Lipocine Inc. · NASDAQ:LPCN
Lipocine — Investor Presentation (November 2018)
62 slides from Lipocine's investor presentation, Nov 8, 2018
Slide 1: Enabling oral drug delivery to improve patient compliance
Enabling oral drug delivery to improve patient compliance November 2018 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: Unique Specialty Pharmaceutical Company
Men's Health Oral Testosterone Replacement Therapy (“TRT”) Oral Androgen Therapy for Fatty Liver Disease (“NAFLD”/ “NASH”) Women's Health Oral Therapy for Prevention of Preterm Birth (“PTB”) Proprietary Drug Delivery Platform Significant Unmet Need In Both Therapeutic Areas 3 Unique Specialty Pharma
Slide 4: Late-Stage Pipeline
Late - Stage Pipeline 4 Oral Product Candidates Targeting Significant Opportunities PRODUCT (Indication) PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA MEN’S HEALTH TLANDO™ (Oral Testosterone Replacement Therapy, TRT) Phlebotomy and ABPM Studies Ongoing LPCN 1111 (Next Gen. Oral TRT) Phase 2 Completed LPCN
Slide 5: Targeted for Testosterone Replacement Therapy
5 Targeted for Testosterone Replacement Therapy
Slide 6: TRT Market is Growing
2018 2017 2016 2014 2015 350 375 400 425 450 475 500 525 550 575 600 625 650 675 Sep 14 Nov 14 Jan 15 Mar 15 May 15 Jul 15 Sep 15 Nov 15 Jan 16 Mar 16 May 16 Jul 16 Sep 16 Nov 16 Jan 17 Mar 17 May 17 Jul 17 Sept 17 Nov 17 Jan 18 Mar 18 May 18 Jul 18 Sep 18 Monthly TRx (000s) FDA Label Guidance Month
Slide 7: 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 8: TLANDO: Path Forward for Resubmission
TLANDO™: Path Forward for Resubmission Confirmed Next Steps in Bring Tlando to Patients Deficiencies and Plan for Resolution Determine extent, if any, of ex vivo conversion of TU to T Obtain definitive evidence pre - approval via ambulatory blood pressure monitoring study to exclude whether TLANDO c
Slide 9: TLANDO: Potential First Oral Option
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% ▪ Met key secondary endpoint - No eligible subjects with T levels >2500 ng/ dL ▪ Other secondary endpoints g
Slide 10: Targeted for NASH with No Approved Product
10 Targeted for NASH with No Approved Product The NASH market could peak at $30 - 40 billion by 2025 1 1. Deutsche Bank industry report, “NASH – the next big global epidemic in 10 years?”, 2014 MB262
Slide 11: LPCN 1144: Well Positioned for Success
LPCN 1144: Well Positioned for Success Unique Mechanism of Action and Well Tolerated Safety Profile ▪ Unique Mechanism Targeting Full Spectrum of NASH Pathogenesis + Collateral Health Benefits – Testosterone deficiency in men is prevalent across the full spectrum of NAFLD – LPCN 1144 results suggest
Slide 12: NAFLD Clinical Progression
Non - Alcoholic Fatty Liver Disease (NAFLD) Clinical Progression 12 Fatty liver is a reversible condition wherein large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis LFTs: Liver function test, especially Alaninine amino transferase (ALT) and Aspartame amino tran
Slide 13: Clinical Relationship Between Testosterone and NAFLD
Clinical Relationship Between Testosterone and NAFLD Across the Full Histological 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, he
Slide 14: LPCN 1144: Targeting Full Spectrum of NASH Pathogenesis
Accumulation of Fat in Liver Cell Damage/ Steatosis Inflammation/ Steatohepatitis Fibrosis Cirrhosis Homeostasis Modifier Anti - Inflammatory Fibrosis Mediator / Regeneration LPCN 1144: Targeting Full Spectrum Of NASH Pathogenesis Plus Collateral Health Benefits ▪ Reduction of elevated ALT levels ge
Slide 15: T Therapy Demonstrated Histological Improvement
T Therapy Demonstrated Histological Improvement Multiple Biopsy Confirmed High Fat/Cholesterol Diet Induced Animal Models Testicular Feminized Mouse 1 Castrated NAFLD Rat 2 Non - Genomic, Metabolic Syndrome Rabbit 3 Castrated Pig 4 ▪ Hepatic lipid deposition ▪ Lipogenesis ▪ Hepatic steatosis ▪
