Novo NordiskNovo Nordisk

A focused global healthcare company A focused global healthcare company with biotech expertisewith biotech expertise

Diabetes Conference atDiabetes Conference at

Union Bank of SwitzerlandUnion Bank of Switzerland October 2001October 2001

Agenda

Introduction

Novo Nordisk: The futureInsulin therapy (NovoRapid®,insulin detemir, delivery systems)

Novo Nordisk diabetes commitment outside insulinOral Antidiabetics (OAD): NN622NN2211

Other conceptsIslet replacement

Metabolic abnormalities associated with Metabolic abnormalities associated with Type 1 and Type 2 diabetesType 1 and Type 2 diabetes

Type 1 Type 2

Elevated blood glucose xxx xxx

Ketosis xx 0

Insulin resistance x xxx

Hypertension x xx

Obesity x xxx

Increased LDL x/0 x/0

Increased triglycerides/FFA 0 xxx

Decreased HDL 0 xxx

Diabetes care: Treatment matters

Only a small number of Only a small number of patients are in controlpatients are in control

Intensive treatment mattersIntensive treatment matters

Dis

trib

uti

on

of

Dis

trib

uti

on

of

pat

ien

tsp

atie

nts

HbA1cHbA1c

* Measured according to Guidelines for Diabetes Care, IDF Europe

** According to epidemiological analysis of the UKPDS data, 1998

HbA1c lowering by one HbA1c lowering by one percentage point reduces percentage point reduces

micro vascular risk by 35%**micro vascular risk by 35%**

Close to 80% are exposed to

arterial or microvascular risk*

Diabetes therapy represents a growth marketDiabetes therapy represents a growth market

Number of diabetics estimated to grow 4% p.a.

Diagnosis rate will increase Some 75 million people are diabetics today without knowing it

Medicine use per diagnosed patient will increaseTreating more assertively reduces burden of late stage complications

Volume growth of at least 5% p.a. sustainableCurrent insulin market volume growth is 7-8%

Key insulin market observationsKey insulin market observations

VolumeVolume

No of people with diabetes No of people with diabetes expected to double by 2025expected to double by 2025

Increased diagnosis rateIncreased diagnosis rate

Intensified therapyIntensified therapy

Product upgradesProduct upgrades

Insulin analoguesInsulin analogues

Insulin delivery systemsInsulin delivery systems

5% annual growth5% annual growth Adding 5% to annual growthAdding 5% to annual growth++

Novo Nordisk to leverage on growthNovo Nordisk to leverage on growth

Building on more than 75 years of experience within Building on more than 75 years of experience within diabetesdiabetes

Dominant position in the European and Japanese insulin Dominant position in the European and Japanese insulin markets – solid growth in the USmarkets – solid growth in the US

More than 2,000 R&D employees dedicated to diabetes, More than 2,000 R&D employees dedicated to diabetes, representing approximately ¾ of R&D resourcesrepresenting approximately ¾ of R&D resources

Most complete portfolio of new insulinsMost complete portfolio of new insulins

Leadership in insulin delivery systems – one new device Leadership in insulin delivery systems – one new device per yearper year

Most comprehensive diabetes Type 2 pipeline in the Most comprehensive diabetes Type 2 pipeline in the industryindustry

Diabetes R&D at Novo Nordisk:Diabetes R&D at Novo Nordisk:Sources of innovationSources of innovation

Clinical researchClinical research

Steno Diabetes CentreSteno Diabetes Centre

Oxford Diabetes CentreOxford Diabetes Centre

Clinical research centres worldwideClinical research centres worldwideEvidence-based medicineEvidence-based medicine

NN disease mgt programmesNN disease mgt programmes

Outcomes data from > 100.000 Outcomes data from > 100.000 individuals with diabetesindividuals with diabetes

Molecular diversity & designMolecular diversity & design

Protein chemistry since ’23Protein chemistry since ’23

Medicinal chemistry since ’68Medicinal chemistry since ’68

Computational chemistry since ’75Computational chemistry since ’75

Rational drug design since ’83Rational drug design since ’83

Combinatorial chemistry since ’93Combinatorial chemistry since ’93 TrinomicsTrinomics

