Lexicon Pharmaceuticals, Inc. · NASDAQ:LXRX
Lexicon Pharmaceuticals — Investor Day (April 2024)
143 slides from Lexicon Pharmaceuticals's investor day presentation, Apr 22, 2024
Slide 1: Lexicon 2024 Investor Day
2024 INVESTOR DAY Lexicon 2024 Investor Day April 22, 2024 PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 2: Introduction
2024 INVESTOR DAY Introduction Lonnel Coats Chief Executive Officer and Director PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 3: Forward-Looking Statements
Forward-Looking Statements • This presentation, including any oral presentation accompanying it, contains “forward-looking statements,” including statements about Lexicon’s strategy and operating performance and events or developments that we expect or anticipate will occur in the future, such as pr
Slide 4: Lexicon's Patient Focused Mission
Lexicon’s Patient Focused Mission We are a biopharmaceutical Precision Science company with a mission of Pioneering Medicine pioneering medicines that Patient Driven transform patients' lives. 4
Slide 5: Lexicon's Evolution from Mammalian Genetics to Integrated Biopharmaceutical Company
Lexicon’s Evolution from a Unique Foundation in Mammalian Genetics to a Fully Integrated Biopharmaceutical Company with an Innovative Pipeline Also from our discovery Advancing from Resulting in unique engine, a novel non- Results - multiple foundational perspective and opioid approach to drug candi
Slide 6: Leveraging Scientific Platform to Build Strong Pipeline Opportunities
Lexicon – Leveraging Scientific Platform and Expertise to Build Strong Pipeline Opportunities for Growth and Partnership Preclinical Phase 1 Phase 2 Phase 3 Registration Approved INPEFA® (Sotagliflozin) Approved for Heart Failure ZYNQUISTA™ (Sotagliflozin) Type 1 Diabetes (Preparation for NDA Resubm
Slide 7: Agenda
Agenda 9:00 – 9:10 Introduction 10:30 – 10:45 15-minute break • Agenda Overview 9:10 – 9:20 Sotagliflozin • MOA overview 10:45 – 11:25 Expert Panel – HCM, T1D, DPNP • New clinical Info • Dr. David Cherney • Dr. Sharlene Day 9:20 – 9:35 INPEFA® (sotagliflozin) – Heart Failure • Dr. Rodica Pop-Busui •
Slide 8: 2024 Investor Day
Ly Lexicon 2024 INVESTOR DAY HERE. NOW.
Slide 9: Sotagliflozin Mechanism Overview and New Clinical Information
2024 INVESTOR DAY Sotagliflozin Mechanism Overview and New Clinical Information Craig Granowitz, M.D, Ph.D. Senior Vice President and Chief Medical Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 10: Sotagliflozin's Unique Mechanism of Action
2024 INVESTOR DAY Sotagliflozin’s Unique Mechanism of Action April 2024 PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 11: Sotagliflozin Inhibits Two Targets With Important Cardiometabolic Profiles
Sotagliflozin Inhibits Two Targets With Important Cardiometabolic Profiles It is an oral inhibitor of sodium-glucose cotransporters -1 (SGLT1) and -2 (SGLT2), responsible for absorption (or reabsorption) of sodium and glucose Endothelial cells Proximal SGLT1 convoluted tubule (S1) SGLT2 is expressed
Slide 12: SGLT Expression is Dysregulated Under Pathologic Conditions
SGLT Expression is Dysregulated Under Pathologic Conditions SGLT1 elevated in: SGLT2 elevated in: Left ventricle Kidney Heart failure1-4 Diabetic nephropathy6 Dilated cardiomyopathy1 Heart failure7,8 Ischemic heart disease with/without type 2 diabetes1-3 Diabetic cardiomyopathy3,4 Small intestine Ty
Slide 13: Outcomes with SGLT1 and SGLT2 Loss of Function Mutations
Outcomes with SGLT1 and SGLT2 Loss of Function Mutations SGLT1 Loss of Function Mutation1 Genetic Variation in SGLT22 Adjusted HR Adjusted HR P Value P Value (95% CI) (95% CI) Incident 0.81 Type 2 0.98 0.006 0.018 diabetes (0.69–0.94) Diabetes (0.97-1.00) Heart Heart 0.97 0.80 0.016 failure or 0.000
Slide 14: A Differentiation Strategy for Sotagliflozin
A Differentiation Strategy for Sotagliflozin Pursue programs Focus on the Explore ways where SGLT-1 mechanistic to tie to clinical offers an advantage differentiation differentiation and SGLT-2 is of SGLT-1 not indicated 14
Slide 15: What's New on Sotagliflozin MOA from ACC Scientific Sessions 2024
2024 INVESTOR DAY What’s New on Sotagliflozin MOA from ACC Scientific Sessions 2024 PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 16: ACC 2024: Mechanistic and Clinical Findings of Sotagliflozin on Stroke
ACC 2024: Mechanistic and Clinical Findings of Sotagliflozin on Stroke Three key areas including Platelet Activation, Endothelial Cell Gene Expression & Ischemic Stroke: 1065-07: 1425-157: 1116-05: “Sotagliflozin, a first-in-class “Sotagliflozin, “Sotagliflozin reduces stroke SGLT1/2 inhibitor, inhi
Slide 17: Sotagliflozin inhibits clotting potential via platelet inhibition
1065-07: “Sotagliflozin, a first-in-class SGLT1/2 inhibitor, inhibits clotting potential in the vessel via inhibition of platelet activation, integrin activation, and aggregation in human platelets” Stanger et al. American College of Cardiology Scientific Sessions, Atlanta, GA. April 4-6, 2024. © 20
Slide 18: Sotagliflozin inhibits integrin activation and aggregation in human platelets
Sotagliflozin inhibits integrin activation and aggregation in human platelets • Washed human platelets treated with sotagliflozin were stimulated with known inflammatory agonists that lead to platelet activation and assessed for aggregation and dense granule secretion • Human whole blood incubated w
Slide 19: Sotagliflozin inhibits integrin activation and aggregation in human platelets
Sotagliflozin inhibits integrin activation and aggregation in human platelets Platelets: Percent Aggregation • Sotagliflozin inhibits platelet activation and adhesion via multiple pathways • Potential mechanism of sotagliflozin reduction in MI and stroke events 1. Stanger et al. “Sotagliflozin, a fi
Slide 20: Sotagliflozin modulated expression of glucose transport and inflammatory proteins
1425-157: “Sotagliflozin, a dual SGLT 1 and 2 inhibitor, modulated expression of glucose transport and inflammatory proteins in endothelial cells following angiotensin II” Sherratt et al. American College of Cardiology Scientific Sessions, Atlanta, GA. April 4-6, 2024 © 2024 LEXICON PHARMACEUTICALS,
