Eli Lilly And Company · NYSE:LLY
Eli Lilly And — Investor Day (December 2021)
29 slides from Eli Lilly And's investor day presentation, December 2021
Slide 1: Diabetes & Obesity
Slide 2: Safe Harbor Provision
SAFE HARBOR PROVISION Lo The presentations for Eli Lilly's investment community meeting contain 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 factors including,
Slide 3: Presenters: Ruth Gimeno and Jeff Emmick
RUTH GIMENO, PH.D. JEFF EMMICK, M.D., PH.D. Vice President, Diabetes Research Vice President, Diabetes and Clinical Investigation Product Development Lite, INVESTMENT COMMUNITY MEETING
Slide 4: Unmet Needs
UNMET NEEDS CURRENT PATIENT OUTCOMES ARE NOT ACCEPTABLE YY A >) S\ ay, . ; NaT Over 100 million people in the US have obesity Re In the US, less than 3% of people with obesity are pharmacologically treated for obesity. The economic impact associated with obesity is over $1 trillion dollars. se] Oe)
Slide 5: Disrupting disease progression in Diabetes & Obesity to improve outcomes
Disrupting disease progression in Diabetes & Obesity to improve outcomes
Slide 6: Moving Earlier in the Disease Cascade
MOVING EARLIER IN THE DISEASE CASCADE TREATING OBESITY TO REDUCE METABOLIC DISEASES AND COMPLICATIONS Y, 2 Disease Progression Disrupting disease progression in diabetes and obesity to improve outcomes Pre-Mature Metabolically Death Healthy Not for promotional use 2021 INVESTMENT COMMUNITY MEETING 6
Slide 7: Tirzepatide Clinical Development Program
TIRZEPATIDE CLINICAL DEVELOPMENT PROGRAM HARNESSING TIRZEPATIDE EFFICACY TO EXPAND ITS POTENTIAL BENEFITS FOR PATIENTS Y, 2 Type2 — Diabetes L Obesity & | Obesity- related metabolic outcomes fe, O. O- O- 2021 2022 2023 2024 Progressing trials in type 2 diabetes as well as other serious chronic disea
Slide 8: Tirzepatide Clinical Development Program
TIRZEPATIDE CLINICAL DEVELOPMENT PROGRAM HARNESSING TIRZEPATIDE EFFICACY TO EXPAND ITS POTENTIAL BENEFITS FOR PATIENTS SY, a, Type 2 Diabetes Obesity & Obesity- related metabolic outcomes 2021 2022 2023 2024 Not an outcomes study; 12D = Type 2 Diabetes; CVOT = Cardiovascular Outcomes; NASH = Non-Alc
Slide 9: Morbidity and Mortality in Obesity: Sleep Apnea
MORBIDITY AND MORTALITY IN OBESITY LEVERAGE TIRZEPATIDE’S WEIGHT LOSS TO STUDY POTENTIAL BENEFIT FOR OBSTRUCTIVE SLEEP APNEA S Y WEIGHT LOSS IMPROVES OSA OSA OPPORTUNITY 15 ( ) Obstructive Sleep Apnea (OSA) is a breathing disorder characterized by narrowing of the upper airway impairing normal venti
Slide 10: Morbidity and Mortality in Obesity: Outcomes
MORBIDITY AND MORTALITY IN OBESITY LEVERAGE TIRZEPATIDE’S WEIGHT LOSS TO PURSUE CLINICALLY MEANINGFUL OUTCOMES Y, , BENEFITS FROM SIGNIFICANT WEIGHT LOSS OBESITY OUTCOMES OPPORTUNITY EVENTS RESOLUTION/REDUCTION (.) Estimated 4 million global deaths and loss of 120 million Dyslipidemia, hypercholeste
Slide 11: Insight into Tirzepatide's Mechanism of Action
