Lipocine Inc. · NASDAQ:LPCN
Lipocine — Corporate Update (August 2018)
32 slides from Lipocine's corporate update, Aug 29, 2018
Slide 1: LPCN 1144 Oral Testosterone in NASH and NASH Cirrhosis
LPCN 1144 Oral Testosterone (T) Non Alcoholic Steatohepatitis (NASH) and NASH Cirrhosis Exhibit 99.1
Slide 2: Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Clinical Progression
Non - Alcoholic Fatty Liver Disease (NAFLD) and Its Clinical Progression 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
Slide 3: Fatty Liver Related Diseases
Fatty Liver Related Diseases Obesity (40% in US) 1 Diabetes (9% in US) 2 Metabolic Syndrome ( MeS ) (>30% in US) 3 NAFLD NASH Cirrhosis 1. CDC, Jun 2018 2. CDC, Jul 2017 3. Moore et al, Prev Chronic Dis, 2017 (CDC) 4. Dandona and Rosenberg, Int J Clin Pract , 2010 (US Census Bureau, Aug 2008) Hypogo
Slide 4: Prevalence of Fatty Liver Disease in US
Prevalence of Fatty Liver Disease in US ▪ NAFLD prevalence in general population is estimated to be 20 - 30% in the Western world 1 Estimated Prevalence of Fatty Liver Disease in US, 2015 ▪ By 2020, prevalence of NAFLD cirrhosis is set to overtake hepatitis B - and C - related cirrhosis 2 ▪ The NASH
Slide 5: Proposed Mechanism of Androgen Action via Androgen Receptor in Males
Proposed Mechanism of Androgen Action via Androgen Receptor (AR) in Males* Normal level and signaling of androgens prevent hepatic fat accumulation in males** * Navarro et al, Obesity 2015 ** Shen and Shi, Int J Endocrinol 2015 5
Slide 6: 1144: Oral T – Proposed Mechanism of Action in Liver Disease is Multidimensional
LPCN 1144: Oral T – Proposed Mechanism of Action in Liver Disease is Multidimensional Targeting NASH Pathogenesis ▪ Homeostasis Modifier 1, 2 ‒ Alter lipid profile ‒ Promote cholesterol storage ‒ Glucose Homeostasis ▪ Anti - inflammatory 2 / Immuno - modulator 3 ‒ Low T results in compromised immune
Slide 7: Low T Association with NAFLD and Cirrhosis
Low T Association with NAFLD and Cirrhosis 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 pa
Slide 8: Testosterone May Play a Protective Role in Hepatic Steatosis and NAFLD Development
Testosterone May Play a Protective Role in Hepatic Steatosis and NAFLD Development* * Nikolaenko et al, Endocrinol 2014 I + RCD [n=6] I + HFD [n=8] C + HFD [n=8] C + HFD + T [n=7] 8 – 10 weeks aged rats fed with high fat – low carbohydrate liquid diet for 15 weeks Control group (Con) I: Intact, C: C
Slide 9: 1144: Lymphatic Delivery of Oral T
LPCN 1144: Lymphatic Delivery of Oral T TLANDO ® (LPCN 1021) Transported via Lymph Not prone to liver issues METHYL TESTOSTERONE (MT) Transported via Liver Prone to liver toxicity Systemic Circulation Thoracic Duct Lymph Duct Liver Liver GI Lumen GI Lumen Systemic Circulation LPCN 1144 (Oral T ester
Slide 10: 1144: Study Details for Serum Biomarkers Data Analysis
LPCN 1144: Study Details for Serum Biomarkers Data Analysis ▪ Oral Testosterone, twice daily dosing regimen ▪ “Study of Oral Androgen Replacement (SOAR) Trial” or 13 - 001 Study – 52 week therapy with oral T and topical active control in 314 hypogonadal subjects ▪ “Dosing Validation (DV) study” or 1
Slide 11: 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
Slide 12: SOAR Trial Comorbidity Distribution
SOAR Trial Comorbidity Distribution 56% 48% 22% 9% 0% 10% 20% 30% 40% 50% 60% Obesity (OBS) Hypertension (HTN) Diabetes (Diab.) Metabolic syndrome (OBS + Diab. + HTN) % of Patients in SOAR Trial % of Patients in 52 Wks SOAR Trial, N=210 12