Slide 21: Sotagliflozin modulated glucose transport and inflammatory proteins in endothelial cells
Sotagliflozin, a dual SGLT 1 and 2 inhibitor, modulated expression of glucose transport and inflammatory proteins in endothelial cells following angiotensin II • Primary human umbilical vein endothelial cells (HUVECs) incubated with sotagliflozin or vehicle prior to inflammatory challenge • Change i
Slide 22: Sotagliflozin reduces stroke outcomes in diabetes and CKD
1116-05: “Sotagliflozin reduces stroke outcomes in patients with diabetes and chronic kidney disease” Aggarwal et al. American College of Cardiology Scientific Sessions, Atlanta, GA. April 4-6, 2024 © 2024 LEXICON PHARMACEUTICALS, INC. ALL RIGHTS RESERVED 22
Slide 23: Sotagliflozin reduces stroke outcomes in patients with diabetes and CKD
Sotagliflozin reduces stroke outcomes in patients with diabetes and chronic kidney disease Sotagliflozin is the only SGLTi that has demonstrated significant reduction in stroke events (SCORED trial) 140 128 Sotagliflozin Placebo 120 109 100 85 85 Total Events 80 75 76 58 60 51 40 22 19 20 10 10 14 7
Slide 24: Sotagliflozin reduces stroke outcomes in patients with diabetes and CKD
Sotagliflozin reduces stroke outcomes in patients with diabetes and chronic kidney disease All-Cause Stroke Ischemic Stroke Hazard Ratio (HR): 0.66 (95% CI: 0.48; 0.91); p = 0.012 Hazard Ratio (HR): 0.68 (95% CI: 0.47; 0.99); p = 0.046 1. Aggarwal et al. “Sotagliflozin reduces stroke outcomes in pat
Slide 25: ACC 2024: Sotagliflozin – Rationale for Reductions in Ischemic Stroke
ACC 2024: Sotagliflozin – Rationale for Reductions in Ischemic Stroke Reduced platelet Reduced endothelial aggregation and cell inflammatory SCORED findings adhesion after known markers after AngII in ischemic stroke inflammatory stimuli challenge © 2024 LEXICON PHARMACEUTICALS, INC. ALL RIGHTS RESE
Slide 26: Thank you
w Lexicon 2024 INVESTOR Pharmaceuticals DAY HERE. NOW. Thank you
Slide 27: INPEFA Heart Failure
2024 INVESTOR DAY INPEFA® Heart Failure Craig Granowitz, M.D, Ph.D Senior Vice President and Chief Medical Officer Tom Garner Senior Vice President and Chief Commercial Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 28: INPEFA for Heart Failure: Clinical Program and Evidence Review
INPEFA (Sotagliflozin) for Heart Failure 01 Clinical Program and Evidence Review 02 Disease Overview 03 Unmet Need 04 Market Opportunity 05 Treatment Positioning 06 Summary and Next Steps 28
Slide 29: INPEFA Heart Failure Data Overview
2024 INVESTOR DAY INPEFA® Heart Failure Data Overview Craig Granowitz, M.D., Ph.D. Senior Vice President and Chief Medical Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 30: INPEFA Approved and Commercially Launched for Treatment of Heart Failure
INPEFA® (sotagliflozin) Approved and Commercially Launched for Treatment of Heart Failure INPEFA granted broad label in INPEFA reduced the risk of total Recently adopted guidelines heart failure (HF), across full occurrence of cardiovascular death, support use of SGLT inhibitors like range of left v
Slide 31: INPEFA Reduced CV Death and Heart Failure Events Across Patient Populations
INPEFA Reduced CV Death and Heart Failure Events Across Patient Populations Cumulative Primary Endpoint Events: Total CV Death, HHF, and Urgent HF Visit1 33% Relative Risk Reduction2 NNT = 4 patient-years3 Placebo: 76.3 events per 100 pt-years sotagliflozin: 51.0 events per 100 pt-years2 25% Relativ
Slide 32: INPEFA Reduced Hospitalization by 50% Following Hospital Discharge
INPEFA Reduced Hospitalization by 50% Following Hospital Discharge Post hoc analysis evaluated readmissions and mortality among patients who began study treatment on or before discharge from their index WHF hospitalization Placebo Events at 30 Days: HR (95% CI) = 0.49 (0.27-0.91), P = 0.023 Events a
Slide 33: Outcomes in Studies Initiating SGLT Inhibitors After Worsening Heart Failure
Outcomes in Studies Initiating SGLT Inhibitors in Patients Hospitalized after Worsening Heart Failure Episode Only one other published study in SGLT inhibitor in hospitalized patients for Heart Failure EMPULSE2* Time to All-cause death or first HF Eventb 1. Pitt, Bertram, et al. “Effect of Sotaglifl
Slide 34: INPEFA Demonstrated a Benefit in Myocardial Infarction and Stroke
INPEFA Demonstrated a Benefit in Myocardial Infarction and Stroke Not Seen with Other SGLT Inhibitors Total CV Death, Non-fatal MI, Non-fatal Stroke 11.6 10.0 Endpoint HR (95% CI) P-value Total fatal or nonfatal MI* 0.68 (0.52-0.89) 0.004 Total fatal or nonfatal stroke* 0.66 (0.48-0.91) 0.012 * Post
Slide 35: 2024 Meta-Analysis of SGLT2i Demonstrates No Effect on Stroke
2024 Meta-Analysis of Data from 11 Studies of SGLT2i in 78,607 Patients Demonstrates No Effect on Stroke Diabetes at high risk for ASCVD trials EMPA-REG OUTCOME 164/4687 (3.5) 69/2333 (3) 12.3 10.5 1.18 (0.89-1.56) CANVAS Program 176/5795 (3) 133/4347 (3.1) 7.9 9.6 0.87 (0.69-1.09) DECLARE-TIMI 58 2
Slide 36: Heart Failure Market and INPEFA Launch
2024 INVESTOR DAY INPEFA® Heart Failure Heart Failure Market and INPEFA Launch Tom Garner Senior Vice President and Chief Commercial Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 37: Heart Failure Burden in the US is Projected to Increase by 2030
The Heart Failure Burden in the United States is Projected to Increase by 2030 to 8.5M Patients and ~$70Bn in Costs US Heart Failure Cost Burden 75B Forecasted Increase $69.7B Future 60% 50B US Estimate 8.5 million with HF1 $43.6B HF Mortality2 Current US Normal 27% 1-year‡ mortality3 End-Stage Hear
Slide 38: Heart Failure Hospitalizations and Re-Admissions Drive Majority of Costs
Heart Failure Hospitalizations and Re-Admissions Drive the Majority of Related Costs and are potentially addressable with INPEFA ~25% of patients hospitalized for 17% Heart Failure Costs (Estimated) Hospitalizations are estimated to account for ~80% HF are readmitted within 30 days post discharge 2-
