Eli Lilly And Company · NYSE:LLY

Eli Lilly And — Technical Presentation (2012)

44 slides from Eli Lilly And's technical presentation, 2012

  1. Slide 1: Lilly Diabetes: Pipeline Update

    Lilly Diabetes: Pipeline Update Not for promotional use © 2012 Eli Lilly and Company

  2. Slide 2: Safe Harbor Provision

    Safe Harbor Provision This presentation contains forward-looking statements that are based on management's current expectations, but actual results may differ materially due to various factors. The company’s results may be affected by such factors as the risks and uncertainties in pharmaceutical res

  3. Slide 3: Lilly Diabetes: An Overview

    Lilly Diabetes: An Overview Enrique Conterno President, Lilly Diabetes Not for promotional use © 2012 Eli Lilly and Company

  4. Slide 4: Our Lilly Diabetes Pipeline: Comprehensive, Complementary, Growing

    Our Lilly Diabetes Pipeline: Comprehensive, Complementary, Growing The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated. The timeli

  5. Slide 5: LY2605541 - Novel Basal Insulin Analog

    LY2605541* - Novel Basal Insulin Analog David Kendall, M.D. *The safety and efficacy of the agent under investigation has not been established. There is no guarantee that the agent will receive regulatory approval and become commercially available for the uses being investigated. Not for promotional

  6. Slide 6: Overview of LY2605541 Discussion

    Overview of LY2605541 Discussion • Unmet Patient Need • Insulin Physiology • Lilly’s Novel Basal Insulin Analog (LY2605541) Phase II Study Results • Summary Not for promotional use © 2012 Eli Lilly and Company Lilly Diabetes 6

  7. Slide 7: Unmet Patient Need

    Unmet Patient Need “Despite 90 years of insulin use and advances in therapy for patients with diabetes, treatment remains associated with notable limitations.” — The Lancet • Further Simplicity – Consistent 24-hr coverage and once-daily dosing for all patients – Flexible dosing characteristics • Red

  8. Slide 8: LY2605541: Engineered to be large in size

    LY2605541: Engineered to be large in size LY2605541 ~26 kDa Insulin Polyethylene Lispro1 Glycol Chain2 5.8 kDa ~20 kDa Functional size2 71–98 kDa For perspective, the functional size of LY2605541 exceeds that of albumin3 (~65 kDa) Large Functional Size Alters2: 1. Humalog®, US prescribing informatio

  9. Slide 9: Physiology of Insulins

    Physiology of Insulins ENDOGENOUS INSULIN INSULIN CURRENT SWITCH TO LY2605541 HYPOTHESIS INITIATION EXOGENOUS INSULIN LY2605541 RELATIVE ACTIVITY LIVER LIVER LIVER Glucose Glucose Glucose FASTING FASTING Utilization Utilization FASTING STATE STATE Utilization STATE MUSCLE MUSCLE MUSCLE Free Fatty Ac

  10. Slide 10: Pharmacokinetics & Pharmacodynamics of LY2605541

    Pharmacokinetics & Pharmacodynamics of LY2605541 in Healthy Subjects and Patients with Type 2 Diabetes 8 Single Dose Study in Healthy Volunteers (N=42) Multi-dose study in type 2 Glucose Infusion Rate (mg/min/kg) 6 diabetes Insulin Glargine 0.5 U/kg (n=17) Insulin Glargine 0.8 U/kg (n=8) • Steady st

  11. Slide 11: LY2605541 Phase II Data

    LY2605541 Phase II Data • Phase II Study Design • Phase II Results Not for promotional use © 2012 Eli Lilly and Company Lilly Diabetes 11

  12. Slide 12: LY2605541: Phase 2 Study Design

    LY2605541: Phase 2 Study Design TYPE 1 DIABETES Patient Treatment Period (16 weeks) Population N= 137 LY2605541 LY2605541 Type 1 DM ≥ 1 yr Adult (18–65 yr) 8 weeks 8 weeks Follow-up Period HbA1c 7.0–10.5% Glargine + Mealtime Insulin Insulin Glargine Insulin Glargine Patient TYPE 2 DIABETES Populatio

  13. Slide 13: Primary Objective: Daily Mean Blood Glucose

    LY2605541: Primary Objective: Daily Mean Blood Glucose TYPE 1 DIABETES Self-Monitored Blood Glucose Profiles N=137 200 LY2605541 met statistical criteria for noninferiority and 200 Baseline Daily Mean Blood Glucose, mg/dL superiority vs insulin glargine Endpoint insulin glargine (LS mean difference