Slide 13: Mean Baseline Liver Enzymes and TG Levels in Patients with Comorbidity Typical of NASH
Mean Baseline Liver Enzymes and TG Levels in Patients with Comorbidity Typical of NASH 13 SOAR Trial (13 - 001) Overall (N=210) Obesity (N=118) Diabetes (N=46) Hypertension (N=100) OBS + Diab . (N=25) OBS + Diab + HTN (N=19) ALT (U/L) 30.5 33.3 29.4 29.0 33.4 30.2 AST (U/L) 24.2 24.7 21.1 23.5 22.3
Slide 14: Substantial Reduction of Clinical Biomarker Levels with LPCN 1144 in Cohorts with NASH Risk Factors
Substantial Reduction of Clinical Biomarker Levels with LPCN 1144 in Cohorts with NASH Risk Factors x2 x5 x2 x5 * N = Total N for subgroup - 15 - 43 - 26 - 52 - 67 - 4.0 - 2.0 - 2.9 - 5.9 - 4.5 -7 -6 -5 -4 -3 -2 -1 0 -80 -70 -60 -50 -40 -30 -20 -10 0 N* = 118 46 100 25 19 Obesity (OBS) Diabetes (Dia
Slide 15: Significant Reduction of Biomarker Levels in Cohort with Elevated ALT and TG
Significant Reduction of Clinical Biomarker Levels with LPCN 1144 in Cohort with Elevated ALT and TG at Baseline * Barritt 4 th et al, Contemp Clin Trials, 2017 ** Sanyal et al, Hepatol , 2015 *** TG normal range 45 – 200 mg/dL x2 x2 x5 TG and ALT mean change post 52 week therapy in patients † N = T
Slide 16: Patients Shifting from Above-normal Levels at Baseline to Normal at End of Study
52% 34% 0% 10% 20% 30% 40% 50% 60% ALT (U/L) TG (mg/dL) % of Patients in SOAR Trial N= 42* Significant Number of Patients on LPCN 1144 Shift from Above - normal Levels at BL to Normal † Levels at EOS * N = Total N for subgroup with above normal biomarker levels at baseline † Normal range: ALT (10 -
Slide 17: Consistent LPCN 1144 Effect on Key Clinical Biomarkers Across Studies
Consistent LPCN 1144 Effect on Key Clinical Biomarkers Across Studies *Patients are for 4 th Quartile (above or upper normal level) of each lab at baseline Alanine amino transferase (ALT), Aspartate amino transferase (AST), Alkaline phosphatase (ALP), Gamma - glutamyl transpeptidase (GGT), Triglycer
Slide 18: Unique Triglyceride Reduction with LPCN 1144
Unique Triglyceride Reduction with LPCN 1144 ▪ TG mean change post therapy in patients on oral T vs non - oral T Therapy * TG normal range: 45 – 200 mg/dL - 63.7 ( - 15%) 13.7 (+3%) -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 Baseli
Slide 19: 1144 Competitive Biomarker Data Comparison
LPCN 1144 Competitive Biomarker Data Comparison
Slide 20: Comparison of ALT Mean Change with Phase 3 Drug Candidates
- 31 - 15 - 38 7 - 8 - 6 -50 -40 -30 -20 -10 0 10 20 Mean BL=82.7 U/L 57.2 U/L 83 U/L 60.4 U/L 69 U/L 56 U/L N=3* 32** 141 123 32 30 LPCN 1144 (Wk 52) Ocaliva (Wk 72) - 25mg Cenicriviroc (Wk 52) - 150mg Selon/Simtu (Wk 24) - 18mg/125mg† Selon/Simtu (Wk 24) - 6mg/125mg† ALT Mean Change from BL (U/L)
Slide 21: Comparison of Triglyceride Mean Change with Phase 3 Drug Candidates
LPCN 1144: Comparison of Triglyceride Mean Change from Baseline with Phase 3 Drug Candidates * Upper limit of normal range (ULN) is 200 mg/dL **, *** SOAR Trial patients with TG > 200 mg/dL and >120 mg/dL at baseline, respectively **** ULN is not reported; typical ULN is 150 mg/dL † Mean change valu
Slide 22: Comparison of Triglyceride Mean Change with Phase 2 Drug Candidates
LPCN 1144: Comparison of Triglyceride Mean Change from Baseline with Phase 2 Drug Candidates * Upper limit of normal range (ULN) is 200 mg/ dL . **, *** SOAR Trial patients with TG > 200 mg/dL and 120 mg/dL at baseline, respectively. **** ULN is not reported; typical ULN is 150 mg/ dL . ‡ Mean chang
