Lipocine Inc. · NASDAQ:LPCN
Lipocine — Investor Presentation (January 2020)
52 slides from Lipocine's investor presentation, Jan 13, 2020
Slide 1: Enabling Oral Drug Delivery to Improve Patient Compliance
Enabling Oral Drug Delivery to Improve Patient Compliance January 2020 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
Clinical Stage Biopharmaceutical Company Innovative Product Candidates for Metabolic and Endocrine Disorders 3 PRODUCT (Indication) PRE - CLINICAL PHASE 1 PHASE 2 PHASE 3 NDA Propriety Drug Delivery Platform LPCN 1144 (Oral Testosterone for Pre - Cirrhotic NASH ) LiFT Phase 2 Paired Biopsy Clinical
Slide 4: LPCN 1144 for Pre-Cirrhotic NASH
Enabling Oral Drug Delivery to Improve Patient Compliance LPCN 1144 for Pre - Cirrhotic NASH
Slide 5: LPCN 1144: Oral Testosterone Therapy Differentiated NASH Treatment Candidate
LPCN 1144: Oral Testosterone Therapy Differentiated NASH Treatment Candidate Targets Unmet Need Mechanistic Evidence Clinical Experience • Efficacy – NASH resolution and/or fibrosis improvement • Acceptable tolerability for chronic use • Improvement of sarcopenia • Improvement of sexual dysfunction
Slide 6: Association Between T and Liver Disease: Pre-clinical Evidence
Association Between T and Liver Disease Pre - clinical Evidence Mouse Model* Method ▪ Testicular - feminized Disease ▪ Hepatic Steatosis ▪ Liver Disease Induction Causes Lower T 6 Induction Method Model T Levels Gene - modified & Diet ob / ob (Obese Mouse) 1 ↓ T db / db (Diabetic Mouse) 2 ↓ T Chemic
Slide 7: Association Between T and Liver Disease: Clinical Evidence
7 Association Between T and Liver Disease Clinical Evidence 1. Sarkar et al., Gastroenterology 156(6):S - 1258 & Poster Sa1623, Digestive Disease Week 2019 2. Sumida et al., Gastroenterol Hepatol 2015 • Levels of free T decreased significantly with the increased incidence of lobular inflammation, he
Slide 8: LPCN 1144 Proposed Mechanism Across Full Spectrum of NASH Pathogenesis
LPCN 1144 Proposed Mechanism 8 Across the Full Spectrum of NASH Pathogenesis Healthy Liver Steatosis Inflammation NASH Fibrosis LPCN 1144 Regeneration Booster 3 ▪ Obesity ▪ Insulin Resistance ▪ Dyslipidemia ▪ Metabolic Syndrome ▪ Hypogonadism (Low T) The removal of pro - fibrotic inputs or the stren
Slide 9: LPCN 1144: Liver Fat Imaging Study Results
- 42% - 40% -60% -50% -40% -30% -20% -10% 0% Mean BL LF = 18.3% Mean BL LF = 20.5% BL ≥ 8% BL ≥ 10% Relative % Change of Liver Fat % Mean Relative* Liver Fat % Change LPCN 1144: Liver Fat Imaging Study (“LFS”) Results Meaningful Relative Liver Fat % Change and Responder Rate 9 LFS was an open - labe
Slide 10: LPCN 1144: Longitudinal Treatment Effect
■ NAFL Free (LF < 5%) ■ NAFL (LF ≥ 5%) 10 NAFLD Free NAFLD Free NAFLD Free NAFLD Free NAFLD Free NAFLD Free 52% 48% Interim (Week 8, N=31) NAFL Free NAFL 63% 38% End of Study (Week 16, N=32) NAFL Free NAFL 34% 66% Baseline (N=32) NAFL Free NAFL LPCN 1144: Longitudinal Treatment Effect Improved NAFL
Slide 11: LPCN 1144: LiFT Study Ongoing
LPCN 1144: LiFT Study* Ongoing Liver Fat Intervention with Oral Testosterone Study 11 Phase 2 paired - biopsy clinical study in NASH subjects (NCT04134091) □ Study Design ▪ Three - arm (1:1:1 randomization, two treatments and placebo), multi - center, double - blind ▪ 225mg twice daily (450mg Daily)
Slide 12: Testosterone Replacement Therapy
Testosterone Replacement Therapy
Slide 13: Hypogonadism Affects Up to 20M Men
Confidential □ Close to 6M men with diagnosed hypogonadism 3 □ 2M men being treated 4 1. US Census data. http://www.infoplease.com/us/census/data/demographic.html. 2. Mulligan T, et al. Int J Clin Pract. 2006 Jul;60(7):762 - 9. 3. Araujo, et al. J Clin Endo Metabol 2007. 92(11):4241 - 7. 4. Symphony
Slide 14: Testosterone Replacement Therapy Market
