American Diabetes Association 77 Scientific Sessions · Slide 1 5,05 4,10 3,50 4,72 11,82 11,82 American Diabetes Association 77th Scientific Sessions Investor and analyst event San

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American Diabetes Association 77th Scientific Sessions

Investor and analyst event

San Diego, 12 June 2017

Manato Ohara, diagnosed with type 1 diabetes Kanagawa, Japan

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Agenda

ADA 2017 investor and analyst event

1 Victoza® - LEADER - Alan Moses, SVP and Chief Medical Officer

2 Tresiba® - DEVOTE - Mads Krogsgaard Thomsen, EVP and Chief Science Officer

3 Injectable semaglutide - Peter Kurtzhals, SVP Global Research

4 Oral semaglutide - Peter Kurtzhals, SVP Global Research

5 Xultophy® 100/3.6 - DUAL VII - Robin Evers, SVP, Medical Affairs, Regulatory Affairs & Safety

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6 Discussion and Q&A

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Alan Moses SVP and Chief Medical Officer

Victoza® - LEADER

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LEADER trial design Regulatory status

LEADER data were submitted to regulatory authorities in Q4 2016 to obtain a cardiovascular indication for Victoza®


Standard of care + placebo (daily blinded injection)

Standard of care + Victoza®

(0.6-1.8 mg once daily)

0 3.5-5.0 years

9,340 patients with type 2 diabetes

Key inclusion criteria • Adults above 50 years with type 2 diabetes and

established cardiovascular disease, or above 60 years with multiple cardiovascular risk factors

• HbA1c 7.0%

CV: cardiovascular Source: Marso et al. Am Heart J 2013;166:823–30; Marso et al. N Engl J Med 2016;375:311–22.

• LEADER data were submitted to regulatory authorities in the EU and the US in order to obtain a cardiovascular indication for Victoza®

• In the US, the FDA has scheduled an Advisory Committee meeting on 20 June 2017 to discuss the proposed cardiovascular indication for Victoza®

• EU and US regulatory feedback is expected in Q3 2017

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Victoza achieved superiority for reducing MACE and also reduced all-cause mortality in the LEADER trial

1Inclusion criteria: Adults above 50 years with type 2 diabetes and established CV disease, above 60 years with multiple CV factors, HbA1C ≥ 7.0% MACE: major adverse cardiovascular events; 3-point MACE comprises cardiovascular death, non-fatal myocardial infarction and non-fatal stroke; CI: confidence interval Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. Symposium 3-CT-SY24, ADA 2016


13% reduction in 3-point MACE with Victoza® compared to placebo

Patients1 with an event (%)

Months

Hazard ratio = 0.87 95% CI (0.78;0.97)

P=0.01

Victoza® Placebo Victoza® Placebo

Months

0

5

10

15

20

0 6 12 18 24 30 36 42 48 54

15% reduction in all-cause death with Victoza® compared to placebo

CI: confidence interval Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. Symposium 3-CT-SY24, ADA 2016

Patients with an event (%)

0

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10

15

20

0 6 12 18 24 30 36 42 48 54

Hazard ratio = 0.85 95% CI (0.74;0.97)

P=0.02

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Victoza® reduced the number of CV deaths and severe hypoglycaemia events in LEADER

1Inclusion criteria: Adults above 50 years with type 2 diabetes and established CV disease, above 60 years with multiple CV factors, HbA1C ≥ 7.0% CV death: cardiovascular death; CI: confidence interval Source: Marso et al. N Engl J Med 2016;375:311–22


22% reduction in CV death with Victoza® compared to placebo

Patients1 with an event (%)

Months

Victoza® Placebo

31% reduction in severe hypoglycaemia with Victoza® compared to placebo

ERR=0.69 95% CI (0.51;0.91)

P=0.01

Mean episodes per 1000 patients

Victoza® Placebo

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30

40

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60

70

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ERR: estimated rate ratio; CI: confidence interval Source: Presented at the American Diabetes Association 77th Scientific Sessions, 359-OR, June 12 2017, San Diego, CA, USA

