#1novo nordisk - a focused healthcare company R&D investor presentation 19 June 2020 novo nordisk#2Agenda 2 R&D investor presentation Introduction Once-weekly insulin Non-alcoholic steatohepatitis Cardiovascular disease Obesity Closing remarks Karsten Munk Knudsen, CFO Martin Lange, SVP, Global Development Martin Lange, SVP, Global Development Marcus Schindler, SVP, Global Drug Discovery Mads Krogsgaard Thomsen, CSO Karsten Munk Knudsen, CFO#3Forward-looking statements R&D investor presentation 3 Novo Nordisk's reports filed with or furnished to the US Securities and Exchange Commission (SEC), including this presentation as well as the company's statutory Annual Report 2019 and Form 20-F, which are both expected to be filed with the SEC in February 2020 in continuation of the publication of the Annual Report 2019, 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, 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, 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, and failure to maintain a culture of compliance. 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 presentation, reference is made to the overview of risk factors in 'Managing risks to protect value' on pp 33-35 of the Annual Report 2019. 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 presentation, whether as a result of new information, future events or otherwise. Important drug information Victoza® is approved for the management of type 2 diabetes only • SaxendaⓇ is approved in the USA and the EU for the treatment of obesity only novo nordisk#4Purpose and sustainability کے ༢ Commercial execution Strategic aspirations 2025 • • Being respected for adding value to society . Progress towards zero environmental impact Ensure distinct core capabilities and evolve culture • Strengthen Diabetes leadership - aim at global value market share of more than 1/3 Strengthen Obesity leadership and more than double current sales¹ • Secure a sustained growth outlook for Biopharm Financials Innovation and therapeutic focus R&D investor presentation • • • Further raise the innovation-bar for diabetes treatment Develop a leading portfolio of superior treatment solutions for obesity Strengthen and progress the Biopharm 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 USA² 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 Based on reported sales in 2019, 2 From 2015 to 2022. IO: International Operatons; CVD: Cardiovascular disease; NASH: Non-alcoholic steatohepatitis; CKD: Chronic kidney disease.#5Current COVID-19 status R&D investor presentation 5 Novo Nordisk status across the value chain Gradual 'return to normal' across regions Production All manufacturing sites operating Medicines available to patients worldwide R&D Commercial • • • • Continuation of on-going clinical trials Trial recruitment negatively impacted, but gradually improving Initiation of some new trials Majority of Novo Nordisk medicines used for chronic treatment Fewer patients initiating (new) treatment Increased Rx duration and stocking resulting in favourable timing effect - but gradual reversal expected F2F: face-to-face; EMEA: Europe, Middle East and Africa; Row: Rest of World International Operations North America Operations • China approaching pre COVID-19 EMEA and ROW cautiously opening up ~50% of affiliates with some F2F interaction with doctors US status varies greatly per state ~70% of sales force partially back in the field Canada cautiously opening up novo nordisk#6US NBRX data show early signs of recovery '000 20 15 10 5 US basal insulin NBRx count in recent 6 months '000 18 16 15.4 14 12 1.12.19 1.1.20 1.2.20 1.3.20 1.4.20 1.5.20 Basaglar Lantus Toujeo TresibaⓇ Levemir® TresibaⓇ decrease of -26% since 13 Mar 2020 7.8 5.6 4.6 2.0 US injectable GLP-1 NBRX count in recent 6 months 8 4 O % 6 + N 10 R&D investor presentation 6 '000 2.0 12.7 1.6 2 0 1.12.19 1.1.20 1.2.20 1.3.20 1.4.20 1.5.20 9.1 1.2. US obesity NBRx count in recent 6 months 1.1 0.6 0.8 3.4 0.4 1.6 0.0 1.12.19 1.1.20 1.2.20 1.3.20 1.4.201 1.5.20 SaxendaⓇ Qsymia Contrave Belviq Other injectable GLP-1s OzempicⓇ Trulicity Victoza® NN inj. GLP-1 NN inj. GLP-1 decrease of Source: US weekly 1x1 NBRX (Xponent, Diabetes 22 May 2020, Obesity 15 May 2020) -20% since 13 Mar 2020 NN Obesity decrease of -28% since 13 Mar 2020 novo nordisk#7R&D investor presentation Early RybelsusⓇ uptake further supports GLP-1 NBRX and TRX market leadership in the US Weekly NBRX share 70% 60% 50% 40% 30% 20% 10% 0% Apr 2019 USA GLP-1 TRX market size and market