Genomics: Incyte since ’95Genomics: Incyte since ’95

Proteomics: CPA since ’97Proteomics: CPA since ’97

Metabonomics since ’99Metabonomics since ’99

Drug target & screeningDrug target & screening

Molecular biology since ’80Molecular biology since ’80

HT screening: Amersham since ’92HT screening: Amersham since ’92

Chemoinformatics since ’95Chemoinformatics since ’95

Dundee MRC consortium since ’98Dundee MRC consortium since ’98

Ultra HT Screening since ’00Ultra HT Screening since ’00

Basic researchBasic research

Hagedorn Research InstituteHagedorn Research Institute

Oxford and Steno Diabetes CentreOxford and Steno Diabetes Centre

Academic collaborationsAcademic collaborations

ConsortiaConsortia

R&D projectsR&D projects

Pharmaceutical needs in diabetes Pharmaceutical needs in diabetes

Type 1

Intervention in -cell destruction

Blood glucose regulation*

Type 2

Blood glucose regulation*

Regulation of energy balance (diabetes-associated obesity)

Reduction of triglycerides, FFA and LDL/HDL ratio (diabetic dyslipidaemia)

* Including, but not restricted to, new pharmaceuticals

Diabetes drug candidates in development Diabetes drug candidates in development at Novo Nordisk at Novo Nordisk

Genotype

Phenotype

ObesityInsulin Resistance

Dyslipidaemia

Type 2diabetes*

Failure of oral drugs

Diet and exercise:

NN education programme

Appetiteregulation:

NN2211

Sensitizers andlipid-lowering agents:

NN2344

NN622

β-cell agents: NovoNorm® NN2211, NN414

Hepatic glucose regulators:NN4201

Insulins:

NovoRapid®, NovoMixTM,

AERx, insulin detemir, LABI

• Type 2 diabetes is preceded by impaired glucose tolerance and occurs when the beta- cell fails. It may also be seen in the absence of obesity and insulin resistance.

The miracle of insulin

Patient J.L., December 15, 1922 February 15, 1923

Going forward in diabetes:Expanding leadership in insulin therapy

Innovation within insulin therapy will continue to drive the insulin market by providing more efficacious, reproducible and convenient treatment modalities

Novo Nordisk will expand leadership in insulin therapy by maintaining the world’s richest insulin therapy portfolio

Insulin analogues

Insulin formulations

Insulin delivery systems

Insulin profiles in type 1 diabetic patients Insulin profiles in type 1 diabetic patients treated with NovoRapidtreated with NovoRapid®® or human insulin or human insulin

Ser

um in

sulin

Time of day

Dinner NPHBreakfast LunchAdapted from Home et al. 1998

NovoRapid®

Soluble human insulin

(0.15 U/kg)

(mU/l) (pmol/l) 600

300

0

100

200

400

500

0

20

40

60

80

100

0600 1200 1800 2400 0600

NovoRapid® appears to have a longer post-prandial duration of action; this may contribute to

insulin coverage until next meal

lower pre-prandial blood glucose levels, comparable with human insulin

flexibility with timing of meals

NovoRapidNovoRapid®® versus insulin lispro versus insulin lispro

Home PD, et al. Diabetes Care 1998;21:1904-1909Gale EAM, et al. Diabetic Medicine 2000;17:209-214

Profile of the ideal basal insulinProfile of the ideal basal insulin

Desirable properties:

SolubilitySoluble at neutral pH

Mixable with other insulins

AbsorptionPredictable

Glucose lowering effectPeakless with low variability

Safety profileLow risk of hypoglycaemia at all times

Injection siteNo local reactions

Limitations of current insulins:

SolubilityMost current basal insulins require re-suspension

AbsorptionHighly variable

Glucose lowering effectNot predictable

Safety profileRisk of hypoglycaemia

Injection siteInjection pain with acidic insulin

Mechanism of protractionMechanism of protraction of i of insulin detemirnsulin detemir

HSA: human serum albumin

Distribution

AbsorptionReceptor

interaction

Insulin detemir versus NPH insulinInsulin detemir versus NPH insulinNight-time glucose profileInsulin detemir versus NPH insulinInsulin detemir versus NPH insulinNight-time glucose profile

Treatment: Insulin detemir NPH insulin

BG (mM)

N = 21

N = 52

5

6

7

8

9

10

11

12

11pm 3am 7am

J. L. Selam et al. :Oral presentation EASD 2001

Findings: Predictable glucose profiles over night with detemir

Insulin detemir showed reduced variability compared to NPH

Insulin detemir versus NPH insulin Insulin detemir versus NPH insulin Hypoglycaemic events:Hypoglycaemic events: reduced for insulin detemir at all timesreduced for insulin detemir at all times

Hermansen et al. Diabetes Care 2001;24:296-301

36%

39%

26%

62%

50

40

30

20

10

0

NPH insulin

Insulin detemir

Time unknown22:30-8:00 8:00-12:00 12:00-22:00

Nu

mb

er o

f ep

iso

des

Findings: Statistatically fewer hypoglycaemic events

Insulin detemir: Results presented at EASDInsulin detemir: Results presented at EASD