Testosterone Replacement Therapy (TRT) Market TRT Market is Growing Without an Oral Option 14 Source: Antares Pharma presentation at JEFFERIES 2019 HEALTHCARE CONFERENCE TRx = Total prescriptions 7.0M 7.9M 7% Up 13% Up 6.5M Total Injectables Topicals
Slide 15: Issues with Current Non-oral TRT Options
Issues with Current Non - oral TRT Options Potential Barrier To Newly Diagnosed and Existing Patients • Black Box Warning – Secondary exposure to testosterone – Pulmonary oil micro embolism (POME) and anaphylaxis shock • Inconvenient application or painful injection • Poor persistence reflects need
Slide 16: ~$2B+ opportunity in an established and growing market
16 ~$2B+ opportunity in an established and growing market
Slide 17: TLANDO Regulatory Update
TLANDO Regulatory Update Post Action Meeting Scheduled for January 2020 • CRL received November 2019 – One deficiency • Did not meet the three secondary endpoints for maximal testosterone concentrations ( Cmax ) – No CMC deficiencies – FDA confirmed serum data reliable and reflects in vivo T measure
Slide 18: Once Daily Oral Testosterone Replacement Therapy
Once Daily Oral Testosterone Replacement Therapy
Slide 19: LPCN 1111: Market Research Physician Intent-to-Prescribe
Future Prescribing Patterns with Entrenchment of Product X BID Future Prescribing Patterns with Entrenchment of Product X QD CE11: Assume Product X is dosed QD vs, BID, adjust percentages to reflect intent - to - prescribe. 1. P<0.01 31% 4% 9% 1% 53% 1% 24% 4% 7% 1% 64% 1% 19 LPCN 1111: Market Resea
Slide 20: Phase 2b Study: Result Summary
Phase 2b Study: Result Summary Met Primary and Secondary Endpoints • Once daily dose for 14 days in an open label, multiple dose PK study in hypogonadal men (n=36 subjects) x Met primary and secondary endpoints x Phase 3 dose identified x No drug related SAEs x Drug related AEs are mild to moderate
Slide 21: Upcoming Milestones
Upcoming Milestones 21 Near Term Value Drivers Event Expected Timing TLANDO™ Post Action Meeting January 2020 LPCN 1148 File Investigational New Drug Application 1Q 2020 TLANDO XR FDA feedback on Phase 3 protocol 2Q 2020 LPCN 1144 LiFT Study Primary Endpoint Results Mid - 2020
Slide 22: Key Financial Metrics
Key Financial Metrics 22 Stock Price, Market Cap, Cash Balance Ticker Symbol LPCN (Nasdaq Capital Market) Closing Stock Price (1/9/20) $0.42/share Market Capitalization (1/9/20) $15.6 million Cash Balance (9/30/19) $16.5 million* † Bank Debt (9/30/19) $7.9 million * $5M restricted and becomes unrest
Slide 23: Lipocine Investment Highlights
Lipocine Investment Highlights 23 Robust Pipeline • Unmet need with no approved drug • Most male NASH patients have low testosterone with signs and symptoms of hypogonadism • LPCN 1144 : A differentiated modality with potential for mono/combo pre - cirrhotic NASH therapy • LPCN 1148 : Targeting cirr
Slide 24: Appendix
LIPOCIN= Appendix
Slide 25: LPCN 1144 for Pre-Cirrhotic NASH
Enabling Oral Drug Delivery to Improve Patient Compliance LPCN 1144 for Pre - Cirrhotic NASH
Slide 26: LPCN 1144: Rationale to Target Pre-Cirrhotic NASH
LPCN 1144: Rationale to Target Pre - Cirrhotic NASH 26 1. Estes et al., Hepatol 2018; 2. Williams et al., Gastroenterology. 2011. *near term target Multi - billion $ Opportunity 11 M Male* NASH Patients 17 M NASH Patients in 2015 1 83M NAFLD Patients in US, 2015 1 Underappreciated conditions Unmet N
Slide 27: LPCN 1144: Multi-Dimensional Mechanism of Action
LPCN 1144: Multi - Dimensional Mechanism of Action Across the Full Spectrum of NASH Pathogenesis 27 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 -
Slide 28: Potential of Testosterone Therapy in NAFLD Preclinical Model Results
Potential of Testosterone Therapy in NAFLD Preclinical Model Results 28 1. Kelly et al., Lif Sci 2014; 2. Nikolaenko et al., BMC Endocrinol 2014; 3. Cai et al., BMC Genomics 2015 Model Mouse Model 1 Rat Model 2 Pig Model 3 Methods ▪ Testicular - feminized + High cholesterol diet ▪ Castrated + High f
