Diagnosis, Monitoring & Treating
Matthias Schweitzer, Head Medical Affairs Diabetes CareCopenhagen, September 15, 2006
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Diabetes diagnosis, monitoring and treatingThe request on diabetes treatment (1)
Microvascularcomplications
Myocardial infarction
HbA1c37%
14%
Deaths related to diabetes21%
1%
Stratton IM, et al. BMJ 2000; 321:405–412.
to lower HbA1c to normal and….
Time
Blo
od G
luco
se
HbA1c = 8%HbA1c = 8%
HbA1c = 8%HbA1c = 8%Results in similar HbA1c !
Diabetes diagnosis, monitoring and treatingThe request on diabetes treatment (2)
… to reduce blood glucose excursions …due to the link between blood glucose excursions, oxidative stress and diabetes complications
However, the situation is poor
J. Olefsky, JAMA 2001:285:628-632
two thirds of patients with diabetes do not achieve HbA1c target and suffer from high blood glucose excursions….
44%
37%
0
10
20
30
40
50
60
Indi
vidu
als
achi
evin
g go
als
(%)
NHANES (1988–1994)
NHANES (1999–2000)
HbA1c< 7.0%
Education Lifestyle Monitoringof BG
Management of Risk Factors
Diabetes diagnosis, monitoring and treatingDiabetes requires effective diabetes management
Information Management & Advice
Drug Treatment
Multi-tasking Diabetes Management
Bergenstal et al. Global Consensus Conference, 2005
Self monitoring of blood glucose (SMBG)The foundation of diabetes self-management
• Real-time, reliable blood glucose concentrations
• Ability to assess pre- and post-prandial hyperglycaemia
• Improved safety through detection of hypoglycaemia
• Possibility of timely therapeutic adjustments
Evidence and trends for SMBG
<=1 2 3 4 5 6 7 8 9 10 > 1
Number of BG measurements per day
6.00
6.25
6.50
6.75
7.00
7.25
7.50
7.75
8.00
8.25
8.50
HbA
1c [%
]
mean mean + 0.95 CI n= 12'725
International survey of insulin pump users: impact of continuoussubcutaneous insulin infusion therapy on glucose control and quality of life. (P. Hammond et al, data on file).USA, Canada, Europe (Germany, Austria, UK, France, Poland) N=14.015
In insulin treated patients, reduction of HbA1c positively correlates with testingfrequency
SMBG improves HbA1c levels in all patients with diabetes
Sarol JN et al., Curr Med Res Opin 21: 173,2005
ROSSO-StudyRRetretroospectivespective SStudytudy „„SSelfelf--monitoringmonitoring of of BloodBlood Glucose (SMBG) andGlucose (SMBG) and OOutcomeutcome in in People People withwith Type 2 DiabetesType 2 Diabetes““
Mortality
-51% -51 %
Morbidity
-51%
-32 %
The RoSSO study including 3,268 patients from 192 randomly selected GP practices in Germany (mean observation period: 6.5 years)
Evidence that SMBG also reduces morbidity and mortality in all patients with diabetes
SMBG is cost-efficient
Costs of monitoring (stripes and lancets)
Costs of consultation fees
Costs additional drug therapies
Costs antidiabetic therapy
Follow-up Costs of diabetes related complications and surgical interventions Costs of diabetes related complications and surgical interventions
SMBG accounts for less than1.0 % of the total diabetes relatedtreatment costs covered by healthinsurances but reduces morbidityby 32 % and mortality by 51 %
C Weber, K Neeser, H Wenzel, B Schneider. Cost of type 2 diabetes in Germany over8 years (the ROSSO study No. 2). Journal of Medical Economics 2006; 9: 1–9
38% 29% 30%
24% 24% 20% 20% 18%
15% 23% 34% 39% 46% 48% 52%
6% 7%
6% 6%
5% 5%5%
5%
13% 12%
10% 10%
9% 8%7% 7%42% 37%
30% 26% 23% 21% 19% 18%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8
Years after diagnosis
Percent Costs
SMBG is an integrated part of a multi-taskingdiabetes management, with proven evidenceRecommended by major clinical guidelines
But reality looks different…..
