Lipocine (LPCN) investor relations material

Unmet Needs and Current Treatment Landscape in Postpartum Depression

• PPD affects 26.3% of women globally, with significant economic and health impacts, including $14.2 billion in annual US costs and adverse outcomes for mothers and children.

• PPD is underdiagnosed and undertreated, with high discontinuation rates for existing therapies and impaired maternal-child bonding.

• Professional guidelines recommend increased screening and direct treatment initiation by OBGYNs, but many women discontinue current treatments due to side effects and long duration.

• SSRIs remain the mainstay but show high discontinuation rates and limited efficacy, while IV brexanolone and oral zuranolone offer rapid relief but have access and tolerability challenges.

• Untreated PPD worsens maternal health and increases risk for negative developmental outcomes in offspring.

LPCN 1154 Clinical Profile and Phase III Study Design

• LPCN 1154 is an oral, bioidentical neuroactive steroid (NAS) formulation of brexanolone, designed for rapid, short-duration (48-hour) at-home treatment of PPD.

• Achieved bioequivalence to IV brexanolone, enabling a streamlined regulatory strategy.

• The phase III trial was a randomized, blinded, placebo-controlled study in women with severe PPD, using a dose bioequivalent to IV brexanolone.

• Ninety participants were randomized to LPCN 1154 or placebo, with primary efficacy measured by change in HAM-D score at hour 60 and follow-up to day 30.

• About 9% of participants were on antidepressants at baseline, and 40% had no prior psychiatric diagnosis, which is atypical for PPD studies.

Study Results, Outlier Site Impact, and Subgroup Analyses

• The primary endpoint was not statistically significant overall, but nominal significance was seen at hour 12; LPCN 1154 was well-tolerated with only mild to moderate adverse events.

• A single high-enrolling outlier site showed anomalous data: high placebo response, low drug detection, and atypical participant profiles.

• Excluding this site, LPCN 1154 demonstrated rapid, durable, and statistically significant improvements in HAM-D scores at all measured timepoints, with placebo-adjusted differences of at least five points and strong effect sizes (Cohen's d 0.5–1.1).

• Median time to first response was 2.6 days for LPCN 1154 versus ~30 days for placebo.

• About 75% of treated participants achieved HAM-D response and 50% remission, with rapid onset as early as 12 hours; subgroup analysis in women with prior psychiatric history confirmed robust, rapid, and sustained efficacy.