Slide 29: Potential of Testosterone Therapy: Rabbit Model
Potential of Testosterone Therapy Results from high fat diet (HFD) induced rabbit model* Giemsa – PAS Staining Red Oil Staining Masson’s Trichrome Staining TRT ↓ fibrosis TRT ↓ steatosis TRT ↓ inflammation RD HFD HFD +T * Vignozzi et al., Mol Cell Endocrinol 2014 29 T: Testosterone; OCA: Obeticholic
Slide 30: T Therapy Effects in Liver Regeneration
T Therapy Effects in Liver Regeneration Results from Hepatectomized Rat Model* 30 *90% hepatectomized, Vic et al., Hepatol 1982 40% recovery 60% recovery Total liver mass recovery completed Day 3 Day 4 Day 15 Testosterone Pretreatment Day 0 Day - 30 Testosterone Hepatectomy No Treatment Group 1 (n=5
Slide 31: LPCN 1144: Clinical Tolerability Experience
LPCN 1144: Clinical Tolerability Experience Oral Prodrug of Endogenous Testosterone 31 Adverse Reaction N=654 subjects Headache 1.50% Acne 0.90% Hematocrit Increased 1.20% Blood Pressure Increased 0.30% Fatigue 0.20% Hypertension 0.60% □ 654 subjects in multiple completed studies with up to 52 - wee
Slide 32: Sarcopenia is Associated with NAFLD/NASH
Sarcopenia is Associated with NAFLD/NASH 1 LPCN 1144 has Potential to Improve Sarcopenia 2,3 32 1. Bhanji et al., Hepatol 2017 2. Bhasin S., J Gerontol 2003 3. Sinclair et al., J Gastroenterol Hepatol 2016 x Sarcopenia endpoint(s) under evaluation in the ongoing LiFT trial 3
Slide 33: Sexual Dysfunction is Associated with NAFLD/NASH
Sexual Dysfunction is Associated with NAFLD/NASH 1 LPCN 1144 has Potential to Improve Sexual Dysfunction 2 33 1. Hawksworth et al., Sex Med Rev 2019 2. Rizk et al., Curr Opin Urol 2017 3. SOAR Trial: SOAR Trial: subjects for ALT BL > 40 U/L (N=33) 3 x Sexual dysfunction endpoint(s) under evaluation
Slide 34: Depression is Prevalent in NAFLD Patients
Depression is Prevalent in NAFLD Patients 1 LPCN 1144 has Potential to Improve Mental Health 2 34 3 1. Ali et al., Psychosomatics 2011 2. Celec et al., Front Neurosci 2015 3. SOAR Trial: subjects for ALT BL > 40 U/L (N=33) x Mental health endpoint(s) under evaluation in the ongoing LiFT trial
Slide 35: Quality of Life is Poor in NAFLD Patients
Quality of Life is Poor in NAFLD Patients 1 LPCN 1144 has Potential to Improve Quality of Life 2 35 1. Assimakopoulos et al., J Psychosom Res 2018 2. Almehmadi et al., Arab J Urol 2016 3. SOAR Trial: subjects for ALT BL > 40 U/L (N=33) 3 x Quality of life endpoint(s) under evaluation in the ongoing
Slide 36: LPCN 1144: Resolution of Liver Injury Markers
LPCN 1144: Resolution of Liver Injury Markers Significant Normalization of Elevated Liver Enzymes* 36 52% 50% 67% 31% 0% 10% 20% 30% 40% 50% 60% 70% ALT AST ALP GGT % of Patients Normalized at EOS N 42 4 6 36 BL 53.6 U/L 59.8 U/L 125.3 U/L 82.2 U/L *1 - Yr SOAR Study (NCT02081300)
Slide 37: LPCN 1144: Reduction of Liver Injury Markers
- 7.9 - 11.1 - 3.4 - 4.2 - 4.8 - 4.5 - 5.2 - 6.5 -16.0 -14.0 -12.0 -10.0 -8.0 -6.0 -4.0 -2.0 0.0 1 2 Mean Change from Baseline ALT, U/L AST, U/L ALP, U/L GGT, U/L LPCN 1144: Reduction of Liver Injury Markers In Patients with Elevated ALT at Baseline (BL) ▪ Liver enzymes mean change from BL to 1 - Yr
Slide 38: LPCN 1144: Effects on Serum Lipid Markers
LPCN 1144: Effects on Serum Lipid Markers In Patients with Elevated Lipids at Baseline (BL) 38 • TG(triglyceride), LDL, Cholesterol, HDL upper normal limit (UNL) is 200 mg/dL, 160 mg/dL, 200 mg/dL, and 60 mg/dL, respective ly. • 1 - Yr SOAR Study (NCT02081300) - 17 - 64 -100 -80 -60 -40 -20 0 BL = 1
Slide 39: ~$2B+ opportunity in an established and growing market
39 ~$2B+ opportunity in an established and growing market
Slide 40: TLANDO Attributes