share USA GLP-1 NBRx market share NN GLP-1 - OzempicⓇ dulaglutide RybelsusⓇ VictozaⓇ TRX volume (million) 2.0 57.3% 1.5 36.2% 1.0 35.7% Source: NBRX-IQVIA Xponent, week ending 29 May 2020 NBRX: New-to-brand prescriptions 13.4% 0.5 8.2% 0.0 May 2020 Apr 2019 - NN GLP-1 - 7 OzempicⓇ dulaglutide - RybelsusⓇ VictozaⓇ TRX share Source: TRX volume is based on monthly data through April 2020; TBRX-IQVIA Xponent, week ending 29 May 2020 TRX: Total prescriptions 60% 48.3% 50% 44.6% 40% 30% 24.9% 20% 21.3% 10% 2.1% 0% May 2020 novo nordisk#8Innovation and therapeutic focus Do + R&D investor presentation • Further raise the innovation-bar for diabetes treatment • Develop a leading portfolio of superior treatment solutions for obesity • • Strengthen and progress the Biopharm pipeline Establish presence in other serious chronic diseases focusing on CVD, NASH and CKD Martin Lange SVP Global Development CVD: Cardiovascular disease; NASH: Non-alcoholic steatohepatitis; CKD: Chronic kidney disease.#9R&D investor presentation Icodec, a once-weekly insulin, is designed to raise the innovation-bar through better control and convenience Steady state pharmacodynamic profile of insulin icodec suitable for once-weekly dosing Glucose infusion rate (mg/kg/min) 5 4 3 2 180 0 9 The phase 2 trial compared once-weekly icodec to once-daily insulin glargine Icodec (weekly) + metformin + DPP-4i (+ daily placebo) Insulin glargine U100 (daily) + metformin + DPP-4i (+weekly placebo) Primary endpoint Change in HbA1c from baseline to week 26 Secondary endpoints • Change in FPG, body weight and SMBG Weekly insulin dose during the last two weeks of treatment Hypoglycaemic episodes Icodec 247 people with type 2 diabetes Once-daily insulin treatment 2 4 Time (days) *Steady-state levels of predicted profiles based on modelled phase 1 data. 6 PK: Pharmacokinetics; FPG: Fasting plasma glucose; SMBG: Self monitoring blood glucose Note: Insulin icodec is the international non-proprietary name novo nordisk#10R&D investor presentation 10 4 5 Breakfast 6 7 * * M +90 min Lunch +90 min Evening meal mujy *Statistically significant at week 26 +90 min Bedtime 04:00 Breakfast next day PPG: Post-prandial control; FPG: Fasting plasma glucose Change Glargine U100 Icodec in HbA1c Icodec showed improved PPG control, HbA1c, and an increased number of patients reaching target in the phase 2 trial Icodec showed statistically significant post prandial control FPG (mmol/L) Icodec The proportion of patients on icodec reaching HbA1c targets was higher Icodec Glargine U100 Numerical improvement in HbA1c over 26 weeks Glargine U100 Proportion of patients 0.0 100% -0.2 -0.4 -0.6 -0.8 -1.0 -1.2 50% -1.15 25% -1.33 72% 75% 68% 49% 39% -1.4 -1.6 0% 04 8 12 16 20 26 < 7.0% ≤ 6.5% Weeks HbA1c target novo nordisk#11R&D investor presentation Once-weekly insulin icodec appeared to have a similar safety profile to once-daily insulin glargine U100 in the phase 2 trial No statistically significant difference in the number of hypoglycaemic events between icodec and glargine U100 11 Insulin icodec appeared to have a safe profile Hyoglycemia during Icodec Glargine U100 Rates of nocturnal events were low the on-treatment N E E period (%) (R) (%) (R) Hypoglycaemia alert 67 368 46 value (Level 1) (53.6) (508.89) (37.7) 148 (210.80) No cardiovascular events Severe (Level 3) or 20 clinically significant (16.0) 38 (52.55) 12 (9.8) 32 No new safety issues identified related to insulin icodec (45.58) (Level 2) hypoglycaemia Severe hypoglycaemia (Level 3) 1 1 0 (0.8) (1.38) N: number of patients with one or or more events; E: number of events; %: percentage of patients with one or more events; R: rate (number of events divided by patient years of exposure multiplied by 100) novo nordisk#12R&D investor presentation Once-weekly insulin icodec displayed a similar safety profile to once-daily insulin glargine U100 in the phase 2 trial No statistically significant difference in the number of hypoglycaemic events between icodec and glargine U100 Severe or clinically significant hypoglycemia Events Rate Forest plot Icodec 38 52.6 Glargine U100 32 45.6 0.2 0.4 0.8 1.6 3.2 6.4 Favors Sema Favors Glargine U100 1 Estimated rate ratio with the 95% confidence interval 1.09 (0.45;2.65)1 12 222 Insulin icodec appeared to have a safe profile Rates of nocturnal events were low No cardiovascular events No new safety issues identified related to insulin icodec novo nordisk#13R&D investor presentation 13 The icodec phase 3 programme will aim to demonstrate