Slide 1: LPCN 1148: A Novel Approach for the Management of Liver Cirrhosis
LPCN 1148 A Novel Approach for the Management of Liver Cirrhosis Phase 2 Study Week 24 Topline Results July 27, 2023 Enabling Effective Oral Drug Delivery
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 product
Slide 3: Liver Cirrhosis
Liver Cirrhosis Cirrhosis is scarring of the liver, when scar tissue replaces healthy tissue, causing damage and reducing liver function Common Causes2 Alcoholic Liver Disease Nonalcoholic Fatty Liver Disease (NAFLD) Chronic Hepatitis B, C https://www.niddk.nih.gov/ Primary Biliary Cholangitis Prima
Slide 4: Cirrhosis: Complications and Recent Trends
Cirrhosis: Complications and Recent Trends Complications Recent Trends • Decompensation events - hepatic • Occurrence of cirrhosis and related deaths are on the rise encephalopathy, varices, ascites, etc. • In the US between 1999 and 2019, greater than three-fold • Compromised liver function, immuni
Slide 5: LPCN 1148 Targeted Mechanism of Action
LPCN 1148 Product Oral androgen receptor agonist Candidate Dosage form comprising testosterone dodecanoate, a unique prodrug of an endogenous hormone Attributes Targeted Mechanism of Action Anabolic1 Ammonia Lowering Androgenic Increase muscle mass and Via Improved liver health6 and Induce hematopoi
Slide 6: Sarcopenia in Cirrhosis Patients: Disease Overview
Sarcopenia in Cirrhosis Patients: Disease Overview A prevalent and serious comorbidity • Sarcopenia is a condition characterized by severe muscle depletion and observed in ~60% of patients with cirrhosis1-2, 4 • Sarcopenia is a predictor for increased morbidity and mortality in cirrhosis1 – 3-fold h
Slide 7: Current Standard of Care And Key Unmet Needs
Current Standard of Care And Key Unmet Needs Options are limited, resulting in significant enduring medical need Current Standard of Care Key Unmet Needs Decompensated Liver Cirrhosis Limited Liver Significant • Management of Etiology Mortality Therapeutic Transplant Options Limitations – Alcohol ce
Slide 8: Hepatic Encephalopathy in Cirrhosis Patients
Hepatic Encephalopathy in Cirrhosis Patients Up to 50% of cirrhosis patients will experience an overt HE episode in their lifetime1 • Overt HE is a debilitating, episodic, neurological disorder with a high recurrence rate • HE is a major complication of advanced liver disease. Patients exhibit globa
Slide 9: Current Standard of Care And Key Unmet Needs in HE
Current Standard of Care And Key Unmet Needs in HE Options are limited, resulting in significant enduring medical need Current Standard of Care Key Unmet Needs Overt HE1 Significant High Recurrence Low Tolerability Mortality • First Line: Lactulose or Lactitol Rate • Refractory Patients: IV or Oral
Slide 10: LPCN 1148: Proof of Concept Study
LPCN 1148: Proof of Concept Study Phase 2, multicenter, double-blinded, placebo-controlled study Study Design: Endpoints: • Male subjects with liver cirrhosis and sarcopenia on the • Primary: Change in Skeletal Muscle Index (L3 region, L3- liver transplant waitlist SMI) at Week 24 in LPCN 1148 treat
Slide 11: Presence of Sarcopenia is Linked with Worse Clinical Outcomes
Presence of Sarcopenia is Linked with Worse Clinical Outcomes Higher rates of death and hepatic encephalopathy Survival (%) Covert HE Overt HE Low muscle mass (sarcopenia) and quality (myosteatosis) Sarcopenia and myosteatosis are associated with are associated with worse overall survival 1 increase
Slide 12: Baseline Characteristics
LPCN 1148 Baseline Characteristics Generally well-balanced between treatment arms 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 L3-SMI (cm2/m2) 47.8 ±7.0 44.8 ± 8.5 Placebo MELD Score 15.9 ± 3.7 18.1 ± 4.6 Medical History ≥ 1 Decompensation Event
Slide 13: Analysis Datasets and Subject Disposition
Analysis Datasets and Subject Disposition LPCN 1148 Placebo Analysis Datasets (N=15) (N=14) Safety set* 15 14 Modified Intent to Treat (mITT)** 15 10 No post-baseline CT scan 0 3 Low compliance 0 1 LPCN 1148 Placebo Subject Disposition (N=15) (N=14) Completed Week 24 15 10 Withdrawal of informed con
Slide 14: Primary Endpoint Met
Primary Endpoint Met LPCN 1148 therapy resulted in a significant increase in L3-SMI at Week 24 L3-SMI Change from Baseline P-value LPCN 1148 Placebo 1148 vs. Timepoint (N=15) (N=10) 1148 CFB Placebo Baseline (cm2/m2) 47.8 (1.8) 45.8 (2.3) N/A NS Week 24 CFB (cm2/m2) 3.62 (0.93) - 0.74 (1.14) <0.001
Slide 15: LPCN 1148 Therapy Resulted in Significantly Fewer HE > Grade 1 Events
LPCN 1148 Therapy Resulted in Significantly Fewer HE > Grade 1 Events Positive clinical outcome achieved LPCN 1148 Placebo Total Parameter (N=15) (N=14) (N=29) Total decompensation events 7 10 17 Total decompensation events > Grade 1 6 10 16 Hepatic Encephalopathy 3 6 9 HE > Grade 1* 2 6 8 Recurrenc
Slide 16: 1148-treated Participants Reported Significant Symptom Improvement
LPCN 1148-treated Participants Reported Significant Symptom Improvement As assessed by PGI-C Patient Global Impression of Change (PGI-C) Scale PGI-C Week 24 Please choose the response below that best % Subjects Responded 1 or 2 50 describes the overall change in your symptoms 45 P=0.006 since you st
Slide 17: Observed Hematologic Benefits
Observed Hematologic Benefits LPCN 1148 therapy resulted in significant increase in hemoglobin P-value Hemoglobin LPCN 1148 Placebo (N=15) (N=14) Change from Vs. Placebo Timepoint Baseline Baseline (g/dL) 11.39 (0.75) 13.04 (0.8) N/A NS Week 24 CFB (g/dL) 1.20 (0.33) -0.05 (0.35) 0.001 0.02 LS Mean
Slide 18: LPCN 1148 Safety
LPCN 1148 Safety Overall LPCN 1148 was well tolerated LPCN 1148 Placebo Parameter (N=15) (N=14) # n # n Total AE events 33 8 36 10 Serious AE events 15 5 16 5 Severe AE events 6 4 10 4 Total Hospital Days 54 5 117 5 • Administration of LPCN 1148 was well tolerated in this end-stage population, with
Slide 19: Study Conclusions
Study Conclusions Positive Week 24 results support benefits of 1148 for men with cirrhosis and sarcopenia • LPCN 1148 met the primary endpoint - resulted in significantly increased skeletal muscle index – Superior to placebo at Week 24 – Significant improvement from baseline as early as Week 12 • Fe
Slide 20: LPCN 1148: Target Product Differentiation
LPCN 1148: Target Product Differentiation • Novel multimodal MOA – Effects not limited to GI tract • Potential to improve sarcopenia and reduce recurrence of HE – Improved efficacy in conjunction with background HE therapies • Attractive benefit to risk profile – Endogenous hormone with favorable sa
Slide 21: Lipocine: Enhancing Health
LIPOCIN= ENHANCING HEALTH