Months

Hazard ratio = 0.78 95% CI (0.66;0.93)

P=0.01

Mean episodes per 1,000 patients

0

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0 6 12 18 24 30 36 42 48 54

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Risk of CV death was 3.7 times higher for patients with a severe hypoglycaemic episode

Association between severe hypoglycaemia and CV death

Patients who experienced a severe hypoglycemic episode were at higher risk of CV death in the LEADER trial


• LEADER showed that patients experiencing severe hypoglyceamia were at greater risk of MACE particularly within the first week following a severe hypoglycaemic episode

• Reduced severe hypoglycaemia in LEADER contributes to, but cannot explain, the beneficial CV outcomes which are hypothesized to be related to an anti-atherosclerotic effect

• Reducing severe hypoglycemia remains a cornerstone of diabetes management

CV death: cardiovascular death; CI: confidence interval; HR: hazard ratio Source: Presented at the American Diabetes Association 77th Scientific Sessions, 359-OR, June 12 2017, San Diego, CA, USA

HR P-value

Risk of CV death after severe hypoglycaemia for all events

3.7 <0.0001

Time after event

7 days 9.6 <0.05

14 days 9.5 <0.05

30 days 12.6 <0.0001

180 days 7.0 <0.0001

365 days 2.6 <0.0001

Hazard ratio

Increased risk of CV death following a severe hypoglycaemic episode

0.5 1 2 4 8 16

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Mads Krogsgaard Thomsen

EVP and Chief Science Officer

Tresiba® - DEVOTE

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Inclusion criteria

• Adults above 50 years with type 2 diabetes and established cardiovascular disease, or above 60 years with multiple cardiovascular risk factors.

DEVOTE trial design Baseline characteristics

The DEVOTE trial was designed to investigate the CV profile of Tresiba® compared to insulin glargine U100


Insulin glargine U100 once daily (blinded vial) + standard of care

Tresiba® once daily (blinded vial) + standard of care

0

7,637 patients

with type 2 diabetes

Trial objective

• To investigate the cardiovascular safety of Tresiba®

CV: cardiovascular; IGlar U100: insulin glargine U100; CKD: chronic kidney disease * The trial was designed to conclude after at least 633 events and a total of 681 events were accrued Source: Presented at the American Diabetes Association 77th Scientific Sessions, Session 3-CT-SY22, June 12 2017, San Diego, CA, USA

Event driven trial*

Tresiba® IGlar U100

Number of patients 3,818 3,819

Sex, Male 62.8% 62.4%

Mean HbA1c 8.4% 8.4%

Mean diabetes duration (years)

16.6 16.2

Mean BMI (kg/m2) 33.6 33.6

Established CV or CKD and age ≥50 years

85.5% 84.9%

With CV risk factors and age ≥60 years

14.1% 14.8%

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The cardiovascular safety of Tresiba® was documented in the cardiovascular outcomes trial DEVOTE


Non-inferiority of Tresiba® vs insulin glargine U100 was confirmed for time to first MACE

1Inclusion criteria: patients with a history of cardiovascular or chronic kidney disease and aged ≥50 or patients with cardiovascular or chronic kidney disease risk factors and aged ≥60 CI: confidence interval; IGlar U100: insulin glargine U100 Source: Presented at the American Diabetes Association 77th Scientific Sessions, Session 3-CT-SY22, June 12 2017, San Diego, CA, USA

The hazard ratio was below 1.0 in favour of Tresiba® in the DEVOTE trial


Months

Tresiba® IGlar U100 • DEVOTE demonstrated a 9% reduction in MACE with Tresiba® relative to insulin glargine U100, with no statistically significant difference between the two treatments

• Tresiba® demonstrated a safe and well-tolerated profile consistent with previous clinical studies conducted with Tresiba®

• DEVOTE data have been submitted to regulatory authorities in the US. Regulatory feedback is expected in H1 2018

