Carnegie 16092003 Noappendix

Forward-looking statements and webcastThis 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 risks, uncertainties and inaccurate assumptions. This may cause actual results to differ materially from expectations. Factors that may affect future results include interest rate and currency exchange rate fluctuations, delay or failure of development projects, production problems, unexpected contract breaches or terminations, government-mandated or market-driven price decreases for Novo Nordisk's products, introduction of competing products, Novo Nordisk's ability to successfully market both new and existing products, exposure to product liability and other lawsuits, changes in reimbursement rules and governmental laws and related interpretation thereof, unexpected growth in costs and expenses.

Risks and uncertainties are further described in reports filed by Novo Nordisk with the US Securities and Exchange Commission (SEC) including the company's Form 20-F, which was filed on 27 March 2003. Novo Nordisk is under no duty to update any of the forward-looking statements after the date of this report or to conform such statements to actual results, unless required by law.

Novo Nordisk has the copyright to the information contained in this conference call. 2003 Novo Nordisk A/S.

Novo Nordisk in diabetes agendaIntroductionDiabetes as a value driverInsulin in conventional therapyNovoMix 30Mimicking real life with intensive treatmentLevemirInsulin deliveryLiraglutide - The first and only once daily human GLP-1 derivative Diabetes care pipeline and beyond

Introduction -Focus of todayDiabetes expertiseProtein expertiseNovoSeven expansionLiraglutidebalaglitazoneNN2501AERx iDMSinsulin analoguesNN414hGH expansionASISDrug delivery expertiseProtein Delivery System unit (PDS)Focus of today

Diabetes as a value driver Diabetes care salesInsulin growth drivers

The evolution of mankind

Type 2 diabetes the metabolic syndrome Glucose-induced insulin secretionTissue response to insulinHepatic glucose productionGlucose uptakeImpairedbeta cellfunctionBasal hyper- insulinemiaPost receptor defectGlucosetransportInsulin bindingInsulin deficiencyInsulin resistanceInsulin resistanceHyperglycemiaGeneticAcquired Obesity AgeGeneticAcquired Glucotoxicity LipotoxicityNovoRapidNote: Light blue indicates selected key products already marketed, Red indicates projects in development, Grey indicates selected projects within researchLevemirTMNovoMix 50 & 70NN2344LiraglutideNN414NovoNormNovoNormLiraglutideNN2501NN1998 AERx iDMSNN344NovoMix30Hepatic enzyme activators/inhibitorsDPPIVPPAR , , Kinase/phosphatase modulatorAppetite regulatorsInsulin mimeticsGlucose-sensitive insulin11HSD1Protein Delivery SystemsStem cellsVaccination

Insulin - the ultimate treatment-Cell functionTime from diagnosisType 2 - slopeType 1 Immediate need for insulin50%-cell function only at approximately 50% at diagnosisType 2 slope observations:Insulin therapy is the ultimate treatment and is typically initiated some 7-12 years after diagnosisSource: Novo Nordisk Type 2 diabetes market research, Xxxxx

The miracle of insulinKey observations:Insulin will continue to be key in treating diabetes andPatient J.L.15 December 192215 February 1923More convenient types of insulin +More convenient delivery systemsIncreased complianceBetter control

Out of guideline controlType 2 - slopeHbA1c10%9%8%7%6%Recommended insulin initiationGuideline controlADAIDFADAEASD/AACENote: ADA is American Diabetes Association, IDF is International Diabetes Federation, EASD is European Association for the Study of Diabetes, AACE is American Association of Clinical EndocrinologistsSource: Novo Nordisk type 2 diabetes market research, Roper Starch, ADA, EASD, IDF, AACE, Wright A., Burden et al, Diabetes Care 2002; 25:330336, Turner RC, Cull et al, JAMA 1999; 281:20052012It is estimated that more than 2/3 of the patients are not in controlReal-life insulin initiation-cell functionTime from diagnosisType 1 immediate need for insulin50%

Mimicking real life with conventional treatmentTime of day010203040506070Insulin (mU/l)Normal free insulin levels Short-acting insulin (e.g. NovoRapid)MealLong-acting insulin Premixed insulin (e.g. NovoMix30)Source: Adapted from Polonsky et al. 1988, and simulated short- and long-acting insulin profiles