• Large proportion of diabetes patients seldom or infrequently perform SMBG
(Harris et al., 1993; Ruggiero et al., 1997)
• Based on strip sales, type 1 patients monitor BG 1-2 times daily on average; type 2 patients 1-2 times weekly
(Adams et al., 2005; Vincze et al., 2004)
• Low frequency of SMBG often is a marker of poor overall regimen adherence
(Van der Ven et al., 2004; Karter et al., 2001)
8 11 15 18 22 0 2 4 6 hours
MDI
CSII
1716151413121110
9876543
100120140160
6080
180200220240260280300
Blood glucose [mg/dl]
Blood glucose [mmol/l]
* T. Lindner, University Hospital Dresden (1994), GermanyT1DM, n=19
Continuous sc. insulin delivery using insulin pumpsGold standard in HbA1c reduction and flattening of the blood glucose profile
NIDDM, severe
NIDDM, mild
nondiabetic
G Reaven et al., Diabetes 1988
Insulin pump treatment is still gold standard for insulin delivery due to existing evidence on improvement of glycemic control (HbA1c) and
reduction of blood glucose excursions
Patients on insulin pumps report highest quality of life as shown in recent randomised clinical studies
Cross-sectional, Controlled Study into Quality of Life Issues Surrounding Insulin Pump Use in Type 1 Diabetes*
Results - once controlled for socio-economic differences :
Better overall rated health (WHOQOL BREF) Better physical Quality of Life (WHOQOL BREF) Better psychological Quality of Life (WHOQOL BREF)Less diabetes related distress (PAID)Less worry less about hypoglycaemia (HFS)Greater satisfaction with treatment (IDSRQ)
* Barnard, K & Skinner, C , EASD 2006, submitted to Practical Diabetes International
WHOQOL BREF – World Health Organisation Quality of Life Brief QuestionnairePAID – diabetes related emotional distressIDSRQ – insulin delivery system rating questionnaireHFS – Hypoglycaemia Fear Scale
Insulin pump use is cost efficient
Health-economical comparison of continuous subcutaneous insulin infusion with multiple daily injections for treatment of Type 1 Diabetes in the US
Roze S et al, Diabetic Medicine 2005
Polonsky, 1999; Wagner et al., 2005
Many different reasons for patients not to test as recommended or initiate pump therapy
• I don’t need it – ‘I know when I’m high or low’
• (usually) don’t need it – I have good control
• Fearful of self-testing
• Pricking fingers hurts
• Confronts me with my diabetes
• Disrupts my activities/ lifestyle
• Need to react to the findings, a hassle
• Results are mostly ‘bad’ (negative evaluation), depressing
• Prompts others to act as my ‘diabetes police’
Roche helps making testing and the use of pumps easier with information management & advice tools
Information Management
Advice
+Accu-Chek Smart Pix
+
+
+
Accu-Chek Smart Printer
Accu-Chek Camit Por
Accu-Chek Compass
Accu-Chek Pocket Compass
Accu-Chek AdvisorInsulin-dosing software
Accu-Chek ProfessionalDecision support
Accu-Chek Spirit
Pocket Compass•Pump/bG history data•bolusRec tool
Accu-Chek Compass
Accu-Chek Camit Pro
Accu-Chek Aviva
-2
-1,5
-1
-0,5
0
0,5
6 7 8 9 10baseline HbA1c (%)
chan
ge a
t D 9
0
AllChange in HbA1c D90 vs D1:
- 0.33 + 0.48 %(p< 0.001, Wilcoxon test)
CSII CSII +D1 D90
Baseline HbA1c > 7.5%Change in HbA1c D90 vs D1:
- 0.41 + 0.57 %(p< 0.017, paired-t-test)
Information management Accu-Chek Pocket Compass
* Eric Renard, Robert Boizel, submitted to Diabetes Care CSII = continuous subcutaneous insulin infusion
Glucose and pump data management software operated on a PDA can contribute to improved diabetes control in CSII treated patients*
Manage and use collected information for treatment decisions Accu-Chek Advisor Insulin-Dosing Software
Accu-Chek Advisor Insulin-Dosing Software
Figure 1:Glycaemic Control – HbA1c
6.8
7
7.2
7.4
7.6
7.8
8
8.2
8.4
8.6
8.8
Baseline 6 Week 3 Month 6 Month
Control
ExperimentalHbA
1c%
*p=0.0029
*p=0.0027
*p=0.215
*p=0.457
Control Experimental p-value Baseline 8.54 ± 0.84 8.44 ± 0.90 0.4576 6 Week 8.24 ± 0.80 7.98 ± 0.81 0.2151 3 Month 8.33 ± 0.91 7.73 ± 0.96 0.0027 6 Month 8.39 ± 0.86 7.70 ± 0.55 0.0029
*Mixed model longitudinal data analysis with preplanned orthogonal contrasts.