superiority on HbA₁ and time in range Insulin icodec phase 3 programme Insulin icodec versus insulin 970 people with type 2 diabetes and insulin naive glargine Icodec (open label) Insulin glargine U100 (open label) 78-week treatment 6 clinical trials enrolling approximately 4,400 people Both type 1 and type 2 diabetes Add-on to OADS, GLP-1s, switching from basal as well as switching from basal- bolus Initiation expected in Q4 2020 Details Add on to OADs and GLP-1s Primary endpoint • Change in HbA1c at week 52 Confirmatory secondary endpoint Time in target range from week 48 to week 52 Insulin icodec versus basal analogues Icodec (open label) Basal analogues (open label) 52-week treatment 1,096 people with type 2 diabetes and insulin naive Details Randomised controlled trial with real world elements Effectiveness of icodec in combination with any non-insulin anti-diabetic medicine in a primary care setting Primary endpoint Change in HbA1c at week 52 OAD: Oral anti-diabetic#14Icodec - key take aways R&D investor presentation 14 Once-weekly insulin icodec showed in the phase 2 trial numerically lower HbA1c reduction compared to glargine U100 significantly better post-prandial glucose control half of patients reached the HbA 1c target of ≤6.5% Icodec appeared to have a safe profile Icodec phase 3 programme expected to begin in Q4 2020 Aim to demonstrate superiority on HbA1c and time in range#15Innovation and therapeutic focus Do + R&D investor presentation Further raise the innovation-bar for diabetes treatment • Develop a leading portfolio of superior treatment solutions for obesity • • Strengthen and progress the Biopharm pipeline Establish presence in other serious chronic diseases focusing on CVD, NASH and CKD Martin Lange SVP Global Development CVD: Cardiovascular disease; NASH: Non-alcoholic steatohepatitis; CKD: Chronic kidney disease.#16R&D investor presentation NASH is a progressive disease with no existing treatment and low diagnosis rates The prevalence of NASH is high, yet the number of treated patients is low Milestones for NASH in 2020 and 2021 2018 2019 2020 2021 53% 19 million patients NASH Phase 2b Semaglutide NASH Phase 2b 10% 4 million patients Phase 1 37% 14 million patients From 2020 to 2030 the number of treated patients is expected to increase from 0.1 million to 1.5 million Phase 2a F4-Sema MRI-Sema Gilead: Sema combo FXR and ACC 16 NASH patients numbers are based on internal estimates. Prevalence numbers include patients with liver fibrosis stages 0, 1, 2, 3, and 4. Treated patients includes patients with liver fibrosis stages 2, 3, and 4 Gilead: Sema combo: semaglutide in loose combination with firsocostat (ACC) or cilofexor (FXR) for the treatment of NASH. ACC: acetyl-CoA carboxylase; FXR: farnesoid X receptor; MRI: magnetic resonance imaging; NASH: non-alcoholic steatohepatitis. novo nordisk#17R&D investor presentation The phase 2 trial investigated semaglutide in the treatment of NASH Semaglutide NASH phase 2 trial design Baseline characteristics Semaglutide 0.1 mg s.c. OD Sema 0.1 mg OD 0.2mg OD 0.4mg OD Sema Sema Placebo 320 patients Semaglutide 0.2 mg s.c. OD Number of patients 80 78 82 80 with NASH fibrosis stage 1, 2, 31 Age (years) 55.2 58.1 54.3 52.4 Semaglutide 0.4 mg s.c. OD Type 2 diabetes (%) 49 51 49 50 Placebo 0.1 mg, 0.2 mg or 0.4 mg Body weight 98.4 97.1 96.6 101.3 72 week treatment BMI (kg/m²) 36.1 35.6 35.2 36.1 BMI classification (%) Primary endpoint < 25 1.3 0 2.4 1.3 • Resolution of NASH and no worsening in liver fibrosis 25 to 30 18.8 23.1 20.7 17.5 30 to 35≤ 35 25.0 26.9 30.5 26.3 55.0 50.0 46.3 55.0 ¹Full list of inclusion criteria: Age 18-75; NASH activity score ≥ 4; NASH fibrosis stage 1,2,3; BMI> 25.0 kg/m2, HbA1c 10%; No other chronic liver disease other than NASH NASH: Non-alcoholic steatohepatitis; s.c.: subcutaneous; OD: once-daily 17#18R&D investor presentation 18 Semaglutide showed significant improvements in NASH resolution in phase 2 and could play a key role in preventing disease progression Semaglutide showed resolution of NASH with no worsening of fibrosis versus placebo in the phase 2 trial¹ Proportion of patients Key take-aways 100% 80% 60% 40% 22.9% 20% 66.7%* 47.3%* 46.9% * 0% Placebo 0.1 mg 0.2 mg 0.4 mg Semaglutide once-daily NASH resolution without worsening of fibrosis is one of two critical endpoints defined by the FDA and EMA² For prevention of NASH disease progression, NASH resolution could be the more relevant endpoint To date, semaglutide NASH results are arguably the most