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

picture placeholder

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