Lipocine Inc. · NASDAQ:LPCN
Lipocine — Investor Presentation (March 2020)
50 slides from Lipocine's investor presentation, Mar 13, 2020
Slide 1: Enabling Oral Drug Delivery to Improve Patient Compliance
Enabling Oral Drug Delivery to Improve Patient Compliance March 2020 Corporate Presentation Exhibit 99.2
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 TLANDO ™ (Oral Testosterone for Testosterone Replacement Therapy “TRT”) PDUFA Date August 28
Slide 4: TLANDO Fixed Dose Oral TRT
LIPOCIN= TLANDO™ Fixed Dose Oral TRT
Slide 5: 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 6: TRT Market is Growing Without Oral Option
2019 2018 2017 2016 2014 2015 350 375 400 425 450 475 500 525 550 575 600 625 650 675 Oct 14 Dec 14 Feb 15 Apr 15 Jun 15 Aug 15 Oct 15 Dec 15 Feb 16 Apr 16 Jun 16 Aug 16 Oct 16 Dec 16 Feb 17 Apr 17 Jun 17 Aug 17 Oct 17 Dec 17 Feb 18 Apr 18 Jun 18 Aug 18 Oct 18 Dec 18 Feb 19 Apr 19 Jun 19 Aug 19 Oct
Slide 7: 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 8: TLANDO Has Potential to Improve Persistence
Source: Adheris Health 2017 TLANDO Has Potential to Improve Persistence Titration Requirements of Current TRTs Cohort Period: February 2016 – January 2017 Analysis Period: 12 Months Look Back: 6 months for new patients Patient Group % Persistent Patients Day 30 Day 180 Day 360 New 50.8% 18.0% 9.2% E
Slide 9: TLANDO Attributes
TLANDO ™ Attributes Fixed Dose Oral TRT Option Convenient Oral Route • Patient and Physician preferred Easy to Prescribe Fixed Dosing Regimen • No additional dose adjustment visits • Less prone to drop out after first Rx • The “right” dose from the start of therapy with TLANDO ™ for all patients • N
Slide 10: TLANDO Regulatory Update
TLANDO Regulatory Update Near Term PDUFA Date 10 PDUFA Date August 28, 2020 NDA Filed February 28, 2020 The NDA incorporates the reanalysis of existing data to address the deficiency discussed in the Post Action Meeting with the FDA Post Action Meeting January 16, 2020 The FDA indicated approach to
Slide 11: LPCN 1144 for Pre-Cirrhotic NASH
Enabling Oral Drug Delivery to Improve Patient Compliance LPCN 1144 for Pre - Cirrhotic NASH
Slide 12: LPCN 1144: Rationale to Target Pre-Cirrhotic NASH
LPCN 1144: Rationale to Target Pre - Cirrhotic NASH 12 1. Estes et al., Hepatol 2018 2. Williams et al., Gastroenterology. 2011 *2015 data ~6.9 M Male NASH F2 - F3 in 2030 1,2 Estimated Market* Currently No Approved Treatment Multi - billion $ Opportunity 3.5 M Male NASH with F2 - F3 1,2 11 M Male N
Slide 13: 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 • NASH resolution and/or fibrosis improvement • Acceptable tolerability for chronic use • Improvement of sarcopenia • Improvement of sexual dysfunction • Improveme
Slide 14: Association Between Testosterone and Liver Disease
14 1. Sarkar et al., Gastroenterology 156(6):S - 1258 & Poster Sa1623, Digestive Disease Week 2019 2. Sumida et al., Gastroenterol Hepatol 2015; 3. Sinclair et al., Liver Trans 2016; 4. Sinclair M. et al., J. of Gastro and Hepatology, 2015; “Low T reported in up to 90% of NASH cirrhosis patients 3 a
Slide 15: LPCN 1144 Proposed Mechanism Across NASH Pathogenesis
LPCN 1144 Proposed Mechanism 15 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 stre
Slide 16: LPCN 1144: Liver Fat Imaging Study
LPCN 1144: Liver Fat Imaging Study (“LFS”) Study Design and Baseline Liver Fat Subject Distribution 16 LFS was an open - label, multi - center single - arm 16 - week study (N=36) with 225 mg BID LPCN 1144 in hypogonadal males LF = liver fat
Slide 17: LPCN 1144: Liver Fat Reduction
LPCN 1144: Liver Fat Reduction Meaningful Relative Liver Fat % Change and Responder Rate 17 LF = liver fat BL = baseline NCT03868059 - 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 (
Slide 18: LPCN 1144: Longitudinal Treatment Effect
18 LPCN 1144: Longitudinal Treatment Effect Improved NAFL Resolution Over Time 34% 52% 63% 0% 20% 40% 60% 80% Baseline 8 Wk 16 Wk NAFL - Free % of Population NAFL Resolution to < 5% Liver Fat (N=31) (N=32) (N=32) NAFL is non - alcoholic fatty liver with ≥ 5% liver fat NCT03868059
Slide 19: LPCN 1144: Reduction of Liver Injury Markers
- 11.1 - 4.2 - 4.5 - 6.5 -16.0 -14.0 -12.0 -10.0 -8.0 -6.0 -4.0 -2.0 0.0 2.0 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 ▪ Liver enzymes mean change from baseline to end of study (1 - Yr), NCT020
Slide 20: LPCN 1144: LiFT Study Ongoing
LPCN 1144: LiFT Study* Ongoing Liver Fat Intervention with Oral Testosterone Study 20 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 21: Upcoming Milestones
Upcoming Milestones 21 Near Term Value Drivers Event Expected Timing TLANDO™ PDUFA Date August 28, 2020 LPCN 1144 LiFT Primary Endpoint Results 2H 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 (3/12/20) $0.415/share Market Capitalization (3/12/20) $19.9 million Cash Balance (12/31/19) $19.1 million* ₸ Bank Debt (12/31/19) $7.1 million * $5M restricted and becomes u
Slide 23: Lipocine Investment Highlights