Hazard ratio = 0.91 95% CI (0.78;1.06)

P<0.001 for non-inferiority

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The hazard ratio was below 1.0 across the individual components of 3-point MACE in the DEVOTE trial


Non-fatal stroke Cardiovascular death Non-fatal

myocardial infarction

Months Months Months


HR = 0.96 95% CI (0.76; 1.21)

P=0.71


HR = 0.85 95% CI (0.68;1.06)

P=0.15

HR = 0.90 95% CI (0.65;1.23)

P=0.50

HR: hazard ratio; CI: confidence interval;MACE: major adverse cardiovascular events; 3-point MACE comprises cardiovascular death, non-fatal myocardial infarction and non-fatal stroke; IGlar U100: insulin glargine U100 Source: Presented at the American Diabetes Association 77th Scientific Sessions, 3-CT-SY22, June 12 2017, San Diego, CA, USA



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Numerical reduction in 4-point MACE in favour of Tresiba® compared to IGlar U100

Numerical reduction in all-cause death in favour of Tresiba® compared to IGlar U100

The hazard ratio was below 1.0 for 4-point MACE and all-cause death in favour of Tresiba® in the DEVOTE trial

HR: hazard ratio; MACE: major adverse cardiovascular events; 4-point MACE comprises cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and unstable angina pectoris requiring hospitalization; CI: confidence interval; IGlar U100: insulin glargine U100 Source: Presented at the American Diabetes Association 77th Scientific Sessions, 3-CT-SY22, June 12 2017, San Diego, CA, USA


Months Months

HR = 0.92 95% CI (0.80;1.05)

P=0.22

HR = 0.91 95% CI (0.76;1.11)

P=0.35


Tresiba® IGlar U100 Patients with an event (%)


0

2

4

6

8

10

12

14

0 5 10 15 20 25 30

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7.0

7.5

8.0

8.5

9.0

0 3 6 9 12 15 18 21 24 27 30

0

2

4

6

8

10

Similar mean HbA1c levels sustained throughout the DEVOTE trial

27% fewer patients in the Tresiba® treated group had a severe hypoglycaemic episode

At similar HbA1c levels, fewer patients on Tresiba® vs IGlar U100 had a severe hypoglycaemia episode in DEVOTE trial

Note: No visits between 12-24 months and no visits between 24-end of trial; ET: end of trial Source: Presented at the American Diabetes Association 77th Scientific Sessions, Session 3-CT-SY22, June 12 2017, San Diego, CA, USA


Months

OR = 0.73 95% CI (0.60;0.89)

P<0.001 for superiority

HbA1c (%)


Tresiba® IGlar U100 Proportion (%) of patients with at least one severe hypoglycaemic episode

0.0 ET

CI: confidence interval; IGlar U100: insulin glargine U100, OR: odds ratio Source: Presented at the American Diabetes Association 77th Scientific Sessions, Session 3-CT-SY22, June 12 2017, San Diego, CA, USA

4.9%

6.6%

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40% reduction in severe hypoglycaemia with Tresiba® versus IGlar U100

53% reduction in nocturnal severe hypoglycaemia with Tresiba® versus IGlar U100

Tresiba statistically significantly reduced the risk of severe hypoglycaemia compared to IGlar U100 in DEVOTE

ERR: estimated rate ratio; CI: confidence interval; IGlar U100: insulin glargine U100 Source: Presented at the American Diabetes Association 77th Scientific Sessions, Session 3-CT-SY22, June 12 2017, San Diego, CA, USA


Months Months

ERR = 0.60 95% CI (0.48;0.76)

P<0.001

ERR = 0.47 95% CI (0.31;0.73)

P<0.001

Mean episodes per patient

Tresiba® IGlar U100 Mean episodes per patient


0.00

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Hypoglycaemia event

Patients Study Hazard ratio

[95% CI]

Nocturnal confirmed

T1D

BEGIN 0.75 [0.60; 0.94]*

0.83 [0.69; 1.00]