Slide 39: SGLT Class Including INPEFA is Positioned for Significant Growth in HF
The SGLT Class – including INPEFA – is Positioned for Significant Growth for the treatment of HF 1 of 3 SGLT1&2 ~11% >70% SGLTs are recommended 1 of 3 SGLT inhibitors Despite Strong growth of foundation of HF indicated for heart endorsement, SGLT SGLT use in heart treatment in guidelines failure – a
Slide 40: New Guidelines Recommend SGLT Inhibitors for All Heart Failure Patients
New Guidelines Recommend SGLT Inhibitors for All Heart Failure Patients AHA/ACC/HFSA 2022 Heart Failure Guidelines AHA/ACC/HFSA Joint Guidelines for the Management of Heart Failure specifically recommend SGLT inhibitors for the prevention and treatment of heart failure. The guidelines recommend that
Slide 41: ACC Expert Consensus Pathways Reference SGLT Inhibitors
ACC Expert Consensus Pathways Reference SGLT Inhibitors and Recognition of Sotagliflozin’s SGLT1 and SGLT2 Mechanism HFpEF2 HFrEF1 2023 Consensus Statement 2024 Consensus Statement "We now have evidence that both SGLT2 and SGLT1 ACC expert consensus statement highlighted the inhibitors are beneficia
Slide 42: What Customers are Telling Us about INPEFA
What Customers are Telling Us about INPEFA and its role in treatment of HF Product Promise: The INPEFA product promise resonates strongly with Cardiologists in helping HCPs to more confidently treat and prevent CV events and change the trajectory of their patients’ disease Clinical Data: INPEFA’s da
Slide 43: INPEFA Coverage Anticipated to Expand in Second Half of 2024
INPEFA Coverage Anticipated to Expand in Second Half of 2024 Current INPEFA Formulary Coverage by Channel 82% 69% 31% 22% 11% 13% 6% 5% Commercial Medicare Medicaid Health Exchange 164.1M Lives 53M Lives 77.3M Lives 20.5M Lives Covered or Better Covered or Better w/o step edit We expect both to subs
Slide 44: Sotagliflozin HCM
2024 INVESTOR DAY Sotagliflozin HCM Craig Granowitz, M.D., Ph.D. Senior Vice President and Chief Medical Officer Tom Garner Senior Vice President and Chief Commercial Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 45: Sotagliflozin HCM: Disease Overview and Regulatory Plan
2024 INVESTOR DAY Sotagliflozin HCM Disease overview, why we believe Sotagliflozin will work, mechanism review, regulatory plan Craig Granowitz, M.D., Ph.D. Senior Vice President and Chief Medical Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 46: Sotagliflozin for Hypertrophic Cardiomyopathy (HCM)
Sotagliflozin for Hypertrophic Cardiomyopathy (HCM) 01 Data Overview and Evidence Supporting Sotagliflozin in HCM 02 Clinical Trial Design 03 Disease Overview / Unmet Need 04 Treatment Landscape 05 Summary and Next Steps 46
Slide 47: Sotagliflozin Inhibits Two Targets With Important Cardiometabolic Profiles
Sotagliflozin Inhibits Two Targets With Important Cardiometabolic Profiles It is an oral inhibitor of sodium-glucose cotransporters -1 (SGLT1) and -2 (SGLT2), responsible for absorption (or reabsorption) of sodium and glucose Endothelial cells Proximal SGLT1 convoluted tubule (S1) SGLT2 is expressed
Slide 48: Sotagliflozin's Efficacy Across LVEF Points to Potential in HCM
Sotagliflozin’s Efficacy Data Across LVEF is Compelling for Heart Failure... And Points to Potential Life-Cycle Management Opportunity in HCM Treatment effect of sotagliflozin was observed in SOLOIST and SCORED patients, regardless of LVEF HR Treatment Effect vs LVEF for Primary Endpoint* • Pooled a
Slide 49: SCORED Data in Patients with LVH Without Hypertension
SCORED Data in Patients with Left Ventricular Hypertrophy without Hypertension Offer Perspective on Potential Application in Patients with HCM Sotagliflozin Reduces the Risk of Cardiovascular Events in Patients With Left Ventricular Hypertrophy Without Hypertension: A Post Hoc Analysis From SCORED P
Slide 50: FDA Feedback Supports Potential Sotagliflozin sNDA in HCM
FDA Feedback Supports Potential Sotagliflozin sNDA with Broad Label in HCM Based on Single Phase 3 Study Primary endpoint: Change from Proposed indication: Sotagliflozin is indicated to baseline in KCCQ Clinical Summary improve symptoms and physical limitations in adults Scale (CSS) score with sympt
Slide 51: Sotagliflozin HCM Commercial Rationale
2024 INVESTOR DAY Sotagliflozin HCM Commercial rationale - “Fitting in the white space between beta blockers and myosin inhibitors” Tom Garner Senior Vice President and Chief Commercial Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 52: HCM Affects ~1M Patients with Persistent Symptoms
HCM affects ~1M patients with patients suffering ongoing and persistent symptoms that negatively impact their quality of life nHCM Symptomatic 66K Patient reported symptoms1 ~30% 89% Shortness of breath 89% Tiredness or fatigue US Diagnosed 89% Lightheadedness or dizziness Prevalence HCM2 81% Flutte
Slide 53: Heart Failure is the Most Prevalent Outcome of HCM
Heart Failure is the Most Prevalent Outcome of HCM 43% have Progressive Heart Failure 17% have Atrial Fibrillation 11% experience Stroke 6% suffer Sudden Cardiac Death Maron, Barry J., et al. “Diagnosis and Evaluation of Hypertrophic Cardiomyopathy.” Journal of the American College of Cardiology, vo
Slide 54: Despite Recent Advances in HCM Treatment, Significant Needs Remain
Despite Recent Advances in HCM Treatment, Significant Opportunities and Stakeholder Needs Remain as Disease Progresses Illustrative oHCM Patient Journey Managing Symptomatic HCM Sotagliflozin Beta Blocker (BB) +/- Cardiac Myosin Surgical Calcium Channel Inhibitor Intervention / Blocker (CCB) (CMI) M
Slide 55: Needs Remain that Sotagliflozin may Address
Despite Recent Advances in HCM Treatment, Significant Opportunities and Stakeholder Needs Remain that Sotagliflozin may Address Sotagliflozin Beta Blocker (BB) +/- Cardiac Myosin Surgical Calcium Channel Inhibitor Intervention / Blocker (CCB) (CMI) Myectomy Patient HCP Payer Improve QoL with limited
Slide 56: HCM Market Poised to Grow Rapidly