NovoMix 30 vs. long-acting insulinNovoMix x 2NPH x 2Change in HbA1c (%)-1.0-0.8-0.6-0.4-0.20.0p < 0.005Source: Submitted to Diabetes, Obesity and MetabolismNote: 403 randomised and exposed to either NovoMix 30 or NPH insulin. NPH is long-acting human insulin.Key observations:NovoMix 30 improves post prandial control compared to human insulin Improved control in patients poorly controlled on oral therapy aloneNovo Nordisk in phase 4 comparing premixed analogues with long-acting insulin analogues

Mimicking real life with intensive treatmentTime of day010203040506070Insulin (mU/l)Normal free insulin levels Short-acting insulin (NovoRapid)MealSource: Adapted from Polonsky et al. 1988, and simulated short- and long-acting insulin profilesLong-acting insulin (LevemirTM)

What kinetic profile should we be looking for in a basal insulin?TimeTimePlasma insulinPlasma insulinWhich is the better profile, A or B?Mean profileIndividual data

Levemir shows significantly less intra-subject variability than glargine and NPHClamp 1Clamp 2Clamp 3Clamp 4TimeTimeGlucose Infusion RateGlucose Infusion RateGraphs of three patients showing individual glucose profiles on four different days receiving identical insulin doses.Heinemann et al, unpublished

Levemir shows less fluctuation in blood glucose level across the day than NPH insulinD. Russell-Jones et al. Diabetologia 2002;45(Suppl. 2):A51

Clinical consequence(hypoglycaemia)Consider a subject with a usual maximum metabolic effect of 2 mg/kg/minThe probability for this subject of experiencing a maximum effect >4 mg/kg/min is: 0.1% if the subject uses Levemir 2.7% if the subject uses Insulin glargine 6.5% if the subject uses NPH insulinHeinemann et al, unpublished

The Levemir puzzle: - It all comes togetherHyposHbA1cWeightPredictable

Pre-filledDurableInt.BGM/DoserPumpsInhaledExisting productsInsulin delivery towards the full portfolioFlexPenNovoPen 3InDuoProjects in developmentAERx iDMSYesYesYes**Yes*CommentsNote: * Focused at next generation pumps; ** Focusing on integrating advanced glucose monitoringNo product onmarket yetPioneer andmarket leaderin segmentPioneer andmarket leaderin segmentInnovator andonly companypresentNovo Nordisk markets the only pump approved analogue

Native GLP-1 is an intestinal hormoneKieffer & Habener (1999): Endocrine Reviews 20: 876-913

Liraglutide is a long-acting GLP-1 derivativeHisAlaGluGlyThrPheThrSerAspLysAlaAlaGlnGlyGluLeuTyrSerIleAlaTrpLeuValLysGlyArgGlyValSerGluPheArg

GLP-1: The pan-antidiabetic agent of the future

People with type 2 diabetes have impared GLP-1 secretionT2D patients*******05101520060120180240Time (min)GLP-1 (pM)IGTNormal subjectsSource: Adapted from Toft-Nielsen et al. ( 2001): J Clin Endocrinol Metab 86:3717-3723

Human GLP-1 has a very short half-life:24 hours coverage is needed for optimal effect24-h GLP-1 s.c. infusion16-h GLP-1 s.c. infusion1001502002503003504004500406081012141618202200020406TimeSource: Modified from J Larsen et al: Diabetes Care 2001; 24:1416-1421 4004501001502002503003500406081012141618202200020406Time

Two concepts in current developmentHuman GLP-1 based derivatives/analoguesLiraglutide (NN2211) Novo Nordisk completed phase 2CJC-1131 (ConjuChem) phase 1/2

Exendin-4 (Gila monster based*)Exenatide/AC2993 (Amylin/Eli Lilly) phase 3ZP-10 (Zealand Pharmaceuticals/Aventis) phase 1

*Approx 50% different from human GLP-1

Key observations from the two conceptsLiraglutideOnce daily PeaklessGood effect on HbA1c and FBGWeight lossNo antibodiesNo injection site reactionsExendin-4 basedTwice dailyPeakGood effect on HbA1cWeight lossAntibodiesHistorical attempts to prolong GLP-1 action have led to injection site reactions

Single-dose liraglutide improves beta cell sensitivity to glucose in type 2 diabetes024681012144681012Glucose (mmol/L)Insulin Secretion Rate Healthy Controls