  14. Slide 14: LY2605541: Change in HbA1c

    LY2605541: Change in HbA1c TYPE 1 DIABETES Mean A1C Throughout 16-Week Mean Change in A1C Crossover Study (N=137) Over 8 Weeks LY2605541 8.0 Insulin Insulin glargine glargine LY2605541 0.0 7.8 Treatment Treatment Period 1 Period 2 -0.1 7.6 -0.2 A1C, % Change A1C, % 7.4 -0.3 7.2 -0.4 –0.4 7.0 -0.5 -0

  15. Slide 15: Primary Objective: FBG Measured by SMBG and Central Laboratory

    LY2605541: Primary Objective: FBG Measured by SMBG and Central Laboratory TYPE 2 DIABETES Insulin glargine (n = 93) LY2605541 (n = 195) 170 NS NS 160 151 147 147 150 FBG (mg/dL) 140 NS 140 129 NS 130 123 117 118 120 110 Baseline Week 12 Baseline Week 12 SMBG Central Laboratory FBG = Fasting Blood Gl

  16. Slide 16: LY2605541: Glycemic Control (Mean A1C)

    LY2605541: Glycemic Control (Mean A1C) TYPE 2 DIABETES Insulin glargine (n = 93) LY2605541 (n = 195) 9 NS 8.5 7.8 8 7.7 NS* A1C (%) 7.5 7.2 7.0 7 6.5 6 Baseline Week 12 Bergenstal et al, ADA 2012 Abstract 347-OR. In Press, Diabetes Care. *Baseline adjusted. Not for promotional use © 2012 Eli Lilly a

  17. Slide 17: LY2605541: Body Weight

    LY2605541: Body Weight TYPE 1 DIABETES Mean Weight Throughout 16-Week Mean Change in Weight Crossover Study (N=137) Over 8 Weeks LY2605541 Insulin glargine 88 Insulin glargine 1.0 0.7 LY2605541 87 86 Treatment Treatment 0.5 Change in Weight, kg Period 1 Period 2 85 Weight, kg 84 0.0 83 82 -0.5 81 80

  18. Slide 18: LY2605541: Change in Body Weight

    LY2605541: Change in Body Weight TYPE 2 DIABETES 0.6 0.31 Insulin glargine (n = 93) 0.4 LY2605541 (n = 195) 0.17 0.2 Mean Weight ∆ (kg) 0 ∆ = –0.84 p = 0.01 vs. Glargine -0.2 -0.4 -0.6 -0.45 p = 0.01 vs. baseline -0.8 -0.58 p = 0.01 vs. baseline Baseline Week 6 Week 12 Bergenstal et al, ADA 2012 Abs

  19. Slide 19: LY2605541: Hypoglycemia

    LY2605541: Hypoglycemia TYPE 1 DIABETES Relative Risk LY2605541/ Insulin Glargine Baseline Insulin Glargine LY2605541 (90% CI) Total Hypoglycemia 3.78 ± 3.92 7.36 ± 6.80 8.74 ± 7.70 1.12 (1.03, 1.23) Rate per 30 days Nocturnal Hypoglycemia 0.46 ± 1.13 1.13 ± 1.42 0.88 ± 1.22 0.75 (0.62, 0.90) Rate p

  20. Slide 20: LY2605541: Hypoglycemia During Weeks

    LY2605541: Hypoglycemia During 12 Weeks TYPE 2 DIABETES Insulin glargine (n = 93) ΔRR = -13% LY2605541 (n = 195) NS 100 2 1.52 1.34 p = 0.16 Events/Patient/30 days 75 1.5 Incidence (%) 63.4 54.4 ΔRR = -48% 50 1 p = 0.02* p = 0.13 0.39 34.4 25.6 0.25 25 0.5 0 0 Total Nocturnal Total Nocturnal Bergens

  21. Slide 21: Time in Hypoglycemia as Measured by CGM

    LY2605541: Time in Hypoglycemia (Blood Glucose ≤ 70 mg/dL) as Measured by Continuous Glucose Monitoring TYPE 2 DIABETES P < 0.01 83 100 Insulin glargine (n=25) Time with Glucose ≤70 mg/dl (Minutes) LY2605541 (n=51) 90 80 NS P = 0.02 70 60 42 38 50 NS 29 40 25 22 30 20 10 11 10 0 Baseline Week 12 Bas

  22. Slide 22: Disinhibition of Lipolysis May Increase Triglyceride Levels

    LY2605541: (Hypothesis) When Switching to LY2605541, Disinhibition of Lipolysis May Lead to Increased Triglyceride Levels ENDOGENOUS INSULIN CURRENT LY2605541 HYPOTHESIS EXOGENOUS INSULIN DISTRIBUTION RELATIVE INSULIN SWITCH TO INITIATION LY2605541 LIPOGENESIS LIPOGENESIS LIPOLYSIS LIPOLYSIS FAT CEL

