Novo Nordisk A focused global healthcare company with biotech expertise Diabetes Conference at Union Bank of Switzerland October 2001

Agenda Introduction Novo Nordisk: The future Insulin therapy (NovoRapid ®,insulin detemir, delivery systems) Novo Nordisk diabetes commitment outside insulin Oral Antidiabetics (OAD): NN622 NN2211 Other concepts Islet replacement

Metabolic abnormalities associated with Type 1 and Type 2 diabetes Type 1Type 2 Elevated blood glucosexxx Ketosisxx0 Insulin resistancexxxx Hypertensionxxx Obesityxxxx Increased LDLx/0 Increased triglycerides/FFA0xxx Decreased HDL0xxx

Diabetes care: Treatment matters Only a small number of patients are in control Intensive treatment matters Distribution of patients HbA1c * Measured according to Guidelines for Diabetes Care, IDF Europe ** According to epidemiological analysis of the UKPDS data, 1998 HbA1c lowering by one percentage point reduces micro vascular risk by 35%** Close to 80% are exposed to arterial or microvascular risk*

Diabetes 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 increase Treating more assertively reduces burden of late stage complications Volume growth of at least 5% p.a. sustainable Current insulin market volume growth is 7-8%

Key insulin market observations Volume No of people with diabetes expected to double by 2025 Increased diagnosis rate Intensified therapy Product upgrades Insulin analogues Insulin delivery systems 5% annual growth Adding 5% to annual growth +

Novo Nordisk to leverage on growth Building on more than 75 years of experience within diabetes Dominant position in the European and Japanese insulin markets – solid growth in the US More than 2,000 R&D employees dedicated to diabetes, representing approximately ¾ of R&D resources Most complete portfolio of new insulins Leadership in insulin delivery systems – one new device per year Most comprehensive diabetes Type 2 pipeline in the industry

Diabetes R&D at Novo Nordisk: Sources of innovation Clinical research Steno Diabetes Centre Oxford Diabetes Centre Clinical research centres worldwide Evidence-based medicine NN disease mgt programmes Outcomes data from > individuals with diabetes Molecular diversity & design Protein chemistry since ’23 Medicinal chemistry since ’68 Computational chemistry since ’75 Rational drug design since ’83 Combinatorial chemistry since ’93 Trinomics Genomics: Incyte since ’95 Proteomics: CPA since ’97 Metabonomics since ’99 Drug target & screening Molecular biology since ’80 HT screening: Amersham since ’92 Chemoinformatics since ’95 Dundee MRC consortium since ’98 Ultra HT Screening since ’00 Basic research Hagedorn Research Institute Oxford and Steno Diabetes Centre Academic collaborations Consortia R&D projects

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 at Novo Nordisk Genotype Phenotype Obesity Insulin Resistance Dyslipidaemia Type 2 diabetes* Failure of oral drugs Diet and exercise: NN education programme Appetite regulation: NN2211 Sensitizers and lipid-lowering agents: NN2344 NN622 β-cell agents: NovoNorm ® NN2211, NN414 Hepatic glucose regulators: NN4201 Insulins: NovoRapid ®, NovoMix TM, 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, 1922February 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 treated with NovoRapid® or human insulin Serum insulin Time of day Dinner NPH BreakfastLunch Adapted from Home et al NovoRapid® Soluble human insulin (0.15 U/kg) (mU/l)(pmol/l)

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 NovoRapid® versus insulin lispro Home PD, et al. Diabetes Care 1998;21: Gale EAM, et al. Diabetic Medicine 2000;17:

Profile of the ideal basal insulin Desirable properties: Solubility Soluble at neutral pH Mixable with other insulins Absorption Predictable Glucose lowering effect Peakless with low variability Safety profile Low risk of hypoglycaemia at all times Injection site No local reactions Limitations of current insulins: Solubility Most current basal insulins require re-suspension Absorption Highly variable Glucose lowering effect Not predictable Safety profile Risk of hypoglycaemia Injection site Injection pain with acidic insulin

Mechanism of protraction of insulin detemir HSA: human serum albumin Distribution Absorption Receptor interaction

Insulin detemir versus NPH insulin Night-time glucose profile Insulin detemir versus NPH insulin Night-time glucose profile Treatment:Insulin detemirNPH insulin BG (mM) N = 21 N = pm3am7am 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 Hypoglycaemic events: reduced for insulin detemir at all times Hermansen et al. Diabetes Care 2001;24: % 39% 26% 62% NPH insulin Insulin detemir Time unknown 22:30-8:008:00-12:0012:00-22:00 Number of episodes Findings: Statistatically fewer hypoglycaemic events

Insulin 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 market Device penetration Insulin analogue penetration 100% 100% 0% (+50% premium) (+30% premium) Increasing turnover per patient USA Japan Europe

AERx iDMS: Pulmonary insulin administration Pulmonary insulin opportunity Non-invasive insulin delivery Mainly poorly controlled Type 2 diabetes patients Expanded insulin sales Product requirements Accuracy, precision, dose adjustment Patient friendly device interface Scaleable manufacturing Aradigm is the ideal partner Liquid insulin formulation Breath control Increment of single insulin units Performance monitoring

