Lipocine Inc. · NASDAQ:LPCN
Lipocine — Investor Presentation (March 2019)
51 slides from Lipocine's investor presentation, Mar 28, 2019
Slide 1: Enabling Oral Drug Delivery to Improve Patient Compliance
Enabling Oral Drug Delivery to Improve Patient Compliance March 28, 2019 Corporate Presentation Exhibit 99.1
Slide 2: Forward-Looking Statements
Forward - Looking Statements This presentation contains forward - looking statements about Lipocine Inc. (the “Company”). These forward - looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward - looking statement s re
Slide 3: Clinical Stage Biopharmaceutical Company, Metabolic and Endocrine Focus
Clinical Stage Biopharmaceutical Company Metabolic and Endocrine Focus 3 PRODUCT (Indication) PRE - CLINICAL PHASE 1 PHASE 2 PHASE 3 NDA LPCN 1144 (Oral Testosterone for NASH) Phase 2 Study in Biopsy Confirmed NASH LPCN 1148 (Oral Testosterone for NASH Cirrhosis) POC Study Planned TLANDO (Oral Testo
Slide 4: Targeted for Non-Alcoholic Steatohepatitis (NASH)
4 Targeted for Non - Alcoholic Steatohepatitis (“NASH”) A silent killer that affects 30 million Americans 1 1. CNBC; published December 30, 2018
Slide 5: Non-Alcoholic Fatty Liver Disease: No Approved Product for the Treatment of NASH
Non - Alcoholic Fatty Liver Disease (“NAFLD”) No Approved Product for the Treatment of NASH 5 LFTs: Liver function test, especially Alaninine amino transferase (ALT) and Aspartame amino transferase (AST) NASH: Non - alcoholic Steatohepatitis, TG: Triglyceride Fatty liver is a reversible condition wh
Slide 6: NASH Pathogenesis Risk Factors and Clinical Progression
NASH Pathogenesis Risk Factors and Clinical Progression Lipid Metabolism Disorders • Dyslipidemia • Insulin resistance • Obesity • T2 diabetes • Metabolic syndrome Inflammation • Lipid peroxidation • Mitochondrial dysfunction • Oxidative stress • Apoptosis • Pro - inflammatory cytokine activation Fi
Slide 7: Clinical Relationship Between Testosterone and NAFLD Across the Full Disease Spectrum
Clinical Relationship Between Testosterone and NAFLD Across the Full Disease Spectrum Hepatic Steatosis NASH Cirrhosis “ Men with low testosterone are at high risk for NAFLD .” 1 Free T ( pg /mL) “ Levels of free T decreased significantly with the increased incidence of lobular inflammation, hepatoc
Slide 8: 1144: Oral Testosterone Targeting The Full Spectrum of NASH Pathogenesis
LPCN 1144: Oral Testosterone Targeting The Full Spectrum of NASH Pathogenesis A Differentiated Oral NASH Therapy Candidate • Well tolerated - suitable for chronic use • Favorable benefits outside the liver Clinical Data to Advance in Phase 2 Testing • Meaningful liver fat reductions as early as eigh
Slide 9: 1144: Multidimensional Mechanism of Action Across NASH Pathogenesis
LPCN 1144: Multidimensional Mechanism of Action Across the Full Spectrum of NASH Pathogenesis Homeostasis Modifier 1, 2 • Alter lipid, cholesterol, and glucose metabolism • Reduce visceral abdominal fat • Modify activity of hepatic lipase, and skeletal muscle/ adipose lipoprotein lipase Anti - infla
Slide 10: 1144: A Differentiated Oral NASH Therapy Candidate
LPCN 1144: A Differentiated Oral NASH Therapy Candidate Prodrug of Endogenous Testosterone Liver Fat Reduction and Key Serum Biomarkers Potential Favorable Benefits in Systems Outside the Liver Suitable for Chronic Use • Over 40% relative mean liver fat reduction after 16 - weeks of treatment • 48%
Slide 11: 1144: Liver Fat Imaging Study Design and Baseline Distribution
LPCN 1144: Liver Fat Imaging Study (“LFS”) Study Design and Baseline Liver Fat Subject Distribution 11 LFS was an open - label, multi - center single - arm 16 - week study (N=36) with LPCN 1144 in hypogonadal males LF = liver fat
Slide 12: 1144: Liver Fat Study Results, Relative Liver Fat Change and Responder Rate
LPCN 1144: Liver Fat Study Results Meaningful Relative Liver Fat % Change and Responder Rate 12 - 33% - 42% - 40% -60% -50% -40% -30% -20% -10% 0% BL ≥ 5% BL ≥ 8% BL ≥ 10% % Liver Fat CBL ( ± SEM) Mean Relative Liver Fat % Change 71% 80% 75% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% BL ≥ 5% BL ≥ 8