Slide 16: LPCN 1144: Compelling Clinical Biomarker Data
- 64 - 35 - 19 - 9 - 21 12 - 33 -80 -60 -40 -20 0 20 LPCN 1144 (Wk 52) BL=1.6xULN‡ LPCN 1144 (Wk 52) BL=1.2xULN Obeticholic acid 25mg (Wk 72) BL=1.3xULN Cenicriviroc 150mg (Wk 52) BL=1.2xULN Selon/Simtu† 18mg/125mg (Wk 24) BL=1.2xULN Selon/Simtu† 6mg/125mg (Wk 24) BL=1.2xULN Aramchol 600mg (Wk 52) B
Slide 17: LPCN 1144: Robust ALT Response
17 † Total N is for patients with ALT > 40 U/L at baseline (ALT normal range is ≤ 40 U/L) 43% 48% 0% 10% 20% 30% 40% 50% 60% N = 42* N = 71* LPCN 1144 (Wk 52) Vitamin E (Wk 120) % of ALT Responders at EOS * ALT Responders: Patients with ALT > 40 U/L at baseline, ending with ≤ 40 U/L and more than 30
Slide 18: LPCN 1144: Collateral Health Benefits
LPCN 1144: Collateral 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 19: LPCN 1144: Summary and Next Steps
LPCN 1144: Oral Testosterone for the Treatment of NASH Summary and Next Steps ▪ Unique Mechanism Targeting Full Spectrum of NASH Pathogenesis + Collateral Health Benefits – Testosterone deficiency in men is prevalent across the full spectrum of NAFLD – LPCN 1144 results suggest therapy has potential
Slide 20: LPCN 1107
LIPOCIN= LPCN 1107
Slide 21: LPCN 1107: Prevention of Preterm Birth Market Landscape
LPCN 1107: Prevention of Preterm Birth (PTB) United States Market Landscape $1B Market Opportunity 3 December 31, 2017 Makena Net Revenue ($M) 4 Makena ® 1 50% Off Guidance 2 30% Compounded 17 - HPC 20% $334 $385 2016 2017 15% 1. Amag estimates Makena market share based on distributor dispensing dat
Slide 22: LPCN 1107: 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 23: Upcoming Milestones
Upcoming Milestones 23 Near Term Value Drivers Event Expected Timing TLANDO™ Complete definitive Phlebotomy study ABPM study results 4Q 2018 1Q 2019 LPCN 1144 Complete In - vivo model Proof - Of - Concept study in biopsy - confirmed NASH POC clinical study results in imaging - confirmed NAFLD/NASH p
Slide 24: Key Financial Metrics
Key Financial Metrics 24 Stock Price, Market Cap, Cash Balance Ticker Symbol LPCN (Nasdaq Capital Market) Closing Stock Price (11/5/18) $1.49/share Market Capitalization (11/5/18) $32.0 million Fully Diluted Shares Outstanding (9/30/18) 25.3 million Cash Balance (9/30/18) $21.9 million* Bank Debt (9
Slide 25: Lipocine Investment Highlights
MEN’S HEALTH • TLANDO™ : Potential first oral TRT option - Differentiated product targeting ~$2.0 billion established US TRT market • LPCN 1144 : Oral prodrug of bio - identical testosterone for NASH - Compelling clinical biomarker data in patients with typical comorbidities of NASH • LPCN 1111 : Ne
Slide 26: Appendix
LIPOCIN= Appendix
Slide 27: TLANDO
LIPOCIN= TLANDO™
Slide 28: Hypogonadism Affects Up to 6M American Men
Hypogonadism Affects Up to 20 M American Men 1,2 28 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 29: TLANDO: Patient Market Research
TLANDO: Patient Market Research Patient Enthusiasm Evident About Oral TRT 29 29 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 30: TLANDO: Physician Market Research
TLANDO: Physician Market Research Oral Agent is Most Important Attribute for Prescribers 30 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 Responde
Slide 31: TLANDO SOAR Study Blood Pressure Data
-4 -3 -2 -1 0 1 2 3 4 5 6 Mean SPB Change (mmHg) 13-001 TLANDO Week 3 (n=193) 13-001 TLANDO Week 7 (n=182) 13-001 TLANDO Week 13 (n=157) 13-001 TLANDO Week 26 (n=144) 13-001 TLANDO Week 39 (n=138) 13-001 TLANDO Week 52 (n=130) 13-001 TLANDO Overall (n=944) TLANDO™ SOAR Study Blood Pressure Data Syst
Slide 32: Oral TU: Dose-Systolic BP Relationship