convincing NASH resolution data shown *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 1 Analysis included patients with fibrosis stage 1, 2 or 3 at baseline 2 FDA guidance on developing treatment for NASH: "Noncirrhotic Non-alcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment Guidance for Industry". EMA guidance on developing treatment for NASH: "Reflection paper on regulatory requirements for the development of medicinal products for chronic non-infectious liver diseases (PBC, PSC, NASH)" NASH: non-alcoholic steatohepatitis.0 novo nordisk#19R&D investor presentation Semaglutide showed numerical improvements in fibrosis and fewer patients had progression of fibrosis vs placebo in phase 2 Semaglutide showed numerical benefits in improvement of fibrosis without worsening of NASH¹ Proportion of patients 100% Fewer patients on semaglutide had progression Proportion of patients 30% of fibrosis compared with placebo¹ 80% 21.4% 20% 60% 47.3% 47.8% 40% 34.3% 35.9% 20% 10% 10.8% 9.4% * 5.8% 19 0% Placebo 0.1mg 0% 0.2mg 0.4mg Placebo 0.1mg 0.2mg 0.4mg Semaglutide once-daily *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. 1 Based on a complete case analysis, using subjects 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. Semaglutide once-daily novo nordisk#20R&D investor presentation 20 Semaglutide showed encouraging phase 2 data across additional important endpoints which are considered relevant by regulators Regulatory guidelines on non-invasive endpoints FDA Non-invasive, disease-specific biomarkers, and imaging modalities that assess liver stiffness or hepatic fat content are acceptable as POC study endpoints as long as the sponsor can scientifically justify them¹ Mean change in ELF from baseline at 72 weeks Relative mean change in liver stiffness³ at 72 weeks 1.0 1 0.9 0.0 -0.02 -0.1 -0.2 -0.3 * -0.4 -0.35 -0.5 * -0.44 0.8 0.7 0.75* 0.69* 0.68* -0.6 -0.7 0.6 * -0.64 -0.8 0.5 Placebo 0.1mg 0.2mg 0.4mg Placebo 0.1mg 0.2mg 0.4mg Semaglutide once-daily Semaglutide once-daily EUROPEAN MEDICINES AGENCY SCIENCE MEDICINES HEALTH Due to the slow development of fibrotic stages and the low prevalence of the disease, the difficulties for the validation of the proposed intermediate endpoints are acknowledged. Future applicants should therefore also take care that a sufficient amount of supportive evidence for long-term efficacy is available. This should consist of standard evaluations such as imaging modalities, other biomarkers (bilirubin, transaminases, but also e.g. ELF-test and other potential future biomarkers)² * statistically significant at 72 weeks (p<0.05 vs placebo). Based on the on-treatment analysis using mixed-effect model repeated measure (MMRM) 1 FDA guidance on developing treatment for NASH: "Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment Guidance for Industry", link 2 EMA guidance on developing treatment for NASH: "Reflection paper on regulatory requirements for the development of medicinal products for chronic non-infectious liver diseases (PBC, PSC, NASH)" 3 % of baseline POC: proof of concept; ELF: enhanced liver fibrosis#21NASH -key take aways R&D investor presentation 21 Semaglutide showed superior NASH resolution and fewer patients showed progression of fibrosis in the phase 2 trial Semaglutide showed improvements in several biomarkers for fibrosis such as ELF and liver stiffness in the phase 2 trial Future development of semaglutide in NASH is being assessed and discussed with regulators NASH: non-alcoholic steatohepatitis; ELF: enhanced liver fibrosis#22Innovation and therapeutic focus Do + R&D investor presentation Further raise the innovation bar for diabetes treatment • Develop a leading portfolio of superior treatment solutions for obesity • • Strengthen and progress the Biopharm pipeline Establish presence in other serious chronic diseases focusing on CVD, NASH and CKD CVD: Cardiovascular disease; NASH: Non-alcoholic steatohepatitis; CKD: Chronic kidney disease. Marcus Schindler SVP Global Drug Discovery#23R&D investor presentation Cardiovascular disease is an area with a large unmet need and strong strategic fit with our core therapy areas ~510 million people live with cardiovascular disease¹, which is estimated to increase to 530 million in 2030 ~18 million people die² each year from cardiovascular disease, an estimated 31% of all deaths globally. Of these CVD deaths, 85% are due to heart attacks and strokes Heart failure, non-fatal stroke and myocardial infarctions have large influence on quality