Slide 1: Virtual KOL Event: Highlighting Unmet Needs in Postpartum Depression and LPCN 1154
Virtual KOL Event Highlighting Unmet Needs in Postpartum Depression and the Clinical Profile of LPCN 1154 June 12, 2026
Slide 2: Agenda
Agenda Time Session Moderator Dr. Mahesh Patel 3 min Opening Remarks President and CEO, Lipocine Postpartum Depression: Clinical Burden, Treatment Landscape, and Remaining Unmet 5 min Dr. Kristina Deligiannidis Needs Dr. Ben Bruno, 10 min LPCN 1154: Clinical Outcomes Highlights VP of Clinical Develo
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: Opening Remarks
Opening Remarks Dr. Mahesh Patel, President and CEO Lipocine
Slide 5: LPCN 1154 (Oral Brexanolone)
LPCN 1154 (Oral Brexanolone) Antidepressant GABAA PAM mechanism validated through FDA approved drugs, Zulresso® and Zurzuvae® Endogenous Neuroactive Steroid (NAS) Potent positive allosteric modulator (PAM) of the GABAA receptor Metabolite of progesterone Synaptic Engagement Acts on both synaptic and
Slide 6: Dr. Deligiannidis biography
Dr. Deligiannidis received her medical degree from and completed her psychiatry residency and chief residency in psychopharmacology research at the University of Massachusetts Medical School. Prior to and during medical school she trained in neuroscience research at the National Institutes of Health
Slide 7: Postpartum Depression: Clinical Burden, Treatment Landscape, and Remaining Unmet Needs
Postpartum Depression: Clinical Burden, Treatment Landscape, and Remaining Unmet Needs Dr. Kristina Deligiannidis
Slide 8: Perinatal Depression is common and costly
Perinatal Depression is common and costly • Perinatal mental health disorders are among the most common complications of pregnancy and the year after delivery (Wisner KL et al, 2013; Fawcett EJ et al, 2019; Masters GA et al, 2022). • Globally, mean prevalence rates of depression during pregnancy or
Slide 9: Perinatal depression is under-diagnosed and undertreated
Perinatal depression is under-diagnosed and undertreated • Numerous professional organizations, including the U.S. Preventative Services Task Force (USPSTF) and American Psychiatric Association (APA), recommend screening for depression in pregnant and postpartum individuals (JAMA 2016; APA position
Slide 10: Perinatal depression is associated with adverse maternal, obstetrical, infant and child outcomes
Perinatal depression is associated with adverse maternal, obstetrical, infant and child developmental outcomes • Decreased maternal functioning (Field, T, 2010) • Psychosis, suicidal ideation and suicide attempt are psychiatric emergencies that lead to psychiatric hospitalization, maternal death (Ro
Slide 11: Postpartum depression is not the baby-blues
Postpartum depression is not the baby-blues The baby blues is not a clinical A patient example: diagnosis, is experienced by “Abby” is a 34-year-old married female with a past psychiatric history approximately 80% of women of depression and anxiety presented for clinical care 8 weeks after in the fi
Slide 12: Psychotherapies and serotonergic antidepressants have been the cornerstone of treatment
Psychotherapies and serotonergic/traditional antidepressants have been the cornerstone of postpartum depression treatment for decades • Psychotherapies: may be used as monotherapy for mild to moderate perinatal depression (Grote NK et al, 2010; Ammerman RT et al, 2013; Dimidijian S et al, 2014; Good
Slide 13: Neuroactive steroids modulate GABAergic and glutamatergic neurotransmission
Neuroactive steroids (NAS) modulate GABAergic and glutamatergic neurotransmission • Natural or synthetic steroids act on the brain by serving as transcription factors in the regulation of gene expression or by interacting with membrane-bound neurotransmitter receptors (Paul SM & Purdy RH 1992) • Man
Slide 14: NAS as a first-in-class antidepressant
NAS as a first-in-class antidepressant • The breakthrough FDA-approval of brexanolone in 2019 represented a first-in-class antidepressant that had rapid- acting antidepressant actions which were maintained even after the acute treatment course was complete. Allopregnanolone; Brexanolone (3α, 5α NAS)
Slide 15: Pharmacologic Treatment Landscape Comparison
Pharmacologic Treatment Landscape Comparison IV Brexanolone (ZULRESSO®) is no longer IV Brexanolone Zuranolone SSRIs/SNRIs available related to the prolonged inpatient 60- (ZULRESSO®) (ZURZUVAE®) Off-Label Use hour monitored infusion, creating logistical and access challenges Synthetic NAS Descripti
Slide 16: LPCN 1154: Clinical Outcomes Highlights
LPCN 1154: Clinical Outcomes Highlights Dr. Benjamin Bruno VP of Clinical Development
Slide 17: 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 LPCN 1154 Test vs. Reference Parameter Brexanolone (90% CI) Cmax 105% 120 115 (92%-118%) (ng/mL)
Slide 18: 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 19: 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 20: 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.