HCM Market Poised to Grow Rapidly, Presenting Expanded Opportunity for Future Therapies ~510K1 Diagnosed HCM Patients Improved Diagnosis Accuracy Earlier Diagnosis ~220K New Therapies New tools for HCM Dx – 2.4x Advocacy to including cardiac Diagnosis Diagnosed Disease support family Additional imag
Slide 57: HCM - Significant Opportunity for Sotagliflozin
HCM - Significant Opportunity for Sotagliflozin • Sotagliflozin has the potential to address key unmet needs across HCM with strong scientific Broad proposed rationale indication (alone or in • Timing of potential sNDA approval could come combination) when disease awareness and unmet need is encompa
Slide 58: Zynquista (sotagliflozin) for Type 1 Diabetes
2024 INVESTOR DAY Zynquista™ (sotagliflozin) for Type 1 Diabetes Regulatory History/Market overview/Unmet need/ Next steps/Early Commercial Plan Jeff Wade President and Chief Financial Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 59: Zynquista (sotagliflozin) for Type 1 Diabetes
Zynquista™ (sotagliflozin) for Type 1 Diabetes 01 Mechanism and Historical Data Overview 02 Summary of Recent FDA Feedback / Interactions 03 Evidence of Benefits in Glycemic Control in T1D Patients with CKD 04 Market Opportunity 05 Disease Progression and Potential Treatment Positioning 06 Summary a
Slide 60: Sotagliflozin Inhibits Two Targets With Important Cardiometabolic Profiles
Sotagliflozin Inhibits Two Targets With Important Cardiometabolic Profiles It is an oral inhibitor of sodium-glucose cotransporters -1 (SGLT1) and -2 (SGLT2), responsible for absorption (or reabsorption) of sodium and glucose Proximal SGLT1 convoluted tubule (S1) SGLT2 is expressed in the SGLT2 kidn
Slide 61: Sotagliflozin Inhibits Two Targets with Important Cardiometabolic Profiles
Sotagliflozin Inhibits Two Targets with Important Cardiometabolic Profiles Histogram of KO/ Historical WT Ratio Oral Glucose Tolerance Test AUC 2SD 1SD 500 Number of KO Lines 400 Mean = 1.00 SD = 0.15 N=2747 300 200 SGLT2 MC4R 100 DPP4 SGLT1 0 0.0 0.5 1.0 1.5 2.0 Low Glucose Normalized Glucose AUC H
Slide 62: Type 1 Diabetes is Very Different from Type 2 Diabetes
Type 1 Diabetes is Very Different from Type 2 Diabetes Autoimmune Disease Absolute Insulin Deficiency Requires Intensive Glycemic Unmet Needs Go Insulin Therapy Far Beyond A1C 62
Slide 63: Glycemic Control with Insulin Alone is Difficult
Insulin is Life-Saving, But Achieving and Maintaining Glycemic Control with Insulin Alone is Difficult Underdosing Overdosing Imprecision Hyperglycemia Hypoglycemia Glucose Variability Diabetic ketoacidosis Weight gain Distress (DKA) 63
Slide 64: 75-80% of People with T1D Do Not Reach ADA Goal of A1C < 7.0%
75-80% of People with T1D Do Not Reach ADA Goal of A1C < 7.0% 100% Adults with T1D (%) 80% 60% 40% 31% ~21% ~23% 20% 13% 12% 0% < 7.0 7.0 - < 8.0 8.0 - < 9.0 9.0 - < 10.0 ≥ 10.0 A1c Ranges State of Type 1 Diabetes Management and Outcomes from the T1D Exchange in 2016–2018. Foster et al. 64
Slide 65: Glucose Variability Has Important Impact on Patients with T1D
Glucose Variability (GV) Has Important Impact on Patients with T1D Fluctuations in Daily Glucose Levels in Two Different Patients1 • Measuring A1C alone gives no information on variability1-4 • Importance of avoiding extreme hyperglycemia and dangerous hypoglycemia • Improvement in time in range sig
Slide 66: Significant Unmet Needs Remain in People with Type 1 Diabetes
Significant Unmet Needs Remain in People with Type 1 Diabetes Reducing glycemic Controlling Reaching A1C goal variability and complications such as without hyperglycemia improving time blood pressure and and hypoglycemia in range reducing heart disease Preventing downstream Preventing associated con
Slide 67: Pivotal Studies: Largest-Ever Phase 3 Program for an Oral Agent in T1D
Pivotal Studies 2,980 T1D Patients Optimized Insulin Largest-Ever Phase 3 Program for an Oral inTandem1 inTandem2 N=793 N=782 Anti-Hyperglycemic Placebo, 200 and 400 mg QD Placebo, 200 and 400 mg QD Agent in Type 1 Diabetes Global Study inTandem3 N=1,405 Placebo, 400 mg QD 67
Slide 68: Sotagliflozin Achieved Primary Endpoint Improving A1C
Sotagliflozin Achieved Primary Endpoint, Significantly Improving A1C on Top of Optimized Insulin inTandem11 inTandem22 A1C, Baseline (%) 7.5 Sotagliflozin 7.6 Sotagliflozin 7.6 7.8 Sotagliflozin 7.7 Sotagliflozin 7.7 Week 24 (%) 7.5 7.2 7.1 7.8 7.4 7.4 Placebo 200 mg 400 mg Placebo 200 mg 400 mg N=2
Slide 69: Sotagliflozin Improved Time in Range
Sotagliflozin Improved Time in Range Time Spent in Target Glucose Range – Pooled CGM Sub-study inTandem1 and inTandem2 Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg 24 h 24 h 24 h 1h 1h 1h 24 min 25 min 18 min Baseline 18 h 10 h 6h 18 h 10 h 6h 18 h 10 h 6h 3 min 12 h 3 min 12 h 33 min 12 h 33 m
Slide 70: Sotagliflozin Significantly Reduced Body Weight at Weeks 24 and 52
Sotagliflozin Significantly Reduced Body Weight at Weeks 24 and 52 inTandem1 inTandem2 2 +1.2 kg 2 +0.8 kg 1 1 +0.3 kg 0 +0.1 kg LS Mean 0 4 8 12 16 20 24 28 32 36 40 44 48 52 0 Change from 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Baseline -1 -1.6 kg* -1.9 kg -1 -1.9 kg* (kg) [SE] -1.9 kg -2 -2 -3.1 k
Slide 71: Weight Loss Primarily Consisted of Reduction in Body Fat
Weight Loss Primarily Consisted of Reduction in Body Fat Week 24 Week 52 Sotagliflozin Sotagliflozin Sotagliflozin Sotagliflozin Placebo 200 mg 400 mg Placebo 200 mg 400 mg 1 0.22 0.5 0.57 0.43 Change from Baseline (kg) 0 0.06 -0.5 -1.61 -1.63 -1 -1.94 -2.06 -1.5 -0.27 -0.55 -2 -0.39 -0.70 -2.5 Fat
Slide 72: Key Safety Measures – Severe Hypoglycemia
Key Safety Measures – Severe Hypoglycemia ≥1 positively adjudicated severe 52 Weeks1 hypoglycemia event, n (%) Sotagliflozin Sotagliflozin Placebo 200 mg 400 mg (N=526) (N=524) (N=525) inTandem1/inTandem2 39 (7.4) 30 (5.7) 23 (4.4) Pooled Analysis (%) 24 Weeks2 Sotagliflozin Placebo - 400 mg (N=703)
Slide 73: Key Safety Measures – Diabetic Ketoacidosis (DKA)
Key Safety Measures – Diabetic Ketoacidosis (DKA) Positively adjudicated DKA 52 Weeks1 event*, n (%) Placebo 200 mg 400 mg inTandem1/inTandem2 1 (0.2) 15 (2.9) 20 (3.8) Pooled Analysis (%) 24 Weeks2 inTandem3 (%) 4 (0.6) - 21 (3.0) *Positively adjudicated DKA was characterized by the adjudication co
