Slide 1: Novel Oral Rapid-Acting Neuroactive Steroid for Treatment of Postpartum Depression
NOVEL ORAL RAPID-ACTING NEUROACTIVE STEROID FOR TREATMENT OF POSTPARTUM DEPRESSION: A PLACEBO-CONTROLLED PHASE 3 CLINICAL TRIAL OF LPCN 1154 Benjamin Bruno, PhD, PharmD Vice President, Clinical Development Lipocine Inc. Presented on behalf of Anthony DelConte MD, Joshua C Weavil PhD, Jonathan Ogle P
Slide 2: Disclosures
Disclosures • Full-time employee of Lipocine Inc. • Own stock in Lipocine Inc. • This work was funded by Lipocine Inc. ASCP │2026 2
Slide 3: 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 candidates and strategic plans an
Slide 4: LPCN 1154 (Oral Brexanolone)
LPCN 1154 (Oral Brexanolone) Mechanism of antidepressant action Endogenous Neuroactive Steroid (NAS) Potent positive allosteric modulator (PAM) of the GABAA receptor Metabolite of progesterone Synaptic Engagement Acts on both synaptic and extra-synaptic GABAA receptors Persistent antidepressant effe
Slide 5: LPCN 1154 – Achieved Standard Bioequivalence to IV Brexanolone
LPCN 1154 – Achieved Standard Bioequivalence to IV Brexanolone Dosing regimen confirmation study results IV Brexanolone (ZULRESSO®) is Efficacious in PPD1 LPCN 1154: Bioequivalent to ZULRESSO® GMR PK IV Test vs. LPCN 1154 Parameter Brexanolone Reference (90% CI) Cmax 105% 120 115 (92%-118%) (ng/mL)
Slide 6: LPCN 1154 – Phase 3 Safety and Efficacy Study Design
LPCN 1154 – Phase 3 Safety and Efficacy Study Design Utilized same dose and regimen as the PK dose confirmation study Study design • Two arm, outpatient, randomized, blinded, placebo-controlled trial in women with postpartum depression at home administration with no required medical monitoring Inclu
Slide 7: Full Analysis Set: Baseline demographics
Full Analysis Set Baseline demographics Characteristics LPCN 1154 Placebo Overall N 45 45 90 Age (years) (Mean, SD) 30.7 (5.41) 30.8 (6.52) 30.8 (5.96) BMI (kg/m2) (Mean, SD) 30.0 (5.96) 29.6 (6.06) 29.8 (5.98) Ethnicity (HISP; %) 64.4 60.0 62.2 Race (White; %) 62.2 66.7 64.4 Antidepressant use at b
Slide 8: Full Analysis Set: HAM-D Change From Baseline
Full Analysis Set: HAM-D Change From Baseline Primary endpoint not met HAM-D Change From Baseline Over Time 0 Hour 1 12 Hour 2 36 Hour 3 60 Day 4 7 Day530 0 HAM-D Change From Baseline Parameter LPCN 1154 Placebo -5 CFB at 60 hours [LSM (SE)] -12.0 (1.27) -10.7 (1.27) ** LSM difference (SE) -1.3 (1.8
Slide 9: Full Analysis Set: Safety
Full Analysis Set: Safety LPCN 1154 was well tolerated LPCN 1154 Placebo Parameter N=45 N=45 n (%) n (%) Any TEAE 8 (17.8) 8 (17.8) Any treatment-related TEAE 5 (11.1) 3 (6.7) Any severe TEAE 2 (4.4) 0 (0.0) Any serious TEAE 1 (2.2) 0 (0.0) TEAEs in ≥ 2 participants in LPCN 1154 arm Headache 2 (4.4)
Slide 10: LPCN 1154 – Subgroup Analysis
LPCN 1154 – Subgroup Analysis* Strong and coherent efficacy with exclusion of outlier site Subgroup Analyses • Anomalies raise substantive questions about data validity for one site (1 out of 15 total) • 39% of LPCN 1154-treated participants had no evidence of study drug in their system • Different
Slide 11: Comparison Between Outlier Site and Other Sites
Comparison Between Outlier Site and Other Sites Epidemiologic outlier: low percentage of patients with prior or current psychiatric diagnosis 100 Percent of Participants 78 78 80 60 60 40 37 23 23 20 7 0 0 Current or history of History of PPD History of Baseline psychiatric diagnosis MDD or MDE HAM-
Slide 12: Comparison Between Outlier Site and Other Sites: Placebo Effect
Comparison Between Outlier Site and Other Sites Placebo effect outlier: high rates of HAM-D response, remission, and change from baseline Placebo Arm HAM-D Comparison Hour 60 Day 30 100 *** *** *** % of Participants or CFB 92 80 64 83 -82 60 -56 * -36 40 30 -31 29 27 19 20 9 0 Response Remission % C
Slide 13: Subgroup Analysis Excluding Outlier Site
Subgroup Analysis Excluding Outlier Site Baseline demographics Characteristics LPCN 1154 Placebo Total N 27 33 60 Age (years) 30.0 (5.9) 31.7 (6.6) 30.9 (6.3) BMI (kg/m2) 31.9 (6.4) 30.5 (6.4) 31.1 (6.4) Ethnicity (HISP; %) 40.7 45.5 43.3 Race (White; %) 55.6 54.5 55.0 Antidepressant use at baseline
Slide 14: Rapid, Durable, and Meaningful Improvement Across All Timepoints
Rapid, Durable, and Meaningful Improvement Across All Timepoints Subgroup analysis* HAM-D Change From Baseline Over Time HAM-D Change From Baseline over Time 0 Hour1 12 Hour 2 36 Hour 3 60 Day 4 7 Day 5 30 Placebo-adjusted Statistical 0 Time Difference Significance Cohen’s d HAM-D Change From Baseli
Slide 15: LPCN 1154 Summary and Conclusions
LPCN 1154 Summary and Conclusions • HAM-D data support rapid and durable treatment effect in two subgroups • Excluding outlier site • PPD with history of psychiatric condition (see poster W98) • Clinically meaningful efficacy as early as 12 hours (HAM-D CFB ~ -11, Cohen’s d > 1) • Median time to fir