Lipocine : LPCN 1154 – Oral Brexanolone for Postpartum Depression (PPD)

Published: 2026-04-15 13:35:08 ET LPCN

Published on 04/15/2026 at 01:35 pm EDT

Oral Brexanolone for Postpartum Depression (PPD)

BrlizioTM is a brand name conditionally approved by FDA

PPD - A Significant Global Health Issue Affecting Families Worldwide

Estimated ~ 24 million new cases of PPD annually worldwide1

Prevalence of PPD in pregnant women

Northern Europe 14%

Northern America 17%

South America 22%

Northern Africa 19%

Western Africa 14%

Eastern Europe 17%

Western Asia 20%

Southern Asia 22%

Eastern Asia 17%

Switzerland

22%

Korea

22%

21%

Brazil

21%

China

18%

Italy

17%

France

15%

Canada

14%

Japan

13%

Germany

10%

South-Eastern Asia 14%

Southern Africa 40%

Oceania 11%

Figure is modified based on data and map from reference Wang et al (2021)

1. Wang et al. Translational Psychiatry (2021) 11:543

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PPD is a Life-Threatening Condition with Few Existing Treatment Options

Short Treatment Duration Benefits

Rapid Relief Benefits

Superior Tolerability Benefits

Prompt Access Benefits

Rapid relief, short treatment duration, and superior tolerability advantages

Maternal depression and suicide can have far-reaching consequences for child development, family function, and the nation's economy1-3

Faster management of depression

Reduces the risk of suicidal thoughts and behaviors

Leads to fewer hospitalizations

Positive outcomes in terms of mother and family relationships

Reduces financial burden

Better compliance

Scheduling flexibility (e.g. weekend) with minimal family disruption

More amenable to discreet treatment

Quicker return to normal daily activities

Low infant sedation risk

Better treatment adherence

Increase treatment success

Reduced risk of complications and

hospitalization

More quality time with family

Less dependence on caregivers

Convenient oral route allows independent use

Increased treatment reach

Reduced stigma-lower visibility of

treatment

Reduced risk of crisis or suicide

Rapid treatment initiation in time sensitive indication

Higher treatment engagement

Reduced health inequities

Mauri et al. Arch Womens Ment Health. 2012; 15(1): 39-47

Chin et al. Curr Psychiatry Rep, 2022; 24(4):239-275

https://www.nytimes.com/2025/07/22/health/post-partum-depression-treatment-pill.html

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PPD - An Expanding Market Opportunity

Awareness drives diagnosis - empowering women with PPD through effective therapies

Estimated patients in the U.S. with PPD5

High clinical and economic burden with consequences beyond the mother

Treatment goal is rapid harm reduction

for both mother and infant

Meaningful negative impact on family

stability, child development, and society

PPD commonly presents with psychiatric comorbidity; 64% report anxiety symptoms1

Suicide is a leading cause of maternal death in the first year postpartum2

− Up to 30% of women with PPD report suicidal ideation3

Increased awareness and effective therapies are expected to meaningfully expand diagnosis among symptomatic women with PPD

3.6M

~ 600,000

~ 240,000

~144,000

Pregnancies in the US6

Postpartum depression7

Diagnosed PPD patients8

Diagnosed are Rx treatedG

Compelling pharmacoeconomic rationale for early, effective intervention4

ZURZUVAE® Rx price: $16,377

ZURZUVAE revenue $66M Q4-2510

Projected peak ZURZUVAE® sales of ~$1B11

ZURZUVAE® is an FDA-approved oral treatment for adults with PPD

1. Farr et al. J Womens Health (Larchmt). 2013 Oct 26;23(2):120-128

5. Foster Rosenblatt market research 2023 (Lipocine internal data)

9. Sage/Biogen HEOR Claims Analysis

2. Chin et al. Curr Psychiatry Rep, 2022; 24(4):239-275

6. National Vital Statistics Report vol 72, num 1, 2023; Vital Statistics Rapid Release, report 10. Biogen 4th Quarter 2025 Financial Results

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3. Mauri et al. Arch Womens Ment Health. 2012; 15(1): 39-47

4. Leerink Center for Pharmacoeconomics, 2025 MEDACorp LLC

26, 2023

7. Van Niel et al. Cleveland Clinic J of Medicine. 2020;87(5):273-277

8. Cox et al. J Clin Psychiatry. 2016;77:9, Beck. AJN. 2006;106:5

11. Sage May 2025 Management Projection

LPCN 1154 - Oral Bioidentical Neuroactive Steroid (NAS) for PPD

Overcoming brexanolone oral delivery challenges

Brexanolone

Oral enablement

Molecular Weight: Lipophilic:

