#1Commercial execution / Innovation and therapeutic focus NASH and Alzheimer's disease CMD22 CAPITAL MARKETS DAY 3 MARCH C Martin Holst Lange EVP Development Camilla Sylvest EVP Commercial Strategy and Corporate Affairs novo nordisk NADIA SADI Nadia lives with NASH Denmark#22 Commercial execution and innovation NASH and Alzheimer's disease 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 2021 and Form 20-F, which both were filed with the SEC in February 2022 in continuation of the publication of this Annual Report 2021, 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, including 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, 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 breeches, 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, failure to recruit and retain the right employees, failure to maintain a culture of compliance, epidemics, pandemics or other public health crises, 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 this Annual Report 2021, reference is made to the overview of risk factors in 'Risk management' of this Annual Report 2021. Unless required by law, Novo Nordisk is under no duty and undertakes no obligation to update or revise any forward-looking statement after the distribution of this Annual Report 2021, 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 in the USA and the EU for the treatment of obesity only CMD22 CAPITAL MARKETS DAY#33 Commercial execution and innovation NASH and Alzheimer's disease Strategic aspirations 2025 Purpose and sustainability (ESG) Commercial execution Progress towards zero environmental impact Being respected for adding value to society Being recognised as a sustainable employer Strengthen Diabetes leadership - aim at global value market share of more than 1/3 More than 25 billion DKK in Obesity sales by 2025 Secure a sustained growth outlook for Rare disease Financials Innovation and therapeutic focus OIIIIII . • • Further raise the innovation-bar for diabetes treatment Develop a leading portfolio of superior treatment solutions for obesity Strengthen and progress the Rare disease pipeline Establish presence in Other serious chronic diseases focusing on CVD, NASH and CKD Deliver solid sales and operating profit growth Deliver 6-10% sales growth in IO • Transform 70% of sales in the US1 Drive operational efficiencies across the value chain to enable investments in future growth assets • Deliver free cash flow to enable attractive capital allocation to shareholders 1 From 2015 to 2022, 70% of sales to come from products launched from 2015. IO: International Operations; CVD: Cardiovascular disease; NASH: Non-alcoholic steatohepatitis; CKD: Chronic kidney disease. Note: The strategic aspirations are not a projection of Novo Nordisk's financial outlook or expected growth. CMD22 CAPITAL MARKETS DAY Novo NordiskⓇ#44 Commercial execution and innovation NASH and Alzheimer's disease NASH and Alzheimer's disease pipeline overview Establishing a presence in NASH and AD NASH: • Address an unmet need with no currently available treatment options FGF-21 NASH Segment scope: F3-F4c Pipeline overview 2022 2023 2024 2025 Phase 2 . Aim for effect on resolution of NASH and no worsening of fibrosis, improvement in fibrosis and no NASH worsening in steatohepatitis NASH - Combination with Gilead (semaglutide 2.4 mg, FXR, ACC inhibitor) Segment scope: F4c patients Phase 2b Alzheimer's disease: • Opportunistic opportunity to slow clinical progression in people with early Alzheimer's disease Alzheimer's disease Semaglutide 2.4 mg NASH Segment scope: F2-F3 Oral semaglutide 14 mg in Alzheimer's disease NASH: Non-alcoholic hepatitis; AD: Alzheimer's Disease; F: Fibrosis stage; F4c: compensated cirrhosis; ACC: firsocostat; FXR: Cilofexor Farnesoid X inhibtor Phase 3 (Part 1) Phase 3 (Part 2) Phase 3 Novo NordiskⓇ CMD22 CAPITAL MARKETS DAY#55 Commercial execution and innovation NASH and Alzheimer's disease Novo Nordisk® In phase 2, semaglutide showed significant improvements in NASH resolution Semaglutide showed resolution of NASH with no worsening of fibrosis versus placebo in the phase 2 trial¹ Proportion of patients 100% Semaglutide showed numerical improvements in fibrosis and fewer patients had progression of fibrosis vs placebo in phase 2 trial¹ Proportion of patients with improvements in fibrosis 100% Proportion of patients with progression of fibrosis 100% 80% 60% 40% 22.9% 20% * * 47.3% 46.9% 0% Placebo 0.1 mg 0.2 mg semaglutide once-daily 80% * 66.7% 80% 60% 60% 47.3% 47.8% 40% 34.3% 35.9% 40% 21.4% 20% 20% 10.8% 9.4% * 5.8% 0% 0% 0.4 mg Placebo 0.1 mg 0.2 mg 0.4 mg Placebo 0.1 mg 0.2 mg 0.4 mg semaglutide once-daily semaglutide once-daily Note: *statistically significant at 72 weeks (p<0.05 vs placebo). Based on a complete case analysis, using people with an evaluable biopsy at end of trial. Analysis included patients with fibrosis stage 1, 2, or 3 at baseline. Data is from the semaglutide in NASH phase 2 trial. NASH: non-alcoholic steatohepatitis CMD22 CAPITAL MARKETS DAY#66 Commercial execution and innovation NASH and Alzheimer's disease Novo Nordisk® Following phase 2 data and breakthrough therapy designation, one phase 3 trial is expectedly needed for regulatory submission Phase 3a ESSENCE trial in NASH ESSENCE trial | NASH F2-F3 patients N = 1,200 Semaglutide 2.4 mg sc. OW + SoC Fixed follow-up R 2:1 Placebo + SoC Primary objectives and endpoints for Part 1 and 2 Part 1 | Improves liver histology vs placebo Two binary histology endpoints at week 72: • • Resolution of NASH and no worsening of liver fibrosis Improvement in liver fibrosis and no worsening of NASH Part 2 | Lowers the risk of liver-related clinical events vs placebo Time to first outcome (composite endpoints) at week 240: • • Histological progression to cirrhosis Death (all cause) Liver-induced MELD score ≥ 15 Structure . Part 1 Part 2 | I I I I I I 72 weeks 240 weeks Biopsy Biopsy Biopsy • Liver transplant • Hepatic decompensation events Regulatory submission expected to be based on part 1 of the trial combined with the results of the already completed phase 2 trial F: Fibrosis stage; NASH: non-alcoholic steatohepatitis; OW: once weekly; R: randomisation; SoC: standard of care (GLP-1s disallowed); MELD: Model for End-stage Liver Disease; BTD: Break-through Designation CMD22 CAPITAL MARKETS DAY#77 Commercial execution and innovation NASH and Alzheimer's disease Novo Nordisk is supporting use of non-invasive tests for diagnosis Development and adoption of non-invasive tests (NITS) Liver biopsy تت NITS Guidelines: NITS represented in guidelines Practitioners: ~80% of HCPs perform NASH diagnostics with use of various NITs, while biopsies are seldomly used NIT development: Several available NITs in clinical practice. ELF test is first prognostic tool to be granted FDA De Novo marketing authorisation Pharma companies: Embedding validation of NITs in clinical trials Novo NordiskⓇ Novo Nordisk activities supporting non-invasive tests in NASH diagnosis External Real world Linking biomarkers and liver histology to outcomes Disease understanding Consortia Collaborations with academia and other healthcare companies NN Development Phase 2 trial with FGF21 Phase 3 ESSENCE trial (part 1 and 2), incl. screening data 19 19 Validate diagnostic tests Validate tests for monitoring Validate tests for prognosis Note: FDA De Novo provides a marketing pathway to classify novel medical devices for which general controls alone, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use, but for which there is no legally marketed predicate device. NITS: Non-invasive tests; NASH: Non-alcoholic hepatitis; HCPs: Healthcare professionals; FDA: the US Food and Drug Agency; NN: Novo Nordisk; ELF: Enhanced liver fibrosis CMD22 CAPITAL MARKETS DAY#88 Commercial execution and innovation NASH and Alzheimer's disease Novo NordiskⓇ NASH patient journey underscores key barriers to overcome for Novo Nordisk to be successful ~22 million people are expected to live with NASH F2-F4c by 2030 Hurdles 25 20 20 NASH 15 prevalence 10 Low disease awareness Inadequate patient No treatment referrals¹ options No prognostic biomarker Few patients receiving diagnosis 5 0 Prevalence Diagnosed Access • Build strong presence . Create urgency to treat in NASH Build strong speciality-referral process Engage Endos, Hepas and PCPS Indicates expected invesment level . Market preparation priorities Increase diagnosis rate Momentum towards NITs in clinical practice and guidelines NITs for diagnosis, screening and monitoring NASH: Non-alcoholic steatohepatitis; Endos: endocrinologist; PCP: primary care physician; NIT: Non-invasive tests; 'Referrals and identification; Hepas: hepatologists; F: Fibrosis stage Source: Estes C, Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease, Hepatology, 2018 Evidence generation Build understanding of importance of addressing underlying cause of disease Stop clinical progression amongst physicians and payers CMD22 CAPITAL MARKETS DAY#99 Commercial execution and innovation NASH and Alzheimer's disease Novo Nordisk® Entering phase 3 development of semaglutide in Alzheimer's disease was based on a number of data points • • Å Real world evidence trials Four RWE studies show reduced risk of dementia or AD with GLP-1 • Danish registry¹ 11% lower risk of dementia per year of GLP-1 exposure TRUVEN claims database¹ 31% lower risk of dementia after >2 years of GLP-1 exposure Danish registry² 42% lower odds of dementia after GLP-1 exposure FAERS (FDA database)³ no Randomised controlled trials 53% lower risk of dementia diagnosis with liraglutide/semaglutide in NN's CVOTs in T2D4 Less decline in cerebral glucose metabolism (FDG-PET) with liraglutide in AD5 Reduced incidence of major adverse CV events in T2D with semaglutide incl. stroke6 Systemic anti-inflammatory effects with semaglutide7,8 Short-term memory improvement with liraglutide in people with obesity⁹ Reduced cognitive decline with dulaglutide in patients with T2D10 Pre-clinical studies Improved memory function with GLP-111 incl. semaglutide 12 Reduced phospho-tau accumulation¹ 13 Reduced neuroinflammation with GLP-114,15 incl. semaglutide16 Reduced atherosclerosis with liraglutide and semaglutide17 Systemic anti-inflammatory effects with semaglutide17 • 64% lower odds of AD after liraglutide exposure AD: Alzheimer's disease; CI: confidence interval; RWE: Real world evidence ¹NN data on file, Danish register: Dementia cases based on diagnosis (ICD10) or treatment (anticholinesterases, memantine) codes; TRUVEN: Dementia cases based on SNOMED ids for all diagnoses (ICD-10) or treatment (anticholinesterases, memantine); 2Wium-Andersen IK et al. Eur J Endocrinol. 2019;181(5):499-507; 3Akimoto H et al. Am J Alzheimers Dis Other Demen. 2020;35:1-11; 4Ballard et al. Presented online at the Alzheimer's Association International Conference (AAIC), 27-31 July 2020; 5Gejl M et al. Front Aging Neurosci 2016;8:108; 6Husain M et al. Diabetes Obes Metab 2020;22:442-451; 7Aroda VR et al. Diabetes Care 2019;42:1724-1732; 8Rodbard HW et al. Diabetes Care 2019;42:2272-2281; 9Vadini F et al. Int J Obes (Lond) 2020;44:1254-1263; 10Cukierman-Yaffe T et al. Lancet Neurol 2020;19:582-590 11Hansen HH et al. J Alzheimers Dis 2015;46:877-888; 12Preliminary data in NN ongoing pre-clinical studies; 13Hansen HH et al. Brain Res 2016;1634:158-170; 14 Brundin L et al. Nature Med 2018;24:900-902; 15Yun SP et al. Nature Med 2018;24:931-938; 16Secher A et al. Oral presentation at Virtual Alzheimer's Disease/Parkinson's Disease International Conference, 9-14 March 2021; 17Rakipovski G et al. JACC Basic Transl Sci 2018;3:844-857 CMD22 CAPITAL MARKETS DAY#1010 Commercial execution and innovation NASH and Alzheimer's disease Novo NordiskⓇ Evoke and evoke+ trials are ongoing with expected completion in 2025 evoke and evoke+ trials have been initiated with 1,840 patients in each trial with a total of 3,680 patients 3 mg 7 mg R 3 mg 7 mg 1:1 Week 0 4 14 mg oral semaglutide QD 14 mg placebo QD Treatment period 104 14 mg oral semaglutide QD 14 mg placebo QD ↑ Confirmatory endpoints 156 Follow-up 161 Objective To confirm superiority of oral semaglutide vs placebo on the change in cognition and function in people with early Alzheimer's disease Primary endpoint Change in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) score from baseline to end of 104 weeks of treatment Inclusion criteria • . Early Alzheimer's disease (mild cognitive impairment or mild dementia) Mini-Mental State Examination (MMSE) ≥ 22/30 Age between 55-85 years evoke + has at least 20% with small vessel pathology AD: Alzheimer's disease; QD: Once-daily; MCI: mild cognitive impairment; QD: once-daily. Note: CDR-SB ratings are utilising in six domains are summed to provide a clinical measure = Sum of Boxes. These are: memory, orientation, judgment and problem solving, community affairs, home and hobbies, personal care. CDR-SB Scores range from 0 to 18 with higher scores representing greater impairment CMD22 CAPITAL MARKETS DAY#1111 Commercial execution and innovation NASH and Alzheimer's disease AD patient journey is complex and underscores key barriers to overcome for Novo Nordisk to be successful Million Significant and growing unmet need Hurdles 80 60 Novo Nordisk® Y Early symptoms dismissed as normal ageing Complex tests and limited screening/ diagnosing skills Lack of prognostic markers and simple tests No DMT options Few patients AD receiving diagnosis 40 prevalence 20 20 • Support healthcare system preparedness Larger number of AD patients expected to enter the system May lead to significant bottle- necks and delay to patient care Market preparation priorities Increase diagnosis rate Support NITs development, e.g. blood-based/digital biomarkers Increase AD education and access to screening tools for PCPs and HCP insight 0 Prevalence Diagnosed patients ■ МСІ Eligible patients Mild dementia Note: MCI and Mild dementia in the graph are both due to AD. AD: Alzheimer's disease; QD: Once-daily; MCI: mild cognitive impairment; DMT: Disease-modifying treatment; PCP: primary care physicians; NITs: Non-invasive diagnostics; HCP: Healthcare professional Source: Alzheimer's Association report: 2020 Alzheimer's disease facts and figures, 2020 (16:391-460) Indicates expected invesment level • Evidence generation Evidence to better understand the impact of delaying disease progression role of neuroinflammation in disease progression CMD22 CAPITAL MARKETS DAY#12Commercial execution / Innovation and therapeutic focus Closing remarks NASH and Alzheimer's disease impact millions of people globally Too often the diseases go undiagnosed and have no or limited treatment options Semaglutide is investigated in specific patient populations for treatment of NASH F2-F3 and MCI and mild dementia due to Alzheimer's disease novo nordisk NADIA SADI Nadia lives with NASH Denmark