SWITCH 1 0.64 [0.56; 0.73]*

0.75 [0.68; 0.83]*

T2D

BEGIN 0.62 [0.49; 0.78]*

0.68 [0.57; 0.82]*

SWITCH 2 0.58 [0.46; 0.74]*

0.75 [0.64; 0.89]*

Severe

T1D

BEGIN 1.12 [0.68; 1.86]

SWITCH 1 0.65 [0.48; 0.89]*

0.74 [0.61; 0.90]*

0.81 [0.42; 1.56]

T2D

SWITCH 2 0.54 [0.21; 1.42]

DEVOTE 0.49 [0.26; 0.94]*

0.60 [0.48; 0.76]*

0.0078125 0.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 40.0078125 0.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 4

0.00781250.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 40.0078125 0.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 4

0.00781250.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 4

0.00781250.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 4

0.0078125 0.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 4

0.0078125 0.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 40.00781250.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 4

0.00781250.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 4

Tresiba® hypoglycaemia results are consistent across BEGIN, SWITCH and DEVOTE trials

Favors insulin degludec

Hazard ratio [95% CI] 2 1 0.5 0.25 0.125

Favours insulin degludec

*Significant difference; †6 month data. BEGIN: nocturnal=00.01–05:59; severe=third-party assistance; SWITCH: nocturnal=severe or BG (<3.1 mmol/L) confirmed with symptoms between 00.01–05:59; severe=third-party assistance and adjudicated; DEVOTE: severe=third-party assistance and adjudicated; nocturnal severe=severe and adjudicated between 00.01–05:59. Source: Ratner et al. Diabetes Obes Metab 2013;15:175–84; Lane et al. Diabetologia 2016;59(Suppl.1):S42; Wysham et al. Diabetologia 2016;59(Suppl.1):S43; Novo Nordisk CA, 29 November 2016.

T2D

T1D

SWITCH 2

DEVOTE

0.0078125 0.015625 0.03125 0.0625 0.125 0.25 0.5 1 2 4

2 1 0.5 0.25 0.125

*Statistically significant difference; Phase 3a BEGIN: nocturnal=00.01–05:59; severe=third-party assistance; Phase 3b SWITCH: nocturnal=severe or BG (<3.1 mmol/L) confirmed with symptoms between 00.01–05:59; severe=third-party assistance and adjudicated; Phase 3b DEVOTE: severe=third-party assistance and adjudicated; nocturnal severe=severe and adjudicated between 00.01–05:59. Source: Ratner et al. Diabetes Obes Metab 2013;15:175–84; Lane et al. Diabetologia 2016;59(Suppl.1):S42; Wysham et al. Diabetologia 2016;59(Suppl.1):S43; Novo Nordisk CA, 29 November 2016.

Favours Tresiba®

Maintenance period

Full treatment period

T1D

T2D

BEGIN

DEVOTE

SWITCH 2

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KurtzhalPeter Kurtzhals

PeterSVP Global Research

Injectable semaglutide

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-1.6 -1.6 -1.5

-1.6

-1.8

-1.4 -1.5

-1.3

-0.9

-1.2

-1.4

-1.1

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-0.4

-2.0

-1.6

-1.2

-0.8

-0.4

0.00.0

-0.1

Semaglutide demonstrated a statistically significant reduction in HbA1c vs comparators in the phase 3a trials

Comparison of HbA1c lowering effect in phase 3a SUSTAIN trials

* p < 0.001; QD: once-daily; QW: once-weekly; sema: semaglutide ** SUSTAIN 1: semaglutide once-weekly versus placebo in drug-naïve subjects with type 2 diabetes; SUSTAIN 5: semaglutide once-weekly versus placebo in subjects with type 2 diabetes added on to insulin; SUSTAIN 6: semaglutide once-weekly versus placebo, added-on to their standard-of-care treatment Source: SUSTAIN 1-5: Ahmann, et al, et al. Presented at the 77th Annual Scientific Sessions of the American Diabetes Association, San Diego, USA. Poster 1080-P; SUSTAIN 6 HbA1c: Marso SP, et al. N Engl J Med 2016;375:1834–44