Slide 74: DKA is a Known Risk in T1D
DKA is a Known Risk in T1D Measurement and reliance on ketones is already standard of care for DKA risk mitigation and management Occurs with absolute insulin deficiency SGLT2 inhibition increases risk of DKA in T1D (e.g. missed doses) or relative insulin • DKA, with or without SGLT2 inhibition, cau
Slide 75: DKA Risk Mitigation Strategy
DKA Risk Mitigation Strategy Consensus Strategy as published in Diabetes Care Verify early symptoms, identify conditions that may be causing ketosis,* and test for ketones The STICH protocol is a ST top the SGLT inhibitor† strategy for mitigating DKA I nject bolus insulin risk in patients with T1D C
Slide 76: Lexicon is Preparing to Resubmit NDA for T1D with CKD
Following FDA Feedback, Lexicon is Preparing to Resubmit NDA for Type 1 Diabetes with CKD • Sotagliflozin studied in largest-ever Phase 3 program for an oral agent in T1D • Since FDA filing for T1D, significant data has been generated demonstrating benefits of sotagliflozin in heart failure, MACE, a
Slide 77: Sotagliflozin Offers Important Potential Benefits for People with T1D and CKD
Sotagliflozin Offers Important Potential Benefits for People with Type 1 Diabetes and Chronic Kidney Disease (CKD) Better glucose control is Improving A1C in people particularly important in with T1D is associated with people with T1D who reduced risk of CKD have CKD progression People with T1D and
Slide 78: Better Glycemic Control is Important for People with T1D and CKD
Better Glycemic Control is Particularly Important for People with T1D Who Have Chronic Kidney Disease (CKD) Rate of eGFR decline by AER and HbA1c strata in PERL p-interaction=0.0008 0 Rate of eGFR decline (ml/min/1.73m2/year) -2 Higher Glucose in People with T1D is HbA1c≤7.5% Associated with More -4
Slide 79: SCORED Data Shows Reduction in Progression of CKD
SCORED Data in Type 2 Diabetes Patients Shows Evidence of Reduction in Progression of CKD Sotagliflozin Placebo HR Endpoint n/N (%) n/N (%) (95% CI) p-value eGFR ↓ 57%, ESKD, renal or CV death 215 (4.1) 273 (5.2) 0.78 (0.65, 0.93) 0.0061 eGFR ↓ 50%, ESKD, renal or CV death 239 (4.5) 306 (5.8) 0.77 (
Slide 80: Consistent Glycemic Control Benefits in T1D Population with CKD
Sotagliflozin Achieved Consistent Glycemic Control Benefits in T1D Population with CKD Pooled Data from inTandem1 and inTandem2 A. Entire Cohort Change in HbA1c (%) from baseline to Week 24 LSM DIFF (95% Cl) P-value Diff in LSMs of Sotagliflozin vs Placebo (95% Cl) Sotagliflozin 200mg -0.36 (-0.44,
Slide 81: Similar Effect on Key Safety Measures in T1D Population with CKD
Sotagliflozin Had Similar Effect on Key Safety Measures in T1D Population with CKD Pooled Data from inTandem1 and inTandem2 Entire Cohort CKD Cohort Sotagliflozin Sotagliflozin Sotagliflozin Sotagliflozin Placebo Placebo 200mg 400mg 200mg 400mg N=526 N=76 N=524 N=525 N=85 N=76 Severe hypoglycemia, 3
Slide 82: Significant Number of People with T1D Already Suffer from CKD
Significant Number of People with T1D Already Suffer from CKD U.S. Epidemiology People in the U.S. with T1D 1.7M adults with T1D1 20 - 25% 21% have Chronic Kidney Disease2 42% with high blood pressure*3 1,700,000 66% are obese or overweight for patients >25 years4 340,000 – 425,000 Total People Peop
Slide 83: Significant Need Exists for Options to Improve Glycemic Control in T1D
Significant Need Exists for Options to Improve Glycemic Control in People with T1D, Especially Those with CKD Patient Managing T1D and struggling to manage glycemic control Type of Primary Adjunctive Other Treatment Glycemic Control Glycemic Control Comorbidity Control Multiple Daily Insulin ACE Inh
Slide 84: Sotagliflozin Has Potential to Improve Glycemic Control for T1D and CKD
Sotagliflozin Has Potential to Improve Glycemic Control for People with T1D and CKD Illustrative Patient Journey Managing T1D with CKD Sotagliflozin Insulin or insulin Treatment for serious analogues kidney disease, CVD, or other complications All people with T1D are on insulin and vast majority con
Slide 85: Endocrinologists Are the Primary Managers of T1D Care
Endocrinologists Are the Primary Managers of T1D Care Nephrologist Self-Referral Key Focus: Renal Outcomes Scripts for glycemic control initiate and remain with the endocrinologist Specialists Ophthalmologist ~90% ~25% Key Focus: Retinal Outcomes Endocrinologist continues PCP / Pediatrician to manag
Slide 86: Endocrinologists Are Excited about On-label Adjunct Treatments
Endocrinologists Are Excited about the Prospect of On-label Adjunct Treatments to Improve Glycemic Control in People with T1D and CKD Strong Preference for Recognition of Importance Some Off-Label Use of Indicated Agents by of Glycemic Control in T1D SGLTs Among KOLs Community Endocrinologists Physi
Slide 87: Concentration of Prescribers Supports Efficient Commercial Opportunity
Concentration of Prescribers Supports Efficient Commercial Opportunity 92% of T1D is treated by 3,000 endocrinologists T1D Treatment Concentration Among Endocrinologists Geographic Distribution of T1D Treatment 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Top 1,000 Top 3,000 Endocrinologists Endocrin
Slide 88: Numerous Studies Underway Utilizing Sotagliflozin in T1D
Numerous Studies Underway Utilizing Sotagliflozin in T1D Opportunities for increased clinical evidence following potential approval and launch JDRF Awards $9 Million for Phase 3 Type 1 Diabetes Sotagliflozin in Patients with Clinical trial that will test sotagliflozin, Multifactorial Intervention He
Slide 89: Summary and Next Steps
Summary and Next Steps • NDA resubmission anticipated mid – 2024 with potential for 6-month review • Anticipate Q1 2025 launch • Pre-launch planning and activities underway • Additional investments including field force planned for time of approval • Unmet need supports potential for broad adoption
Slide 90: 2024 Investor Day
Ly Lexicon 2024 INVESTOR DAY HERE. NOW.