Slide 23: Comparison with Obeticholic Acid
- 31 - 38 -45 -40 -35 -30 -25 -20 -15 -10 -5 0 ALT Mean Change from BL (U/L) Comparison of ALT Mean Change LPCN 1144 (Wk 52) Obeticholic acid (Wk 72)† LPCN 1144: Comparison of Key NASH Biomarker Mean Change from Baseline with Obeticholic Acid ▪ Obeticholic Acid (FXR agonist) – FLINT Study, P2, 72 we
Slide 24: Comparison with Elafibranor
▪ Elafibranor (PPAR - a, d agonist) – P2, 52 weeks, 120mg dose ‡ LPCN 1144: Comparison of Key NASH Biomarker Mean Change from Baseline with Elafibranor LPCN 1144 ALT Mean BL 62.2 U/L N 22* Mean Change from BL, (SE) - 20 ( ± 3.1) U/L * SOAR Trial patients with ALT > 50 U/L ‡ Ratziu et al, Gastroenter
Slide 25: Comparison with Cenicriviroc
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from Baseline with Cenicriviroc ▪ Cenicriviroc (CCR2/CCR5 inhibitor) – P2, 52 weeks, 150mg dose ‡ Mean BL 57.2 U/L 60.4 U/L N 32* 123 Mean BL 1.2xULN* 1.2xULN*** N 141** 123 * Upper limit of normal range (ULN) is 200 mg/ dL . ** SOAR Trial pati
Slide 26: Comparison with Selonsertib / Simtuzumab
- 35 - 21 12 -40 -30 -20 -10 0 10 20 TG Mean Change from BL (mg/dL) Comparison of TG Mean Change LPCN 1144 (Wk 52) Selon/Simtu (Wk 24) - 18mg Selon/Simtu (Wk 24) - 6mg LPCN 1144: Comparison of Key NASH Biomarker Mean Change from Baseline with Selonsertib / Simtuzumab ▪ Selonsertib / Simtuzumab (ASK1
Slide 27: Comparison with MGL 3196
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from Baseline with MGL 3196 ▪ MGL 3196 † (THR - b agonist) – P2, 12 weeks, 80mg ± 20mg dose ‡ - 23.1% - 13.5% -30% -20% -10% 0% ALT Mean Change from BL (%) Comparison of ALT Mean Change LPCN 1144 (Wk 52) MGL 3196 N 32* 47** * SOAR Trial Patient
Slide 28: Comparison with Injectable NGM282
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from Baseline with Injectable NGM282 ▪ NGM282 (FGF19 analog) – P2, 12 weeks, 3mg and 6mg dose ‡ * Upper limit of normal range (ULN) is 200 mg/ dL . ** Patients are with TG > 120 mg/ dL at baseline. *** ULN is not reported; typical ULN is 150 mg
Slide 29: Comparison with BMS-986036
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from Baseline with BMS - 986036 ▪ BMS 986036 (Peg - FGF21) – P2, 16 weeks, 10mg and 20mg dose ‡ * Upper limit of normal range (ULN) is 200 mg/ dL . ** Patients are with TG > 120 mg/ dL at baseline. *** ULN is not reported; typical ULN is 150 mg
Slide 30: Comparison with GS-0976
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from Baseline with GS - 0976 ▪ GS 0976 (ACC inhibitor) – P2, 12 weeks, 20mg dose ‡ * Upper limit of normal range (ULN) is 200 mg/ dL . ** Patients are with TG > 120 mg/ dL at baseline. *** ULN is not reported; typical ULN is 150 mg/ dL . † Mean
Slide 31: Comparison of ALT Responders with Vitamin E
LPCN 1144: Comparison of ALT Responders ** from Baseline with Vitamin E ▪ ALT Improvement predicts histological response † (PIVENS Vitamin E study results ‡ ) ▪ Vitamin E (anti - oxidant) – 96 weeks, 800 IU dose ‡ Sanyal et al, New Eng J Med, 2010 * Total N is for patients with ALT > 40 U/L at basel
Slide 32: Summary of LPCN 1144 Clinical Biomarker Results and Next Steps
Summary of LPCN 1144 Clinical Biomarker Results and Next Steps ▪ Summary – Consistent lowering of key biomarkers levels in patients with comorbidities typical of NASH – Significant reduction of key biomarkers levels in patients with elevated ALT and TG, adjunct markers often used in clinical diagnos