318.5 g/mol Log P ≈ 5.0

Poor aqueous solubility: Saq <1.0 μg/mL

Source: Giliyar et al. Drug Delivery Technology, Jan 2006, Vol 6 No.1

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LPCN 1154 - Distinctive Pharmacological Pathway

Validated through approved IV Brexanolone

Modulation of GABAergic Inhibition1

Synaptic GABAA receptors especially those containing the γ subunit which mediate phasic inhibition, short bursts of inhibitory signaling)

Extrasynaptic GABAA receptors, especially those containing the δ subunit, which mediate tonic inhibition, sustained inhibitory tone

Modulating TLR Signaling Pathways2

Reduce pro-inflammatory cytokines (e.g., IL-1β, TNF-α) and increase anti-inflammatory cytokines (e.g., IL-10)

Modulate inflammatory processes associated with neuropsychiatric disorders

1 Meltzer-Brody and Kanes, Neurobiology of stress, 2020

2. Balan et al. Life 2024, 14, 582

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LPCN 1154 - Poised to Lead the Market and Set the Standard of Care

LPCN 1154 (Brlizio) is expected to provide more rapid relief of PPD than approved treatments, with only a short (48-hour) treatment requirement.

Therapy overview - LPCN 1154 vs. existing options

Oral Brexanolone

(LPCN 1154)

Zuranolone

(ZURZUVAE®)

SSRIs/SNRIs

Off-Label Use

Description

Bioidentical NAS

Synthetic NAS Derivative

Synthetic SSRI/SNRI

Median Time to Response Onset

2.6 days*

9 Days1

Weeks

CNS depressant AEs

Low3

High2

Moderate4

Onset of Action

Hours

Days

Weeks

Treatment Duration

48 Hours

14 Days

Months

SSRIs / SNRIs have slow onset, longer treatment duration, and lower response rates. Additionally side effects such as sexual dysfunction, changes in sleep pattern and weight gain are common.

Zuranolone (ZURZUVAE®) treatment is associated with frequent CNS depressant effects such as somnolence, dizziness, and sedation.

No head-to-head clinical trials have been conducted. Data are derived from published reports of different clinical trials at different points in time, with differences in trial design, size, and patient populations.

1. Deligiannidis et al., Am J Psychiatry 180:9, September 2023

2. Zurzuvae label; Somnolence (36%), dizziness (13%), dose Reduction (14%), and discontinuation (2%),

3. Defined as less than 5% with no drug discontinuations, drug-related SAEs, loss of consciousness, or excessive sedation

4. https://www.uptodate.com/contents/image?imageKey=PSYCH%2F143603

*internal data, Psychiatric History Subset

Median time to response is defined as time to 50% of participants experiencing response (≥50% reduction in HAM-D)

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LPCN 1154 - Phase 3 Safety and Efficacy Study Design

Utilizes same dose and regimen as the PK dose confirmation study

Study design

Two arm, outpatient, randomized, blinded, placebo-controlled in women with postpartum depression at

home administration with no medical monitoring

Inclusion criteria Endpoints

LPCN 1154

Placebo

Rating Scales: Administered at baseline, 12h, 36h, 60h, 7 day and 30 day

Primary endpoint: HAM-D change from baseline at hour 60

Severe PPD (HAM-D ≥26)

Age ≥15 yrs

N= 90 women

Treatment period

Hour

0 48 60

Primary Analysis Timepoint

Day 30

https://clinicaltrials.gov/study/NCT06979544

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Overall population

Baseline Demographics

Characteristics

LPCN 1154

Placebo

Overall

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

AD use at baseline (%)

8.9

HAM-D at baseline (Mean, SD)

28.3 (2.8)

28.2 (3.1)

28.3 (2.9)

History of psychiatric condition (based on MINI) (N, %)

24 (53.3)

30 (66.7)

54 (60.0)

History of depression

19 (42%)

38 (42%)

15 sites randomized participants

MINI: Mini-International Neuropsychiatric Interview AD: Antidepressant

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Efficacy Results

Placebo-Adjusted HAM-D17 Score Change from Baseline

Timepoint

Overall Population

N=G0

History of Psychiatric Condition Subset*

N=54

Placebo-adjusted Difference

Statistical Significance

Placebo-adjusted Difference

Statistical Significance

Hour 12

-3.9

P < 0.01

-7.2

P < 0.001

Hour 36

-1.7

NSS

-5.0

P < 0.05

Hour 60

-1.3

NSS

-6.1

P < 0.01

Day 7

-1.2

NSS

-4.2

NSS

Day 30

-2.3

NSS

-5.3

P < 0.05

NSS: Not Statistically Significant. Mixed model for repeated measures, least squares means placebo-adjusted difference. P-values are nominal except for Hour 60 Overall Population.