Slide 21: 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 22: Strong and Coherent Efficacy with Exclusion of Outlier Site
LPCN 1154 - Strong and Coherent Efficacy with Exclusion of Outlier Site Subgroup Analysis* 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 23: Comparison Between Outlier Site and Other Sites
Comparison Between Outlier Site and Other Sites Outlier subgroup: 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-A ≥20
Slide 24: Comparison Between Outlier Site and Other Sites: Placebo effect
Comparison Between Outlier Site and Other Sites Outlier subgroup: Placebo effect - 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 Re
Slide 25: Baseline Demographics: Non-Outlier Sites
Baseline Demographics Subgroup Analysis: Non-Outlier Sites 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 26: HAM-D Change From Baseline: Non-Outlier Sites
Rapid, Durable, & Meaningful Improvement Across All Timepoints Subgroup Analysis: Non-Outlier Sites HAM-D Change From Baseline Over Time HAM-D Change From Baseline over Time 0 Hour1 12 Hour 2 36 Hour3 60 Day4 7 Day530 Placebo-adjusted Statistical 0 Time Difference Significance Cohen’s d HAM-D Change
Slide 27: Responder & Remitter Results Corroborate Strong Treatment Effect
Responder & Remitter Results Corroborate Strong Treatment Effect Subgroup Analysis: Non-Outlier Sites Percent of Participants with HAM-D Response Percent of Participants with HAM-D Remission 80 60 HAM-D Remitter (%) HAM-D Responder (%) 60 40 40 20 20 0 0 Hour 12 Hour 36 Hour 60 Day 7 Day 30 Cumulati
Slide 28: Fastest Observed Onset in PPD; Clinically Meaningful Relief at 12 Hours
LPCN 1154 – Fastest Observed Onset in PPD; Clinically Meaningful Relief at 12 Hours Subgroup Analysis: Non-Outlier Sites Excluding Outlier Site At 12 Hours (N=60) HAM-D171 -7.1 *** (Cohen’s d = -1.10) -6.3 ** HAM-A1 (Cohen’s d = -0.86) HAM-D17 38.5% vs 6.3% ** Response2 (Active vs Placebo) HAM-D61 -
Slide 29: Rapid and Sustained Target Engagement
Rapid and Sustained Target Engagement LPCN 1154 – PK/PD correlation PK/PD Correlation: Mechanistic Validation (qEEG EC) • β band qEEG activity is a validated, 140 70 objective biomarker of GABAA receptor Mean Brexanolone Plasma Concentration (ng/ml) Mean qEEG % CBL Beta power EC (12 - 25 HZ) 120 Bre
Slide 30: HAM-D Change From Baseline: PPD with History of Psychiatric Diagnosis
Rapid, Durable, & Statistically Significant Improvement Across Multiple Timepoints Subgroup Analysis: PPD with History of Psychiatric Diagnosis HAM-D Change From Baseline Overtime HAM-D Change From Baseline over Time 0 Hour1 12 Hour 2 36 Hour 3 60 Day 4 7 Day 5 30 0 Placebo-adjusted Statistical Time
Slide 31: LPCN 1154 Summary and Conclusions
LPCN 1154 Summary and Conclusions Subgroup analyses • HAM-D data support rapid and durable treatment effect in two subgroups • Excluding outlier site • PPD with history of psychiatric condition • Clinically meaningful efficacy as early as 12 hours (HAM-D CFB ~ -11, Cohen’s d > 1) • Median time to fi
Slide 32: Dr. Jain biography
Dr. Jain (MD, MPH) is a clinical professor in the Department of Psychiatry at the Texas Tech University Health Sciences Center School of Medicine - Permian Basin in Midland. He is also in private practice in Austin, TX. Dr. Jain attended medical school at the University of Calcutta in India. He then
Slide 33: Recent LPCN 1154 Clinical Data: Clinical Interpretation and Relevance to Practice
Recent LPCN 1154 Clinical Data: Clinical Interpretation and Relevance to Practice Dr. Rakesh Jain
Slide 34: Comments on Observed Safety of LPCN 1154
Comments on Observed Safety of LPCN 1154 (Full Analysis Set) LPCN 1154 was self-administered at-home 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