Soluble at neutral pH: No re-suspension required

Contributes to reproducible pharmacokinetic profile

Mixable with other insulin products

Novel mechanism of protraction:Protracted action due to albumin binding

Predictable action profile

Low intra-patient variability:Contributes to low risk of hypoglycaemia

Safety:Reduced risk of hypoglycaemic events versus NPH

Novo Nordisk devices in diabetes care

First pen (NovoPen 1) launched in 1985

In the US, launch of the first pen in 1988

Upgrading the insulin marketUpgrading the insulin market

De

vic

e p

en

etr

atio

nD

ev

ice

pe

ne

trat

ion

Insu

lin a

nal

og

ue

Insu

lin a

nal

og

ue

pe

ne

tra

tio

np

en

etr

ati

on

100%

100%

100%

100%

0%0%

(+50

% p

rem

ium

)(+

50%

pre

miu

m)

(+30

% p

rem

ium

)(+

30%

pre

miu

m)

Increasing turnover Increasing turnover per patientper patient

US

A

Jap

anE

uro

pe

AERx iDMS: Pulmonary insulin administration

Pulmonary insulin opportunityNon-invasive insulin delivery

Mainly poorly controlled Type 2 diabetes patients

Expanded insulin sales

Product requirementsAccuracy, precision, dose adjustment

Patient friendly device interface

Scaleable manufacturing

Aradigm is the ideal partnerLiquid insulin formulation

Breath control

Increment of single insulin units

Performance monitoring

Pulmonary insulin delivery: Competition

Aradigm Inhale Alkermes

Speciality Systemic + local delivery

Systemic delivery

Systemic

Device Single dose, liquid aerosol

Single dose -

Size Portable, not pocket-sized

Portable, not pocket-sized

Portable, pocket sized

Formulation Liquid, disposable unit dose

Dry powders, disposable unit dose

Dry powders

Breath Control Yes, patient training device

None Breath activated device

Comments Phase II, Novo Nordisk

Phase III, Pfizer/Aventis

Phase I, Eli Lilly

The insulin market: Overall conclusionsThe insulin market: Overall conclusions

Both Type 1 and 2 diabetes

Mainly specialist driven, but GPs very important in US

Few players, large volumes

Inexpensive and reimbursed treatment

Necessitates multiple daily injections and glucose monitoring

Patients start too late on insulin

Devices increasingly important

Need for education on importanceof treating more assertively

Insulin products Actrapid®, Insulatard®, Monotard®,

Mixtard®, Ultratard®, Velosulin®, Novolin®, NovoRapid®, NovoMix™ (registration), Insulin detemir (Phase 3), LABI (Phase 1)

Insulin delivery systems NovoPen®, NovoLet®, PenMate™,

Innovo®, InnoLet®, In-Duo™, FlexPen, AERx/NN1998 (Phase 2)

Committed to 1 new device per year

Novo Nordisk in type 2 diabetes careNovo Nordisk in type 2 diabetes care

NovoNorm®/Prandin® – the 1st prandial glucose regulator

NN622 – the dual-acting insulin sensitiser

NN2211 - a long-acting GLP-1 analogue

00

2020

4040

6060

00 11 22 33 44 55 66Years from randomisationYears from randomisation

Adapted from UK Prospective Diabetes Study (UKPDS) Adapted from UK Prospective Diabetes Study (UKPDS) Group. Group. DiabetesDiabetes. 1995; 44:1249-1258.. 1995; 44:1249-1258.

-Cell function ( % of healthy ) -Cell function ( % of healthy ) Diet and exerciseDiet and exercise Oral productsOral products

(approx 66%)(approx 66%)

Oral/insulinOral/insulin(approx 7%)(approx 7%)

InsulinInsulin(approx 27%)(approx 27%)

Type 2 diabetes disease management Type 2 diabetes disease management throughout lifethroughout life

00

5050

100100

150150

200200

250250

300300

350350

19961996 19971997 19981998 19991999 20002000 20012001

MA

TQ

1.19

96=

100

MA

TQ

1.19

96=

100

Growth within the OAD marketGrowth within the OAD market

Sales development in USDSales development in USDCAGR: 26%CAGR: 26%

No of treated patientsNo of treated patients CAGR: 13%CAGR: 13%

Growth in USD 5.8 bn OAD marketGrowth in USD 5.8 bn OAD marketKey observations Novo Nordisk