Liraglutide a significant alternativeFasting serum glucoseWeight change10-1-2-30-1-2-3-4mM%Note: Data from the double-blind, double-dummy, randomised, parallel group dose titration phase 2 study including a total of 144 patients with an average HbA1c of 9.4-9.5%. All changes are from baseline; that is, FSG of 13.0-13.2 mM and an average weight of 91-94 kg. p

Liraglutide - expected propertiesEffectSide effectsOther aspects

Diabetes care pipeline

CompoundTypeIndicationPhaseLevemir (insulin detemir)InsulinType 1+2 diabetesFiled EU+USNovoMix 50 and 70InsulinType 1+2 diabetesPhase 3AERx iDMS (NN1998)InsulinType 1+2 diabetesPhase 3Liraglutide (NN2211)GLP-1 analogueType 2 diabetesPhase 2Balaglitazone (NN2344)OADType 2 diabetesPhase 2NN414OADType 1+2 diabetesExp. phase 2NN344InsulinType 1+2 diabetesPhase 1NN2501OADType 2 diabetesPhase 1

Evolution of a diabetes project: A competitive edge of Novo Nordisk Stem cell-derived -cellsIdentify & clone targetEstablish biological functionHigh throughput screeningIn vitro biological profileChemistryIn vivo diabetes modelsDevelop-ment candidateStable cell linesDiabetesexpertiseDiabetesmodelsDiabetes related proteins

Future treatment of diabetes key observationsKey observations:Near term treatment focused on substitutionInsulin analoguesInhaled insulinGLP-1 analoguesMid-term treatment focused on new alternative innovative therapiesLonger term treatment focused at preventionVery long term treatment focused on curing diabetesNovo Nordisk position:Near term developmentAll analogue segmentsNN1998 (AERx iDMS)NN2211Mid-term developmentNN2501NN414Insulin and OAD projects with breakthrough potentialCuring diabetes is the vision of Novo Nordisk

Investor informationInvestor Relations contacts Novo Nordisk A/S Investor Relations Novo All, DK2880 BagsvrdFax (+45) 4443 6633 Peter Haahr Tel (direct): (+45) 4442 1207 E-mail: [email protected] Palle Holm Olesen Tel (direct): (+45) 4442 6175 E-mail: [email protected]

Christian Kanstrup Tel (direct): (+45) 4443 7801 E-mail: [email protected]

Investor Relations Office USTel (direct): (+1) 609 919 7846Share information Novo Nordisks B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol NVO. For further company information, visit Novo Nordisk on the internet at http://www.novonordisk.com

13LRS:[Below find comments for inspiration:In Novo Nordisk we believe we have at least three core competencies which we try to exploit.Our Diabetes knowledge stems from now 80 years of experience in development and marketing of diabetes care productsAll since the beginning but especially since the early 1980's we have been in the forefront of developing better and more convenient drug delivery systems and that is still very much in focusProtein expertise also comes from our long-term experience in producing and also improving both formulations and production methods of these difficult therapeutic proteinsAll-in-all we have with this trinity raised the barriers to entry for competitors and also increased the opportunities for our self.]

The insulin business case still remain the same

A: this is physiological plasma insulin profile, rapid onset, rapid time to maxium concentration and quick return to the baseline level before next meal. In conclusion: normal insulin physiology is characterised by a basal level of insulin and post-prandial surges. B:Insulin profiles after subcutaneous injection of soluble human insulin and NPH (blue curve) at night, rise more slowly, low insulin peak and remain elevated longer, and fail to return to baseline levels before the next meal.C:subcutaneous injection of NovoRapid before meals in combination with night time NPH insulin mimic the endogenous insulin with rapid absorption, high insulin peak and quick return to baseline before next meal.

when mention the HI curve, draw the attention to the clinical impact from each point, delayed onset, low peak and prolong the duration.