Lipocine Investment Highlights Near Term TLANDO PDUFA with a Promising Pipeline • TLANDO™: Differentiated product profile with potential for market expansion • TLANDO XR: Unique long acting oral with potential to maintain leadership • ~$2B+ opportunity in an established and growing market with favor
Slide 24: Appendix
LIPOCIN= Appendix
Slide 25: TRT Market Dynamics
LIPOCIN= TRT Market Dynamics
Slide 26: Current Market Dynamics in TRT Space
Current Market Dynamics in TRT Space Prime Opportunity for TLANDO™ • 85% of physicians have strong interest in oral • 95% of TRT patients likely to ask their doctor about TLANDO ™ Patient and physicians preferred 1 • Able to have high share of voice with far less competitive promotion than in the pa
Slide 27: Once Daily Oral Testosterone Replacement Therapy
Once Daily Oral Testosterone Replacement Therapy
Slide 28: 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% 28 LPCN 1111: Market Resea
Slide 29: 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 Phase 3 dose identified x No Drug related SAEs x Drug Related AEs are Mild to Moderate ▪ Next step: Pivotal study protocol su
Slide 30: LPCN 1144 for Pre-Cirrhotic NASH
Enabling Oral Drug Delivery to Improve Patient Compliance LPCN 1144 for Pre - Cirrhotic NASH
Slide 31: Unmet Needs in Pre-Cirrhotic NASH
Unmet Needs in Pre - Cirrhotic NASH 31 Currently No Approved Treatment 1. Bhanji et al, Hepatol 2017 2. Koo et al, J Hepatol 2017 3. Petta et al, Aliment Pharmacol Ther 2017 4. Hawksworth et al., Sex Med Rev 2019 5. Duman et al., J Sex Med. 2016 6. Ali et al., Psychosomatics 2011 7. Assimakopoulos e
Slide 32: LPCN 1144: Multi-Dimensional Mechanism of Action
LPCN 1144: Multi - Dimensional Mechanism of Action Across the Full Spectrum of NASH Pathogenesis 32 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 33: Potential of Testosterone Therapy in NAFLD Preclinical Model Results
Potential of Testosterone Therapy in NAFLD Preclinical Model Results 33 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 34: 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 34 T: Testosterone; OCA: Obeticholic
Slide 35: T Therapy Effects in Liver Regeneration
T Therapy Effects in Liver Regeneration Results from Hepatectomized Rat Model* 35 *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 36: LPCN 1144: Clinical Tolerability Experience
LPCN 1144: Clinical Tolerability Experience Oral Prodrug of Endogenous Testosterone 36 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 studies with up to 52 - week exposure
Slide 37: Sarcopenia is Associated with NAFLD/NASH
Sarcopenia is Associated with NAFLD/NASH 1 LPCN 1144 has Potential to Improve Sarcopenia 2,3 37 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 Comorbidity Therapeutic
Slide 38: Sexual Dysfunction is Associated with NAFLD/NASH
Sexual Dysfunction is Associated with NAFLD/NASH 1 T Therapy has Potential to Improve Sexual Dysfunction 2 38 1. Hawksworth et al., Sex Med Rev 2019 2. Rizk et al., Curr Opin Urol 2017 3. SOAR Trial: SOAR Trial: subjects with baseline ALT > 40 U/L (N=33) 3 x Sexual dysfunction endpoint(s) under eval
Slide 39: Depression is Prevalent in NAFLD Patients
Depression is Prevalent in NAFLD Patients 1 T Therapy has Potential to Improve Mental Health 2 39 3 1. Ali et al., Psychosomatics 2011 2. Celec et al., Front Neurosci 2015 3. SOAR Trial: subjects with ALT BL > 40 U/L (N=33) x Mental health endpoint(s) under evaluation in the ongoing LiFT trial Comor
Slide 40: Enabling Oral Drug Delivery to Improve Patient Compliance
Enabling Oral Drug Delivery to Improve Patient Compliance
Slide 41: LPCN 1148: Oral T for Cirrhosis
LPCN 1148: Oral T for Cirrhosis No FDA Approved Drug 41 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 42: High Economic Burden of a Liver Transplant
High Economic Burden of a Liver Transplant Transplant Only Cure for Liver Cirrhosis 42 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 43: Impact of Low Testosterone on Cirrhosis
Impact of Low Testosterone* on Cirrhosis Progressive Drop in T level With Increasing Disease Severity 1 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 4 S
Slide 44: LPCN 1107 Prevention of Preterm Birth
LPCN 1107 Prevention of Preterm Birth Enabling Oral Drug Delivery to Improve Patient Compliance 44
Slide 45: Unmet Medical Need: One Preterm Birth Every Minute
• 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 Nationa
Slide 46: 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
Slide 47: LPCN 1107: First Oral HPC for Prevention of PTB
LPCN 1107 – First Oral HPC for Prevention of PTB Injectable IM 17 - HPC, Makena® (Standard of Care) 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®) □ Orphan drug designated • Maj
Slide 48: Makena PK-PD Correlation
• 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 48
Slide 49: 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 Treatment A 400 mg BID Treatment B 600 mg BID
Slide 50: PK Results: LPCN 1107 vs. Injectable Makena
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 * PK results obtained from post 5 weeks for weekly IM Injection & post 8 days of BID dos