INSIGHT INTO TIRZEPATIDE’S MECHANISM OF ACTION AMBITIOUS PROGRAM OF PRECLINICAL AND CLINICAL STUDIES TO UNDERSTAND MOA Y, 2 BETA CELL FUNCTION TZP enhances first phase insulin secretion and improves beta cell function GIP potentiates insulin secretion in response to a meal WEIGHT LOSS TZP decreases
Slide 12: Clamp Disposition Index
First Phase ISR % Change from Baseline to Week 28 0 100 200 300 400 500 -20% * 298% # * 466% M-value % Change from Baseline to Week 28 0 20 40 60 80 -2% * 35% # * 63% Clamp Disposition Index % Change from Baseline to Week 28 Placebo 100 200 300 400 500 600 700 800 0 4.23% * Semaglutide 1.0mg 338% #
Slide 13: Engaging Multiple Mechanisms to Reverse Obesity
ENGAGING MULTIPLE MECHANISMS TO REVERSE OBESITY ACHIEVE BARIATRIC SURGERY-LIKE WEIGHT LOSS WITH ASSOCIATED METABOLIC BENEFITS STRONG CLINICAL PIPELINE OPPORTUNITY IN OBESITY ~4 Years & Beyond (_) Multiple opportunities to address high unmet need * tirzepatide has demonstrated impressive weight loss
Slide 14: GIP, GLP-1 and Glucagon Triple Receptor Agonist
GIP, GLP-1 AND GLUCAGON TRIPLE RECEPTOR AGONIST en Las, PHASE 1 DATA SUPPORT POTENTIAL FOR BARIATRIC SURGERY LIKE WEIGHT LOSS 12-WEEK PROOF OF CONCEPT IN T2D DIFFERENTIATED WEIGHT LOSS 3 2 mE od 23 Ede 4 353 ° SEG Dro 6 ToD as = 38 (5) -12: T 1 @ Placebo ™ Low Dose 8 15 22 29 36 43 50 57 64 71 78 85
Slide 15: Oxyntomodulin Body Weight Change from Baseline
-0.42 kg 3 12 weeks Change from Baseline 0 Body Weight (kg) -1.62 kg -3 -3.20 kg LSMean -6 -9 -7.82 kg -11.14 kg -12 ▪ -15 ▪ 1 8 15 22 29 36 43 50 57 64 71 78 85 92 99 106113 ▪ Time (day) Placebo OXM-III 1.5/3/4.5 mg OXM-III 2/4/6/8/10 mg
Slide 16: Small Molecule Oral Incretins
SMALL MOLECULE ORAL INCRETINS EXPANDING REACH OF THE GLP-1 MECHANISM FOR PATIENTS WITH DIABETES & OBESITY Y, 2 OPPORTUNITY TO EXPAND REACH LILLY’S GLP-1R NPA CO Option for patients unwilling to take an injection ©) GLP-1R NPA (LY3502970) is Lilly's most advanced oral incretin, aiming to treat both T
Slide 17: GLP-1R NPA (LY3502970)
GLP-1R NPA (LY3502970) A CONVENIENT, EASY-TO-USE ORAL INCRETIN 12-WEEK PROOF OF CONCEPT IN T2D SMALL MOLECULE: GLP-1R NPA MEAN A IN AIC [%) EAN OM NBnee Ne Kel FROM BASELINE. C OC Phase 1 data support once daily dosing with no food or 0.48 0 water restrictions 0 | |] ©) A 12-week proof of concept st
Slide 18: Weekly Basal Insulin Fc (BIF)
WEEKLY BASAL INSULIN Fc (BIF) THE NEXT FRONTIER OF BASAL INSULIN THERAPY POTENTIAL BEST-IN-CLASS WEEKLY INSULIN Changes in serum concentrations Serum concentration [% maximum] 200 iss — Glargine U100 o 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Treatment weeks BIF combines a novel single-chain variant o
Slide 19: Weekly Basal Insulin Fc: Phase 2 Results
WEEKLY BASAL INSULIN Fc (BIF) PHASE 2 RESULTS DEMONSTRATED COMPARABLE RESULTS TO INSULIN DEGLUDEC Y, 2 PHASE 2 - INSULIN-NAIVE PEOPLE WITH T2D PHASE 2 FINDINGS CO A large Phase 2 program included people with T2D [insulin 8.5 naive & basal switch] and people with T1D; degludec (DEG) 8.06 % --BIF used