Slide 91: LX9211 Diabetic Peripheral Neuropathic Pain
2024 INVESTOR DAY LX9211 Diabetic Peripheral Neuropathic Pain Craig Granowitz, M.D, Ph.D Senior Vice President and Chief Medical Officer Tom Garner Senior Vice President and Chief Commercial Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 92: LX9211: Mechanism and PROGRESS Study Overview
2024 INVESTOR DAY LX9211 Diabetic Peripheral Neuropathic Pain Mechanism and PROGRESS Study Overview Craig Granowitz, M.D, Ph.D Senior Vice President and Chief Medical Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 93: LX9211 for Diabetic Peripheral Neuropathic Pain (DPNP)
LX9211 for Diabetic Peripheral Neuropathic Pain (DPNP) 01 Mechanism and Historical Data Overview 02 PROGRESS Study Overview 03 Market Opportunity 04 Disease Progression and Potential Treatment Positioning 05 Summary and Next Steps 93
Slide 94: LX9211 Potential to Redefine Standard of Care for DPNP Patients
LX9211 has the Potential to Redefine the Standard of Care for Patients Suffering with DPNP – Fast Track Designation by FDA High Unmet Proof of Concept Medical Need Achieved Potential for Late-Stage Clinical Significant Development Commercial Underway Opportunity 94
Slide 95: Lexicon Identified AAK1 as Most Compelling Target for Neuropathic Pain
Lexicon Identified AAK1 as the Most Compelling Target for Neuropathic Pain among the Nearly 5,000 Targets Evaluated in the Genome5000 Program Genetic Knockouts of AAK1 Demonstrated Effects Genetic Knockouts of AAK1 Demonstrated among the Primarily on Chronic Rather than Acute Pain Strongest Chronic
Slide 96: Genome5000 Supported Selection of AAK1 Over Other Targets
Lexicon Identified AAK1 as the Most Compelling Target for Neuropathic Pain among the Nearly 5,000 Targets Evaluated in the Genome5000 Program Genetic Knockouts of AAK1 Demonstrated Genome5000 Supported Selection of AAK1 over Resistance to Neuropathic Pain Other Putative Targets with Less Compelling
Slide 97: Preclinical Models Suggest AAK1 Inhibition Across Neuropathic Pain Indications
Preclinical Models Suggest that Inhibiting AAK1 Has Potential Applications Across a Broad Range of Neuropathic Pain Indications LX9211 Has Demonstrated Benefits in Multiple Preclinical Models of Neuropathic Pain LX9211 reduced neuropathic pain in the streptozotocin (STZ)-induced painful LX9211 reduc
Slide 98: Phase 2 Study of LX9211 in DPNP Designed to Demonstrate Effect Versus Placebo
Phase 2 Study of LX9211 in DPNP was Designed to Demonstrate Effect Versus Placebo RELIEF-DPN-1: Efficacy, Safety, and PK of LX9211 in Patients with DPNP Single-blind Screening Period Placebo Double-blind Treatment Single-blind Safety Study design permitted (Up to 2 Weeks) Run-in Period Period (6 Wee
Slide 99: LX9211 Achieved the Primary Endpoint in RELIEF-DPN-1
LX9211 Achieved the Primary Endpoint in RELIEF-DPN-1 Clinically and statistically significant reduction in average daily pain score (ADPS) at Week 6 compared to placebo* in the low dose arm with results that plateaued in the high dose arm Effect on ADPS consistent across age, sex, use of baseline DP
Slide 100: Benefits in Both Burning Pain and Pain Interference with Sleep
Significant and Clinically Meaningful Benefits Demonstrated in Both Burning Pain and Pain Interference with Sleep Both are commonly reported challenges experienced by DPNP patients LS Mean Change from Baseline LS Mean Change from Baseline in Burning Pain in Interference in Sleep Placebo Placebo 1 LX
Slide 101: PROGRESS Phase 2b Study – Enrollment Underway, Topline Data Expected Q2 2025
PROGRESS Phase 2b Study – Patient Enrollment Underway, First Topline Data Read-out Expected in Q2 2025 Patient Population Treatment Period Safety Follow-up LX9211 10 mg Study Enrollment: LX9211 20 mg Adult patients ~400 patients, with a diagnosis R LX9211 20 mg for 7 days/10 mg thereafter ~100 patie
Slide 102: LX9211 Has Entered Late-stage Development for DPNP
LX9211 Has Entered Late-stage Development for DPNP • Potential first-to-market opportunity with very few novel treatments in development for DPNP or neuropathic pain generally • DPNP represents the largest and fastest growing The PROGRESS Study neuropathic pain market opportunity is designed to enab
Slide 103: LX9211 Market Overview and Treatment Positioning
2024 INVESTOR DAY LX9211 Diabetic Peripheral Neuropathic Pain Market Overview and Treatment Positioning Tom Garner Senior Vice President and Chief Commercial Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 104: DPNP Represents Significant Unmet Medical Need
DPNP Represents Significant Unmet Medical Need Neuropathic Pain – DPNP Represents ~25% • Current standard of care of Total Addressable Market does not eliminate neuropathic pain for ~20 Million Patients most patients, and many experience undesirable side effects • Potential for first drug with a new
Slide 105: Diabetic Patients Are Diagnosed and Managed by PCPs or Endocrinologists
Diabetic Patients Are Most Frequently Diagnosed and Managed by PCPs or Diabetologists/Endocrinologists No response to anti-convulsants/ Uncontrolled diabetes anti-depressants, ~30% of those (not specific to DPNP) with DPNP PCP Diabetologist/Endocrinologist Pain Specialist • Initial management of • R
Slide 106: LX9211 Has Potential To Be Used Across DPNP Treatment Paradigm
LX9211 Has Potential To Be Used Across DPNP Treatment Paradigm First line pharmacologic treatment for DPNP is typically gabapentin. LX9211 would likely be used in patients with inadequate response to that first line, either on its own or in combination. 1st Line 2nd Line 3rd Line 4th Line Switch Swi
Slide 107: Executive Summary - LX9211
