Lipocine Inc. · NASDAQ:LPCN
Lipocine — Corporate Update (October 2018)
49 slides from Lipocine's corporate update, Oct 1, 2018
Slide 1: Oral Testosterone (T) Non Alcoholic Steatohepatitis (NASH) and NASH Cirrhosis
Oral Testosterone (T) Non Alcoholic Steatohepatitis (NASH) and NASH Cirrhosis 1 Exhibit 99.2
Slide 2: LPCN 1144: Well Positioned for Success
LPCN 1144: Well Positioned for Success Differentiated Mechanism of Action and Well Tolerated Safety Profile ▪ Targeted for NASH Epidemic with No Approved Product – The NASH market could peak at $30 - 40 billion by 2025 1 ▪ Unique Mechanism Targeting Full Spectrum of NASH Pathogenesis + Collateral He
Slide 3: Non-Alcoholic Fatty Liver Disease (NAFLD) Clinical Progression
Non - Alcoholic Fatty Liver Disease (NAFLD) Clinical Progression 3 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 trans
Slide 4: Co-Morbidities Associated with NASH
Co - Morbidities Associated with NASH Fatty Liver Related Diseases 4 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 ,
Slide 5: Testosterone Deficiency Relevant in Chronic Liver Diseases
Testosterone Deficiency Relevant in Chronic Liver Diseases* Significant Overlap of NASH with Hypogonadism 5 1. Guay A.T., J Androl 2009; 2. Dhindsa et al., Diabetes Care 2010; 3. Guay et al., Int J Impotent Res 2010; 4. Younossi et al., Hepatol 2016; 5. Rector et al., Gastroenterol 2008 * Kim et al,
Slide 6: 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 7: Proposed Mechanism of Androgen Action via Androgen Receptor in Males
Proposed Mechanism of Androgen Action via Androgen Receptor (AR) in Males* 7 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 8: Oral T 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 9: Low T Association with NAFLD and Cirrhosis
Low T Association with NAFLD and Cirrhosis 9 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 10: Testosterone Deficiency Induces NAFLD/NASH; Treatment Improves Liver Functions
Testosterone Deficiency Induces NAFLD/NASH Testosterone Treatment Improves Liver Functions 1 10 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 11: Lymphatic Delivery of Oral T Via Chylomicron
LPCN 1144: Lymphatic Delivery of Oral T Via Chylomicron 11 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
Slide 12: Study Details for Serum Biomarker Data Analyses
LPCN 1144: Study Details for Serum Biomarker Data Analyses ▪ Oral Testosterone, twice daily dosing regimen − Included subjects with typical comorbid conditions associated with NASH − Liver enzymes, lipids and cholesterol (NASH biomarkers) levels were monitored − Key serum NASH biomarkers were evalua
Slide 13: SOAR Trial Comorbidity Distribution
LPCN 1144: SOAR Trial Comorbidity Distribution 13 56% 48% 22% 9% 0% 10% 20% 30% 40% 50% 60% Obesity (OBS) Hypertension (HTN) Diabetes (Diab.) MeS* (OBS + Diab. + HTN) % of Patients in SOAR Trial % of Patients in 52 Wks SOAR Trial, N=210 * MeS : Metabolic Syndrome
Slide 14: Liver Enzymes and TG Mean BL Levels in Patients with Comorbidities
LPCN 1144: Liver Enzymes and TG Mean BL Levels in Patients with Comorbidities Typical of NASH 14 SOAR Trial (13 - 001) Overall (N=210) Obesity (N=118) Diabetes (N=46) Hypertension (N=100) OBS + Diab . (N=25) MeS (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
Slide 15: 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 16: Substantial Reduction of Clinical Biomarker Levels in Cohorts with NASH Risk Factors
LPCN 1144: Substantial Reduction of Clinical Biomarker Levels in Cohorts with NASH Risk Factors 16 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 (Diab
Slide 17: Significant Reduction of Biomarkers in Cohort with Elevated ALT and TG
LPCN 1144: Significant Reduction of Clinical Biomarker Levels in Cohort with Elevated ALT and TG at BL 17 * 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 = Total N
Slide 18: Consistent Effects on Key Clinical Biomarkers Across Studies
LPCN 1144: Consistent Effects on Key Clinical Biomarkers Across Studies 18 Alanine amino transferase (ALT), Aspartate amino transferase (AST), Alkaline phosphatase (ALP), Gamma - glutamyl transpeptidase (GGT), Triglyceride (TG) Liver enzymes and TG mean change post therapy in patients in two separat
Slide 19: M12 Study: TG Mean Change from Baseline