Baseline SUSTAIN 1

8.1% SUSTAIN 3

8.3% SUSTAIN 4

8.2% SUSTAIN 2

8.1%

Ch

an

ge i

n H

bA

1c (

%)

*

SUSTAIN 5 8.4%


Sema 1 mg Sema 0.5 mg Exenatide QW Insulin glargine QD Sitagliptin 100 mg Placebo**

SUSTAIN 6 8.7%

*

* *

*

*

* *

*

* *

*

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Semaglutide demonstrated a statistically significant reduction in weight vs comparators the the phase 3a trials

Comparison of weight reductions in phase 3a SUSTAIN trials

-4.5

-6.1 -5.6

-5.2

-6.4

-4.9

-3.7 -4.3

-1.9

-3.5 -3.7 -3.6

-1.0

-1.9

1.2

-1.4 -0.7

-7.0

-6.0

-5.0

-4.0

-3.0

-2.0

-1.0

0.0

1.0

Baseline SUSTAIN 1

92kg SUSTAIN 3

96kg SUSTAIN 4

93kg SUSTAIN 2

89kg

Ch

an

ge i

n w

eig

ht

(kg

)

-6.1

*

SUSTAIN 5 92kg



SUSTAIN 6 92kg

* *

*

*

*

*

*

*

*

*

*

* p < 0.001; QD: once-daily; QW: once-weekly; sema: semaglutide ** SUSTAIN 1: semaglutide once-weekly versus placebo in drug-naïve subjects with type 2 diabetes; SUSTAIN 5: semaglutide once-weekly versus placebo in subjects with type 2 diabetes added on to insulin; SUSTAIN 6: semaglutide once-weekly versus placebo, added-on to their standard-of-care treatment Source: SUSTAIN 1-5: Lingvay, et al. Presented at the 77th Annual Scientific Sessions of the American Diabetes Association, San Diego, USA. Oral presentation 243-OR; SUSTAIN 6: Vilsbøll, et al. Presented at the 77th Annual Scientific Sessions of the American Diabetes Association, San Diego, USA. Poster 1125-P

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54

43 41

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30 35

13

25 30

4 9 2

5

0

10

20

30

40

50

60

SUSTAIN 2

8.1%

89kg

25-56% of patients on semaglutide achieved ≥1% HbA1c reduction and weight loss ≥5% in the SUSTAIN 1–5 trials

Patients achieving HbA1c reduction ≥1% and weight loss ≥5% across SUSTAIN 1–5 clinical trials

*p<0.001 vs comparator; †p<0.001 vs semaglutide 0.5 mg ; QD: once-daily; QW: once-weekly; sema: semaglutide * * SUSTAIN 1: semaglutide once-weekly versus placebo in drug-naïve subjects with type 2 diabetes; SUSTAIN 5: semaglutide once-weekly versus placebo in subjects with type 2 diabetes added on to insulin Source: Presented at the American Diabetes Association 77th Scientific Sessions, Poster 1124-P, June 12 2017, San Diego, CA, USA

SUSTAIN 1

8.1%

92kg

SUSTAIN 3

8.3%

96kg

SUSTAIN 4

8.2%

93kg

Proportion of patients (%)

SUSTAIN 5

8.4%

92kg



Baseline

*

* *

*†

* *†

*†

*

*

HbA1c

Weight

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15

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Semaglutide produces a positive effect on atherosclerosis in mouse models which may have a positive impact on MACE


Semaglutide demonstrated a 26% reduction in MACE compared to placebo

Note: pooled data reported for both semaglutide and placebo MACE: Major adverse cardiovascular event; Confidence interval * No adjustment for multiple tests Source: Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The New England journal of medicine. 2016

In mouse models of atherosclerosis, lower levels of plaque is observed with semaglutide


