Slide 1: LPCN 1154 for Depression
LPCN 1154 for Depression R&D Event, July 9th 2025
Slide 2: Introduction and agenda
Introduction Dr. Mahesh Patel President and CEO Lipocine Postpartum Depression Landscape Dr. Kristina Deligiannidis Professor and Director, Women's Behavioral Health Zucker Hillside Hospital, Northwell Health, New York LPCN 1154 Target Product/Label Attributes Dr. Anthony DelConte Medical Director L
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: Lipocine Pipeline
Lipocine Pipeline Development Candidate (Indication) Pre-Clinical Phase 1 Phase 2 Pivotal Next Steps/Status LPCN 1154 Phase 3 Postpartum Depression Topline results Q2/26 LPCN 2401 POC study as adjunct to GLP-1 Obesity Management - adjunct to GLP-1 Expected patient dosing Q3/25 LPCN 1148 P2 study com
Slide 5: LPCN 1154 - Oral Bioidentical Neuroactive Steroid (NAS) for PPD
LPCN 1154 - Oral Bioidentical Neuroactive Steroid (NAS) for PPD Overcoming brexanolone oral delivery challenges Brexanolone Oral enablement Brexanolone (allopregnanolone) is a positive allosteric modulator (PAM) of the GABAA receptor Molecular Weight: 318.5 g/mol Lipophilic: Log P ≈ 5.0 Poor aqueous
Slide 6: PPD Treatment Landscape
PPD Treatment Landscape Dr. Kristina Deligiannidis
Slide 7: Dr. Kristina Deligiannidis
Dr. Kristina Deligiannidis Relationships and affiliations Research/grant/contract funding Royalties • National Institutes of Health • NIH Employee Invention • CDC/NIOSH Consulting • New York State Office of Mental Health (contract) • Lipocine Inc • Feinstein Institutes for Medical Research, Northwel
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 (1 in 5) (Wisner KL et al, 2013; Fawcett EJ et al, 2019; Masters GA et al, 2022). • Globally, mean prevalence rates of depression during preg
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 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 as cornerstone treatment
Psychotherapies and serotonergic/traditional antidepressants have been the cornerstone of postpartum depression treatment for decades • Psychotherapies: used as a main treatment modality for mild to moderate perinatal depression (Grote NK et al, 2010; Ammerman RT et al, 2013; Dimidijian S et al, 201
Slide 13: Challenges with traditional serotonergic antidepressants
Challenges with use of traditional serotonergic antidepressants for postpartum depression Slow onset of action, takes 86% of patients report at least one side effect with 55% on average 6-8 weeks for reporting one or more bothersome side effects after patients to experience taking an SSRI for 75 day
Slide 14: Neuroactive steroids modulate GABAergic and glutamatergic neurotransmission
Neuroactive steroids are pregnenolone metabolites which modulate GABAergic and glutamatergic neurotransmission • Natural or synthetic steroids which act on the brain by serving as transcription factors in the regulation of gene expression or by interacting with membrane- bound neurotransmitter recep
Slide 15: NAS enhance tonic and phasic inhibition through GABAA receptors
NAS enhance tonic and phasic inhibition through synaptic and extrasynaptic GABAARs Postsynaptic GABA-A receptors, which are pentameric chloride channels composed of 2α2βγ subunits, mediate the phasic portion of GABAergic inhibition, while extrasynaptic GABA-A receptors, pentamers composed of 2α2βδ s
Slide 16: Failure of the brain's GABA system to adapt may lead to depression
Under stress conditions, failure of the brain’s GABA system to adapt to current or abnormal NAS levels may lead to brain circuit dysfunction= clinical depression Figure 2: Meltzer-Brody S & Kanes S. Neurobiology of Stress. 2020. Lipocine│R&D Event, July 2025 16
Slide 17: Brexanolone as a first-in-class antidepressant
Brexanolone 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. • However, brexanolone administrat
Slide 18: Clinical characteristics of neuroactive steroid antidepressants