*Post hoc analysis

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Primary Endpoint: HAM-D CFB at Hour 60

Primary endpoint not met

HAM-D Change From Baseline over Time

Hour 12

Hour 36

Hour 60

Day 7

Day 30

0 1 2 3 4 5

HAM-D Change From Baseline

-5

-10

-15

-20

** p<0.01

https://clinicaltrials.gov/study/NCT06979544

Mixed model for repeated measures, least squares means placebo-adjusted difference. P-values are nominal except for Hour 60 Overall Population.

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Patients with PPD and Psychiatric Conditions

Appropriate for Subgroup Analysis

Well defined condition characterized via standardized tool, MINI

Validated structured clinical interview for DSM and ICD psychiatric disorders

Commonly used in clinical trials

FDA agreed on using MINI to diagnose major depressive episode in this study

Prone to higher severity and chronicity

The risk of PPD was more than 20 times higher for women with a depression history, compared to women without1

High prevalence of psychiatric conditions in patient with PPD

65 - 82% prior history of depression2,3

This group often show lower placebo effect

Aligns with known antidepressant effects of brexanolone

IV administered brexanolone demonstrated substantially higher treatment effect in patients with prior personal PPD history4

1. Depress Anxiety. 2017 Feb;34(2):178-187

2. BMC Pregnancy Childbirth. 2014 Dec 10:14:402

3. J Clin Psychiatry. 2020 Jan 21;81(1):19m12929

4. Lancet 2018; published online Aug 31. http://dx.doi. org/10.1016/S0140-6736(18)31544-7.

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PPD with History of Psychiatric Conditions

Baseline demographics

Characteristics

LPCN 1154

Placebo

Overall

Age (years) (Mean, SD)

31.0 (5.5)

30.8 (6.6)

30.9 (6.1)

BMI (kg/m2) (Mean, SD)

31.6 (6.6)

30.1 (6.7)

30.8 (6.6)

Ethnicity (HISP; %)

41.7

50.0

46.3

Race (White; %)

50.0

60.0

55.6

AD use at baseline (%)

12.5

13.3

13.0

HAM-D at baseline (Mean, SD)

28.9 (3.5)

28.6 (3.5)

28.7 (3.5)

History of psychiatric condition (based on MINI) (N, %)

24 (100)

30 (100)

54 (100)

Similar characteristics as overall study population, including baseline HAM-D

- Slightly lower number of Hispanic participants (46% vs 62%)

https://clinicaltrials.gov/study/NCT06979544

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PPD with History of Psychiatric Conditions

HAM-D Change from Baseline

* p<0.05; ** p<0.01; *** p<0.001

https://clinicaltrials.gov/study/NCT06979544

Mixed model for repeated measures, least squares means placebo-adjusted difference. P-values are nominal except for Hour 60 Overall Population.

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Overall Population Safety

LPCN 1154 was well tolerated

Parameter

LPCN 1154

N=45

n (%)

PLACEBO

N=45

n (%)

Overall

N=90

n (%)

Any TEAE

8 (17.8)

16 (17.8)

Any treatment-related TEAE

5 (11.1)

3 (6.7)

8 (8.9)

Any severe TEAE

2 (4.4)

0 (0.0)

2 (2.2)

Any serious TEAE

1 (2.2)

0 (0.0)

1 (1.1)

TEAEs in ≥ 2 participants in LPCN 1154 arm

Headache

2 (4.4)

3 (6.7)

5 (5.6)

Dizziness

2 (4.4)

0 (0.0)

2 (2.2)

Somnolence

2 (4.4)

0 (0.0)

2 (2.2)

Nausea

2 (4.4)

0 (0.0)

2 (2.2)

100% of participants completed dosing

No treatment-related severe or serious TEAEs

All dizziness, somnolence, and nausea were mild-moderate and resolved without intervention

https://clinicaltrials.gov/study/NCT06979544

TEAE: Treatment-emergent adverse event (any AE that occurred after first dose of study drug)

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Clinically meaningful signals

Consistent efficacy signal in patients with PPD and history of psychiatric conditions

HAM-D placebo adjusted change from baseline less than or equal to 4 at all timepoints