Experience in the OAD market from NovoNorm®/Prandin®

Novartis partner on NN622 for North America

Broad pipeline of innovative approaches for Type 2 diabetes

NovoNormNovoNormTMTM/Prandin/Prandin®®

NovoNormNovoNormTMTM/Prandin/Prandin®®

NN304NN304

NN1998NN1998

NN2344NN2344

Glucose-induced Glucose-induced insulin secretioninsulin secretion

Tissue response Tissue response to insulinto insulin

ImpairedImpairedbeta cellbeta cellfunctionfunction

Basal hyper- Basal hyper- insulinemiainsulinemia

Post Post receptor receptor defectdefect

GlucoseGlucosetransporttransport

Insulin Insulin bindingbinding

NN414

NN4201NN4201

Genetic

Acquired

Obesity

Age

Genetic

Acquired

Obesity

Age

Insulin deficiencyInsulin deficiency

Insulin resistanceInsulin resistance

NovoRapidNovoRapid®®

Type 2 Diabetes – the Metabolic Type 2 Diabetes – the Metabolic Syndrome Syndrome

Insulin deficiencyInsulin deficiency

Insulin resistanceInsulin resistance

HyperglycemiaHyperglycemia

NN2211NN2211

NN2211NN2211

NN622

NN622Genetic

Acquired Glucotoxicity Lipotoxicity

Genetic

Acquired Glucotoxicity Lipotoxicity

Hepatic Hepatic glucose glucose productionproduction

Glucose Glucose uptakeuptake

NN622

Elevated lipid levels are detrimental in Elevated lipid levels are detrimental in type 2 diabetestype 2 diabetes

MUSCLE

TG accumulation

Insulin resistance

B CELLS

TG accumulation

Disturbed insulinsecretion(hyperinsulinaemia)

AD

IPO

SE

TI S

SU

EA

DIP

OS

E T

ISS

UE

FFAFFA

Increasedhepatic glucose output(hyperglycaemia)

LIVER

• Increased VLDL • Decreased HDL• Increased small dense LDL Atherosclerosis

NN622: The dual acting PPARNN622: The dual acting PPAR// agonist agonist conceptconcept

insulin

Glucoseclearancerate

Glucoseproduction

+ -Inhibition of lipolysis,fat re-distribution

Fattyacids PPAR

PPAR

Triglyceride,Cholesterol

AGGTCA N AGGTCA Target gene

Transcription

PPRE

Nucleus

RXRPPAR

AGGTCA N AGGTCA Target gene

Transcription

PPRE

Nucleus

RXRPPAR

Effect on hepatic glucose productionEffect on hepatic glucose productionComparison between NN622, Avandia, Actos and a fibrateComparison between NN622, Avandia, Actos and a fibrate

Hep

atic

glu

cose

ou

tpu

t(m

g/kg

x m

in)

Vehicl

e

NN622:

3 m

g/kg

Avand

ia: 3

mg/

kg

Actos:

3 m

g/kg

Fibrat

e: 3

mg/

kg

0

1

2

3

4

5

6

7

8

NN622 shows superior efficacy in suppressing glucose production by the liver.

Source: Ye et al. Diabetes 2001; 50: A316

NN622 possesses potent lipid-lowering NN622 possesses potent lipid-lowering activity in cholesterol-fed ratsactivity in cholesterol-fed rats

HDL Cholesterol

VLDL Cholesterol

0

25

50

75

100

* *

Pla

sm

a H

DL

ch

ole

ste

rol

(mg

/dL

)

*

**

0

10

20

30

40

Pla

sm

a V

LD

L c

ho

leste

rol

(mg

/dL

)

*

**

*

Triglycerides

0

100

200

**

*

Pla

sma

Tri

gly

ceri

des

(mg

/dL

)

Source: Data on file

Triglycerides in liver and muscleTriglycerides in liver and muscleComparison between NN622, Avandia, Actos and a fibrateComparison between NN622, Avandia, Actos and a fibrate

*P < 0.05, ** P < 0.01, *** P < 0.001 vs Vehicle

Liver:mmol/g

0

10

20

30

******

Red muscle:mmol/g

Vehicle

NN62

2

Avand

ia

Fibr

ate

Actos

0

2

4

6

*******

*

00

2020

4040

6060

00 11 22 33 44 55 66Years from randomisationYears from randomisation

Adapted from UK Prospective Diabetes Study (UKPDS) Adapted from UK Prospective Diabetes Study (UKPDS) Group. Group. DiabetesDiabetes. 1995; 44:1249-1258.. 1995; 44:1249-1258.