Executive Summary - LX9211 Potential to address unmet needs for DPNP patients and demonstrate compelling value proposition • Potential to use LX9211, alone or in combination with other treatments, for patients not at goals with current options; this represents a substantial proportion of drug-treate
Slide 108: Thank you / Break
2024 INVESTOR DAY Thank you 15 MINUTE BREAK
Slide 109: Expert Panel Introduction
2024 INVESTOR DAY Expert Panel Introduction Craig Granowitz, M.D., Ph.D. Senior Vice President and Chief Medical Officer PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 110: Expert Panel – HCM, T1D and DPNP
Expert Panel – HCM, T1D and DPNP Rodica Pop-Busui, Sharlene M. Day, MD MD, PhD Presidential Associate 2023 President for Medicine Professor, University of and Science, the American Pennsylvania Diabetes Association Division of Cardiovascular University of Michigan Medicine Division of Endocrinology
Slide 111: HCM Panel Discussion – FDA Feedback Supports sNDA for HCM
HCM Panel Discussion – Exhibit 1 FDA Feedback Supports Potential for Sotagliflozin sNDA for HCM Based on Single Successful Phase 3 Study with KCCQ Primary Endpoint Primary endpoint: Change from Proposed indication: Sotagliflozin is indicated to baseline in KCCQ Clinical Summary improve symptoms and
Slide 112: PROGRESS Phase 2b Study – Topline Data Expected Q2 2025
PROGRESS Phase 2b Study – Patient Enrollment Underway, First Topline Data Read-out Expected in Q2 2025 Patient Population Treatment Period Safety Follow-up LX9211 10 mg Study Enrollment: LX9211 20 mg Adult patients ~400 patients, with a diagnosis R LX9211 20 mg for 7 days/10 mg thereafter ~100 patie
Slide 113: Sotagliflozin Offers Important Potential Benefits for T1D and CKD
Sotagliflozin Offers Important Potential Benefits for People with Type 1 Diabetes and Chronic Kidney Disease (CKD) Better glucose control is Improving A1C in people particularly important in with T1D is associated with people with T1D who reduced risk of CKD have CKD progression People with T1D and
Slide 114: 2024 Investor Day
HERE. NOW. w Lexicon 2024 INVESTOR * DAY
Slide 115: LX9851 Obesity and Quality Weight Management
2024 INVESTOR DAY LX9851 Obesity and Quality Weight Management Characteristics in animal models and why it will be an important fit in the Obesity market; Path and timing to IND submission Alan Main, Ph.D. Executive Vice President, Innovation and Chemical Sciences PRECISION SCIENCE. PIONEERING MEDIC
Slide 116: LX9851 Development Candidate ACSL5 Inhibitor
2024 INVESTOR DAY LX9851 Development Candidate ACSL5 Inhibitor April 2024 PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 117: Chronic Weight Management with an Oral Agent
Chronic Weight Management with an Oral Agent Opportunities beyond initial weight loss with a GLP-1 agonist: • Oral agent for chronic weight management • Reduction in body fat that spares lean body mass • Improved metabolic profile, with reduced cholesterol Weight and triglycerides, improved insulin
Slide 118: LX9851 Introduction: Target and Potential Indications
LX9851 Introduction Target and Potential Indications Target: Acyl CoA Synthetase 5 (ACSL5) Gene Family: Acyl coenzyme A (CoA) long-chain synthase families (ACSLs) Human/Mouse Homology: 81% Expression: Highly expressed in the GI (jejunum) and liver Cellular Location: Endoplasmic reticulum and mitocho
Slide 119: ACSL5 Acts at the First Step in the Lipid Biochemical Cascade
ACSL5 Acts at the First Step in the Lipid Biochemical Cascade Long Chain Fatty Acids ACSL5 Free Fatty Acids ACSL 5 ACSL5 inhibition redirects free fatty acids to the intestine activating the ileal brake mechanism, which leads to satiety and improvements in metabolic parameters without steatorrhea or
Slide 120: Compelling KO Phenotype for Metabolism
Compelling KO Phenotype for Metabolism Acsl5 Mouse Knockout (KO) Phenotype Counters aspects of the metabolic syndrome • Lean and resistant to diet-induced obesity • Decreased atherosclerotic plaque • Glucose tolerance with lower insulin levels • Resistant to hepatic steatosis in NASH model • Decreas
Slide 121: Phenotypic Screen Identified ACSL5 as Compelling Metabolic Syndrome Target
Phenotypic Screen Identified ACSL5 as Compelling Potential Metabolic Syndrome Target Much Lower Cholesterol and Triglycerides and Modestly Lower Body Fat on Standard Diet % Body Fat LBM Characteristics of Acsl5 KO Phenotype Compared to Genome5000™ Assessment of Nearly 5,000 Genes Cholesterol Triglyc
Slide 122: High Fat Diet Revealed Potential for Reduced Body Fat with Preserved Lean Mass
High Fat Diet (HFD) Revealed Another Important Characteristic of Target: Potential for Reduced Body Fat with Preserved Lean Body Mass Acsl5 KO Mice on HFD Have Substantially Less Body Fat with No Difference in Lean Body Mass Standard Diet (Chow) High Fat Diet (HFD) 122
Slide 123: Acsl5 KO and LX9851-Treated Mice Show Similar Decreases in Body Weight and Fat
Acsl5 KO Mice and Wild Type (WT) Mice Treated with LX9851 Show Similar Decreases in Body Weight and Body Fat When Fed HFD Acsl5 KO LX9851 (LP-960345) 55 Control LP-960345 at 30 mg/kg 50 Body Weight (g) 45 40 BW * ** 35 30 6 Adipose Weight Adipose Weight (g) 5 4.40 ** 4 3.11 Body Fat 3 2 *p <0.05 vs
Slide 124: Acsl5 KO and LX9851-Treated Mice Show Decreased Food Consumption
Acsl5 KO Mice Switched from Chow to HFD, and HFD-fed WT Mice Treated with LX9851, Show Decreased Food Consumption Acsl5 KO LX9851 (LP-960345) Food Consumption 3.5 100 Average (g)/animal/day 3 90 79.01 80 *** 2.5 70 62.76 60 FC (AUC) 50 2 40 30 1.5 20 Control LP-960345 at 30 mg/kg 10 1 0 Control LP-9
Slide 125: Acsl5 KO Mice Choose Low Fat Diet over Very High Fat Diet