M12 - 778 Study: TG Mean Change from Baseline - 9.1% - 25.5% -30% -20% -10% 0% N = 6 9 Placebo 225mg BID TG Mean Change from BL (%) LPCN 1144 TG Mean Change in M12 - 778 Placebo Controlled Study (Day 22) 19
Slide 20: M12 Study: ALT and AST Mean Change from Baseline
M12 - 778 Study: ALT and AST Mean Change from Baseline 14.8% - 32.6% -40% -30% -20% -10% 0% 10% 20% N = 6 9 Placebo 225mg BID ALT Mean Change from BL (%) LPCN 1144 ALT Mean Change in M12 - 778 Placebo Controlled Study (Day 22) - 14.5% - 26.0% -30% -25% -20% -15% -10% -5% 0% N = 6 9 Placebo 225mg BID
Slide 21: M12 Study: ALP and GGT Change from Baseline
M12 - 778 Study: ALP and GGT Change from Baseline - 7.5% - 18.5% -20% -15% -10% -5% 0% N = 6 9 Placebo 225mg BID ALP Mean Change from BL (%) LPCN 1144 ALP Mean Change in M12 - 778 Placebo Controlled Study (Day 22) - 3.2% - 19.0% -20% -15% -10% -5% 0% N = 6 9 Placebo 225mg BID GGT Mean Change from BL
Slide 22: Patients Shifting ALT and TG from Above-Normal to Normal Levels
LPCN 1144: Significant Number of Patients for ALT and TG Shift from Above - Normal Levels at BL to Normal † Levels at EOS 22 52% 34% 0% 10% 20% 30% 40% 50% 60% ALT (U/L) TG (mg/dL) % of Patients in SOAR Trial N= 42* * N = Total N for subgroup with above normal biomarker levels at baseline † Normal r
Slide 23: LDL Reduction and Shift of LDL-C to Normal Levels
LPCN 1144: LDL Reduction and Significant Number of Patients for LDL - C Shift from Above - normal Levels at BL to Normal* Levels at EOS 23 - 15 -25 -20 -15 -10 -5 0 LDL - C Mean Change from BL (mg/dL) Above - normal LDL - C at BL† (N=16) 56.3% 0% 10% 20% 30% 40% 50% 60% Above-normal at BL (N=16) to
Slide 24: Patient Shifts from Above-normal GGT to Normal
LPCN 1144: Significant Patient Number of Shifts from Above - normal GGT at BL to Normal* GGT at EOS ▪ GGT can also be an early marker of oxidative stress and indirect serum marker of fibrosis 24 - 10.2 -15 -10 -5 0 GGT Mean Change from BL (U/L) Above - normal GGT at BL† (N=36) 30.6% 0% 10% 20% 30% 4
Slide 25: LPCN 1144: Robust ALT Response
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: Unique TG Reduction
LPCN 1144: Unique TG Reduction ▪ TG mean change post therapy in patients on oral T vs non - oral T therapy 27 - 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 28: Oral T TG Comparison with Topical T Across Co-Morbidities
LPCN 1144: Oral T TG Comparison with Topical T Across Various Co - Morbidities 28 -100 -80 -60 -40 -20 0 20 40 60 80 100 Overall Obesity Diabetes Hypertension OBS & Diab Metabolic syndrome* TG Mean Change from BL (mg/dL) Oral T Topical T * Metabolic syndrome: Obesity + Diabetes + Hypertension N Over
Slide 29: 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 30: Oral T Delivery More In Tune with Normal Circadian Variation
Disruption of the circadian rhythm is associated with the metabolic syndrome and NAFLD. 1 The rhythmic secretion of hormones plays an important role in metabolic homeostasis. 1 Plasma hepatic lipase activity and Lipoprotein Lipase activity displays circadian rhythms in various tissues follows a sign
Slide 31: Oral Testosterone for the Treatment of NASH: Summary and Next Steps
LPCN 1144: Oral Testosterone for the Treatment of NASH Summary and Next Steps ▪ Targeted for NASH epidemic with no currently approved product ▪ Unique mechanism targeting full spectrum of NASH pathogenesis + collateral health benefits ▪ Well tolerated safety profile ▪ Compelling clinical biomarker d
Slide 32: LPCN 1144 Competitive Biomarker Data Comparison
32 LPCN 1144 Competitive Biomarker Data Comparison (Separate Studies/Not Head to Head)
Slide 33: Comparison of TG Mean Change with Phase 2 Drug Candidates
LPCN 1144: Comparison of TG Mean Change from BL with Phase 3 Drug Candidates 33 * 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 values for Selons
Slide 34: Comparison of TG Mean Change with Phase 2 Drug Candidates
LPCN 1144: Comparison of TG Mean Change from BL with Phase 2 Drug Candidates 34 * 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 for GS 0976
Slide 35: Comparison of ALT Mean Change with Phase 2 Drug Candidates
LPCN 1144: Comparison of ALT Mean Change from BL with Phase 3 Drug Candidates 35 - 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) Obeticholic acid (Wk 72) - 25mg Cenicriviroc (Wk 52) - 150mg Selon/S
Slide 36: Comparison with Obeticholic Acid
