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Novo Nordisk®

Research and early


development

Marcus Schindler
CSO and EVP of Research & Early development

7 MARCH

JOANNA LOUISE SHARMAN-SOARES


ROBERT KITCHEN
Digital Science and Innovation
Research Centre Oxford
UK
2 Research & early development Innovation and therapeutic focus Novo Nordisk®

Forward-looking statements
Novo Nordisk’s reports filed with or furnished to the US Securities and Exchange Commission (SEC), including the statutory Annual Report 2023 and Form 20-F, which both were filed with the SEC in
January 2024 in continuation of the publication of the Annual Report 2023, this presentation, and written information released, or oral statements made, to the public in the future by or on behalf of Novo
Nordisk, may contain forward-looking statements. Words such as ‘believe’, ‘expect, ‘may’, ‘will’, ‘plan’, ‘strategy’, ‘prospect’, ‘foresee’, ‘estimate’, ‘project’, ‘anticipate’, ‘can’, ‘intend’, ‘target’ and other words
and terms of similar meaning in connection with any discussion of future operating or financial performance identify forward-looking statements. Examples of such forward-looking statements include,
but are not limited to:

• Statements of targets, plans, objectives or goals for future operations, including those related to Novo Nordisk’s products, product research, product development, product introductions and
product approvals as well as cooperation in relation thereto,

• Statements containing projections of or targets for revenues, costs, income (or loss), earnings per share, capital expenditures, dividends, capital structure, net financials and other financial
measures,
• Statements regarding future economic performance, future actions and outcome of contingencies such as legal proceedings, and
• Statements regarding the assumptions underlying or relating to such statements.

These statements are based on current plans, estimates and projections. By their very nature, forward-looking statements involve inherent risks and uncertainties, both general and specific. Novo
Nordisk cautions that a number of important factors, including those described in this presentation, could cause actual results to differ materially from those contemplated in any forward-looking
statements.

Factors that may affect future results include, but are not limited to, global as well as local political and economic conditions, such as interest rate and currency exchange rate fluctuations, delay or failure
of projects related to research and/or development, unplanned loss of patents, interruptions of supplies and production, including as a result of interruptions or delays affecting supply chains on which
Novo Nordisk relies, shortages of supplies, including energy supplies, product recalls, unexpected contract breaches or terminations, government- mandated or market-driven price decreases for Novo
Nordisk’s products, introduction of competing products, reliance on information technology including the risk of cybersecurity breaches, Novo Nordisk’s ability to successfully market current and new
products, exposure to product liability and legal proceedings and investigations, changes in governmental laws and related interpretation thereof, including on reimbursement, intellectual property
protection and regulatory controls on testing, approval, manufacturing and marketing, perceived or actual failure to adhere to ethical marketing practices, investments in and divestitures of domestic
and foreign companies, unexpected growth in costs and expenses, strikes and other labour market disputes, failure to recruit and retain the right employees, failure to maintain a culture of compliance,
epidemics, pandemics or other public health crises, the effects of domestic or international crises, civil unrest, war or other conflict and factors related to the foregoing matters and other factors not
specifically identified herein.

For an overview of some, but not all, of the risks that could adversely affect Novo Nordisk’s results or the accuracy of forward-looking statements in the Annual Report 2023, reference is made to the
overview of risk factors in ‘Risk Management’ of the Annual Report 2023.

Unless required by law, Novo Nordisk has no duty and undertakes no obligation to update or revise any forward-looking statement after the distribution of the Annual Report 2023, whether as a result of
new information, future events, or otherwise.

Important drug information


Victoza® and Ozempic® are approved for the management of type 2 diabetes only
Saxenda® and Wegovy® are approved for the treatment of obesity only
3 Research & early development Innovation and therapeutic focus Novo Nordisk®

Strategic aspirations 2025

• Further raise the innovation-bar for diabetes


treatment

therapeutic focus
• Progress towards zero environmental impact • Develop a leading portfolio of superior treatment

Innovation and
• Being respected for adding value to society solutions for obesity
sustainability
Purpose and

• Being recognised as a sustainable employer • Strengthen and progress the Rare disease pipeline
• Establish presence in Cardiovascular & emerging
(ESG)

therapy areas

• Deliver solid sales and operating profit growth


• Strengthen Diabetes leadership - aim at global value
market share of more than 1/3 • Drive operational efficiencies across the value chain to
enable investments in future growth assets
• More than 25 billion DKK in Obesity sales by 2025
Commercial