Accu-Chek Advisor Insulin-Dosing SoftwareEnables tighter glycaemic control
Intensified Insulin Treatment
+
0 6 12
Intensified Insulin Treatment
months
* Satish Garg et al
Glycemic control and prevention of hypoglycemia in intensively treated subjects with type 1 diabetes using Accu-Chek Advisor insulin dosing software*
Manage and use collected information for treatment decisions Accu-Chek Professional Decision Support
Accu-Chek Professional Decision Support
Accu-Chek Professional Decision Support
To support timing and dosing of prandial insulinsupply to reduce bloodglucose excursions:
– Insulin Lyspro– Insulin Aspart– Insulin Glulisine– Inhaled Insulin
Accu-Chek Professional Decision Support
100
150
200
250
300
fasting beforelunch
beforedinner
bedtime
Pote
ncy
to d
ecre
ase
HbA
1c -0.5 %
-1.0 %
-1.5 %
-2.0 %
-2.5 %
-3.0 %
-3.5 %
SMBGOAD GLP-1 Insulin
Information Management & Advice
SMBG + OAD
SMBG + Insulin
Increased potency of HbA1c reduction if components of diabetes management work together
SMBG + Insulin +Inf. Manag.& Advice
Completingthe
Circle of Care
Insulin Pump Users
Circle of Care SolutionsCombining our areas of expertise
Non Insulin Dependent
Insulin Dependent
Collect
Analyze
Act
Enable People with Diabetes to live the life they want…
Summary
• Diabetes mellitus is epidemic and a leading cause of morbidity, mortality and increasing cost in health care systems
• Therefore, multi-tasking diabetes management is required with proven evidence for every component - education, lifestyle changes, monitoring blood glucose, drug treatment and CV risk management
• Roche Diabetes Care contributes to better diabetes management and patients self-care through continuous development of new products and technologies
• Roche Diabetes Care provides ongoing clinical evidence for its Accu-Chek products including information management & advice tools to increase the level of knowledge, encourage compliance and enable patients to take control and manage their diabetes
Roche Pharma and Metabolic DiseasesNew pillar of growth
Viktor Boerlin, Clinical Research & Licensing LiaisonCopenhagen, September 15, 2006
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MabThera
AvastinHerceptin
Tarceva
OmnitargMircera
OncologyXeloda
R1492ARQ
9 phase I compounds
MabTheraActemra
R1594 Hum anti CD-20
RA/ Autoimmune
4 phase I compounds
R1503 p38 kinase inh.