Slide 13: 1144: Liver Fat Study Results, NAFLD Resolution
100% of patients experiencing NAFLD resolution had at least 35% of relative liver fat reduction from baseline * Resolution of NAFLD is defined as when BL liver fat ≥ 5% is reduced to < 5% at EOS. 28% 48% 0% 10% 20% 30% 40% 50% Resolution of NAFLD % of Subjects Resolution of NAFLD* 8 Wks 16 Wks - 45%
Slide 14: 1144: Liver Fat Based Subject Distribution at Each Visit
LPCN 1144: Liver Fat Study Results Liver Fat Based Subject Distribution at Each Visit 14 38% 32% 6% 24% Baseline Pre treatment 55% 18% 6% 21% 8 Week Treatment 65% 15% 12% 9% 16 Week Treatment ■ LF < 5% (NAFLD Free) ■ 5% ≤ LF < 8% ■ 8% ≤ LF < 10% ■ LF > 10% NAFLD Free NAFLD Free NAFLD Free Longer The
Slide 15: 1144: Next Step Advancing Forward
LPCN 1144: Next Step Advancing Forward • Initiate Phase 2 clinical study in biopsy confirmed NASH subjects – Study Design • Three - arm, placebo controlled • Biopsy confirmed F2/F3 NASH male hypogonadal subjects with NAS ≥ 4 • Paired biopsy at baseline and EOS • 36 - weeks duration – IND cleared by
Slide 16: For Treatment of NASH Cirrhosis
16 For Treatment of NASH Cirrhosis
Slide 17: 1148: Oral T for NASH Cirrhosis, No FDA Approved Drugs
LPCN 1148: Oral T for NASH Cirrhosis No FDA Approved Drugs - Transplant Only Cure Cirrhotic Liver US Prevalence Cirrhotic Patients Characteristics: • Increased morbidity and mortality • Symptoms of hypogonadism: hair distribution, anemia, sexual dysfunction, testicular atrophy, muscle wasting, fatig
Slide 18: Low Testosterone Increases Adverse Outcome in Male Cirrhotic Patients
Low Testosterone Increases Adverse Outcome in Male Cirrhotic Patients T Levels Fall Progressively with Increasing Disease Severity 1 • Low T reported in up to 90% of NASH cirrhosis patients 2 and is a predictor of mortality 3 • Low T associated with: – Increased risk of major infections, death and/
Slide 19: 1148: NASH Cirrhosis Oral T Therapy
LPCN 1148: NASH Cirrhosis Oral T Therapy Potentially help patients survive longer while waiting for a liver transplant • T levels positively correlate with muscle mass in men and modulates bone density, hemoglobin production, insulin resistance, and immunity , commonly impaired in cirrhosis 1 • Test
Slide 20: Targeted for Testosterone Replacement Therapy
20 Targeted for Testosterone Replacement Therapy Annual TRx ~7M
Slide 21: Issues with Current Non-oral TRT Options
Issues with Current Non - oral TRT Options • Black Box Warning – Secondary exposure to testosterone – Pulmonary oil micro embolism (POME) and anaphylaxis shock • Inconvenient application or painful injection • Poor persistence reflects need for oral – Average days on therapy is 100 days • More than
Slide 22: TLANDO: Potential First Oral Option Progressing to NDA Resubmission
TLANDO™: Potential First Oral Option Progressing to NDA Resubmission 22 Deficiency 1 Determine extent, if any, of ex vivo conversion of TU to T Deficiency 2 Characterize blood pressure effects of TLANDO for appropriate regulatory action Deficiency 3 Provide justification for non - applicability of C
Slide 23: TLANDO: Potential First Oral Option Profile
TLANDO™: Potential First Oral Option Profile Demonstrated Clinically with Target Label Regimen ▪ Met primary endpoint - 80% response rate in “worst - case analysis” vs. FDA requirement of 75% - Justification for non - applicability of Cmax based missed secondary endpoints Efficacy ✔ ▪ 591 subject ex
Slide 24: Upcoming Milestones: Near Term Value Drivers
Upcoming Milestones 24 Near Term Value Drivers Event Expected Timing TLANDO™ NDA Resubmission 2Q 2019 LPCN 1144 Phase 2 Study Start in Biopsy Confirmed NASH Patients 2H 2019
Slide 25: Key Financial Metrics