of life 23 23 OVERLAPPING PATIENT SEGMENTS IN T2D, OBESITY AND CVD1 ILLUSTRATIVE CVD T2D Obesity Novo Nordisk's focus within CVD is on atherosclerotic cardiovascular disease and heart failure driven by the large unmet need and link to Novo Nordisk core therapeutic areas type 2 diabetes and obesity • 70% of diabetes patients die from atherosclerotic CVD • 40% of patients who are hospitalised for heart failure have diabetes 1 GBI Research Proprietary Epidemiology Database, 2018 2 www.who.int/health-topics/cardiovascular-diseases/#tab-tab_1 CVD: Cardiovascular disease; T2D: Type 2 diabetes novo nordisk#24R&D investor presentation 24 Novo Nordisk's ambition within cardiovascular disease At least one product launched between 2024-2028 targeting atherosclerotic cardiovascular disease or heart failure with a highly innovative, first to market product serving a significant unmet need in a large patient population In-licensing/acquisition of mid-stage assets STATEN BIOTECHNOLOGY CORVIDIA Tection Correcti Accelerate internal pipeline Subcutaneous PCSK9i - Phase 1 results expected Q2 2020#25R&D investor presentation CANTOS post-hoc analysis: MACE reduction only in patients whose IL-6 was lowered below median No. at risk: Placebo Canakinumab: Cumulative Incidence 0.00 0.05 0.10 0.15 0.20 0.25 HR (95% CI) Placebo On Treatment IL-6: >=1.65 ng/L 1.0 1.06 (ref) P (ref) (0.90.1.25) 0.49 On Treatment IL-6: <1.65 ng/L 0.64 (0.54,0.77) <0.0001 1 2 3 4 5 LO Follow-up (years) 1597 1501 1411 1254 635 153 1619 1617 1524 1559 1211 562 123 1371 772 211 IL1B lowering Limited IL6 effect Significant IL6 effect No CVD effect IL-6 >=1.65 ng/L IL-6 <1.65 ng/L 1411 1501 Source: Eur Heart J, Volume 39, Issue 38, 07 October 2018, Pages 3499-3507. MACE: Major adverse cardiovascular events; CVD: Cardiovascular disease; HR: Heart rate. CVD risk lowering 25#26R&D investor presentation IL-6 antibody is targeting inflammation-driven CVD in patients with CKD Pattern Recognition Moieties including NLRP3 M1 Macrophage Vascular calcification M2 Macrophage Th17 Osteoclast Cytokines, Ox LDL AGE Hypoxia Thrombin IL-1ẞ, other cytokines Treg IL-6: Interleukin 6; CVD: Cardiovascular disease; CRP: C-reactive protein Monocyte/ Macrophages Endothelial Smooth Muscle Cells Ceils IL-6 Cardiomyocytes Cardiomyocyte injury Collagen deposition/ Cardiac Fibrosis CRP, SAA, Fibrinogen 26#27R&D investor presentation Acquisition of Corvidia Therapeutics supports Novo Nordisk's ambition within cardiovascular disease 27 22 C CORVIDIA Precision Cardiovascular Therapeutics Boston, USA, based company focused on R&D and commercialisation of transformative medicines for life threatening diseases Lead compound "Ziltivekimab", an anti-IL-6 monoclonal antibody, to reduce cardiovascular risk in atherosclerotic CVD with chronic kidney disease and inflammation, currently in phase 2 development Population: Estimated 5 million patients with ASCVD have CKD and inflammation with no approved therapies Target: IL-6 axis is shown to be a central mediator of inflammatory cardiovascular risk, and specifically in CKD patients correlating with high CV event rates Compound: Advanced fully human anti-IL6 ligand mAb with potential for optimal dosing to maximize efficacy- safety profile compared to existing anti-IL6 ASCVD: atherosclerotic cardiovascular disease; mAb: monoclonal antibody; CKD: chronic kidney disease; CVD: cardiovascular disease Differentiation: Ziltivekimab has potential to become first-in-class and best in class product in a patient population with limited treatments options available#28R&D investor presentation Data from a phase 2a trial with Ziltivekimab indicate lowering of hsCRP, which is a marker for inflammation Data from a phase 2a trial in CKD stage 5 patients with inflammation Trial design of ongoing phase 2b (RESCUE) 7.5 mg Q4W (66 patients) 15 mg Q4W (66 patients) Placebo Ziltivekimab 2 mg 6 mg 20 mg N=61 12 16 16 17 % of patients CKD stage 3-5 hsCRP >2 mg/L 30 mg Q4W (66 patients) hsCRP<2.0 14.3 43.8 60.0 90.9* mg/L, Week 12 Placebo Q4W (66 patients) 24-week treatment Conclusions: Ziltivekimab effectively reduces C-reactive protein (CRP) in patients with CKD on dialysis Ziltivekimab substantially reduced markers of inflammation with a trend towards improving NT-proBNP without adversely affecting lipoprotein lipids, neutrophils or platelets SOURCE: https://www.ahajournals.org/doi/10.1161/circ.140.suppl 1.13727. Primary endpoint Reduction of inflammation measured as reduction in C- reactive protein Purpose/timing