• Deliver free cash flow to enable attractive capital


execution

Financials
• Secure a sustained growth outlook for Rare disease
allocation to shareholders

Note: The strategic aspirations are not a projection of Novo Nordisk's financial outlook or expected growth
4 Research & early development Innovation and therapeutic focus Novo Nordisk®

Innovation starts with addressing unmet needs, improving


outcomes and reaching more patients
Diabetes care Obesity care

537
million people with
~15% 813
million people with
~2%
of people in of people medically
diabetes1 good control2 obesity3 treated

Rare disease Cardiovascular &


Haemophilia emerging therapy areas

0.6 ~35% 32% >30 >250 >800


million people with of people being treated of global deaths million people million people million people
haemophilia4 caused by CVD5 affected by affected by affected by
HFpEF6 MASH7 CKD8

1International Diabetes Federation: Diabetes Atlas 10 th edition, 2021; 2Real-world studies indicate between 30-55% of patients reach HbA1c target <7% .e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388968/, taking 42.5% in good control of
treated people; 3World Obesity Atlas, 2023; 4WFH annual survey 2020 (120 of 147 countries responded): Prevalence by calculating expected number of patients using 20.9 per 100.000 in haemophilia - Identified patients as proxy for receiving some
sort of treatment; 5WHO. Cardiovascular Diseases 2023; 6Chris J Kapelios et al Cardiac Failure Review 2023;9:e14.; 7Younossi ZM et al. Hepatology. 2023;77:1335-1347; 8Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int
Suppl (2011). 2022 Apr;12(1):7-11
CKD: Chronic kidney disease; CVD: Cardiovascular disease; HFpEF: Heart failure with preserved ejection fraction; MASH: Metabolic dysfunction-associated steatohepatitis; WHO: World Health Organization
5 Research & early development Innovation and therapeutic focus Novo Nordisk®

Research and early development focuses on continuing and


expanding leadership in diabetes and obesity
Therapy area priorities Strategic research focus

Driving leadership in diabetes and obesity with novel and


1 Diabetes Obesity disease modifying therapies

2 CVD RBD Delivering next generation insulins and GLP-1 therapies

Improving the quality of health for people while reducing


3 MASH RED CKD
risks of co-morbidities

Focusing on scalability and building upon core protein and


4 AD/PD
peptide capabilities with siRNA, cell and gene therapies

AD: Alzheimer’s disease; CKD: Chronic kidney disease; CVD: Cardiovascular disease; MASH: Metabolic dysfunction-associated steatohepatitis; PD: Parkinson’s disease; RBD: Rare blood disorders; RED: Rare endocrine disorders;
siRNA: Small interfering ribonucleic acid
Note: Research and early development comprises activities from research until phase 2
6 Research & early development Innovation and therapeutic focus Novo Nordisk®

Increased access to human data together with AI-driven analyses


enables discovery of new targets
Human data input Target discovery engine Increasing probability for clinical success

De-risk translation from


Genetics, samples, multi-omics
animal models to humans

Diverse cohorts
80% more
African American cohort AI driven data mining and targets screened in 2023 compared to 2022.
Genes & Health Industry Consortium analyses linking disease to novel Capacity increasing in 2024
UK biobank targets

Disease cohorts
Alliance Genomic Discovery (Obesity)
ATTRACT (CVD) In silico analyses
Cellfi (Diabetes)
Significant number
of new targets expected to
Leverage real world evidence enter phase 1
Human centric in vitro assays
in early discovery

AI: Artificial intelligence; CVD: Cardiovascular disease


7 Research & early development Innovation and therapeutic focus Novo Nordisk®

SELECT trial provides a unique opportunity to identify new


targets and biomarkers for future projects
SELECT trial data set Fuels future research Potential outcomes

Samples from • New drug targets and molecular


Human data for drug discovery
>17,000 people mechanisms

Identify and validate new biomarkers • Responder subtype profiles enabling


Collected over 5 years precision medicine
and 1,270 events
Linking novel targets to disease • Prediction of disease progression and
treatment response
CVD, obesity, pre-diabetes,
Enhanced by digital and AI capabilities
and CKD endpoints

Proteomics for 3 time points


from ~11,000 people
AI-driven
data mining and
Genetic data from analyses
~11,000 people