Oral TU: Dose - Systolic BP Relationship Differences Between Single/Triplicate/ABPM Measurements Brand Mean Single SBP Mean Triplicate SBP Mean ABPM Daytime SBP Study / Dose D SBP from baseline Study / Dose D SBP from baseline Study / Dose D SBP from baseline JATENZO (High Dose) CLAR 09007 Day30 / P
Slide 33: LPCN 1111 QD TLANDO
33 LPCN 1111 QD TLANDO
Slide 34: LPCN 1111: Next-Generation Oral TRT
LPCN 1111: Next - Generation Oral TRT ▪ Novel prodrug of testosterone for oral delivery ▪ Once - daily potential expected to sustain and improve market share of oral T franchise ▪ Once - daily feasibility established in Phase 2a and 2b clinical trials – Single - daily oral dose provides T levels in
Slide 35: LPCN 1107
LIPOCIN= LPCN 1107
Slide 36: 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 37: LPCN 1107: First Oral PTB Candidate
LPCN 1107: First Oral PTB Candidate 37 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 38: LPCN 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‡‡ 38 ‡: Assuming 100% of 140,000 eligible US population treated ‡‡: Assuming ~$51,600 medical costs/PTB
Slide 39: LPCN 1107: First Oral PTB Candidate Commercial Outlook
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 40: LPCN 1107: HPC PK-PD Correlation
LPCN 1107: HPC PK - PD Correlation 40 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 2 46.3% 27.0% 29.6% 31.3%
Slide 41: LPCN 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 41 PK Study: Oral LPCN 1107 vs IM HPC, Makena Treatment D 250mg Weekly Treatment C 800mg BI
Slide 42: LPCN 1107: Dose-Finding PK Study Results
LPCN 1107: Dose - Finding PK Study Results 1 42 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 43: LPCN 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
Slide 44: LPCN 1144
LIPOCIN= LPCN 1144
Slide 45: Testosterone Deficiency Relevant in Chronic Liver Diseases
Testosterone Deficiency Relevant in Chronic Liver Diseases* Significant Overlap of NASH and Hypogonadism 45 1. SOAR Trial demographics, 2. Younossi et al., Hepatol 2016, 3. Dhindsa et al., Diabetes Care 2010 * Kim et al, Male hypogonadism and liver disease in Male hypogonadism and basic clinical and
Slide 46: Proposed Mechanism of Androgen Action via Androgen Receptor
Proposed Mechanism of Androgen Action via Androgen Receptor (AR) in Males* 46 Normal level and signaling of androgens prevent hepatic fat accumulation in males** * Navarro et al, Obesity 2015 ** Shen and Shi, Int J Endocrinol 2015
Slide 47: Low T Association with NAFLD and Cirrhosis
Low T Association with NAFLD and Cirrhosis 47 x After adjusting for age, smoking, diabetes, exercise, BMI, TG and HDL, the lowest T quintile (110 – 317 ng/dL) have OR † of 5.12 (2.43 – 10.77) for NAFLD x Low T (<8.3 nmol/L; 239 ng/dL) remained a significant predictor of reduced survival in cirrhotic
Slide 48: Free T Association with NASH Progression
Free T Association with NASH Progression 48 Free T and NAFL/NASH Free T and Stages of NASH Fibrosis Patients with NASH show significantly lower free T than those with non - alcoholic fatty liver (NAFLD) 1 1. Sumida et al, Gastroenterol Hepatol 2015 Free T Free T
Slide 49: Testosterone Deficiency Induces NAFLD/NASH
Testosterone Deficiency Induces NAFLD/NASH Testosterone Treatment Improves Liver Functions 1 49 Intact + Normal Diet I + RCD (Control) Intact + High Fat Diet I + HFD Castrated + High Fat Diet C + HFD Castrated + High Fat Diet + Testosterone C + HFD + T 1 Rat Study ( Nikolaenko et al, Endocrinol 2014
Slide 50: LPCN 1144: Proposed Multidimensional Mechanism of Actions
LPCN 1144: Oral T Proposed Multidimensional Mechanism of Actions ▪ 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 - inflammatory 2 / Immuno - modu
Slide 51: LPCN 1144: Post-hoc Analysis Methods