Key Financial Metrics 25 Stock Price, Market Cap, Cash Balance Ticker Symbol LPCN (Nasdaq Capital Market) Closing Stock Price (3/26/19) $2.19/share Market Capitalization (3/26/19) $52.3 million Cash Balance (12/31/18) $20.3 million* Bank Debt (12/31/18) $10.0 million * $5 M restricted
Slide 26: Appendix
LIPOCIN= Appendix
Slide 27: Targeted for pre-cirrhosis NASH
27 Targeted for pre - cirrhosis NASH
Slide 28: 1144: Additional Health Benefits Observed in Hypogonadal Subjects with Elevated ALT
LPCN 1144: Additional Health Benefits Observed in Hypogonadal Subjects with Elevated ALT* SF - 36, Short Form - 36 (0 - 100); PDQ, Psychosexual Daily Questionnaire (0 - 7); * ALT > 40 U/L at Baseline in 52 week SOAR Trial (N=3 3) Mental Component Summary Mental Health Role Emotional Maintained Erect
Slide 29: 1144: General Safety
LPCN 1144: General Safety Well Tolerated • Extensive clinical safety database with LPCN 1144 – 700+ subjects in 14 studies with up to 52 week exposure – No drug related SAEs – Safety profile well - characterized and demonstrated no unexpected risks – Good gastrointestinal tolerability with no signs
Slide 30: 1144: Gastrointestinal Safety
LPCN 1144: Gastrointestinal Safety Gastrointestinal Disorders ≥ 1% in SOAR Trial (52 Weeks) 0 5 10 15 % Subjects LPCN 1144 Topical T 30
Slide 31: 1144: Consistent Liver Function Improvement Across Studies
LPCN 1144: Consistent Liver Function Improvement Across Studies* Effect Observed as Early as 3 Weeks - 17.4% - 10.3% - 5.1% - 9.6% - 18.8% - 13.2% - 10.1% - 18.5% -30% -25% -20% -15% -10% -5% 0% ALT AST ALP GGT Mean Change from BL ( ± SEM) SOAR (52 Week) 16-002 (3 Week) Mean BL (U/L) 53.6 55.6 32.0
Slide 32: 1144: Normalization of ALT, GGT, TG, LDL-C, and Lp-PLA2
LPCN 1144: Oral T Appreciable % of Patients Experienced Normalization of ALT, GGT, TG, LDL - C, and Lp - PLA2 32 52% 31% 34% 56% 52% 0% 10% 20% 30% 40% 50% 60% ALT* GGT* TG* LDL-C* Lp-PLA2* % of Normalized Patients from Above - normal at Baseline Normalization of Biomarkers with LPCN 1144 N 42 36 73
Slide 33: LPCN 1144: Oral T Unique TG Reduction Compared to Topical Gel
• 52 Week SOAR Trial TG mean change post therapy in patients on oral T vs non - oral T therapy LPCN 1144: Oral T Unique TG Reduction Compared to Topical Gel 33 - 63.7 13.7 -80 -60 -40 -20 0 20 40 60 Mean BL = 320 mg/dL 323 mg/dL N = 73/210 34/104 LPCN 1144 Topical T Mean Change from Baseline (mg/ dL
Slide 34: LPCN 1144: Oral T Unique Effects on Liver Compared to Topical Gel
• 52 Week SOAR Trial LPCN 1144: Oral T Unique Effects on Liver Compared to Topical Gel 34 - 4.8% 3.3% -10% -5% 0% 5% 10% Mean BL = 71.8 U/L 72.5 U/L LPCN 1144 Topical T Mean Change from Baseline ALP Mean Change after 52 Week - 19.5% 8.3% -30% -20% -10% 0% 10% 20% Mean BL = 30.3 nmol/L 30.4 nmol/L LP
Slide 35: TLANDO
LIPOCIN= TLANDO™
Slide 36: Hypogonadism Affects Up to 13M American Men
Hypogonadism Affects Up to 20 M American Men 1,2 36 Significant Number of Untreated Hypogonadal Males ~6M Men with diagnosed hypogonadism 3 2.2M Men currently being treated 4 700,000 New naïve patients each year 5 1. US Census data. http://www.infoplease.com/us/census/data/demographic.html. 2. Mulli
Slide 37: TLANDO: Patient Market Research
TLANDO™: Patient Market Research Patient Enthusiasm Evident About Oral TRT 37 37 80% of interviewed TRT patients 30% 30% “Oral Form ” 30% “It’s not Gel”, “ Not Injection” “ Ease of Use” Likely or Highly Likely to Ask Physician to Prescribe TLANDO What Most Like About TLANDO? Other • TLANDO generates
Slide 38: TLANDO: Physician Market Research
TLANDO™: Physician Market Research Oral Agent is Most Important Attribute for Prescribers 38 QUESTION: What is the most important advantage of TLANDO? 66% 10% 8% 8% 5% 3% No/Low Risk of… Good Efficacy Easy Dosing/ Administration Easy/Less Titration Few Side Effects/ Well-tolerated N=212 (All Respond
Slide 39: TLANDO: Definitive Phlebotomy Study
TLANDO™: Definitive Phlebotomy Study Ex Vivo Conversion Assessment ▪ Study objective: ‒ To evaluate the extent, if any, of clinically meaningful ex vivo conversion of TU to T in serum blood collection tubes to confirm the reliability of TLANDO data results ▪ Study design: ‒ Open - label, single dose