Slide 20: Weekly Basal Insulin Fc: Phase 3 Program
WEEKLY BASAL INSULIN Fc (BIF) PHASE 3 PROGRAM EXPECTED TO START IN 2022 Y, 2 COMPREHENSIVE QWINT-1: Insulin Naive T2D vs glargine () The QWINT program will consist of five QWINT-2: Insulin Naive T2D vs degludec global Phase 3 registration studies in all relevant diabetes populations QWINT-3: Basal S
Slide 21: Glucose-sensing insulin transforming insulin therapy
Glucose-sensing insulin transforming insulin therapy
Slide 22: Existing Portfolio Has Established Our CV Presence
EXISTING PORTFOLIO HAS ESTABLISHED OUR CV PRESENCE FOCUSED R&D EFFORTS PROVIDE ADDITIONAL OPPORTUNITY TO LEVERAGE OUR EMERGING CV PRESENCE S Y ASCVD HEART FAILURE Unmet Need Unmet Need @ Despite wide availability of LDL-C lowering therapies, there @ Heart failure is associated with 50% mortality in
Slide 23: Cardiovascular Opportunity
CARDIOVASCULAR OPPORTUNITY NEW APPROACHES AND MODALITIES TO ADDRESS KEY UNMET MEDICAL NEED Y, 2 STRONG CLINICAL PIPELINE OPPORTUNITY IN CARDIOVASCULAR AScvD Preclinical Phase 1 Phase 2 QO ASCVD » ANGPTL3 siRNA aims to reduce CV events in subjects with high triglycerides by lowering atherogenic remna
Slide 24: ANGPTL3 siRNA (LY3561774)
ANGPTL3 siRNA (LY3561774) Dicerna ASCVD RISK REDUCTION BY LOWERING REMNANT LIPOPROTEIN PARTICLES Lilt, 12-WEEK PROOF OF CONCEPT IN SUBJECTS . ANGPTL3 siRNA WITH ELEVATED TRIGLYCERIDES a 40 ) Developed in collaboration with DICERNA to silence mRNA wn 8 * C) The GalNAc-conjugated siRNA enables specifi
Slide 25: Pipeline Catalysts and Milestones
TIRZEPATIDE NASH NME IL-2 CONJUGATE PIRTOBRUTINIB PIRTOBRUTINIB NILEX Ulcerative Colitis B-Cell Malignancies R/R CLL Combination * Commercial Collaboration TAU siRNA GGG TRI-AGONIST GBA1 GENE THERAPY TIRZEPATIDE TIRZEPATIDE Alzheimer’s Obesity Gaucher Disease Type 2 CV Outcomes Obesity ^ Rolling sub
Slide 26: Diabetes & Obesity Summary
DIABETES & OBESITY SUMMARY O Disrupting the devastating consequences of obesity and diabetes disease progression = Moving earlier in disease cascade to treat obesity to reduce metabolic diseases and complications = Ambitious new Phase 2 & 3 studies for tirzepatide for obesity outcomes, obstructive s
Slide 27: Presenters and Q&A Panel
RUTH GIMENO, PH.D. Vice President, Diabetes Research and Clinical Investigation DAN SKOVRONSKY, M.D., PH.D. Chief Scientific and Medical Officer, and President of Lilly Research Laboratories JEFF EMMICK, M.D., PH.D. Vice President, Diabetes Product Development : MIKE MASON President, Lilly Diabetes
Slide 28: Appendix
APPENDIX
Slide 29: References
REFERENCES Unmet Needs references + Decision Resource Group (version 2021) + Internal analysis of "National healthcare expenditure data” (CMS) + CecchiniM. (2018). "Use of healthcare services and expenditure in the US in 2025: The effect of obesity and morbid obesity.” PLoS One 13(11). + Barnes (201