Slide 35: HAM-D Change From Baseline: Non-Outlier Sites
Rapid, Durable, & Meaningful Improvement Across All Timepoints Subgroup Analysis: Non-Outlier Sites HAM-D Change From Baseline Over Time HAM-D Change From Baseline over Time 0 Hour1 12 Hour 2 36 Hour3 60 Day4 7 Day530 Placebo-adjusted Statistical 0 Time Difference Significance Cohen’s d HAM-D Change
Slide 36: Major Depressive Disorder
Major Depressive Disorder Multiple pathophysiological pathways contribute to MDD • 9.2% of Americans aged ≥12 years experienced MDD in the past-year,1 resulting in an economic cost >$380 billion in 20232 • Landscape of pharmacologic treatment is rapidly evolving, including NMDA receptor modulation,
Slide 37: HAM-D Change From Baseline: PPD with History of Psychiatric Diagnosis
Rapid, Durable, & Statistically Significant Improvement Across Multiple Timepoints Subgroup Analysis: PPD with History of Psychiatric Diagnosis HAM-D Change From Baseline Overtime HAM-D Change From Baseline over Time 0 Hour1 12 Hour 2 36 Hour 3 60 Day 4 7 Day 5 30 0 Placebo-adjusted Statistical Time
Slide 38: Recent LPCN 1154 Clinical Data: Clinical Interpretation and Relevance to Practice
Recent LPCN 1154 Clinical Data: Clinical Interpretation and Relevance to Practice Dr. Kristina Deligiannidis
Slide 39: LPCN 1154 Demonstrated Differentiated Efficacy Signal
LPCN 1154 Demonstrated Differentiated Efficacy Signal Zurzuvae LPCN 1154 – Including Non-Outlier Sites LS Mean CBL in HAM-D Total Score Over Time in Study1 LS Mean CBL in HAM-D Total Score Over Time 0 0 Placebo LS Mean Change from Baseline LS Mean Change from Baseline ZURZUVAE 50 mg -5 -5 (HAM-D Tot
Slide 40: PPD Therapy Overview – LPCN 1154 and Existing Options
PPD Therapy Overview – LPCN 1154 and Existing Options Oral Brexanolone Zuranolone SSRIs/SNRIs LPCN 1154 (Brlizio) is expected to provide (LPCN 1154) (ZURZUVAE®) Off-Label Use rapid relief of PPD with a short (48-hour) treatment Synthetic NAS Description Bioidentical NAS Synthetic SSRI/SNRI derivativ
Slide 41: Why LPCN 1154 Matters Now, Next Steps, and Concluding Remarks
Why LPCN 1154 Matters Now, Next Steps, and Concluding Remarks Dr. Mahesh Patel, President and CEO Lipocine
Slide 42: PPD – An Expanding Market Opportunity
PPD – An Expanding Market Opportunity Awareness drives diagnosis - empowering women with PPD through effective therapies • High clinical and economic burden Estimated patients in the U.S. with PPD5 with consequences beyond the mother • Treatment goal is rapid symptom relief to improve outcomes for m
Slide 43: Differentiated Target Attributes as a Rapid-Acting PPD treatment
Differentiated Target Attributes as a Rapid-Acting PPD treatment* Strong candidate to meet FDA RAAD criteria FDA Criteria for Rapid-Acting Efficacy demonstrated within 1 week Anti-Depressants (RAAD) Rapid relief as early as 12 hr Median Time to Response* Onset: 2.6 days For rapid-acting antidepressa
Slide 44: LPCN 1154 Next Regulatory Steps
LPCN 1154 Next Regulatory Steps FDA meeting to align Submit Validation Applied for on clinical data study protocol Breakthrough Therapy package and confirm and Fast Track NDA submission Designations with pathway FDA Lipocine│KOL Event, June 2026 44
Slide 45: LPCN 1154 – Potential “Game Changer” for Fast Acting Depression Therapy
LPCN 1154 – Potential “Game Changer” for Fast Acting Depression Therapy Key takeaways LPCN 1154 Large, attractive market opportunity Rapid & Durable Relief Differentiated product profile addressing unmet needs Streamlined path to NDA submission Superior Tolerability Issued and pending patent protect
Slide 46: Q&A
Q&A Lipocine│KOL Event, June 2026 46