Lipocine Inc. · NASDAQ:LPCN
Lipocine — Corporate Update (March 2019)
31 slides from Lipocine's corporate update, Mar 28, 2019
Slide 1: Oral Testosterone (T) Non Alcoholic Steatohepatitis (NASH)
Oral Testosterone (T) Non Alcoholic Steatohepatitis (NASH) 1 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: NAFLD: No Approved Product for the Treatment of NASH
Non - Alcoholic Fatty Liver Disease (“NAFLD”) No Approved Product for the Treatment of NASH 3 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 4: 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 5: 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 6: Lymphatic Delivery of Oral T via Chylomicron
LPCN 1144: Lymphatic Delivery of Oral T via Chylomicron 6 Via Lymphatic Route Via Direct First Pass
Slide 7: 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 8: Multidimensional Mechanism of Action Across the Full Spectrum of 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 9: 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 10: Liver Fat Imaging Study (LFS) Study Design and Baseline Liver Fat Subject Distribution
LPCN 1144: Liver Fat Imaging Study (“LFS”) Study Design and Baseline Liver Fat Subject Distribution 10 LFS was an open - label, multi - center single - arm 16 - week study (N=36) with LPCN 1144 in hypogonadal males LF = liver fat
Slide 11: 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 11 - 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 12: LPCN 1144: Meaningful NAFLD Resolution and Relative Liver Fat Reduction
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 13: Liver Fat Study Results: Subject Distribution at Each Visit
LPCN 1144: Liver Fat Study Results Liver Fat Based Subject Distribution at Each Visit 13 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 14: 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 15: General Safety: Well Tolerated
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 16: Gastrointestinal Safety
LPCN 1144: Gastrointestinal Safety Gastrointestinal Disorders ≥ 1% in SOAR Trial (52 Weeks) 0 5 10 15 % Subjects LPCN 1144 Topical T 16
Slide 17: Significant Reduction in ALT Levels
LPCN 1144: 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 17
Slide 18: Reduction in Liver Enzyme Levels
LPCN 1144: 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 18
Slide 19: Post-hoc Analysis Methods
LPCN 1144: Post - hoc Analysis Methods • Analyses were performed involving hypogonadal male cohorts with baseline liver enzymes* and lipids** – Active - controlled, randomized, open label study (SOAR) NCT02081300, (N=210) with 52 week treatment - 225mg ц 75mg BID • Treatment arm: LPCN 1144 • Control
Slide 20: 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 21: Reductions of Elevated ALT in Patients at Risk of NAFLD
LPCN 1144: Reductions of Elevated ALT in Patients at Risk of NAFLD -25 -20 -15 -10 -5 0 0 13 26 39 52 Mean Change from BL ( ± SEM), U/L Study Period (Week) Sustained Reduction of Elevated ALT** Mean BL (U/L) 54.4 54.9 54.3 57.4 55.0 - 12 - 13 - 15 - 16 - 13 -25 -20 -15 -10 -5 0 OBS T2D HTN OBS & T2D
Slide 22: LPCN 1144: Reductions of Elevated TG in Patients at Risk of NAFLD
▪ Active Controlled 52 Week Study (SOAR) LPCN 1144: Reductions of Elevated TG in Patients at Risk of NAFLD -120 -100 -80 -60 -40 -20 0 0 13 26 39 52 TG Mean Change from BL ( ± SEM), mg/dL Study Period (Week) Sustained Reduction of Elevated TG** ** Patients + for TG > 200 mg/dL at BL (N=73); TG mean
Slide 23: Oral T Mean LDL Reduction for Patients with Elevated LDL at Baseline
LPCN 1144: Oral T Mean LDL Reduction for Patients with Elevated LDL at Baseline • 52 Week SOAR Trial 23 - 3 - 15 -25 -20 -15 -10 -5 0 BL = 114 mg/dL 175 mg/dL Overall (N=194) Above-Noraml at BL* (N=16) Mean Change from BL (mg/dL) LDL - C Change from Baseline * LDL - C upper normal limit is 160 mg/dL
Slide 24: Oral T: 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 24 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 25: LPCN 1144: Robust ALT Response, Good Potential for Histological Improvement
25 † 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 26: LPCN 1144 Comparison with Topical Testosterone
26 LPCN 1144 Comparison with Topical Testosterone
Slide 27: Comparison of PK Profile with Topical T and Injectable T
LPCN 1144: Comparison of PK Profile with Topical T and Injectable T Mean (+SD) Serum Total Testosterone Concentrations on Day 24, LPCN 1021 - 16 - 002 study results (PK Set, N=90) Mean (SD) Serum Total Testosterone Concentrations (ng/ dL ) at 14 - 24 Weeks Mean ( ± SD) Serum Total Testosterone Conce
Slide 28: 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 28 - 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 29: LPCN 1144: Oral T TG Reduction Comparison with Topical T Across Comorbidities
▪ 52 Week SOAR Trial LPCN 1144: Oral T TG Reduction Comparison with Topical T Across Various Comorbidities 29 -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 +
Slide 30: 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 30 - 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 31: 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