R1438R1658 (JTT-705)
Metabolism
3 phase I compounds
R1440
R1583 (GLP-1)
4 phase I compoundsNeurology
4 phase 0 compounds
ON HAND PROMISING LATE STAGE
EMERGING MID-TERM
EARLY STAGE
CellCept
Roche: Existing and future pillars of growth
Oral anti-diabetic treatment market worth $9 bn in 2005Forecasted growth driven by emerging new products classes addressing current shortcomings
0
5
10
15
20
25
30
2002 2003 2004 2005 2006E 2014E
Novel productsGlitazonesSUs/ Metformin
Source: Roche analysis, Wood Mackenzie, IMS data
Market forecast oral anti-diabetic products ($bn)
PPAR γ Agonists Hyperglycemia
LIVER
PANCREASGlucose
GUT
MUSCLE
ADIPOSE TISSUE
SulfonylureasMeglitinides
Metformin
α-GlucosidaseInhibitors
PPAR γ AgonistsMetformin
Type 2 Diabetes - multiple organ dysfunction Requires combination treatment for improved efficacy
Current options
Type 2 DiabetesDisease progression despite intensive therapy
• Life style interventions (diet, exercise) efficacious, but seldom practicable
• Adherence to oral anti-diabetic therapy is 36 %-87 % 2
• Tolerability/ safety issues
• Treatment goals not reached in 64 % 3
• Better therapeutic strategies needed:- Early diagnosis and therapy- Early combination therapy- Lower treatment targets - Better drugs- Disease-modifiers
United Kingdom Prospective Diabetes Study 1
0 3 6 9 12 15
HbA
1c (%
)
6
7
8
9
0 3 6 9 12 15
Years from randomization
Conventional therapy
Intensive therapy
6.2% upper limit of normal range
1 Adapted from: UKPDS Group. The Lancet 1998; 352: 854 2 Cramer. Diabetes Care 2004; 27: 1218 3 Koro. Diabetes Care 2004; 27: 17
PPAR γ Agonists Hyperglycemia
LIVER
PANCREASGlucose
GUT
MUSCLE
ADIPOSE TISSUE
SulfonylureasMeglitinides
Metformin
α-GlucosidaseInhibitors
PPAR γ AgonistsMetformin
DPP-IVGLP-1GKA
GKADPP-IVGLP-1
Primary goal: effective glycemic controlIncreasing trend for combination Tx - oral and insulin
Current optionsGKA: Glucokinase activatorNew Roche options
Glucagon-like peptide-1 (GLP-1)Important therapeutic target for type 2 diabetes
• GLP-1 is a 37-amino acid peptide hormone, expressed by K and L-cells of the small and large intestine, and in neurones in the nucleus of solitary tract (NTS)
• Food ingestion leads to a biphasic release of GLP-1 into the circulation
• Biological activities of GLP-1:- Stimulation of glucose-dependent insulin secretion and biosynthesis- Inhibition of glucagon secretion- Delay of gastric emptying- Induction of satiety and inhibition of food intake
• Short half life: rapidly broken down by dipeptidyl peptidase-IV (DPP-IV)
• Reduced GLP-1 response to food in T2D patients
• GLP-1 induces pancreatic β-cell proliferation/ differentiation (preclinical data)
R1583/ BIM-51077: Opted-in with Ipsen (July ’06)Data published at ADA 2006
R1583/ BIM-51077 is an analogue of GLP-1 with increased stability
Immediate release formulation
• Phase II: 28 days of continuous s.c. infusion
• Demonstrated significant lowering of fasting blood glucose concentration and HbA1c, good tolerability, trend to increase insulin secretion and decrease body weight and appetite
Sustained release formulation
• Preclinical data in beagle dog: s.c. injection with a small needle
• Achieved sustained release profile and long duration of release
R1583/ BIM-51077Phase II 28 days continuous infusion
24h profile of blood glucose concentrationsDay 28, mean glucose concentration [mmol/L]
Breakfast Lunch Dinner
18 T2D patients treated with metformin, 12 active, 6 placebo, 28-day continuous subcutaneous infusion of BIM-51077 IRF
4
6
8
10
12
14
prebreakfast
1h poststart
breakfast
2h poststart
breakfast
3h poststart
breakfast
4h poststart
breakfast
pre lunch 1h poststartlunch
2h poststartlunch
3h poststartlunch
4h poststartlunch
predinner
1h poststart
dinner
2h poststart
dinner
3h poststart
dinner
4h poststart
dinner
5h poststart
dinner
1h poststart
9inner
prebreakfast
Placebo 400 µg/d
Summary and outlookR1583/ BIM-51077 (GLP-1)
• Greater binding potency than native protein
• Extended metabolic half life (22-fold more stable in plasma)