TLANDO ™ Attributes Patient and Physician Preferred Option Convenient Oral Route: • No risk of accidental T transference • Non - invasive; easy to use • Less cumbersome/burdensome • Potential for higher persistence/adherence Fixed Dosing Regimen • Easy to use for patients and physicians to prescribe
Slide 41: Enabling Oral Drug Delivery to Improve Patient Compliance
Enabling Oral Drug Delivery to Improve Patient Compliance
Slide 42: LPCN 1148: Oral T for Cirrhosis
LPCN 1148: Oral T for Cirrhosis No FDA Approved Drug 42 Alcoholic liver disease Nonalcoholic Fatty Liver Disease (NAFLD) Chronic hepatitis B Chronic hepatitis C Cryptogenic 44,478 deaths in 2017 2 Estimated 1.3 M patients with liver cirrhosis 1 Liver Cirrhosis in US 1: Estes C. et al., Hepatology, 2
Slide 43: High Economic Burden of a Liver Transplant
High Economic Burden of a Liver Transplant Transplant Only Cure for Liver Cirrhosis 43 30 Days Pre - Transplant: $41,400 Procurement: $94,000 Hospital Transplant Admission: $463,200 Physician during Transplant Admission: $56,000 180 Days Post - Transplant Discharge: $126,900 Op Immunosuppressants &
Slide 44: Impact of Low Testosterone on Cirrhosis
Impact of Low Testosterone* on Cirrhosis Progressive drop in T level with increasing disease severity 1 44 Increased risk of major infections, death and/or transplantation rates 1 Worsening of sarcopenia 3 Increased risk of for hepatic decompensation 3 Higher Child - Pugh score 3/ Higher MELD score
Slide 45: Low Testosterone: Independent Predictor of Mortality in Late Stage Cirrhosis
Low Testosterone (T) An independent predictor of mortality in late stage cirrhosis 1 45 □ Low T (<8.3 nmol/L) associated with increased risk of major infections, death and/or transplantation rates 1 1. Sinclair M. et al., J. of Gastro and Hepatology 2015, 2.Moctezuma - Velazquez et al., Ann Hepatol
Slide 46: LPCN 1107 Prevention of Preterm Birth
LPCN 1107 Prevention of Preterm Birth 46 Enabling Oral Drug Delivery to Improve Patient Compliance
Slide 47: Unmet Medical Need: Preterm Birth
47 • A leading cause of neonatal mortality • ≥ $26 billion economic impact 2 • 10% of all US pregnancies 3 – PTB in singleton pregnancies: 8.1% • Medical costs for PTB infants are ~10x higher than for full term infants 4 1. Pediatric Research (2006) 60, 775 – 776 2. Institute of Medicine of the Nati
Slide 48: LPCN 1107 Opportunity
LPCN 1107 Opportunity Market Potential: ~1 billion Potential to be the First Oral HPC for Prevention of Recurrent PTB • Preferred route - of - administration is oral • ~140,000 annually pregnancy with history of at least one singleton spontaneous PTB* Potential for Clinical Success • Superior Cavg t
Slide 49: LPCN 1107 – First Oral HPC for Prevention of PTB
LPCN 1107 – First Oral HPC for Prevention of PTB Injectable IM 17 - HPC, Makena® and SubQ HPC, Makena® (Standard of Care) 49 LPCN 1107 Oral 17 - HPC □ Twice daily dose • No injection site reactions • Steady state achieved in 7 days □ Higher HPC levels (potentially better efficacy than Makena®) □ Orp
Slide 50: Makena PK-PD Correlation: HPC Concentration and PTB Rate
50 • Lower % PTB rate can be expected with daily Cavg 2 HPC levels ≥ 8.2 ng/mL 1. Caritis et al., Am J Obstet Gynecol. 2014 (N=315 subjects) 2. Ctrough for IM HPC Cavg , Makena PK - PD Correlation HPC Concentration and PTB Rate 1 46.3% 27.0% 29.6% 31.3% N=315 KP72
Slide 51: LPCN 1107: Dose Finding Clinical Study
LPCN 1107: Dose Finding Clinical Study PK Study: Oral LPCN 1107 vs IM HPC, Makena • 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 51 Treatment A 400 mg BID Treatment B 600 mg B
Slide 52: Dose Finding Study: PK Results
Dose Finding Study: PK Results * LPCN 1107 vs. Injectable Makena® • Average HPC levels at target LPCN 1107 greater than the comparator, Makena® • HPC levels below 8.2 ng/ml: 0% subjects on LPCN 1107 vs. 20% subjects on IM Injection 52 * PK results obtained from post 5 weeks for weekly IM Injection &