  23. Slide 23: LY2605541: Lipid and Liver Enzyme Values

    LY2605541: Lipid and Liver Enzyme Values TYPE 1 DIABETES After 8 Wks After 8 Wks LS Mean Difference of Insulin Glargine LY2605541 Change from Baseline p- Baseline Treatment Treatment (90% CI) Value HDL-cholesterol, mg/dL 60 ± 2 59 ± 2 54 ± 2 -5 (-7, -3) <.001 LDL-cholesterol, mg/dL 96 ± 3 92 ± 3 102

  24. Slide 24: LY2605541: Lipid and Liver Enzyme Values

    LY2605541: Lipid and Liver Enzyme Values TYPE 2 DIABETES LS Mean After 12 Wks Difference of Insulin Insulin After 12 Wks Change from Glargine Glargine LY2605541 LY2605541 Baseline P Baseline Treatment Baseline Treatment (90% CI) Value HDL-cholesterol, mg/dL 49 ± 2 50 ± 2 48 ± 1 48 ± 1 1 (-1, 3) 0.36

  25. Slide 25: Phase III Design & Summary

    Phase III Design & Summary Not for promotional use © 2012 Eli Lilly and Company Lilly Diabetes 25

  26. Slide 26: Large Phase III Program (IMAGINE) Underway

    Large Phase III Program (IMAGINE) Underway • Partnering with Boehringer Ingelheim on comprehensive Phase III clinical trial program • Five Pivotal Studies in Type 1 and Type 2 Patients currently enrolling approximately 5,000 patients • Treat-to-Target with Glycemic Control as Primary Endpoint • 3 St

  27. Slide 27: Summary

    Summary • LY2605541 is a novel basal insulin analog with a long, flat pharmacodynamic profile • Improved glycemic control • Results of the type 1 diabetes study showed that LY2605541 was associated with greater improvements in mean blood glucose and A1c as compared to insulin glargine • In the type

  28. Slide 28: Dulaglutide: Investigational GLP-1 Analog

    Dulaglutide*: Investigational GLP-1 Analog Mary Jane Geiger, M.D., Ph.D., FACP *The safety and efficacy of the agent under investigation has not been established. There is no guarantee that the agent will receive regulatory approval and become commercially available for the uses being investigated.

  29. Slide 29: Today's Overview

    Today’s Overview A look at dulaglutide, Lilly’s investigational, once weekly GLP-1 analog Past • Previous Phase II results Present • What is Ambulatory Blood Pressure Monitoring? • Why an Ambulatory Blood Pressure Monitoring Study? • Dulaglutide’s Effect on Ambulatory Blood Pressure & Heart Rate Fut

  30. Slide 30: Dulaglutide: A Recombinant GLP-1 Fc Fusion Protein

    Dulaglutide: A Recombinant GLP-1 Fc Fusion Protein • Dulaglutide is a recombinant fusion protein linking a human GLP-1 peptide analog and a variant of a human IgG4 Fc fragment GLP-1 peptide • Dulaglutide was engineered for: Linker peptide – Duration of pharmacodynamic activity Modified IgG4 – DPP-IV

  31. Slide 31: Overview of Two Prior Phase II Trials

    Overview of Two Prior Phase II Trials Two Glycemic Endpoint Trials • Significant dose dependent reductions in A1c and fasting glucose with dulaglutide compared with placebo • Dose dependent reductions in body weight with dulaglutide • Safety findings on dulaglutide - Low incidence of nausea/vomiting

  32. Slide 32: Phase II Trial: Dulaglutide's Effect on Ambulatory Blood Pressure

    Phase II Trial: Dulaglutide’s Effect on Ambulatory Blood Pressure and Heart Rate in Patients with Type 2 Diabetes Not for promotional use © 2012 Eli Lilly and Company Lilly Diabetes 32

  33. Slide 33: What is Ambulatory Blood Pressure Monitoring?

    What is Ambulatory Blood Pressure Monitoring? • Ambulatory blood pressure monitoring (ABPM) is an automated technique in which blood pressure (BP) is recorded over an extended period of time, typically 24 hours • BP is recorded every 15 to 30 N Engl J Med 2006;354:2368-74. minutes on a workday • Abo

  34. Slide 34: Why an Ambulatory Blood Pressure Study?

    Why an Ambulatory Blood Pressure Study? • Studies1,2 have shown that GLP-1 analogs may be associated with reductions in systolic blood pressure (SBP) and small increases in heart rate (HR). These findings are based on clinic vital sign measurements. • ABPM enables an evaluation of the duration of ac