-Cell function ( % of healthy ) -Cell function ( % of healthy ) Diet and exerciseDiet and exercise Oral productsOral products

(approx 66%)(approx 66%)

Oral/insulinOral/insulin(approx 7%)(approx 7%)

InsulinInsulin(approx 27%)(approx 27%)

Type 2 diabetes disease management Type 2 diabetes disease management throughout life: throughout life: -cell failure leads to T2D-cell failure leads to T2D

Increased insulin staining intensity after NN2211 treatment

-cell volume Proliferation0.00

0.25

0.50

0.75

1.00

(%)

NN2211 prevents diabetes in ZDF ratsNN2211 prevents diabetes in ZDF rats

Control

NN2211

NN2211 prevents the progression of diabetes in ZDF rats

Proliferation and volume of -cells are normalized

NN2211: Effect on fasting and post-prandial NN2211: Effect on fasting and post-prandial blood glucose in type 2 patientsblood glucose in type 2 patients

-2 0 2 4 6 8 10 12 14 16 18

4

5

6

7

8

9

10

11

12

NN2211Placebo

Time (hours)

Mea

n gl

ucos

e pr

ofile

s(m

mol

/l)

Dosing

Insulinpulse

analysis

Standardmeal

GLP-1 effects:

Insulin

-cell survival

Glucagon

Appetite

GI-emptying

NovoNordisk commitment to the cure of T1D : Stem cell research at Hagedorn Research Inst.

Cell type 1Cell type 2Cell type 3

Cell type 210

Beta cellZygote /ES-cell

Pancreatic Stem Cell

Islet Stem Cell

Goal: To mature or differentiate beta cells from stem-cell stages

Adult stem cell

Pancreatic islet cells

Hematopoietic cells

Cardiomyocytes

Neurons Hepatocytes

Immunologically

compatible transplant

Autologous stem cell therapyPatient

Modified from Nature Medicine 5:975-7, 1999

In Type 1 diabetes protection against autoimmune destruction will be necessary

Clinical stage diabetes pipelineClinical stage diabetes pipeline

NN2211NN2211 (GLP-1 analogue)(GLP-1 analogue)

NN1215NN1215 (LABI)(LABI)

NN1998NN1998 (AERx)(AERx)

NN4201NN4201 (Hepatic glucose regulator)(Hepatic glucose regulator)

NN304NN304 (Basal analogue) (Basal analogue)

NN414NN414 (Insulin secretion)(Insulin secretion)

NN622NN622 (Dual-acting sensitiser)(Dual-acting sensitiser)

Phase 1Phase 1 Phase 2Phase 2 Phase 3Phase 3

NN2344NN2344 (Insulin sensitiser)(Insulin sensitiser)

Forward-looking statements

This presentation contains forward-looking statements as the term is defined This presentation contains forward-looking statements as the term is defined in the US Private Securities Litigation Reform Act of 1995 in the US Private Securities Litigation Reform Act of 1995

Such forward-looking statements are subject to risk and uncertainties that Such forward-looking statements are subject to risk and uncertainties that may cause actual results to differ materially from expectations, including may cause actual results to differ materially from expectations, including unexpected developments in the international currency exchange and unexpected developments in the international currency exchange and securities markets, government-mandated or market-driven price decreases securities markets, government-mandated or market-driven price decreases for Novo Nordisk's products in the company's major markets and the for Novo Nordisk's products in the company's major markets and the introduction of competing products within Novo Nordisk's core businesses introduction of competing products within Novo Nordisk's core businesses

These and other risks and uncertainties, are further described in reports filed These and other risks and uncertainties, are further described in reports filed with the US Securities and Exchange Commission (SEC) by Novo Nordisk with the US Securities and Exchange Commission (SEC) by Novo Nordisk and readily available to the public, including the company's Form 20-F, which and readily available to the public, including the company's Form 20-F, which was filed on 2 was filed on 2 MayMay 20002000. . A Form 20-F for 2000 will be filed by the end of A Form 20-F for 2000 will be filed by the end of June 2001June 2001

Investor Information

Investor Relations Contacts:

Novo Nordisk A/S Investor Relations Novo Allé DK 2880 BagsværdDenmark Fax (+45) 4444 2314.

Peter HaahrPhone (+45) 4442 1207 E-mail: pehr@novonordisk.com

Palle Holm Olesen Phone (+45) 4442 6175 E-mail: phoo@novonordisk.com

Rasmus Holm-JørgensenPhone (+1) 212 867 0123 E-mail: rrhj@novonordisk.com

Share information

Novo Nordisk’s B shares are listed on the stock exchanges in Copenhagen and London. Its ADSs are listed on the New York Stock Exchange under the symbol "NVO". For further company information, visit Novo Nordisk on the World Wide Web at

http://www.novonordisk.com