Lipocine Inc. · NASDAQ:LPCN
Lipocine — Investor Presentation (January 2020)
23 slides from Lipocine's investor presentation, Jan 13, 2020
Slide 1: LPCN 1144 for Pre-Cirrhotic NASH
Exhibit 99.2 Enabling Oral Drug Delivery to Improve Patient Compliance LPCN 1144 for Pre-Cirrhotic NASH
Slide 2: LPCN 1144: Rationale to Target Pre-Cirrhotic NASH
LPCN 1144: Rationale to Target Pre-Cirrhotic NASH Currently No Approved Treatment Estimated Market Unmet Need Efficacy – NASH Resolution and/or Fibrosis Improvement 83M NAFLD Patients in US, 20151 Acceptable Tolerability for Chronic Use 17 M NASH Patients in 20151 Underappreciated conditions Improve
Slide 3: LPCN 1144: Oral Testosterone Therapy
LPCN 1144: Oral Testosterone Therapy Differentiated NASH Treatment Candidate • Efficacy – NASH resolution and/or fibrosis improvement • Acceptable tolerability for chronic use Targets Unmet Need • Improvement of sarcopenia • Improvement of sexual dysfunction • Improvement of mental health • Anti-ste
Slide 4: Association Between T and Liver Disease
Association Between T and Liver Disease Preclinical Evidence ▪ Low T Induces Liver Disease ▪ Liver Disease Induction Causes Lower T T Mouse Induction Method Model Levels Model* ob/ob (Obese Mouse)1 ↓T Gene-modified & Diet Method ▪ Testicular-feminized db/db (Diabetic Mouse)2 ↓T TAA (Mouse/Rat)3 ↓T C
Slide 5: Association Between T and Liver Disease
Association Between T and Liver Disease Clinical Evidence • Reportedly 75% of Biopsy-Confirmed NASH Male Patients Have Low T (< 372 ng/dL)1 • Levels of free T decreased Free T (ng/dL) significantly with the increased incidence of lobular inflammation, hepatocyte ballooning, NAFLD activity score, and
Slide 6: LPCN 1144 Proposed Mechanism
LPCN 1144 Proposed Mechanism Across the Full Spectrum of NASH Pathogenesis Healthy Liver LPCN 1144 Comorbidities ▪ Obesity ▪ Insulin Resistance ▪ Dyslipidemia ▪ Metabolic Syndrome ▪ Hypogonadism (Low T) Regeneration Steatosis Booster3 Inflammation Oxidative Stress NASH Fibrosis The removal of pro-fi
Slide 7: Potential of Testosterone Therapy in NAFLD
Potential of Testosterone Therapy in NAFLD Preclinical Model Results Model Mouse Rat Pig Model1 Model2 Model3 Methods ▪ Testicular-feminized ▪ Castrated + High fat ▪ Castrated + High fat + High cholesterol diet and cholesterol diet diet Disease ▪ Hepatic Steatosis ▪ NAFLD ▪ Hepatic steatosis, inflam
Slide 8: Potential of Testosterone Therapy
Potential of Testosterone Therapy Results from high fat diet (HFD) induced rabbit model* Effects on TNF-α (Inflammatory/Fibrosis Marker) Effects on Liver Histology Masson’s Trichrome Red Oil Giemsa–PAS Staining Staining Staining RD HFD HFD +T TRT ↓ fibrosis TRT ↓ steatosis TRT ↓ inflammation * Vigno
Slide 9: T Therapy Effects in Liver Regeneration
T Therapy Effects in Liver Regeneration Results from Hepatectomized Rat Model* No Treatment 100% died within Group 1 (n=50) 40 hours T Treatment 80% survived Group 2 (n=50) beyond 40 hours Liver Mass Recovery (50% had a normal life span) Testosterone 40% 60% Total liver mass Pretreatment recovery re
Slide 10: Liver Fat Imaging Study (LFS) Results
LPCN 1144: Liver Fat Imaging Study (“LFS”) Results Meaningful Relative Liver Fat % Change and Responder Rate LFS was an open-label, multi-center single-arm 16-week study (N=36) with LPCN 1144 in hypogonadal males (NCT03868059) Mean Relative* Liver Fat % Change Responder Rate** for Liver Fat % 0% Cha
Slide 11: Longitudinal Treatment Effect
LPCN 1144: Longitudinal Treatment Effect Improved NAFL Resolution Over Time Baseline (N=32) Interim (Week 8, N=31) End of Study (Week 16, N=32) NAFL NAFLD NAFLD NAFLD NAFLD NAFLD NAFLD NAFL Free Free NAFL Free Free NAFL NAFL Free Free Free NAFL Free Free 34% 38% 66% 52% 48% 63% ■ NAFL Free (LF < 5%)