• Good safety profile, no antibodies against BIM-51077
• Significant and rapid effect on 24h blood glucose following continuous infusion
• Sustained effect on fasting blood glucose over 28 days
• Trend to increase insulin secretion, to decrease HbA1c, and decrease body weight and appetite
Start of phase II early ‘07 (sustained release formulation)Frequency of administration planned: once a week and beyond
Dipeptidyl peptidase (DPP-IV) inhibitorsEmerging new class of oral anti-diabetic drugs
• Protects GLP-1 and Glucose-dependent Insulinotropic Polypeptide (GIP) from rapid degradation
• Main benefits– Can be taken orally– Potential for monotherapy and combination (metformin, glitazones or
sulfonylureas)– Good safety profile expected– No weight gain– Preclinical evidence for β-cell protection
• Main disadvantages– ‘Rich’ competitive environment
Summary and outlookR1438 (DPP –IV inhibitor)
• Potentially best in class molecule
• 2 phase II trials ongoing – Mono- and combination therapy with metformin– To complete end 2006/ early 2007– Filing planned in 2009
• Back-up compounds in earlier stages of development
Liver Glucose Production
GKA
Glucose Glucose 6-P
Pancreaticβ-cells
GK
GlucoseGlucose
6-PGK
Insulin secretion
Hepatocyte
Glycogen
Bloodglucoselevels
Glucokinase Activator (GKA)New class – Roche in leading position
• Glucokinase: key enzyme regulating whole body glucose homeostasis
• GKAs address 2 of the underlying T2D pathologies
– Impaired insulin secretion
– Increased liver glucose production
• Genetic loss of GK activity leads to early type 2 diabetes (MODY2)
Summary and outlookR1440 (GKA)
• First in class molecule
• Phase II ongoing in T2D – Four studies currently running (mono- or combination with metformin, safety
combination with sulfonylurea, titration study)– Initiated in Q4 ’05– First data in 2007– Filing planned in 2009
• Main benefits of this class– Oral– Addresses two underlying pathogenic mechanisms of T2D
CETP inhibition Novel strategy to raise HDL
A-I
Liver
CECE
FCFCLCAT
FC
Bile
SR-BI
A-I
ABCA1
Macrophage
CEB
LDLR
VLDL/LDL
CETP
CE
TG
FC
X
Feces
CETP inhibitor
ABCA1: ATP-binding cassette, sub-family AA-I: apolipoprotein 1CE: cholesteryl esterCETP: CE transfer proteinFC: free cholesterol
LCAT:l ecithin-cholesterol acyltransferaseLDL: low-density lipoproteinLDLR: LDL receptorSR-BI: scavenger receptor class-B type ITG: triglycerideVLDL: very-low-density lipoprotein
Nascent HDLMature
HDL
-50
-40
-30
-20
-10
0
10
20
Week 0 Week 1 Week 2 Week 4 Week 8
Placebo 300 mg 600 mg 900 mg
0
5
10
15
20
25
30
35
Week 0 Week 1 Week 2 Week 4 Week 8
CETP activity% change
de Grooth GJ et al. Circulation 2002;105:2159-65
R1658 (JTT-705; CETP inhibitor): phase IIa dataMonotherapy
HDL-C% change
Summary and outlookR1658 / JTT-705
• Roche and Japan Tobacco signed agreement for development and commercialization in October 2004
– Roche has exclusive worldwide rights, excluding Japan and Korea
• Clinical efficacy data confirms benefits of CETP inhibition in hyperlipidemia/ dyslipidemia
• Well-tolerated, with a similar overall safety profile to placebo
• Phase II in dyslipidemia (combination with pravastatin)
– primary endpoint: percentage and absolute change from baseline at week 12 in HDL-C level (efficacy)
– already seen encouraging efficacy data
– safety trial ongoing
– go/ no go decision for phase III in 2007
√
√
√
√
√
Status as of June 30, 2006 Unless stated otherwise, submissions will occur in US and EU
2006 2007 2008 2009
Xeloda mCRC 2nd line combo
AvastinRCC (EU)
Phase IIIPhase II
post 2009
ActemraRA / sJIA
CellCeptlupus nephritis
Major Roche managed projected submissionsBalanced portfolio of first in class/ best in class
Xeloda mCRC 2nd line combo
Xelodaadj. BC
MabTheraCLL (EU)
Mircera (CERA)cancer anaemia
R1438type II diabetes
R1440type II diabetes
R1273 (Omnitarg)solid tumors (EU)
R1658dyslipidemia
Avastinadj. CC (EU)
Avastinovarian Ca (EU)
R667 emphysema
Avastinprostate Ca (EU)
R1594RA (EU)
R873male erectile dysfunction
