Title: Novo Nordisk A focused global healthcare company with biotech expertise Diabetes Conference at Union Bank of Switzerland October 2001
1Novo NordiskA focused global healthcare
company with biotech expertiseDiabetes
Conference atUnion Bank of Switzerland October
2001
2Agenda
- 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
3Metabolic abnormalities associated with Type 1
and Type 2 diabetes
4Diabetes care Treatment matters
Only a small number of patients are in control
Intensive treatment matters
Distribution of patients
HbA1c lowering by one percentage point reduces
micro vascular risk by 35
HbA1c
Measured according to Guidelines for Diabetes
Care, IDF Europe According to epidemiological
analysis of the UKPDS data, 1998
5Diabetes 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
6Key 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
7Novo 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 RD employees dedicated to
diabetes, representing approximately ¾ of RD
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
8Diabetes RD at Novo NordiskSources of
innovation
- Clinical research
- Steno Diabetes Centre
- Oxford Diabetes Centre
- Clinical research centres worldwide
- Basic research
- Hagedorn Research Institute
- Oxford and Steno Diabetes Centre
- Academic collaborations
- Consortia
- Evidence-based medicine
- NN disease mgt programmes
- Outcomes data from gt 100.000 individuals with
diabetes
RD projects
- Molecular diversity design
- Protein chemistry since 23
- Medicinal chemistry since 68
- Computational chemistry since 75
- Rational drug design since 83
- Combinatorial chemistry since 93
- 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
- Trinomics
- Genomics Incyte since 95
- Proteomics CPA since 97
- Metabonomics since 99
9Pharmaceutical 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
10Diabetes drug candidates in development at Novo
Nordisk
Insulin Resistance Dyslipidaemia
Obesity
Type 2 diabetes
Failure of oral drugs
Phenotype
Diet and exercise NN education programme
Sensitizers and lipid-lowering agents NN2344
NN622
ß-cell agents NovoNorm NN2211, NN414 Hepatic
glucose regulators NN4201
Insulins NovoRapid, NovoMixTM, AERx, insulin
detemir, LABI
Appetite regulation NN2211
- 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.
11The miracle of insulin
Patient J.L., December 15, 1922
February 15, 1923
12Going forward in diabetesExpanding 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 worlds richest
insulin therapy portfolio - Insulin analogues
- Insulin formulations
- Insulin delivery systems
13Insulin profiles in type 1 diabetic patients
treated with NovoRapid or human insulin
14NovoRapid versus insulin lispro
- 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
Home PD, et al. Diabetes Care 1998211904-1909 Ga
le EAM, et al. Diabetic Medicine 200017209-214
15Profile 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
16Mechanism of protraction of insulin detemir
Absorption
Receptor interaction
Distribution
HSA human serum albumin
17Insulin detemir versus NPH insulin Night-time
glucose profile
BG (mM)
Insulin detemir showed reduced variability
compared to NPH
N 21
9
8
N 52
7
6
5
11pm
3am
7am
Treatment
Insulin detemir
NPH insulin
Findings Predictable glucose profiles over night
with detemir
J. L. Selam et al. Oral presentation EASD 2001
18Insulin detemir versus NPH insulin Hypoglycaemic
events reduced for insulin detemir at all times
Findings Statistatically fewer hypoglycaemic
events
Hermansen et al. Diabetes Care 200124296-301
19Insulin 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
20Novo Nordisk devices in diabetes care
- First pen (NovoPen 1) launched in 1985
- In the US, launch of the first pen in 1988
21Upgrading the insulin market
100
Increasing turnover per patient
Insulin analogue penetration
(30 premium)
USA
Europe
Japan
0
100
Device penetration
(50 premium)
22AERx 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
23Pulmonary 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
24The insulin market Overall conclusions
- 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
- 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
25Novo 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
26Type 2 diabetes disease management throughout
life
Diet and exercise
Oral products (approx 66)
?-Cell function ( of healthy )
60
40
Insulin (approx 27)
20
Oral/insulin (approx 7)
0
0
1
2
3
4
5
6
Years from randomisation
Adapted from UK Prospective Diabetes Study
(UKPDS) Group. Diabetes. 1995 441249-1258.
