Lipocine Inc. · NASDAQ:LPCN
Lipocine — Technical Presentation (2023)
22 slides from Lipocine's technical presentation, 2023
Slide 1: LPCN 1148 Improves Sarcopenia and Clinical Outcomes in Patients with Decompensated Cirrhosis
The Stravitz‐Sanyal Institute ORAL LPCN 1148 IMPROVES SARCOPENIA AND CLINICAL OUTCOMES IN PATIENTS WITH DECOMPENSATED CIRRHOSIS Benjamin J Bruno1, Joshua C Weavil1, Jonathan Ogle1, Nachiappan Chidambaram1, Elizabeth J Carey2, Christopher J Danford3, Zachary P Fricker4, Joseph S Galati5, William M Le
Slide 2: Forward-Looking Statements
Forward‐Looking Statements This presentation contains "forward‐looking statements" that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and include statements that are not historical facts regarding our product development efforts, our strategi
Slide 3: Sarcopenia is commonly present in decompensated cirrhosis and impacts clinically meaningful outcomes
Sarcopenia is commonly present in those with decompensated cirrhosis and impacts clinically meaningful outcomes • How patients feel: • Health related quality of life • How patients function: • Frailty • Activities of daily living • How patients survive: • Hepatic encephalopathy • Mortality • Peri‐tr
Slide 4: Multiple mechanisms contribute to sarcopenia in cirrhosis
Multiple mechanisms contribute to sarcopenia in cirrhosis Androgens: • Linked to muscle mass • Inhibits myostatin • Modulates mTOR • Increases protein synthesis • Decreases turnover ‐ 90% of males with cirrhosis have low testosterone Sinclair et al, Aliment Pharmacol Ther, Volume: 43, Issue: 7, Page
Slide 5: LPCN 1148: A novel MOA for management of cirrhosis
LPCN 1148: A novel MOA for management of cirrhosis Product Oral androgen receptor agonist Candidate Dosage form comprising testosterone dodecanoate, a unique prodrug of the endogenous hormone Attributes Targeted Mechanism of Action Anabolic1 Ammonia Lowering Androgenic Increase muscle mass and Via I
Slide 6: Central Hypothesis: LPCN 1148 will improve sarcopenia and clinically significant outcomes
Central Hypothesis: LPCN 1148 will improve sarcopenia, sarcopenia related outcomes and clinically significant outcomes in patients with cirrhosis
Slide 7: Aims and objectives
Aims and objectives Specific Aims Objectives • To perform a phase 2 proof of • To generate proof of concept of concept study to establish the overall benefit of LPCN 1148 to short term safety and efficacy of support further development of LPCN 1148 in male patients with this drug in the study popula
Slide 8: Study population
Study population Inclusion criteria Exclusion criteria • Adult males • Failure to obtain consent • Cirrhosis • Active severe encephalopathy • Sarcopenia – defined by BMI‐ • Active infection adjusted SMI* • Uncontrolled or recurrent GI • Listed for liver transplantation bleed in past 6 months • Prior
Slide 9: Study Design
Study Design: Study Design • Two‐arm (1:1 randomization, N=29) • Oral LPCN 1148, T dodecanoate, vs. Placebo • Standard of care treatments/therapies allowed • 24‐week placebo‐controlled • Followed by 28‐week open‐label extension (OLE) • All subjects receive LPCN 1148 during OLE SCREENING TREATMENT: 5
Slide 10: Endpoints
Endpoints Secondary endpoints Primary endpoint (p value not adjusted for multiplicity) • Baseline‐adjusted change in Skeletal • Feel and function: Muscle Index (L3 region, L3‐SMI) at • 6 min walk test Week 24 in LPCN 1148 treated • patient reported outcomes (PGI‐C) participants compared to placebo •
Slide 11: Baseline characteristics
LPCN 1148 Baseline characteristics LPCN 1148 Placebo (N=15) (N=14) Age (years) 58.3 ± 7.5 58.8 ± 9.5 BMI (kg/m2) 29.2 ± 5.3 29.0 ± 8.6 Placebo L3‐SMI (cm2/m2) 47.8 ±7.0 44.8 ± 8.5 MELD Score 15.9 ± 3.7 18.1 ± 4.6 Medical History ≥ 1 Decompensation Event# 14 (93%) 14 (100%) ≥ 2 Decompensation Event 1