R1503RA
AvastinNSCLC squamous (EU)
Xelodaadj. CC combo
R1492solid tumors
Herceptingastric Ca (EU)
Avastinpancreatic Ca (EU)
R1558bacterial infections
TarcevaNSCLC 1st line chemo (EU)
Tarceva+AvastinNSCLC 2nd line (EU)
MabTheraRA DMARD inadeq. resp. (EU)
Tarceva+AvastinNSCLC 1st line
maint (EU)
AvastinmBC 1st line extension(EU)
Avastinpancreatic Ca (EU)
MabTheraRA DMARD inadeq. resp. (EU)
HerceptinmBC hormonal (EU)
AvastinmCRC 1st line combo
extension (EU)
Mircera (CERA)renal anaemia
AvastinNSCLC 1st line (EU)
AvastinmBC 1st line (EU)
Xeloda mCRC 1st line combo
Xeloda gastric Ca (EU)
HerceptinAdj. BC (EU)
Roche Pharma and MetabolismSummary
• Roche Pharma has built, within a short time, a strong and efficient R&D organization in vascular and metabolic diseases
• The R&D pipeline in vascular and metabolic diseases is rich:- 4 compounds in phase 2- 3 compounds in phase 1- 3 compounds in phase 0- Nearly 30 % of research projects are in the vascular and metabolic area
• Vascular and metabolic diseases will be one of the future pillars for Roche Pharma
Appendix
Global prevalence of diabetesStrongly driven by obesity and ageing
0
50
100
150
Developedcountries
LatinAmerica
India &China
OtherAsia,Africa
2000 2030
Major healthcare challenge
• Expanding prevalence > 350 mio by 2030
• Type 2 diabetes accounts for 90% - 95% of all diabetics
• Diagnosis usually late and 40% of all type 2 diabetics are unaware of their condition
• About 65% of death in type 2 diabetic patients are due to cardio-vascular disease
• Significant burden to healthcare funding– US annual direct costs estimated at
USD 92 bn (2002) 2
Estimated number of people with diabetes by region 1
Sources: 1 Wild et al., Diabetes Care 2004; 27: 1047 2 National Diabetes Fact Sheet; http://www.cdc.gov/diabetes/pubs/estimates.htm. Accessed August 29, 2006
Trends in diabetes (1)
• New treatment options (e.g. GLP-1, DPP-IV, GKA) which might expand or keep the non-insulin user segment stable are needed to normalise blood glucose and help further improve diabetes management - together with SMBG
• Major trend in insulin delivery is non-invasive methods including inhalable, oral and patch technology
• These non-invasive methods support the use of insulin and insulin dose adoption for each meal on the basis of regular SMBG
• New technologies in insulin delivery might primarily improve convenience and patients compliance, thus reimbursement is a critical issue
• Higher convenience might result in more T2D treated with insulin with improved glycemic control – currently tested in clinical trials
Trends in diabetes (2)
• Continuous monitoring of blood glucose is gaining momentum and has potential to provide significantly more patient data and information on glucose trends than spot monitoring
• However extensive data generated by CGM requires analysis and advice in order to be safely and effectively used in diabetes management
• CMBG has not yet received reimbursement and can be used only in addition with spot monitoring
• Roche is focusing on two different CGM systems for distinct purposes:– consumer minimally invasive continuous monitoring system for daily use based on
needle type sensor technology– continuous monitoring high precision research tool (CMRT) for medical research
using micro-dialysis technology
Trends in diabetes (2)
Trends in diabetes (3)
• The healthcare industry continues to explore a variety of intervention models to engage patients and their healthcare providers to reinforce healthy behaviors that will improve clinical outcomes and reduce medical costs
• Today’s most effective programs are those that empower patients to manage their disease while providing a direct link back to the healthcare provider to offer feedback and modify treatment
• Remote Care Management (RCM) is designed to be an intervention model that utilizes patient biometric data (i.e. blood glucose levels) to monitor patients and offer healthcare providers actionable information that may be used to help modify treatment