LPCN 1144: Post - hoc Analysis Methods ▪ Analyses of LPCN 1144 therapy results were performed with multiple clinical studies involving hypogonadal male cohorts with baseline liver enzymes* and lipids** • Placebo - controlled, randomized, double blind study ( M12 - 778 ) with four week treatment x An
Slide 52: LPCN 1144: General Safety
LPCN 1144: General Safety ▪ LPCN 1144 is a prodrug of bioidentical sex hormone – History of safe Ex - US Oral TU use for decades – 8,400 patients / 15,600 patient years of use of over 19 years • Data assures well - characterized safety with respect to prostate, hypertension, polycythemia and liver d
Slide 53: Significant Reduction in Liver Enzyme Levels
Significant Reduction in Liver Enzyme Levels • Placebo Controlled 4 Week Study (M12 - 778) - 47.4% - 47.3% - 11.5% - 21.0% - 11.0% - 6.6% - 15.8% - 16.7% -60% -50% -40% -30% -20% -10% 0% LPCN 1144 225mg BID LPCN 1144 300mg BID Placebo - adjusted Mean Change ( ± SEM ) ALT AST ALP GGT 53
Slide 54: Significant Reduction in ALT Levels
Significant Reduction in ALT Levels • Placebo Controlled 4 Week Study (M12 - 778) 2 - 11 - 11 -15 -10 -5 0 5 N = 6 9 9 Placebo LPCN 1144 225mg BID LPCN 1144 300mg BID ALT Mean Change from BL ( ± SEM), U/L p = 0.01 p = 0.02 54
Slide 55: Sustained Reductions from BL of Elevated ALT Levels
Sustained Reductions from BL of Elevated ALT Levels • 52 - Week SOAR Trial -25 -20 -15 -10 -5 0 0 13 26 39 52 Mean Change from BL ( ± SEM), U/L Study Period (Week) ALT* * LPCN 1144 Patients for ALT > 40 U/L at BL (N=42); ALT mean BL = 53.6 U/L 55
Slide 56: Reduction of ALT in Patients with NAFLD/NASH Comorbidities
Reduction of ALT in Patients + with NAFLD/NASH Comorbidities + SOAR trial * Metabolic syndrome: obesity + diabetes + hypertension - 4.0 - 2.0 - 2.9 - 5.9 - 4.5 -10 -8 -6 -4 -2 0 OBS T2D HTN OBS & T2D MetS* ALT Mean Change from BL ( ± SEM), U/L Mean BL (U/L) 33.3 29.4 29.0 33.4 30.2 N 118 46 100 25 1
Slide 57: Reductions of TG in Patients at Risk of NAFLD
Reductions of TG in Patients at Risk of NAFLD - 15 - 43 - 26 - 52 - 67 -100 -80 -60 -40 -20 0 OBS T2D HTN OBS & T2D MetS* TG Mean Change from BL ( ± SEM), mg/dL Mean BL (mg/dL) 205 209 187 237 253 N 118 46 100 25 19 † SOAR Trial; * Metabolic syndrome: obesity + diabetes + hypertension -120 -100 -80
Slide 58: Consistent Liver Function Improvement Across Studies
Consistent Liver Function Improvement Across Studies* - Effect Observed as Early as Week 3 - 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 32.6 74.0
Slide 59: Significant % of Patients Experienced Normalization of TG and LDL-C
Significant % of Patients Experienced Normalization of TG and LDL - C 34% 56% 42% 40% 0% 10% 20% 30% 40% 50% 60% TG (mg/dL) LDL-C (mg/dL) % of Patients in Normal at EOS from Above - normal at BL SOAR Trial* 16-002 Study** TG and LDL - C normal range upper limit is 200 and 160 mg/dL, respectively; *
Slide 60: LPCN 1144: Unique TG Reduction
LPCN 1144: Unique TG Reduction ▪ TG mean change post therapy in patients on oral T vs non - oral T therapy 60 - 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 ) TG Mean Change after 52 Week for Patients with
Slide 61: LPCN 1144: Oral T TG Comparison with Topical T
LPCN 1144: Oral T TG Comparison with Topical T Across Various Co - Morbidities 61 -100 -80 -60 -40 -20 0 20 40 60 80 100 Overall Obesity Diabetes Hypertension OBS & Diab MeS* TG Mean Change from BL (mg/dL) Oral T Topical T * MeS : Metabolic syndrome (Obesity + Diabetes + Hypertension) N Overall Obes
Slide 62: Comparison of Advanced Candidates with Biopsy Results
Comparison* of Advanced Candidates with Biopsy Results Phase 2 end points: ▪ At least 2 point reduction in NAFLD NAS: at least one point reduction either in lobular inflammation or hepatocellular ballooning with no worsening of fibrosis stage 62 Agent Primary target mechanism Reported Trial Results