Acsl5 KO Mice Choose Low Fat Diet over Very High Fat Diet • 18 week-old Acsl5 KO mice were acclimated on 10% fat as lard diet (LFD) for 2 weeks • Mice were then simultaneously offered 60% fat as lard diet (VHFD) and LFD VHFD LFD 125
Slide 126: Inhibiting ACSL5 Influences Preference for Low Fat over High Fat Diet
Inhibiting ACSL5 Influences Preference for Low Fat over High Fat Diet WT Mice Receiving ACSL5 Inhibitors Prefer LFD Over HFD WT males fed chow diet were divided into 3 groups and offered: • Both control HFD and LFD • Both HFD and LFD containing LP-856866, 60 mg/kg as dietary admixture • Both HFD and
Slide 127: ACSL5 Inhibition Delays Gastric Emptying
ACSL5 Inhibition Delays Gastric Emptying Acsl5 KO ACSL5 Inhibitor (LP-795701) • Oral gavage of 3H-Triolein (TG consisting of glycerol bound to 3 oleic acids) • Tissues and biological samples collected at 6 hours following lipid loading • Lipid loading immediately following oral dosing of 200 mg/kg L
Slide 128: Inhibiting ACSL5 Affects Incretin Levels
Inhibiting ACSL5 Affects Incretin Levels ACSL5 Inhibitors Increase GLP-1 and PYY, Consistent with KO Phenotype LP-856866 LX9851 (LP-960345) Active GLP-1 GLP-1 (Total) 0.6 0.025 * * 0.5 0.43 0.0143 Active GLP-1 (pg/mg) 0.020 GLP-1 (pg/mg) 0.31 0.4 0.015 0.3 0.010 0.2 0.0048 0.005 0.1 0.000 0 PYY FGF-
Slide 129: Inhibiting ACSL5 Improves Glucose Tolerance with Less Insulin
Inhibiting ACSL5 Improves Glucose Tolerance with Less Insulin HFD-fed Acsl5 KO Mice and Mice Treated with LX9851 Show Improved Glucose Tolerance and Lower Insulin Levels Acsl5 KO LX9851 (LP-960345) 30 Blood Glucose (mmol/L) OGTT Glucose Levels 25 Glucose (mg/dL) 20 15 ** ** *** 10 5 ** 0 0 15 30 60
Slide 130: Inhibiting ACSL5 Lowers Cholesterol and Triglycerides
Inhibiting ACSL5 Lowers Cholesterol and Triglycerides ApoE/Acsl5 Double KO Mice Fed Western HFD for 3 Months: Reduced Cholesterol, TGs and Atherosclerotic Plaque Cholesterol Triglycerides Aortic Plaque 27% Decrease 49% Decrease 39% Decrease 56% Decrease 59% Decrease 73% Decrease 130
Slide 131: Acsl5 KO Mice Show Decreased Liver Fat After 5 Months on HFD
Acsl5 KO Mice Show Decreased Liver Fat After 5 Months on 45% HFD TG (mg/liver) TG (mg/liver) ***p < 0.001 vs Control 131
Slide 132: Human Genetic Evidence Supporting a Role for ACSL5 in Metabolic Disorders
Human Genetic Evidence Supporting a Role for ACSL5 in Metabolic Disorders Various SNPs in ACSL5 have been identified that strongly suggest a role in TG lowering, T2DM, and weight management. • rs7903146: One of the most strongly associated T2DM diabetes loci resides within TCFL2 gene. rs7903146 vari
Slide 133: LX9851 Selected as Development Candidate
LX9851 (LP-960345) Selected as Development Candidate LP-960345 has the following attributes: • Highly active in biochemical and cell-based functional assays • Selective against biologically relevant ACSLs • Good in vitro drug metabolism • Good PK/PD • hERG activity >30mM • Clean in CEREP-87 in vitro
Slide 134: LX9851 and Semaglutide Combination Reduces Body Weight in DIO Mice
Combination of LX9851 and Semaglutide Demonstrates Greater Reduction in Body Weight in HFD-fed DIO Mice 52 Semaglutide, LX9851 and Combination 50 48 46 ** *** 44 Body Weight (g) * 42 ** 40 * *** *** ** ** *** 38 36 ** Control #1: PBS 34 Control #2: HPMC Semaglutide Semaglutide + 345 32 LP-960345 30
Slide 135: LX9851 and Semaglutide Further Reduces Food Consumption
Combination of LX9851 and Semaglutide Further Reduces Food Consumption in HFD-fed DIO mice Semaglutide, LX9851 and Combination Food Consumption 350 4500 Cumulative Feed Intake (g/day) 300 4080.35 4000 3795.80 Food Consumption AUC 250 3500 3014.10 2897.00 Control #1: PBS 3000 200 Control #2: HPMC 250
Slide 136: LX9851 Helps Maintain Weight Loss after Semaglutide Discontinuation
LX9851 Helps Maintain Weight Loss after Semaglutide Discontinuation in HFD-fed DIO mice 52 Semaglutide Withdrawal After Initial Weight Loss 50 48 46 * * Body Weight (g) 44 ** 42 * 40 38 * 36 ** *** ** Control #1: PBS 34 Semaglutide treatment Semaglutide (0-14); w/o (15-28) withdrawn after day 14 32
Slide 137: LX9851 Has a Unique Profile for Chronic Weight Management
LX9851 Has a Unique Profile Addressing the Most Important Needs and Opportunities for Chronic Weight Management Opportunities beyond initial weight loss with a GLP-1 agonist: Unique opportunity • Oral agent for chronic weight management in projected $41 billion • Reduction in body fat that spares le
Slide 138: 2024 Investor Day
Ly Lexicon 2024 INVESTOR DAY HERE. NOW.
Slide 139: Closing Remarks
2024 INVESTOR DAY Closing Remarks Lonnel Coats Chief Executive Officer and Director PRECISION SCIENCE. PIONEERING MEDICINE. PATIENT DRIVEN.
Slide 140: Pipeline Market Opportunities in Areas of Significant Value and Rapid Growth
Pipeline Market Opportunities in Areas of Significant Value and Rapid Growth Diabetic Heart Type 1 Weight Diabetes HCM Neuropathic Failure with CKD $3.7 Bn Pain Management $7 Bn $1 Bn* $1 Bn $41 Bn *CKD estimated at 20 -25% of total $4B T1D market. *Estimates provided are global and based on interna
Slide 141: Significant Number of Planned Catalysts Through 2025
Significant Number of Planned Catalysts Through 2025 Pipeline Indication Planned Catalyst 2024 – 2025 • Potential launch inflection in second half of INPEFA® (sotagliflozin) • INPEFA Heart Failure 2024 Sotagliflozin • Hypertrophic Cardiomyopathy • Phase 3 study commencement mid-2024 • Type 1 Diabete
Slide 142: Lexicon Commitment to Growth and Expansion
Lexicon Commitment to Growth and Expansion Targeted Capital Allocation Partnership Opportunities Seamless Execution to Support Near- to Maximize Value Term Return Recent successful capital raise supports plans for execution 142
Slide 143: 2024 Investor Day
Ly Lexicon 2024 INVESTOR DAY HERE. NOW.