Determine a dose for a potential phase 3 CVOT Phase 2 results expected H2 2020 hsCRP: High sensitivity C-reactive protein; CKD: chronic kidney disease; NT-proBNP: N-terminal-pro hormone BNP; Q4W: intravenously every 4 weeks; CVOT: cardiovascular outcomes trial 28#29CVD - key take aways R&D investor presentation Large unmet need in CVD with 510 million patients and 18 million annual deaths Aspiration to have at least one product launched between 2024- 2028 targeting ASCVD or HF Completed acquisition of mid-stage compound, Ziltivekimab, targeting ASCVD with CKD and inflammation is a key step in delivering on Novo Nordisk CVD ambition Ziltivekimab is a fully human ligand monoclonal antibody with potential for optimised efficacy and safety profile and thereby potential to become first-in-class and best-in-class product in a patient population with limited treatments options available CVD: cardiovascular disease; ASCVD: atherosclerotic cardiovascular disease; HF: heart failure; CKD: chronic kidney disease#30Innovation and therapeutic focus Do + R&D investor presentation Further raise the innovation-bar for diabetes treatment • Develop a leading portfolio of superior treatment solutions for obesity • • Strengthen and progress the Biopharm pipeline Establish presence in other serious chronic diseases focusing on CVD, NASH and CKD Mads Krogsgaard Thomsen EVP & Chief Science Officer CVD: Cardiovascular disease; NASH: Non-alcoholic steatohepatitis; CKD: Chronic kidney disease.#31R&D investor presentation The semaglutide obesity phase 3a STEP programme has completed Phase 3 STEP programme STEP 1 Semaglutide 2.4 mg Placebo Semaglutide 1 mg 2019 Weight management n=1,961 Duration: 68 weeks 2020 STEP 2 Semaglutide 2.4 mg Placebo STEP 3 Weight management with T2D n=1,210 Duration: 68 weeks Semaglutide 2.4 mg + IBT Weight management with IBT n=611 Duration: 68 weeks Placebo + IBT Sema 2.4 mg Placebo STEP 4 Sema 2.4 mg Sema: Semaglutide; IBT: Intensive behaviour therapy Sustained weight management n=902 Duration: 68 weeks 2021 Prep for filing Regulatory review and decision 31#32R&D investor presentation Semaglutide 2.4mg showed strong weight loss across the STEP programme STEP 1 Weight mgmt STEP 3 Weight mgmt with IBT STEP 4 Sustained weight mgmt After 68 weeks After 20 weeks 105.8 107.2 96.1 Baseline body weight Sema 105.3 Change from baseline in BW (%) STEP 2 Weight mgmt with T2D 99.8 -6 -8 864202 +6%! Placebo Sema IBT Sema + IBT Placebo Sema Placebo 6.5 Sema -2.4 -5.0 -5.2 -10 * -8.8 -12 * -10.6* -14 -16 -18 * -16.9* -17.6* -18.2 *Statistically significant, based on the trial product estimand (secondary statistical approach): treatment effect if all people adhered to treatment and did not initiate other anti-obesity therapies IBT: Intensive behavioural therapy; Mgmt: Management; Sema: Semaglutide; BW: Body weight; T2D: Type 2 diabetes Placebo -3.1 32#33R&D investor presentation In the STEP 1 trial, people treated with semaglutide had a superior weight loss of up to 16.9% The pivotal STEP 1 trial showed greater than Data from STEP 1 % change in body weight 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -20 04 8 12 16 20 16% weight loss • Average age 46 Placebo: -2.4% • 74.1% women • Average BMI - 37.9 kg/m² Semaglutide: -16.9% 36 44 52 60 68 28 Time since initiation (weeks) Change in body weight in % depicts observed means since time of randomisation; trial product estimand. BMI: body mass index; SF-36: Short Form (36) Health Survey; IWQOL-lite-CT: Impact of Weight on Quality of Life-Lite questionnaire Improvements in lipid profiles as well as C- reactive protein Semaglutide improved health-related quality of life as measured by SF-36 and IWQOL-lite-CT novo nordisk 33 33#34R&D investor presentation 34 In STEP 1, 34.8% of patients treated with semaglutide reached ≥20% weight loss and reported improved quality of life versus placebo Categorical weight loss Proportion of patients Sema 2.4 mg showed a statistically significant treatment difference versus placebo in the IWQOL-Lite-CT PRO 100% 92.4% 80% 60% 40% 33.1% ■Sema 2.4 mg ■Placebo IQWOL-Lite-CT I 74.8% Physical function 54.8% Physical 34.8% Psychological 20% 11.8% Total 5.0% 2.0% 0% ≥5% ≥10% Weight loss ≥15% ≥20% ETD [95% CI] 9.43 [7.50 11.35] * 9.14 [7.31 10.96] * 10.50 [8.81 12.19] * 10.02 [8.42 11.62] * Favours placebo Favours semaglutide -202468 10 12 14 Descriptive statistic only. Based on the on-treatment data, i.e. data for subjects that are on-treatment at week 68 Sema: semaglutide * statistically