Slide 12: Resolution of Liver Injury Markers
LPCN 1144: Resolution of Liver Injury Markers Significant Normalization of Elevated Liver Enzymes* 70% 67% 60% 52% % of Patients Normalized at EOS 50% 50% 40% 31% 30% 20% 10% 0% ALT AST ALP GGT 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) 12
Slide 13: Reduction of Liver Injury Markers
LPCN 1144: Reduction of Liver Injury Markers In Patients with Elevated ALT at Baseline (BL) ▪ Liver enzymes mean change from BL to 1-Yr EOS (NCT02081300) ALT, U/L AST, U/L ALP, U/L GGT, U/L 0.0 -2.0 -3.4 Mean Change from Baseline -4.2 -4.5 -4.0 -4.8 -5.2 -6.0 -6.5 -7.9 -8.0 -10.0 x2 -11.1 x2 -12.0 x
Slide 14: Effects on Serum Lipid Markers
LPCN 1144: Effects on Serum Lipid Markers In Patients with Elevated Lipids at Baseline (BL) TG Change from Baseline LDL Change from Baseline 0 0 Mean TG CBL (mg/dL) Mean LDL CBL (mg/dL) -20 -5 -3 -17 -40 -10 -60 -15 -80 -20 -64 -15 -100 -25 BL = 192 mg/dL BL = 320 mg/dL BL = 114 mg/dL BL = 175 mg/dL
Slide 15: LiFT Study Ongoing
LPCN 1144: LiFT Study* Ongoing Liver Fat Intervention with Oral Testosterone Study 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) ▪ 20-25 bi
Slide 16: Appendix
Appendix 16 LIPOCIN= ENHANCING HEALTH
Slide 17: LPCN 1144: Multi-dimensional Mechanism of Action
LPCN 1144: Multi-dimensional Mechanism of Action Across the Full Spectrum of NASH Pathogenesis Anti-inflammatory2/ Homeostasis Regeneration Anabolic/Androgenic Antioxidant/Immuno- Modifier1, 2 Booster5,6 Agent9 modulator3 • Alter lipid, • Restore • Stimulate satellite • T induces muscle cholesterol,
Slide 18: Clinical Tolerability Experience
LPCN 1144: Clinical Tolerability Experience Oral Prodrug of Endogenous Testosterone ❑ 654 subjects in multiple completed studies with up to 52-week exposure ▪ No death, no drug-related SAEs, no major cardiovascular events, no hepato-toxic events were reported. Adverse Reaction N=654 subjects Headach
Slide 19: Sarcopenia is Associated with NAFLD/NASH
Sarcopenia is Associated with NAFLD/NASH1 LPCN 1144 has Potential to Improve Sarcopenia2,3 3 ✓ Sarcopenia endpoint(s) under evaluation in the ongoing LiFT trial 1. Bhanji et al., Hepatol 2017 2. Bhasin S., J Gerontol 2003 3. Sinclair et al., J Gastroenterol Hepatol 2016 19
Slide 20: Sexual Dysfunction is Associated with NAFLD/NASH
Sexual Dysfunction is Associated with NAFLD/NASH1 LPCN 1144 has Potential to Improve Sexual Dysfunction2 3 ✓ Sexual dysfunction endpoint(s) under evaluation in the ongoing LiFT trial 1. Hawksworth et al., Sex Med Rev 2019 2. Rizk et al., Curr Opin Urol 2017 20 3. SOAR Trial: SOAR Trial: subjects for
Slide 21: Depression is Prevalent in NAFLD Patients
Depression is Prevalent in NAFLD Patients1 LPCN 1144 has Potential to Improve Mental Health2 3 ✓ Mental health endpoint(s) under evaluation in the ongoing LiFT trial 21 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)
Slide 22: Quality of Life is Poor in NAFLD Patients
Quality of Life is Poor in NAFLD Patients1 LPCN 1144 has Potential to Improve Quality of Life2 3 ✓ Quality of life endpoint(s) under evaluation in the ongoing LiFT trial 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 (
Slide 23: Decreased Non-HDL Lipid
LPCN 1144: Decreased Non-HDL Lipid Decrease in Non-HDL in 1-Yr SOAR Trial (NCT02081300) 0% -2% Non-HDL Mean Change from BL (%) -4% -6% -8% -10% -12% -14% Overall OBS T2D HTN OBS/T2D MetS n 207 116 45 98 24 18 Baseline, mg/dL 149 151 135 143 140 138 OBS: Obesity, T2D: Type 2 diabetes, HTN: Hypertensi