AI: Artificial intelligence; CKD: Chronic kidney disease; CVD: Cardiovascular disease
8 Research & early development Innovation and therapeutic focus Novo Nordisk®

Accelerating innovation through partnerships and acquisitions to


grow and advance pipeline
Number of partnerships1 and acquired assets to date Selected key highlights of partnerships and acquisitions

60+ Heart failure


active partnerships (including 7 acquisitions) Phase 1 initiated in 2023 Cell
Therapy

37 Haemophilia A
partnerships focused on Proof of concept in non- Gene
cardiometabolic diseases and obesity human primates 2023
Therapy

21 Obesity
partnerships exploring new MoAs Phase 1 initiated in 20242 Small
Molecules

~50%
Atherosclerotic
of partnerships have resulted in projects
cardiovascular disease Small
entering the pipeline as of today
Phase 1 initiation expected Molecules
in 2024

1Partnerships
include drug-enabling technology and drug-based strategic partnerships and acquisitions; 2INV-347
MoA: Mode of action
9 Research & early development Innovation and therapeutic focus Novo Nordisk®

CB1R inverse agonism holds potential as a novel mechanism of


action both as monotherapy and add-on treatment
CB1R are found throughout the body Inversago next-generation CB1R molecules INV-347 shows weight loss in DIO
mice models
ILLUSTRATIVE
INV-202/347
0

Change in body weight (%)


CB1 Inverse agonists
receptor

-15

-30

• Novel design minimising brain penetration


-45
Peripheral CB receptors type 1 0 35
Central CB receptors type 1 Time (days)

Monlunabant (INV-202) appeared to have a Control group INV-347 10 mg/kg


• CB1 biology plays a role in regulation of safe and well-tolerated profile with no INV-347 0.4 mg/kg INV-347 20 mg/kg
energy homeostasis1 serious or severe treatment-emergent
INV-347 2 mg/kg
adverse events in a phase 1 trial

1DörnyeiG, et al. Biomedicines. 2023 Jan 21;11(2):306. doi: 10.3390/biomedicines11020306


CB: Cannabinoid; CB1R: Cannabinoid receptor type 1; DIO: Diet induced obesity
10 Research & early development Innovation and therapeutic focus Novo Nordisk®

Integrating siRNA technology into Novo Nordisk adds


capabilities to access intracellular targets across therapy areas
Integration of Dicerna siRNA platform is deployed across all therapy areas

GalXCTM GalXC-PlusTM
Dicerna partnership since 2019, acquired in 2021 and
now Global Nucleic Acid Therapies
Enables RNA silencing in + Enables RNA silencing in
hepatic cells extra-hepatic cells

Allows Novo Nordisk to access patented siRNA research Disease targets Diabetes Obesity
(expressed genes)
technology platform
CVD
~5,000
extracellular
Investments made in CMC capabilities to deliver targets MASH CKD
Cell
industrial scale siRNA therapeutics across therapy areas ​
~21,000
Brain
intracellular disorders
targets

Boston presence enables Novo Nordisk to tap into RBD RED

surrounding life science ecosystem

CKD: Chronic kidney disease; CMC; Chemistry manufacturing and controls; CVD: Cardiovascular disease; MASH: Metabolic dysfunction-associated steatohepatitis; RBD: Rare blood disorders; RED: Rare endocrine disorders; RNA: Ribonucleic acid;
siRNA: Small interfering ribonucleic acid
11 Research & early development Innovation and therapeutic focus Novo Nordisk®

siRNA platform expected to deliver and mature across therapy


areas in alignment with corporate strategy
Progress with the siRNA platform Distribution of siRNA portfolio projects Phase 1 initiation ambition with siRNA

3
11 phase 1 trial initiations with
GalXCTM since 2017

RivflozaTM the first Novo


Nordisk siRNA drug, approved
in 2023

… phase 1 initiations on
First extra-hepatic phase 1 trial
average per year across
with GalXC-PlusTM in 2023
disease areas with the
siRNA platform is
on track
50% of upcoming phase 1 trials
expected to be with GalXC- Diabetes and Obesity RBD and RED
PlusTM
CVD and MASH Other projects