significant; p-values other than physical function were not controlled for multiplicity PRO: patient reported outcome; CI: confidence interval, ETD: estimated treatment difference, IWQOL-Lite-CT: Impact of Weight on Quality of Life-lite:#35R&D investor presentation 35 In the STEP 4 trial, people on semaglutide sustained weight loss versus placebo and experienced a 18.2% weight loss after 68 weeks STEP 4 showed significantly greater weight loss post run-in than placebo Randomisation Data from STEP 4 % change in body weight 0 -2 -4 -6 -8 -10 -12 -10.5% -14 -16 -18 -20 0 4 8 12 16 20 24 28 36 Placebo: -5.2% • Semaglutide: -18.2% 44 52 60 68 Time since initiation (weeks) Change in body weight in % depicts observed means since time of randomisation; trial product estimand. BMI: body mass index • Average age 46 79% women Average BMI 38.4 kg/m² Trial highlights that obesity is a chronic disease requiring sustained treatment Improvements on a panel of cardiovascular risk markers novo nordisk#36R&D investor presentation 36 In STEP 4, 41.2% of patients treated with semaglutide reached ≥20% weight loss and reported improved quality of life versus placebo Sema 2.4 mg showed a statistically significant treatment difference versus placebo in the SF-36 patient reported outcome Categorical weight loss Proportion of patients SF-36 scores 100% | 90.5% ■Sema 2.4 mg ■ Placebo Physical functioning 80.8% Role-physical 80% 65.5% 60% 50.0% 40% 20% 41.2% 20.9% 9.8% 5.1% 0% ≥5% ≥10% Weight loss ≥15% ≥20% Descriptive statistics only. Based on the on-treatment data, i.e. data for subjects that are on- treatment at week 68 Sema: semaglutide Bodily pain General health Vitality Social functioning Role-emotional Mental health Physical component summary Mental component summary Favours placebo Favours semaglutide ETD [95% CI] * 2.46 [1.59 3.32] 1.44 [0.42 2.47] * 2.23 [-0.06 4.53] 1.86 [0.73 3.00] * 4.31 [1.61 2.41 [0.07 : 7.02] * 4.76] * 1.64 [0.52 2.76] 2.93 [1.80 4.06] 1.68 [0.64 2.72] * 3.44 [2.28 4.60] * * * -1 0 1 2 3 4 5 6 7 8 * statistically significant; p-values other than physical functioning were not controlled for multiplicity CI: confidence interval, ETD: estimated treatment difference, Sema: semaglutide, SF-36: Short Form (36) Health Survey#37R&D investor presentation 37 The safety profile for semaglutide in obesity was similar to other GLP-1s and in STEP 1, showed a similar time to 1st discontinuation Safety profile for semaglutide 2.4 mg in STEP 1 - 4 appeared safe and well tolerated Semaglutide appeared to have a safe and well-tolerated profile in the individual STEP trials GI side effects were, expectedly, the most frequent adverse events The time to first discontinuation¹ was similar for semaglutide 2.4 mg compared to placebo in STEP 1 Discontinued patients (%) 35 30 25 20 15 10 5 0 Sema 2.4 mg Placebo 1Time from randomisation to first discontinuation of trial product (temporary or permanent, whichever came first). 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 Time from randomisation (weeks) novo nordisk#38R&D investor presentation In the phase 2 trial, AM833 plus lifestyle intervention decreased weight by up to 10.8% as monotherapy after 26 weeks Dose-finding phase 2 trial for AM833 38 Weight loss for AM833 plus lifestyle intervention² at different doses with increased weight loss for higher doses³ Placebo AM833 AM833 Lira 0.6mg AM833 4.5 mg QW 2.4mg 3.0mg % change in body weight AM833 AM833 AM833 AM833 2.4 mg QW 0.3mg 1.2mg 4.5mg 0 AM833 1.2 mg QW 706 people¹ with obesity or overweight Mean baseline: 107.4 kg -2 AM833 0.6 mg QW with co-morbidities and HbA1c < 6.5% -4 AM833 0.3 mg QW Liraglutide, 3.0 mg QD -6 Placebo -8 26-week treatment -10 - 10.8% -12 0 2 4 6 Primary endpoint Change from baseline to week 26 in body weight (%) Safety 1 Obesity is defined as BMI ≥ 30.0 and overweight as BMI 27.0-29.9 kg/m² 8 10 12 14 16 18 20 22 24 26 Weeks AM833 appeared to have a safe and well-tolerated profile at all dose levels 2 Lifestyle intervention is defined as counselling for a reduced-calorie diet and increased physical activity 3 Data based on the trial product estimand novo nordisk#39R&D investor presentation 39 AM833 and semaglutide decreases appetite via two complementary mechanisms Semaglutide and AM833 are distributed to specific regions in the hypothalamus and hindbrain Semaglutide Hypothalamus AN 961 people with BMI: 27.0 39.9 kg/m² Phase 1 trial design C6: amylin 4.5 mg OW + sema 2.4 mg OW C5: amylin 2.4 mg OW + sema 2.4 mg OW C4: amylin 1.2 