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from BL with Obeticholic Acid • Obeticholic Acid (FXR agonist) – FLINT Study, P2, 72 weeks, 25mg dose ‡ 36 - 31 - 38 -50 -40 -30 -20 -10 0 ALT Mean Change from BL (U/L) Comparison of ALT Mean Change LPCN 1144 (Wk 52) Obeticholic acid (Wk 72)† M
Slide 37: Comparison with Elafibranor
Elafibranor Elafibranor LPCN 1144: Comparison of Key NASH Biomarker Mean Change from BL with Elafibranor • Elafibranor (PPAR - a, d agonist) – P2, 52 weeks, 120mg dose ‡ 37 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 ‡ Ratz
Slide 38: Comparison with Cenicriviroc
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from BL with Cenicriviroc • Cenicriviroc (CCR2/CCR5 inhibitor) – P2, 52 weeks, 150mg dose ‡ 38 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 patient
Slide 39: Comparison with Selonsertib / Simtuzumab
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from BL with Selonsertib / Simtuzumab • Selonsertib / Simtuzumab (ASK1 inhibitor) – P2, 24 weeks, 18mg or 6mg Selonsertib with fixed Simtuzumab dose ‡ 39 - 35 - 21 12 -40 -30 -20 -10 0 10 20 TG Mean Change from BL (mg/dL) Comparison of TG Mean
Slide 40: Comparison with MGL 3196
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from BL with MGL 3196 • MGL 3196 † (THR - b agonist) – P2, 12 weeks, 80mg ц 20mg dose ‡ 40 - 15.0 - 13.5 -20 -15 -10 -5 0 ALT Mean Change from BL (U/L) Comparison of ALT Mean Change LPCN 1144 (Wk 52) MGL 3196 N 32* 47** * SOAR Trial Patients wi
Slide 41: Comparison with Injectable NGM282
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from BL with Injectable NGM282 • NGM282 (FGF19 analog) – P2, 12 weeks, 3mg and 6mg dose ‡ 41 * 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/ d
Slide 42: Comparison with BMS-986036
- 35 - 11 - 9 -40 -30 -20 -10 0 TG Mean Change from BL (mg/dL) Comparison of TG Mean Change LPCN 1144 (Wk 52) BMS986036 (Wk 16) - 10mg BMS986036 (Wk 16) - 20mg - 31% - 34% - 22% -40% -30% -20% -10% 0% ALT Mean Change from BL (%) Comparison of ALT Mean Change † LPCN 1144 (Wk 52) BMS-986036 (Wk 16) -
Slide 43: Comparison with GS 0976
- 35 51 -40 -20 0 20 40 60 TG Mean Change from BL (mg/dL) Comparison of TG Mean Change LPCN 1144 (Wk 52) GS - 0976 (Wk 12) - 20mg† - 31 - 44 -50 -40 -30 -20 -10 0 ALT Mean Change from BL (U/L) Comparison of ALT Mean Change LPCN 1144 (Wk 52) GS - 0976 (Wk 12) - 20mg† LPCN 1144: Comparison of Key NASH
Slide 44: Comparison with Aramchol
LPCN 1144: Comparison of Key NASH Biomarker Mean Change from BL with Aramchol 44 • LPCN 1144* – 52 weeks, randomized • Aramchol ‡ – P2, 52 weeks, 600mg dose * SOAR Trial patients with ALT > 50 U/L at baseline (Mean BL = 62.2 U/L), N=22 30 40 50 60 70 0 13 26 39 52 Mean Level (U/L) Visit (Wks) ALT Me
Slide 45: Absolute Liver Fat Change of Select NASH Drugs in Development
Absolute Liver Fat Change of Select NASH Drugs in Development - 0.9 - 1.0 - 1.3 - 2.0 - 0.1 - 9.7 - 2.0 - 6.8 - 1.1 - 3.4 - 3.4 - 11.9 - 4.6 - 5.2 - 0.8 - 3.2 -14 -12 -10 -8 -6 -4 -2 0 NGM282 (12W) GS-0976 (ACC) (12W) BMS-986036 (16W) GS-4997 (ASK1) (24W) Aramchol (52W) OCA (72W) Data Comparison of
Slide 46: Relative Liver Fat Change of Select NASH Drugs in Development
1 Selonsertib (SEL) +/ - Simtuzumab (SIM) open label pooled study data; simtuzumabdata used as proxy for placebo data 2 Placebo - subtracted data; secondary analysis of OCA FLINT trial 3 Relative change in LFC for BMS - 986036 calculated from reported baseline values and absolute changes 4 Absolute
Slide 47: Select NASH Biopsy Results: Reported Effect on Resolution of NASH
Select NASH Biopsy Results – Reported Effect on Resolution of NASH 36 47 22 19 8 <1 19 27 21 21 13 12 6 0 7 6 0 20 40 60 Vitamin E (96W) Pioglitazone (96W) OCA (72W) Elafibranor (52W) Cenicriviroc (52W) Selonsertib 6 or 18 mg/day Aramchol (52W) MGL-3196 Resolution of NASH in % of Patients 1 Active D
Slide 48: Select NASH Biopsy Results: Reported Effect on Fibrosis
Select NASH Biopsy Results † – Reported Effect on Fibrosis *Calculated from publication, which reported separate results for each dose. † Results from separate studies, not head to head, with different endpoint definitions; Time points and populations may diffe r a mong studies. 48 41 44 35 20 37 31
Slide 49: 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 49 Agent Primary target mechanism Reported Trial Results