Weeks

Hazard ratio = 0.74 (95% CI: 0.58;0.95)

P=0.02 for superiority*

semaglutide placebo

0

4

8

12

16

1 2 3 4

Note: Semaglutide in LDL Receptor Knock-Out Mice Comparator: Vehicle, WD mice Source: Presented at the American Diabetes Association 77th Scientific Sessions, 244-OR, June 12 2017, San Diego, CA, USA

Plaque area (%)

Comparator Sema 4µg/kg

Sema 12µg/kg

Sema 60µg/kg

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7

8

9

10

11

0 8 16 24 32 40 48 56 64 72 80 88 96 104

6

7

8

9

10

11

0

0 8 16 24 32 40 48 56 64 72 80 88 96 104

In SUSTAIN 6 patients with diabetic retinopathy events had HbA1C reductions of up to 2.5%-points after 16 weeks


Change in HbA1c (%) in overall population (N=3.297)

Change in HbA1c (%) in patients with diabetic retinopathy event (N=79)

HbA1c (%) Sema 1.0 mg Placebo 1.0 mg

Sema 0.5 mg Placebo 0.5 mg HbA1c (%) Sema 1.0 mg Placebo 1.0 mg

Sema 0.5 mg Placebo 0.5 mg

Sema: semaglutide Source: Presented at the American Diabetes Association 77th Scientific Sessions, Session Update on Cardiovascular Outcomes Trials (CVOTs); Cardiovascular Outcomes with Semaglutide in Subjects with Type 2 Diabetes Mellitus (SUSTAIN 6) – Tina Vilsbøll, June 9 2017, San Diego, CA, USA

0

Weeks Weeks

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KurtzhalPeter Kurtzhals

PeterSVP Global Research

Oral semaglutide

Slide 23

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5.5

6.0

6.5

7.0

7.5

8.0

0 2 4 6 8 10 12 14 16 18 20 22 24 26

-8.0

-6.0

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HbA1c reduction from a mean baseline of 7.9% Weight loss from a mean base line of 92 kg

Oral semaglutide demonstrated clinically relevant reductions in HbA1c and body weight in the phase 2 trial

Inclusion criteria: Type 2 diabetes; 7.0% ≤ HbA1c ≤ 9.5%; treatment with diet and exercise with or without metformin; sc: subcutaneous; sema: semaglutide


Placebo Sema 2.5 mg Sema 5 mg Sema 10 mg Sema 20 mg Sema 1 mg sc Sema 40 mg

HbA1c (%) Weight loss (kg)

0.0

Weeks Weeks

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A post-dose fasting period of ≥ 30 min results in clinically relevant semaglutide exposure

Proportion of patients achieving HbA1c levels below 7% in the phase 2 trial

With a post-dose fasting period ≥30 min oral semaglutide demonstrated relevant dose-response rates in phase 2


0

200

400

600

800

1000

15 min 30 min 60 min 120 min

AUC0-24h, Day 10

(nmol·h/L)

Note: Patients were exposed to semaglutide in combination with different water volume with dosing (50/120 mL) and duration of post-dose fasting (15/30/60/120 min) to evaluate dosing conditions. Semaglutide exposure (AUC0-24h,Day 10) was unaffected by water volume (p=0.54) AUC: Area under curve; ETR: Estimated Treatment Ratio, *p < 0.001; **p = 0.190; ***p = 0.002 Source: Presented at the American Diabetes Association 77th Scientific Sessions, Poster 1201-P, June 11 2017, San Diego, CA, USA

ETR: 1.98*

(95% CI: 1.43;2.75)

ETR: 1.25**

(95% CI: 0.90;1.73)

ETR: 1.68***

(95% CI: 1.20;2.34)

28

44

81 84 86 88 93

0

20

40

60

80

100

Placebo2.5 mg 5 mg 10 mg 20 mg 40 mg 1 mg sc

Proportion of patients (%)