mg OW + sema 2.4 mg OW C3: amylin 0.6 mg OW + sema 2.4 mg Ow C2: amylin 0.3 mg OW + sema 2.4 mg OW Homeostatic signals through hypothalamus AM8331 Hindbrain AP NTS Meal-generated signals through hindbrain AP: area postrema; AN: arcuate nucleus; NTS, nucleus tractus solitarius; OW: once-weekly. ¹AM833 may act in other brain areas, including the hypothalamus, nucleus accumbens and the ventral tegmental area C1: amylin 0.16 mg OW + sema 2.4 mg OW Primary endpoint 20-week treatment Number of treatment emergent adverse events recorded from time of first dosing until follow-up 1 Inclusion criteria: Males or females of non-child-bearing potential, age ≥18-55 yrs. Atherosclerotic cardiovascular disease risk < 5%, double-blinded, placebo controlled, randomised 12:4. BMI: body-mass index; OW: once-weekly. Note: Cohort 6 has yet not finalised. novo nordisk#40R&D investor presentation 40 Phase 1 results for AM833 and semaglutide showed a 17% weight reduction after only 20 weeks % change in body weight Weight loss for different doses of AM833 and semaglutide in phase 1¹ Highlights from phase 1 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -20 0 4 8 12 Weeks AM833 0.16 mg sema 2.4 mg AM833 0.3 mg sema 2.4 mg AM833 0.6 mg sema 2.4 mg sema 2.4 mg Mean baseline: 95.1 kg 16 AM833 1.2 mg sema 2.4 mg 20 - 9.5% + 17.1% • • AM833 2.4 mg sema 2.4 mg 1 Data are observed means, 20 weeks phase 1b trial dosing increments with semaglutide (sema) and AM833 once-weekly with a 16 week dose-escalation regimen. Data is based on the trial product estimand: treatment effect if all people adhered to treatment and did not initiate other anti-obesity therapies • • 66% of people on AM833 + semaglutide 2.4 mg high dose achieved >15% weight loss in 20 weeks AM833-semaglutide 2.4 mg appeared safe and well-tolerated The level of GI disorders observed was comparable to what was generally seen for GLP-1s in monotherapy Next steps Multi-dose PK study of AM833- semaglutide 2.4 mg expected to be initiated in H2 2020 Phase 3 programme expected to begin in 2021 novo nordisk#41R&D investor presentation Progression of obesity pipeline supports the Obesity strategy and our efforts in closing the treatment gap % 0 5 10 15 20 20 Novo Nordisk's current pipeline is closing the treatment gap ILLUSTRATIVE Today's marketed treatment options Semaglutide 2.4 mg Obesity - key take aways Finalisation of STEP programme with: • Up to 17% weight loss in STEP 1 to 4 Expected filing with regulators around the turn of this year, 2020 IQWOL-lite-CT and SF-36 results supporting patient-value for obesity treatment Progressing once-weekly sc AM833 in combination with semaglutide into phase 3 25 30 Weight loss over time Pipeline Bariatric surgery IWQOL-lite-CT: Impact of Weight on Quality of Life-Lite questionnaire; SF-36: Short Form (36) Health Survey sc: subcutaneous 41 novo nordisk#42R&D investor presentation 42 We continue progressing on the strategic aspirations Purpose and sustainability ༢ Commercial execution 0 Being respected for adding value to society Progress towards zero environmental impact Ensure distinct core capabilities and evolve culture • • Patient flows impacted by COVID-19, but early signs of recovery Early RybelsusⓇ uptake further supports GLP-1 NBRX and TRX market leadership in the US While barriers in the obesity market still remain, recent readouts are important milestones to achieve the aspiration of more than doubling obesity sales¹ III Financials Innovation and therapeutic focus ⚫||||| • • • • • Once-weekly insulin progressing to phase 3 Semaglutide showed encouraging profile in NASH Strategic expansion into CVD with acquisition of Corvidia Semaglutide 2.4mg in obesity phase 3 results Promising result of AM833 and Semaglutide in obesity Deliver solid sales and operating profit growth • Deliver 6-10% sales growth in IO Transform 70% of sales in the USA² 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 Based on reported sales in 2019, 2 From 2015 to 2022. IO: International Operatons; CVD: Cardiovascular disease; NASH: Non-alcoholic steatohepatitis; CKD: Chronic kidney disease.#43R&D investor presentation 43 Thank you for watching our R&D investor presentation • • • There will now be a short intermission before the Q&A session starts at 16.00 CET Please dial in to the Q&A session now for which you have received separate dial-in details upon request We ask you to keep the camera switched off and your microphone muted, unless called upon, throughout the entire Q&A session novo nordisk