Clinical characteristics of neuroactive steroid antidepressants • Rapid onset of action, within days, treatment course not to be repeated • No (up/down) titration required for oral neuroactive steroids • A different side effect profile as compared to serotonergic antidepressants, whose side effects
Slide 19: Use of antidepressants during lactation/breastfeeding
Use of antidepressants during lactation/breastfeeding The National Library of Medicine at the NIH maintains the Drugs and Lactation Database (LactMed) found at: https://www.ncbi.nlm.nih.gov/books/NBK501922/ A relative infant dose (RID) less than 10% of maternal dosage is acceptable per FDA. Antidepr
Slide 20: Conclusions
Conclusions Perinatal depression/postpartum depression is common Untreated perinatal depression is associated with myriad adverse outcomes Neuroactive steroid antidepressants are rapid-acting medications Neurosteroid antidepressants require a shorter course of treatment than traditional antidepressa
Slide 21: LPCN 1154 Target Product/Label Attributes
LPCN 1154 Target Product/Label Attributes Dr. Anthony DelConte Medical Director
Slide 22: PPD Screening & Treatment Incorporated into Multiple Guidelines
PPD Screening & Treatment Incorporated into Multiple Guidelines Early Diagnosis of PPD is key • The American Academy of Pediatrics (AAP)1 and the American College of Obstetricians and Gynecologists (ACOG)2,3 have both issued guidelines that patients should be screened for PPD during pregnancy and po
Slide 23: Market Research Insights
Market Research Insights • Patients with a history of MDD are more likely to develop PPD • Many patients feel unprepared to discuss PPD and often feel embarrassed to mention their symptoms Physician • Both OBGYNs and Psychiatrists conduct screening, diagnose and treat PPD patients Observations • T
Slide 24: Market Research Insights
Market Research Insights • Patients express concerns regarding potential side effects and the stigma associated with taking antidepressants • Patients are often lost to follow-up leading to poor persistence and adherence Patient Observations • Patients are the least satisfied with current options
Slide 25: Robust Efficacy of Brexanolone in PPD
Robust Efficacy of Brexanolone in PPD Bioidentical Neuroactive Steroid (NAS) IV Brexanolone Remission Rates2 60 50 HAM-D Change From Baseline 40 Remission Rate (%) 30 20 10 0 1 2 2.5 3 7 30 Days Since Initiation of Treatment Efficacious at lower (60 µg/kg/hr) Remission defined as HAM-D scores ≤7 out
Slide 26: Users of Oral NAS for Treatment of PPD
Users of Oral NAS for Treatment of PPD Majority have had no prior PPD treatment - only 2% PPD patients currently treated with oral NAS PPD Treatment Pathways Previous PPD Treatment of ZURZUVAE® Users ZURZUVAE® No Pharmacological ZURZUVAE® with without Treatment Prior PPD Treatment Prior PPD Treatmen
Slide 27: LPCN 1154 Target Product Profile to Address Unmet Medical Need
LPCN 1154 Target Product Profile to Address Unmet Medical Need Mechanism of Action and Target Attributes • A positive allosteric modulator (“PAM”) of the GABAA receptor • Acting on both post-synaptic and extrasynaptic sites on GABAA receptor • Chemically identical to endogenous allopregnanolone (bre
Slide 28: LPCN 1154 - Current therapies relative to LPCN 1154
LPCN 1154 - Oral Bioidentical NAS for PPD Current therapies relative to LPCN 1154 SSRIs / SNRIs Zuranolone Oral Brexanolone Off-Label Use (ZURZUVAE®) (LPCN 1154) Synthetic Synthetic NAS Description Bioidentical NAS SSRIs have slow onset, low remission & response SSRI/SNRI Derivative rates Administra
Slide 29: LPCN 1154 Development/Next Steps
LPCN 1154 Development/ Next Steps Dr. Benjamin Bruno VP of Clinical Development
Slide 30: Clinical Development and Phase 1 Clinical Studies