  35. Slide 35: Dulaglutide's Phase II ABPM Study Design

    Dulaglutide’s Phase II ABPM Study Design Multicenter, randomized, double blind, placebo (PBO) controlled, 26-week study in patients with Type 2 diabetes on ≥ 1 oral antihyperglycemic medications (OAM) (N=755) Safety Follow-up Treatment Period Period Dula 0.75 mg + OAM (N=254) Primary Objective Dula

  36. Slide 36: Study Objectives

    Study Objectives Primary Objective • To demonstrate that changes from baseline in mean 24-hour systolic blood pressure (SBP) of dulaglutide 0.75 mg and 1.5 mg doses are noninferior (NI) to PBO at 16 weeks, as measured by ABPM using a NI margin of 3 mmHg Secondary Objectives • To examine the effects

  37. Slide 37: Mean Systolic Blood Pressure, Change from Baseline

    Mean 24 Systolic Blood Pressure, Change from Baseline -2.79 (-4.58, -1.00)** -2.66 (-4.53, -0.79)* 2 *p=0.002 -1.07 (-2.83, 0.68) -1.71 (-3.54, 0.12) **p<0.001 24-hr SBP, Change from Baseline 1 (mmHg, LSMean ± SE) 0 -1 Placebo -2 Dula 0.75 mg Dula 1.5 mg -3 -4 -5 Week 16 Week 26 ITT population. MMRM

  38. Slide 38: Mean Diastolic Blood Pressure, Change from Baseline

    Mean 24 Diastolic Blood Pressure, Change from Baseline 1.5 0.32 (-0.80, 1.43) 0.50 (-0.68, 1.68) 24-hr DBP, Change from Baseline 1.0 0.42 (-0.67, 1.52) 0.16 (-1.00, 1.31) (mmHg, LSMean ± SE) 0.5 0 Placebo Dula 0.75 mg -0.5 Dula 1.5 mg -1.0 -1.5 Week 16 Week 26 ITT population. MMRM analysis. LSMean =

  39. Slide 39: Mean Heart Rate, Change from Baseline

    Mean 24 Heart Rate, Change from Baseline 6 2.84 (1.52, 4.16) 3.50 (2.10, 4.91) 24-hr HR, Change from Baseline 24-hr HR, Change from Baseline 5 1.62 (0.32, 2.92) LSMean ± SE) (bpm, LSMean ± SE) 4 1.26 (-0.13, 2.64) 3 Placebo 2 Dula 0.75 mg Dula 1.5 mg (bpm, 1 0 Week 16 Week 26 ITT population. MMRM an

  40. Slide 40: HbA1c, Change from Baseline

    HbA1c, Change from Baseline Baseline A1c = 7.9% overall Week 16 Week 26 0.0 HbA1c, Change from Baseline -0.2 (%, LSMean ± SE) -0.4 Placebo Dula 0.75 mg -0.6 Dula 1.5 mg -0.8 -1.0 * -1.2 * *‡ -1.4 Week 16 * † Week 26 *p<0.001 vs. PBO †p=0.054 Dula 1.5 mg vs. Dula 0.75 mg ITT population. MMRM analysis

  41. Slide 41: TEAEs reported in ≥5% of Patients in Any Group

    TEAEs reported in ≥5% of Patients in Any Group Dulaglutide Dulaglutide Placebo 0.75 mg 1.5 mg Adverse Event (N=250) (N=254) (N=251) n (%) n (%) n (%) Any TEAE 162 (64.8) 156 (61.4) 160 (63.7) Diarrhea 19 (7.6) 23 (9.1) 31 (12.4) Headache 24 (9.6) 21 (8.3) 25 (10.0) Nausea 15 (6.0) 18 (7.1) 34 (13.5)

  42. Slide 42: Phase II ABPM Study Conclusions

    Phase II ABPM Study Conclusions • This is the first large, prospective, randomized trial using ABPM to assess long-term effects of a GLP-1 analog (dulaglutide) on blood pressure and heart rate • The primary objective of the study was met: – Both doses of dulaglutide were noninferior to placebo for s

  43. Slide 43: Phase III Development Program

    Phase III Development Program • Five pivotal studies, AWARD 1 – 5, fully enrolled • Long-term Phase III cardiovascular outcome study, REWIND, currently enrolling patients • If Phase III trials are successful, Lilly could submit to regulators as early as 2013 Estimated Trial Study Description Complet

  44. Slide 44: Questions & Answers

    Questions & Answers Not for promotional use © 2012 Eli Lilly and Company

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