Slide 12: Subject disposition and analysis data-sets
Subject disposition and analysis data‐sets LPCN 1148 Placebo Subject Disposition (N=15) (N=14) Completed Week 24 15 10 Withdrawal of informed consent post liver transplant 0 2 Death 0 1 Hospitalized 0 1 LPCN 1148 Placebo Analysis Datasets (N=15) (N=14) Safety set* 15 14 Modified Intent to Treat (mIT
Slide 13: Primary endpoint was met: improvement in skeletal muscle index
Primary endpoint was met‐ improvement in skeletal muscle index L3‐SMI Absolute Change From Baseline Placebo Subjects 14 Change in L3‐SMI (cm2/m2) 12 Placebo 1148 10 8 6 4 2 0 ‐2 0 12 24 36 ‐4 ‐6 Week LS mean (SE), LOCF, †P<0.05 for change from baseline; * P=0.007 vs. placebo
Slide 14: Further recurrence of overt hepatic encephalopathy was decreased with LPCN 1148
Further recurrence of overt hepatic encephalopathy was decreased with increased time to recurrence with LPCN 1148 LPCN 1148 Placebo Parameter (N=15) (N=14) Total decompensation events 7 10 Total decompensation events > Grade 1 6 10 Hepatic encephalopathy events 3 6 HE > Grade 1 2* 6 Recurrence of HE
Slide 15: LPCN 1148 improved patient reported outcomes
LPCN 1148 improved patient reported outcomes Patient Global Impression of Change (PGI-C) Scale PGI‐C Week 24 Please choose the response below that best % Subjects Responded 1 or 2 describes the overall change in your symptoms 50 P=0.006 since you started using the study treatment. 40 33.3 % Responde
Slide 16: LPCN 1148 improved anemia in cirrhosis
LPCN 1148 improved anemia in cirrhosis LPCN 1148 P-value Hemoglobin LPCN 1148 Placebo (N=15) (N=13) Change from Vs. Placebo Timepoint Baseline Baseline (g/dL) 11.39 (0.84) 13.04 (0.66) N/A NS Week 24 CFB (g/dL) 1.30 (0.40) -0.16 (0.23) 0.003 0.005 Mean (SE) LPCN 1148 Placebo Anemia Status (N=15) (N=
Slide 17: LPCN 1148 produced trends in improvement in other secondary end-points
LPCN 1148 produced trends in improvement in other secondary end‐points Parameter LPCN 1148 Placebo Deaths (n) 0 1 Days in hospital (total) 54 117 Length of hospital stay (median, days) 3 5 6 min walk test (feet)* 270 -16 EncephalApp Stroop Test (total time, seconds)* -4.8 13.8 *mean change from base
Slide 18: LFI: Observed change from baseline comparable to placebo
LFI: Observed change from baseline for LPCN 1148 is comparable to that of placebo at 24 week study duration LPCN 1148 P-value LPCN 1148 Placebo (N=15) (N=12) Change from Vs. Placebo Timepoint Baseline Baseline 4.04 (0.23) 3.88 (0.34) N/A NS Week 24 CFB -0.05 (0.18) -0.17 (0.17) NS NS Mean (SE) • Sim
Slide 19: LPCN 1148 - AE profile
LPCN 1148 ‐ AE profile LPCN 1148 Placebo Parameter (N=15) (N=14) # n # n Total AEs 33 8 36 10 Serious AEs 15 5 16 5 Severe AEs 6 4 10 4 • Administration of LPCN 1148 was well tolerated in this end‐stage population, with rates and severities of adverse events (AEs) similar to those within the placebo
Slide 20: Summary and conclusions
Summary and conclusions • LPCN 1148, an oral androgen receptor agonist improved sarcopenia in adult male patients with cirrhosis. • It was further associated with improvement in encephalopathy, anemia, total number of days hospitalized, and patient reported outcomes which are all clinically meaningf
Slide 21: Acknowledgements
Acknowledgements • We acknowledge the contribution of all of the investigators and staff for this trial and express our gratitude to the patients who participated in this study
Slide 22: LPCN 1148 improved myosteatosis
LPCN 1148 improved myosteatosis Muscle Quality CBL Week 24 20 * 10 Relative Change in Muscle Areas (%) 0 ‐10 IMAT HQM ‐20 ‐30 ‐40 1148 Placebo Substantial Changes in Muscle Quality seen with LPCN 1148 Therapy • Decrease in intramuscular adipose tissue (IMAT) • Significant increase in high quality mu