CVD: Cardiovascular disease; MASH: Metabolic dysfunction-associated steatohepatitis; RBD: Rare blood disorders; RED: Rare endocrine disorders; siRNA: Small interfering ribonucleic acid
Note: A project is defined when a target is identified and assigned team ask for resources to evaluate proof of concept
12 Research & early development Innovation and therapeutic focus Novo Nordisk®

Core capabilities together with additional drug modalities open


up new opportunities across therapy areas
Core Novo Nordisk capabilities Modalities accelerated via partnerships &
acquisitions

Proteins/ Cell Small Gene


siRNA
Peptides/mAB Therapy Molecules Therapy

Diabetes

Obesity
Therapy areas

CVD

RBD

MASH

RED

CKD

Active pipeline Exploratory

CKD: Chronic kidney disease; CVD: Cardiovascular disease; mAB: Monoclonal antibody; MASH: Metabolic dysfunction-associated steatohepatitis; RBD: Rare blood disorders; RED: Rare endocrine disorders; siRNA: Small interfering ribonucleic acid
Note: Currently active means Novo Nordisk is currently pursuing research projects, while exploratory indicates active early exploration activities and/or partnerships initiated
13 Research & early development Innovation and therapeutic focus Novo Nordisk®

Novo Nordisk's modality portfolio has expanded since 2018 with


more projects using newer platforms
Distribution of research and phase 1 projects across modalities Strategic changes made since 2018

Build upon core capabilities with new


modalities

More than one modality per target


1+ biology

Focus on automation and scalability

Building in silico capabilities to better


predict

Increased investments

2018 2024

Proteins & Peptides siRNA1 Small molecules Cell therapy Gene therapy

1primarily
siRNA projects
siRNA: Small interfering ribonucleic acid
14 Research & early development Innovation and therapeutic focus Novo Nordisk®

The research and early development pipeline is broad and has


increased across therapy areas since 2018
Growing research and phase 1 pipeline since 2018 Strategic changes made since 2018

~80%

Continued key focus on diabetes and


obesity

Broadening and advancing CVD pipeline

Increased commitment in Rare blood


disorders

Increased investments

2018 Pipeline 2024 Pipeline

Diabetes CVD CKD RED


Obesity RBD MASH Other

CKD: Chronic kidney disease; CVD: Cardiovascular disease; MASH: Metabolic dysfunction-associated steatohepatitis; RBD: Rare blood disorders; RED: Rare endocrine disorders
15 Research & early development Innovation and therapeutic focus Novo Nordisk®

Next-generation innovation drives the phase 1 pipeline within


diabetes
Diabetes phase 1 pipeline Once monthly GIP/GLP-1 co-agonist

NN1845 – GSI

Co-agonist to GIP
Mode of action
and GLP-1 receptors
NN1471 – Pumpsulin

Improved convenience
Differentiation
NN9041 – DNA Immunotherapy 12 injections yearly

Diabetes
Once monthly sc
NN9904 – OW oral semaglutide Dosing injection

NN9650
Phase 1 results
NN9650 – OM GIP/GLP-1 co-agonist (OM GLP-1/GIP) Next steps
expected in 2025

NN9541 – OW GIP/GLP-1 co-agonist

DNA: Deoxyribonucleic acid; GIP: Gastric inhibitory polypeptide; GSI: Glucose sensitive insulin; OM: Once-monthly; OW: Once-weekly; sc: Subcutaneous
16 Research & early development Innovation and therapeutic focus Novo Nordisk®

Oral amycretin is a novel, unimolecular co-agonist of both GLP-1


and amylin receptors that successfully completed phase 1 trial
Obesity phase 1 pipeline Amycretin combines several beneficial effects of GLP-1 and amylin

NN9542 – OW GIP/GLP-1 co-agonist


NN9487 Co-agonist to the GLP-1
Mode of action
Oral amycretin and amylin receptor

Complementary
NN9441 – INV-347 biologies for additive
Differentiation
effect
Obesity

Dosing Once daily oral


NN9487 – Oral amycretin

GLP-1 Amylin Further clinical


Next steps
development
receptor receptor
NN9490 – Sc amycretin

GIP: Gastric inhibitory polypeptide; OW: Once-weekly; Sc: Subcutaneous


17 Research & early development Innovation and therapeutic focus Novo Nordisk®

Amylin shows potential for additional and complementary


benefits to GLP-1 in metabolic diseases
Amylin and GLP-1 are endocrine peptide Weight loss in a 20-week phase 1 Cagrilintide improves body composition in
hormones obesity trial obesity DIO rat model3
Mean baseline body weight: 94.6 kg, n = 96 100