SC: subcutaneous Note: oral semaglutide doses are: 2.5 mg, 5 mg, 10 mg, 20 mg, 40 mg; 1 mg sc: 1 mg semaglutide with subcutaneous injections; Oral semaglutide dosed fasting in the morning with maximum 120 mL water and 30 minutes post-dose fasting. Source: ENDO 2016; Boston, Massachusetts; April 2, 2016, session OR15-3

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Ten phase 3a trials ongoing with oral semaglutide; first trial results expected in Q1 2018


Note: Preliminary estimated timing of trials from first patient first visit (FPFV) to last patient last visit (LPLV), n = approximate number of randomised people; MACE: Major Cardiovascular Events; OAD: oral anti-diabetic

2016 2017 2018

PIONEER 1: monotherapy 26 weeks, n=704

PIONEER 2: vs empagliflozin 52 weeks, n=816

PIONEER 3: vs sitagliptin 78 weeks, n=1,860

PIONEER 4: vs liraglutide 52 weeks, n=690

PIONEER 5: moderate renal impairment 26 weeks, n=324

PIONEER 6: cardiovascular outcomes Event driven (>122 MACE), n=3,176

PIONEER 7: flexible dose escalation 52 weeks, n=500

PIONEER 8: insulin add-on 26+26 weeks, n=720

PIONEER 9: JAPAN monotherapy 52 weeks, n=230

PIONEER 10: JAPAN OAD combination 52 weeks, n=336

52 weeks extension trial

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Robin Evers SVP Medical Affairs, Regulatory Affairs & Safety

Xultophy® 100/3.6 DUAL VII

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DUAL VII phase 3b trial design Baseline characteristics

DUAL VII was designed to confirm the glycaemic efficacy of Xultophy® 100/3.6 versus basal-bolus treatment


Xultophy® IGlar

U100+IAsp

Number of patients 252 254

Weight (kg) 87.2 88.2

Mean HbA1c 8.2% 8.2%

Mean diabetes duration (years)

13.2 13.3

Mean BMI (kg/m2) 31.7 31.7

Daily insulin dose (units)

34 33

insulin glargine U100 + insulin aspart (≤4 times) + metformin

IDegLira + metformin

26 weeks

506 patients with type 2

diabetes

Randomisation (1:1)

End of treatment

Trial objective

• To confirm the efficacy of Xultophy® 100/3.6 versus basal-bolus therapy in terms of glycaemic control

BMI: Body Mass Index; IGlar U100: insulin glargine U100; IAsp: insulin aspart Key inclusion criteria: Adults with type 2 diabetes and BMI ≤40kg/m2; HbA1c 7.0-10.0% and current basal insulin therapy 20-50 units insulin glargine U100 + metformin per day Source: Presented at the American Diabetes Association 77th Scientific Sessions, 136-OR, June 10 2017, San Diego, CA, USA

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5.5

6

6.5

7

7.5

8

8.5

5.5

6.0

6.5

7.0

7.5

8.0

8.5

-2 0 2 4 6 8 10 12 14 16 18 20 22 24 26

Similar mean HbA1c levels sustained throughout the DUAL VII trial

Patients on Xultophy® 100/3.6 used less insulin units than patients on basal-bolus treatment

IGlar U100: insulin glargine U100; IAsp: insulin aspart; ETD: end of trial dose Source: Presented at the American Diabetes Association 77th Scientific Sessions, 136-OR, June 10 2017, San Diego, CA, USA


Weeks

HbA1c (%) Dose (units)

0.0 0

20

40

60

80

100

0 2 4 6 8 10 12 14 16 18 20 22 24 26

Weeks

40.4 units

84.1 units 52.3 units basal* 32.1 units bolus*

In DUAL VII Xultophy® 100/3.6 demonstrated an insulin sparing effect compared to basal-bolus treatment

* Based on observed mean values at end of trial from the safety analysis set Source: Presented at the American Diabetes Association 77th Scientific Sessions, 136-OR, June 10 2017, San Diego, CA, USA