Pulmonary insulin delivery: Competition AradigmInhaleAlkermes SpecialitySystemic + local delivery Systemic delivery Systemic DeviceSingle dose, liquid aerosol Single dose- SizePortable, not pocket-sized Portable, pocket sized FormulationLiquid, disposable unit dose Dry powders, disposable unit dose Dry powders Breath ControlYes, patient training device NoneBreath activated device CommentsPhase II, Novo Nordisk Phase III, Pfizer/Aventis Phase I, Eli Lilly

The 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 importance of 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 care NovoNorm ® /Prandin ® – the 1st prandial glucose regulator NN622 – the dual-acting insulin sensitiser NN a long-acting GLP-1 analogue

Years from randomisation Adapted from UK Prospective Diabetes Study (UKPDS) Group. Diabetes. 1995; 44:  -Cell function ( % of healthy ) Diet and exercise Oral products (approx 66%) Oral/insulin (approx 7%) Insulin (approx 27%) Type 2 diabetes disease management throughout life

MATQ1.1996=100 Growth within the OAD market Sales development in USD CAGR: 26% No of treated patients CAGR: 13% Growth in USD 5.8 bn OAD market Key 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

NovoNorm TM /Prandin ® NN304 NN1998 NN2344 Glucose-induced insulin secretion Tissue response to insulin Impaired beta cell function Basal hyper- insulinemia Postreceptordefect Glucosetransport Insulinbinding NN414 NN4201 Genetic Acquired Obesity Age Genetic Acquired Obesity Age Insulin deficiency Insulin resistance NovoRapid® Type 2 Diabetes – the Metabolic Syndrome Insulin deficiency Insulin resistance Hyperglycemia NN2211 NN2211 NN622 Genetic Acquired Glucotoxicity Lipotoxicity Genetic Acquired Glucotoxicity Lipotoxicity Hepaticglucoseproduction Glucoseuptake NN622

Elevated lipid levels are detrimental in type 2 diabetes MUSCLE TG accumulation Insulin resistance B CELLS TG accumulation Disturbed insulin secretion (hyperinsulinaemia) ADIPOSE TISSUE FFA Increased hepatic glucose output (hyperglycaemia) LIVER Increased VLDL Decreased HDL Increased small dense LDL  Atherosclerosis

NN622: The dual acting PPAR  /  agonist concept insulin Glucose clearance rate Glucose production + - Inhibition of lipolysis, fat re-distribution Fatty acids PPAR PPAR Triglyceride, Cholesterol AGGTCA N AGGTCA Target gene Transcription PPRE Nucleus RXR PPAR  AGGTCA N AGGTCA Target gene Transcription PPRE Nucleus RXR PPAR 

Effect on hepatic glucose production Comparison between NN622, Avandia, Actos and a fibrate Hepatic glucose output (mg/kg x min) Vehicle NN622: 3 mg/kg Avandia: 3 mg/kg Actos: 3 mg/kg Fibrate: 3 mg/kg NN622 shows superior efficacy in suppressing glucose production by the liver. Source: Ye et al. Diabetes 2001; 50: A316

NN622 possesses potent lipid-lowering activity in cholesterol-fed rats HDL Cholesterol VLDL Cholesterol Triglycerides Source: Data on file

Triglycerides in liver and muscle Comparison between NN622, Avandia, Actos and a fibrate *P < 0.05, ** P < 0.01, *** P < vs Vehicle Liver: mmol/g *** Red muscle: mmol/g Vehicle NN622 Avandia Fibrate Actos *** ** *

Years from randomisation Adapted from UK Prospective Diabetes Study (UKPDS) Group. Diabetes. 1995; 44:  -Cell function ( % of healthy ) Diet and exercise Oral products (approx 66%) Oral/insulin (approx 7%) Insulin (approx 27%) Type 2 diabetes disease management throughout life:  -cell failure leads to T2D

Increased insulin staining intensity after NN2211 treatment  -cell volume Proliferation (%) NN2211 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 blood glucose in type 2 patients NN2211 Placebo Time (hours) Mean glucose profiles (mmol/l) Dosing Insulin pulse analysis Standard meal 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 1 Cell type 2 Cell type 3 Cell type 210 Beta cell Zygote / 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 CardiomyocytesNeuronsHepatocytes Immunologically compatible transplant Autologous stem cell therapy Patient Modified from Nature Medicine 5:975-7, 1999 In Type 1 diabetes protection against autoimmune destruction will be necessary

Clinical stage diabetes pipeline NN2211 (GLP-1 analogue) NN1215 (LABI) NN1215 (LABI) NN1998 (AERx) NN4201 (Hepatic glucose regulator) NN304 (Basal analogue) NN414 (Insulin secretion) NN622 (Dual-acting sensitiser) Phase 1 Phase 2 Phase 3 NN2344 (Insulin sensitiser)

Forward-looking statements This presentation contains forward-looking statements as the term is defined in the US Private Securities Litigation Reform Act of 1995 Such forward-looking statements are subject to risk and uncertainties that may cause actual results to differ materially from expectations, including unexpected developments in the international currency exchange and securities markets, government-mandated or market-driven price decreases for Novo Nordisk's products in the company's major markets and the introduction of competing products within Novo Nordisk's core businesses These and other risks and uncertainties, are further described in reports filed 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 was filed on 2 May A Form 20-F for 2000 will be filed by the end of June 2001

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