Insulin profiles after subcutaneous injection of soluble human insulin and NPH (blue curve) at night do not match the profile of physiological insulin secretion (shown in yellow).The data were obtained from two separate studies. In the first study, blood samples from 14 healthy men and women were collected at 15-30 minute intervals during 24 hours. Meals were taken at 0900, 1300, and 1800 hours (orange bars).1The pharmacokinetic profile of plasma insulin after subcutaneous injection of pre-meal soluble human insulin and night time NPH insulin was exemplified by pharmacokinetic modelling, using known pharmacokinetic information on soluble human insulin in healthy subjects and patients with type 1 diabetes.Although absolute insulin values cannot be compared between studies because of differences in experimental conditions, comparisons can be made between insulin profiles.In healthy volunteers, free insulin levels rose to peak concentration within 30-60 minutes after meals and then fell rapidly, reaching baseline levels before the next meal. Insulin levels remained low during the night and there was no evidence of an elevation in the early morning.1 The results demonstrate that insulin profile after injection of soluble human insulin before meals is unphysiological. Insulin concentrations rise more slowly, remain elevated longer, and fail to return to baseline levels before the next meal.ReferencePolonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. JCI 1988; ****As shown in this slide, subcutaneous injection of a rapid-acting insulin analogue before meals in combination with night time NPH insulin mimic the endogenous insulin release after meals more closely than pre-meal injections of soluble human insulin and night time NPH.The data were obtained from two separate studies. In the first study, blood samples from 14 healthy men and women were collected at 15-30 minute intervals during 24 hours. Meals were taken at 0900, 1300, and 1800 hours (orange bars).1The pharmacokinetic profile of plasma insulin after subcutaneous injection of pre-meal insulin aspart and night time NPH insulin was exemplified by pharmacokinetic modelling, using known pharmacokinetic information on insulin aspart in healthy subjects and patients with type 1 diabetes.Although absolute insulin values cannot be compared between studies because of differences in experimental conditions, comparison can be made between insulin profiles.The results demonstrate that insulin profile after injection of insulin aspart before meals is more physiological. ReferencePolonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. JCI 1988;81:442-448A: this is physiological plasma insulin profile, rapid onset, rapid time to maxium concentration and quick return to the baseline level before next meal. In conclusion: normal insulin physiology is characterised by a basal level of insulin and post-prandial surges. B:Insulin profiles after subcutaneous injection of soluble human insulin and NPH (blue curve) at night, rise more slowly, low insulin peak and remain elevated longer, and fail to return to baseline levels before the next meal.C:subcutaneous injection of NovoRapid before meals in combination with night time NPH insulin mimic the endogenous insulin with rapid absorption, high insulin peak and quick return to baseline before next meal.

when mention the HI curve, draw the attention to the clinical impact from each point, delayed onset, low peak and prolong the duration.

Insulin profiles after subcutaneous injection of soluble human insulin and NPH (blue curve) at night do not match the profile of physiological insulin secretion (shown in yellow).The data were obtained from two separate studies. In the first study, blood samples from 14 healthy men and women were collected at 15-30 minute intervals during 24 hours. Meals were taken at 0900, 1300, and 1800 hours (orange bars).1The pharmacokinetic profile of plasma insulin after subcutaneous injection of pre-meal soluble human insulin and night time NPH insulin was exemplified by pharmacokinetic modelling, using known pharmacokinetic information on soluble human insulin in healthy subjects and patients with type 1 diabetes.Although absolute insulin values cannot be compared between studies because of differences in experimental conditions, comparisons can be made between insulin profiles.In healthy volunteers, free insulin levels rose to peak concentration within 30-60 minutes after meals and then fell rapidly, reaching baseline levels before the next meal. Insulin levels remained low during the night and there was no evidence of an elevation in the early morning.1 The results demonstrate that insulin profile after injection of soluble human insulin before meals is unphysiological. Insulin concentrations rise more slowly, remain elevated longer, and fail to return to baseline levels before the next meal.ReferencePolonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. JCI 1988; ****As shown in this slide, subcutaneous injection of a rapid-acting insulin analogue before meals in combination with night time NPH insulin mimic the endogenous insulin release after meals more closely than pre-meal injections of soluble human insulin and night time NPH.The data were obtained from two separate studies. In the first study, blood samples from 14 healthy men and women were collected at 15-30 minute intervals during 24 hours. Meals were taken at 0900, 1300, and 1800 hours (orange bars).1The pharmacokinetic profile of plasma insulin after subcutaneous injection of pre-meal insulin aspart and night time NPH insulin was exemplified by pharmacokinetic modelling, using known pharmacokinetic information on insulin aspart in healthy subjects and patients with type 1 diabetes.Although absolute insulin values cannot be compared between studies because of differences in experimental conditions, comparison can be made between insulin profiles.The results demonstrate that insulin profile after injection of insulin aspart before meals is more physiological. ReferencePolonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. JCI 1988;81:442-448So for our basal insulins we seek a low, flat mean profile. But is this sufficient?This slide builds and invites audience participation!Profile B initially appears to be superior, but we must remember this is a mean profile. When the individual data are added profile A can be seen to be less variable and hence pose a reduced risk of nocturnal hypo. Thus..Single centre, parallel group, randomised, double-blind study with four dosing days54 patients with type 1 diabetes mellitus (51 patients completed the study)S.c. injections of 0.4 U/kg of Insulin Detemir, NPH insulin or Insulin Glargine into the thighEuglycaemic glucose clamps (target blood glucose 5.5 mmol/L) for 24 h post-dose