Clinical Development and Phase 1 Clinical Studies Formulation Screening Studies Dose Finding Studies Two studies Two studies N = 17, Postmenopausal Women N = 20, Postmenopausal women • Brexanolone is orally available in capsule and tablet Pilot crossover study including IV brexanolone formulations •
Slide 31: Dose linear exposure across all single and multidose regimens
Clinical Development and Phase 1 Clinical Studies (Cont’d) Dose linear exposure across all single and multidose regimens Single Dose Multidose 120 600 200 3000 R² = 0.9892 R² = 0.9884 100 500 2500 160 AUC24-56 (ng*h/mL) AUC (ng*hr/mL) 80 400 2000 Cmax (ng/mL) Cmax (ng/mL) 120 R² = 0.9406 60 300 1500
Slide 32: LPCN 1154 Dosing Regimen Confirmation Study
LPCN 1154 Dosing Regimen Confirmation Study Study Design 24 post-menopausal women Randomized, crossover design Period 1 Period 2 PK endpoints N = 12 LPCN 1154 IV Brexanolone Randomization N = 24 Screening N = 12 IV Brexanolone LPCN 1154 Study First dose Final drug First dose Final drug Study Enrollm
Slide 33: Dosing Regimen Confirmation Study Results
LPCN 1154 Dosing Regimen Confirmation Study Results LPCN 1154 met standard bioequivalence criteria to IV Brexanolone Comparative Exposure • LPCN 1154 was well tolerated • No sedation or somnolence events observed PK GMR (%) 90% CI LB 90% CI UB • All events were mild to moderate Parameter Test vs. Re
Slide 34: Well Tolerated in the Completed Clinical Studies
Well Tolerated in the Completed Clinical Studies No adverse events of excessive sedation or loss of consciousness CNS Depressant Events Non-CNS Depressant Adverse Events Total unique participants 58 Total unique participants 58 Preferred Term n (%) Preferred Term n (%) Somnolence 7 (12.1) Venipunctu
Slide 35: LPCN 1154 Phase 3 Safety and Efficacy Study
LPCN 1154 Phase 3 Safety and Efficacy Study Based on FDA feedback – Outpatient setting with no medical monitoring requirement Study design Two arm, outpatient, randomized, blinded, placebo-controlled in women with postpartum depression Inclusion criteria Endpoints Primary endpoint: LPCN 1154 HAM-D c
Slide 36: Phase 3 Rationale for Success and Study Updates
LPCN 1154 Phase 3 Safety and Efficacy Study Rationale for Success Study Updates • Brexanolone has established efficacy (IV infusion) • Study initiated March 2025 • LPCN 1154 has demonstrated • First patient dosed June 2025 comparable exposure to IV infusion • Expected first DSMB 2H 2025 • Study size
Slide 37: Regulatory status
Regulatory status Expected NDA submission mid-2026 Status Clinical development plan Single Phase 3 randomized placebo control trial in women with PPD – Ongoing Ongoing – Following FDA feedback, outpatient study without continuous healthcare provider supervision Supporting dosing regimen confirmation
Slide 38: Concluding Remarks
Concluding Remarks Dr. Mahesh Patel President and CEO
Slide 39: Postpartum Depression - An Expanding Market Opportunity
Postpartum Depression (PPD) - An Expanding Market Opportunity Compelling pharmacoeconomic rationale10 • High economic burden Estimated patients in the U.S. with PPD3 • Goal of medical intervention is to prevent harm to mother and infant • Negative impact on 3.6M Pregnancies in the US4 family/society
Slide 40: LPCN 1154 "Best in Class" Oral Treatment for Depression
LPCN 1154 “Best in Class” Oral Treatment for Depression Key takeaways • Significant market opportunity • Differentiated product attributes addressing unmet needs • Streamlined pathway to NDA submission • Dosing regimen confirmed • Phase 3 safety & efficacy study: ongoing • Topline data expected Q2/2
Slide 41: LPCN 1154 Opportunities in Additional Depression Disorders
LPCN 1154 Opportunities in Additional Depression Disorders Prevalence Significant Unmet Needs in Depression Disorders Robust Adequate and durable remission/response; treat anxiety MDD: Per NIMH, in 2020, an estimated Efficacy comorbidity 21.0 million adults (8.4%) in the US had at least one major de
Slide 42: Q&A
Q&A Lipocine│R&D Event, July 2025 42