Supporting secondary responder and remission endpoint trends

Numerically superior to placebo across multiple scales (HAM-D, MADRS, HAM-A) at all time points

Preliminary competitive label differentiation

Onset as early as 12 hours, short treatment duration, ease of access, sustained durability, and superior safety

Amenable to additional development paths - MDD/TRD

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LPCN 1154 - Significantly Better Tolerated

Adverse Reaction

LPCN 1154A (N=45)

Placebo (N=45)

Zuranolone (N=171)

Placebo (N=169)

Key Adverse Reactions

Somnolence and sedation

19-36%

6-11%

Dizziness

8-13%

6-9%

Fatigue

1-2%

Diarrhea

5-9%

2-3%

Memory impairment

Tremor

Anxiety

Dose reductions

1% with LPCN 1154 due to rash

Up to 14% with Zuranolone

Due to somnolence and dizziness

Treatment discontinuations

0% with LPCN 1154

Up to 4.1% with Zuranolone

Majority due to nervous system AEs

No treatment-related SAEs with LPCN 1154

One SAE of confusional state reported with Zurzuvae in Phase 3 PPD trials

- "In each clinical study, some Zurzuvae-treated patients developed confusional state. One of these cases was severe, and was also associated with somnolence, dizziness, and gait disturbance"

Comparison to Zurzuvae safety*

* Per label; two separate studies

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LPCN 1154 Demonstrated Differentiated Efficacy Signal

Zuranolone

Placebo

(5)

-3.4 at Day 3

ZURZUVAE 50 mg

10)

15)

On drug¹

Off drug¹

20)

LS Mean Change from Baseline (HAM-D Total Score)

Mean CBL in HAM-D Total Score Over Time (Days) in Study 1

(

HAM-D Change from Baseline

(5)

(10)

(15)

LPCN 1154: PPD with History of Psychiatric Conditions

Mean CBL in HAM-D Total Score Over Time

***

HAM-D Change from Baseline Over Time

(

0 (baseline)

3 8 15 21 28 45

Time (day)

(20)

0 Hour 12 Hour 36 Hour 60 Day 7 Day 30

Placebo (n) ZURZUVAE

50 mg (n)

96 95

98 93

90 83 85

93 84 84

LPCN 1154 (N=24) Placebo (N=30)

Timepoint

Hour 12

Hour 36

Hour 60

Day 7

Day 30

Placebo-Subtracted Difference

-7.2

(-10.8, -3.7)

-5.0

(-9.6, -0.5)

-6.1

(-10.7, -1.5)

-4.2

(-9.4, 1.0)

-5.3

(-10.2, -0.5)

(95% CI)

Differential HAMD-17 Total Score at Day 15*

Study Number

Mean Placebo Subtracted Difference (95% CI)

-4.0 (-6.3, -1.7)

-4.2 (-6.9, -1.5)

*CBL in the HAMD-17 Total Score at Day 3 was 3.4 units

¹ Both phases were double-blind.

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LPCN 1154 - Differentiated Target Attributes as a Rapid-Acting PPD treatment*

Potential to meet RAAD criteria

FDA Criteria for Rapid-Acting Anti-Depressants (RAAD)

Efficacy demonstrated within 1 week

For rapid-acting antidepressants, the timing of effect considerations include the following:

Efficacy generally should be demonstrated within 1 week for a rapid-acting antidepressant. Some novel antidepressants are thought to be effective within hours or days. In such cases, an earlier primary efficacy endpoint would be appropriate.

Durability of effect beyond the initial response should be characterized. To demonstrate both early onset of action and durability of effect, a primary efficacy endpoint early in the course of treatment would be chosen, with continued observation of drug-placebo differences over time.

Rapid relief as early as 12 hr over Zurzuvae of 3 days Rapid time to response 2.6 days over Zurzuvae of 9 days

Durability of effect beyond the initial response

Effect lasts ~1 month post treatment

Superior tolerability

Bioidentical, low CNS depressant effect (<5%), and devoid of psychotomimetic effects

Ultrashort treatment duration

48-hour treatment

Prompt access

At home use without burdensome monitoring

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/major-depressive-disorder-developing-drugs-treatment

*Based on subgroup based hypothesis generating results

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LPCN 1154 "Best-in-Class" Oral Treatment for PPD

Key takeaways

- Next steps: finalize validation study protocol based on FDA feedback

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Disclaimer

Lipocine Inc. published this content on April 15, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on April 15, 2026 at 17:34 UTC.