1335 study.Reduced variability was shown across the day and particularly overnight in a 6-month, parallel-group study of 747 patients with type 1 diabetes randomised to receive either once-daily Levemir or NPH insulin with HSI at mealtimes. A subset of patients (n = 133) underwent continuous blood glucose monitoring for a 3-day period. The data were used to calculate the individuals mean fluctuation in blood glucose over 24 hours from their 24-hour mean blood glucose concentration, as shown here. A statistical (ANOVA) analysis of these data suggested that the degree of within-patient fluctuation in blood glucose was lower with Levemir both over 24 hours (by some 14%, p = 0.039) and over the nocturnal hours (by some 22%, p = 0.005).

Lower and More Predictable Fasting Blood Glucose and Reduced Risk of Nocturnal Hypoglycaemia With OnceDaily Insulin Detemir Versus NPH In Subjects With Type 1 DiabetesD. RUSSELL-JONES 1 , J. BOLINDER 2 , R. SIMPSON 3

Background and Aims: Insulin detemir is a soluble basal insulin analogue with neutral pH and a unique mechanism of protraction providing more predictable and stable glucose levels with less intra-subject variation than other basal insulins. This trial compared glycaemic control, risk of hypoglycaemia, and difference in body weight after 6 months of treatment with insulin detemir or NPH, combined with human soluble insulin (HSI) as bolus insulin. Materials and Methods: In all, 747 (479 M/268 F) subjects with type 1 diabetes were randomised (2:1; insulin detemir: NPH) in a 6-month, multi-national, multi-centre, open, parallel-group trial design. Treatment groups were well matched; age (mean (SD)): 40.5 (12.3) years; mean duration of diabetes 16.9 (10.7) years; mean BMI: 25.2 (3.4) kg/m 2 ; mean HbA 1c : 8.35 (1.21) %. Results: Glycaemic control, as measured by HbA 1c after 6 months, was similar in both treatment groups: mean difference (insulin detemir NPH) 0.12% (95% CI: [0.25; 0.02]). Nevertheless, fasting plasma glucose levels were lower for subjects on insulin detemir (1.16 mmol/L; p=0.001). Intra-subject variation in self-measured fasting blood glucose levels for these subjects was lower than for subjects on NPH (p4 mg/(kgmin)), which can lead to hypoglycemia will be 0.1% if the subject uses insulin detemir, nearly 3% with insulin glargine, and above 6% with NPH insulin.GLP-1 is modified this way in order to get a long-acting compound. The protract is similar to NN304 (our long-acting insulin analogue)LRS:For NN414 I am happy to be able to inform you that we have initiated explorative phase 2 trials investigating NN414 in individuals with either type 1 diabetes, Impaired Glucose Tolerance or type 2 diabetes. The aim of the studies is to explore the concept of beta-cell rest in diabetes treatment. NN414 is a beta-cell-selective compound which in preclinical studies has shown a beneficial effect on glycaemic control. These exploratory phase 2 trials are expected to conclude in the first half of 2004. The outcome of these trials will affect the direction and indication to pursue with this compound towards clinical proof of concept. Furthermore we have started phase 3 trials on Levemir in Japan. In other main regions we expect a launch of Levemir during 2004 depending on the approval process.Regarding our project focused at pulmonary delivery of insulin, that is AERx iDMS, all available data, including information from the ongoing phase 3 study in Australia and New Zealand, continue to support our belief that the AERx iDMS is safe and effective. However, there are some manufacturing changes we will undertake to optimise the commercial strip and device production processes. As a consequence, the additional clinical studies required for regulatory filing are not expected to be initiated before the end of 2004. We continue to have confidence in our partner Aradigm and will continue to support their efforts financially and scientifically as they work on the changes needed to get this innovative product to market.

Documents

Carnegie 16092003 Noappendix