ETD:–0.02% 95% CI (–0.16; 0.12)

p<0.0001 for non-inferiority

Xultophy® 100/3.6 IGlar U100 + IAsp Xultophy® 100/3.6 IGlar U100 + IAsp

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-2

-1

0

1

2

3

0 2 4 6 8 10 12 14 16 18 20 22 24 26

0.0

1.5

3.0

4.5

0 2 4 6 8 10 12 14 16 18 20 22 24 26

89% reduction in hypoglycaemia1 with Xultophy® 100/3.6 vs basal-bolus treatment Change in body weight over time

Xultophy® 100/3.6 demonstrated a reduction in both hypoglycaemia and weight vs basal-bolus in DUAL VII

ERR: estimated rate ratio; CI, confidence interval; IAsp, insulin aspart; IGlar U100: insulin glargine U100

1Severe or blood glucose-confirmed symptomatic hypoglycaemia Source: Presented at the American Diabetes Association 77th Scientific Sessions, 136-OR, June 10 2017, San Diego, CA, USA


Weeks Weeks

ERR = 0.11 95% CI (0.08;0.17)

p<0.0001

Number of episodes per patient

Change in body weight (kg)

–0.9 kg

+2.6 kg

0 2 4 6 8 10 12 14 16 18 20 22 24 26

Xultophy® 100/3.6 IGlar U100 + IAsp Xultophy® 100/3.6 IGlar U100 + IAsp

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0

20

40

60

80

100

38% of patients on Xultophy® 100/3.6 achieved HbA1c<7% with no hypoglycaemia and no weight gain in DUAL VII Patients achieving HbA1c <7% with no hypoglycaemia and no weight gain

NS: Not significant; * Statistically significant in favour of Xultophy®; OR: Odds ratio ; HbA1c: glycated haemoglobin A1c 1Severe or BG-confirmed symptomatic hypoglycaemia was based on hypoglycaemic episodes during a subject’s last 12 weeks of treatment BG, blood glucose; CI: confidence interval; Iasp: insulin aspart; IGlar U100: insulin glargine 100 Source: Presented at the American Diabetes Association 77th Scientific Sessions, 136-OR, June 10 2017, San Diego, CA, USA


HbA1c <7% HbA1c <7%, no hypoglycaemia1 and no weight gain

HbA1c <7%, no hypoglycaemia1

HbA1c <7%, no weight gain

66 67 58

34 38

6

43

16

Proportion of subjects (%)

Xultophy® 100/3.6 IGlar U100 + IAsp

OR: 0.91NS

OR: 4.46*

OR: 2.58*

OR: 10.39*

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Significant regulatory news flow in 2017


Project Q1 2017 Q2 2017 Q3 2017 Q4 2017

1 Study conducted in adult growth hormone disorder

Diabetes Haemophilia Growth disorders

Tresiba®

Victoza®

Once-weekly semaglutide

N9-GP

Fast-acting insulin aspart

N9-GP CHMP opinion

EU approval

Somapacitan

Concizumab

Results available Regulatory milestone

US resubmission

US regulatory decision

REAL 1 phase 3a data1

SUSTAIN 7 phase 3b data


LEADER CHMP opinion & US regulatory decision

Obesity

Semaglutide obesity Phase 2 data

√

Japan submission CHMP opinion

Japan submission


US submission DEVOTE

√

√

√

EU SWITCH approval √

CHMP: Committee for Medicinal Products for Human Use in Europe

US label update decision for SWITCH

Phase 1 data √

√

√

EU submission DEVOTE

EU regulatory decision √

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Q&A session

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Share information Investor Relations contacts

Investor contact information


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In North America:

Kasper Veje +1 609 235 8567 [email protected]

Novo Nordisk A/S Investor Relations Novo Allé, DK-2880 Bagsværd

Upcoming events

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Documents

American Diabetes Association 77 Scientific Sessions · Slide 1 5,05 4,10 3,50 4,72 11,82 11,82 American Diabetes Association 77th Scientific Sessions Investor and analyst event San