Slide 40: TLANDO: Ambulatory Blood Pressure Monitoring Study
TLANDO™: Ambulatory Blood Pressure Monitoring Study Results Consistent with a Recently Approved Testosterone Replacement Therapy ▪ Study objective: ‒ To characterize blood pressure effects of TLANDO for appropriate FDA regulatory action, including Risk Evaluation and Mitigation Strategy (“REMS”) bey
Slide 41: LPCN 1107
LIPOCIN= LPCN 1107
Slide 42: High PTB Medical Costs
High PTB Medical Costs • 12% of all US pregnancies 1 (475 - 500K) result in PTB (< 37 weeks) - a leading cause of neonatal mortality and morbidity • First year medical costs for PTB infants are ~ 10x higher than for full term infants 2 • 28% of preterm births are to women with histories of early del
Slide 43: 1107: Prevention of Preterm Birth, US Market Landscape
LPCN 1107: Prevention of Preterm Birth (PTB) United States Market Landscape $1B Market Opportunity 3 December 31, 2017 HPC TRx 4 Makena ® 1 50% Off Guidance 2 30% Compounded 17 - HPC 20% 117% 1. Amag estimates Makena market share based on distributor dispensing data and all other market share based
Slide 44: 1107: First Oral PTB Candidate
LPCN 1107: First Oral PTB Candidate 44 Characteristics of the Only Approved Product Options for PTB IM HPC, Makena ® : ▪ 20 - 25% patients below reported better efficacy HPC level threshold ▪ Total of 18 - 22 injections – Injection location: Upper - outer quadrant of the gluteus maximus – Weekly vis
Slide 45: 1107: Oral HPC, First Oral PTB Candidate
LPCN 1107 - Oral HPC ▪ Potential for superior efficacy with Phase 3 target dose ▪ No patient discomfort upon administration ▪ Steady state achieved in 7 days ▪ Orphan drug designation – Major contribution to patient care ▪ Next steps: – Explore partnering opportunities LPCN 1107: First Oral PTB Cand
Slide 46: 1107: Economic Impact
LPCN 1107: Economic Impact Potential Lower PTB Rate – US and Resulting Savings Assuming 4.3% lower PTB rate relative to Makena® ~6000 fewer annual PTBs‡ Estimated annual cost saving in ~$310M‡‡ 46 ‡: Assuming 100% of 140,000 eligible US population treated ‡‡: Assuming ~$51,600 medical costs/PTB
Slide 47: 1107: First Oral PTB Candidate, Commercial Outlook/Drivers
LPCN 1107: First Oral PTB Candidate First Oral HPC for Prevention of Recurrent PTB • Preferred route - of - administration is oral Strong Exclusivity Position • Orphan Drug Designation • Technology/IP protection Potential for Superior Efficacy • Fewer PTB babies with significant healthcare cost savi
Slide 48: 1107: HPC PK-PD Correlation
LPCN 1107: HPC PK - PD Correlation 48 HPC Concentration and PTB Rate with IM HPC, Makena 1 N=315 1. Caritis et al., Am J Obstet Gynecol. 2014 (N=315 subjects) 2. C trough ; C avg for IM Makena® • Lower % PTB rate can be expected with daily C avg 2 HPC levels ≥ 8.2 ng/mL 46.3% 27.0% 29.6% 31.3%
Slide 49: 1107: Dose Finding Study Design
LPCN 1107: Dose Finding Study Design • Open - label, four - period, four - treatment study • 12 healthy pregnant women - Ages 18 - 35 years; 16 - 18 weeks gestation • All subjects received all four treatments 49 PK Study: Oral LPCN 1107 vs IM HPC, Makena Treatment D 250mg Weekly Treatment C 800mg BI
Slide 50: 1107: Dose-Finding PK Study Results
LPCN 1107: Dose - Finding PK Study Results 1 50 Oral LPCN 1107 vs IM HPC, Makena 1. PK results obtained post 8 days of BID dosing for LPCN 1107 and post 5 weeks for weekly IM HPC, Makena Lower reported PTB rate threshold • HPC levels below 8.2 ng/mL: – Target LPCN 1107 Phase 3 dose was 0% vs 20% sub
Slide 51: 1107: Advancing to Phase 3 Readiness
LPCN 1107: Advancing to Phase 3 Readiness Phase 3 Special Protocol Assessment – Progress ▪ Concurrence with FDA to date: – Study Design Elements • Single Phase 3 study • Open label, active comparator, two parallel arms (1:1 randomization) • General inclusion and exclusion criteria and treatment dura