Delta fat mass, g


Amylin GLP-1
50

Change in body weight (%)


0
-50
-100

β-cells in L-cells in -9,8%


pancreas intestines 100

Delta lean mass, g


50
Amylin and GLP-1 both have a role in1,2: -17,1% 0
• Appetite regulation (hunger and satiety) Semaglutide 2.4mg -50
• Glucose control
CagriSema (2.4 mg sema and 2.4 mg cagri) -100

Amylin is also involved in2,3:


Novo Nordisk amylin analogues have Control HFD 10 nmol/kg
• Bone homeostasis appeared to have safe and well-tolerated
1 nmol/kg Control, LFD
• Body composition profiles in clinical trials
3 nmol/kg

1Campbell et.al. Cell Metabolism 2013 (17) 819-837; 2Hay et al. Pharmacological reviews 2015 (67) 564-600; 3Daquin et.al. 2004 164(4):509-14
Cagri: Cagrilintide; DIO: Diet induced obesity; g: gram; HFD: High-fat diet; LFD: Low-fat diet; nmol: nanomole; Sema: semaglutide
18 Research & early development Innovation and therapeutic focus Novo Nordisk®

Phase 1 results in obesity allows further clinical development of


amycretin
Oral amycretin phase 1 trial in obesity was successfully completed Results from exploratory endpoint on body weight change

Mean baseline body weight: ~89 kg, n = 16


3

0 -1.1

Change in body weight (%)


-3

-6
Phase 1 key findings

• Pharmacokinetic profile allows for further clinical development -9

• 13.1% weight loss after 12 weeks -12 -13,1

• Amycretin appeared to have a safe and well-tolerated profile


-15
0 4 8 12
• Adverse effects in line with previous Novo Nordisk GLP-1 and
Time since randomisation (weeks)
CagriSema trials
Oral amycretin Placebo
19 Research & early development Innovation and therapeutic focus Novo Nordisk®

Drug development in diabetes and obesity is built around core


Novo Nordisk capabilities
Core Novo Nordisk capabilities Innovation through different approaches

Building a broad
Deep biology understanding pipeline
Maximise value in

>
incretin/amylin • GLP-1
biology
Maximise GLP-1 • Amylin
franchise

>
Protein/peptide development • GLP-1 • GIP

>
and engineering
• Amylin • Novel
• GLP-1
• GIP • Novel
• Novel

Efficient large-scale production


of proteins Key drivers for innovation

Speed Differentiation parameters Scalability

MoA: Mechanism of action; GIP: Gastric inhibitory polypeptide


20 Research & early development Innovation and therapeutic focus Novo Nordisk®

New standalone and tri-agonist molecule to enter phase 1 within


the next 12 months, with new concepts to follow
Expected phase 1 initiations within the next 12 months Focus areas for upcoming projects

New amylin New tri-agonist

• Phase 1 initiation expected in 2024 • Phase 1 initiation expected within next Regulating appetite and
12 months energy expenditure
• New molecule for mono-therapy provides
opportunity for weight management • Potential for improved weight loss
efficacy
• Potential for combination therapy
• Potential for improved effect on Weight maintenance
obesity related comorbidities

Lean body mass


preservation

+ + Sustained release

ILLUSTRATIVE
21 Research & early development Innovation and therapeutic focus Novo Nordisk®

Phase 1 aspiration of bringing more targets from research to


development faster is on track for 2025
Key drivers increasing number of Number of phase 1 initiations in 2020 and aspirations towards 2025
phase 1 initiations
~3x numbers of assets

Increased investments across


portfolio​

Target discovery engine delivers


targets that are relevant to human
disease

5
Leverage AI/digital capabilities
throughout drug discovery process

Early pipeline growth delivers more


phase 1 opportunities​
2020 2024 2025

Phase 1 initiations achieved Planned Aspiration

AI: Artificial intelligence


Novo Nordisk®

Closing remarks
Continue to build on core capabilities and expand
beyond with new modalities

Pipeline is expanding, driven by internal target


discovery and supported by external partnerships

Phase 1 initiation ambition of 3x is on track

JOANNA LOUISE SHARMAN-SOARES


ROBERT KITCHEN
Digital Science and Innovation
Research Centre Oxford
UK

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