27Growth within the OAD market
Growth in USD 5.8 bn OAD market
Key observations Novo Nordisk
350
Sales development in USD CAGR 26
- Experience in the OAD market from
NovoNorm/Prandin - Novartis partner on NN622 for North America
- Broad pipeline of innovative approaches for Type
2 diabetes
300
250
200
MATQ1.1996100
150
No of treated patients CAGR 13
100
50
0
1996
1997
1998
1999
2000
2001
28Type 2 Diabetes the Metabolic Syndrome
NN622
NN622
Genetic Acquired Glucotoxicity Lipotoxicity
Insulin deficiency
Insulin deficiency
Impaired beta cell function
Hepatic glucose production
Glucose-induced insulin secretion
Post receptor defect
Hyperglycemia
Tissue response to insulin
Glucose uptake
Basal hyper- insulinemia
NN622
Glucose transport
Insulin resistance
Insulin resistance
Insulin binding
Genetic Acquired Obesity Age
29Elevated lipid levels are detrimental in type 2
diabetes
MUSCLE
Increased hepatic glucose output (hyperglycaemia)
Insulin resistance
TG accumulation
FFA
ADIPOSE TISSUE
LIVER
Disturbed insulin secretion (hyperinsulinaemia)
B CELLS
- Increased VLDL
- Decreased HDL
- Increased small dense LDL
- ? Atherosclerosis
TG accumulation
30NN622 The dual acting PPARa/g agonist concept
31Effect on hepatic glucose productionComparison
between NN622, Avandia, Actos and a fibrate
NN622 shows superior efficacy in suppressing
glucose production by the liver.
Source Ye et al. Diabetes 2001 50 A316
32NN622 possesses potent lipid-lowering activity in
cholesterol-fed rats
HDL Cholesterol
Triglycerides
VLDL Cholesterol
Source Data on file
33Triglycerides in liver and muscleComparison
between NN622, Avandia, Actos and a fibrate
P lt 0.05, P lt 0.01, P lt 0.001 vs Vehicle
34Type 2 diabetes disease management throughout
life ?-cell failure leads to T2D
Diet and exercise
Oral products (approx 66)
?-Cell function ( of healthy )
60
40
Insulin (approx 27)
20
Oral/insulin (approx 7)
0
0
1
2
3
4
5
6
Years from randomisation
Adapted from UK Prospective Diabetes Study
(UKPDS) Group. Diabetes. 1995 441249-1258.
35NN2211 prevents diabetes in ZDF rats
- NN2211 prevents the progression of diabetes in
ZDF rats - Proliferation and volume of ?-cells are normalized
Control
1.00
NN2211
0.75
()
0.50
0.25
0.00
b
-cell volume
Proliferation
- Increased insulin staining intensity after NN2211
treatment
36NN2211 Effect on fasting and post-prandial blood
glucose in type 2 patients
GLP-1 effects Insulin ? ?-cell
survival ? Glucagon ? Appetite
? GI-emptying ?
12
Placebo
11
NN2211
10
9
(mmol/l)
Mean glucose profiles
8
7
6
Insulinpulseanalysis
Standardmeal
5
Dosing
4
-2
0
2
4
6
8
10
12
14
16
18
Time (hours)
37NovoNordisk commitment to the cure of T1D Stem
cell research at Hagedorn Research Inst.
Cell type 1
Goal To mature or differentiate beta cells from
stem-cell stages
Cell type 2
Cell type 3
Beta cell
Zygote / ES-cell
Pancreatic Stem Cell
Islet Stem Cell
Cell type 210
38Autologous stem cell therapy
Patient
Adult stem cell
Pancreatic islet cells
Hematopoietic cells
Cardiomyocytes
Neurons
Hepatocytes
In Type 1 diabetes protection against autoimmune
destruction will be necessary
Immunologically compatible transplant
Modified from Nature Medicine 5975-7, 1999
39Clinical stage diabetes pipeline
Phase 1
Phase 2
Phase 3
- NN414 (Insulin secretion)
- NN4201 (Hepatic glucose regulator)
- NN2344 (Insulin sensitiser)
- NN622 (Dual-acting sensitiser)
40 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 2000. A Form
20-F for 2000 will be filed by the end of June
2001
41Investor Information
- Investor Relations ContactsNovo Nordisk A/S
Investor Relations Novo Allé DK2880
BagsværdDenmark - Fax (45) 4444 2314. Peter HaahrPhone (45)
4442 1207 E-mail pehr_at_novonordisk.com - Palle Holm Olesen
Phone (45) 4442 6175 E-mail
phoo_at_novonordisk.com - Rasmus Holm-JørgensenPhone (1) 212 867 0123
E-mail rrhj_at_novonordisk.com
Share informationNovo Nordisks 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
42(No Transcript)