Company: LBRX
Filing Date: 2025-09-08
Form Type: S-1/A
Source: 0001193125-25-197877
Chunk: 215

Company: LB PHARMACEUTICALS INC
Filing Date: 2025-09-08
Form: S-1/A
Chunk 215
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 written for this indication. A non-racemic form of amisulpride showed strong antidepressant
activity in two independent third-party, placebo-controlled bipolar depression trials with an approximately 17 to 18-point reduction in MADRS from baseline observed in each trial. The non-racemic form of amisulpride has been shown to be substantially similar to amisulpride in preclinical models. Our planned Phase 2 trial for bipolar depression will utilize a fixed-flexible dose of LB-102. This trial design allows us to evaluate two doses of LB-102 in the trial, thereby increasing the chances for a patient to derive clinical benefit from treatment with LB-102, while retaining the advantages of a two-arm trial, which is known to mitigate the risk of a high placebo rate. Additionally, flexible dose trials typically have better
signal detection than fixed dose trials for depression, as flexible dose trials lower the magnitude of symptom reduction with placebo. We believe LB-102 has the potential to provide improved tolerability and
clinical activity in bipolar depression compared to currently available treatments worldwide, which are associated with troubling adverse events and insufficient efficacy for certain symptoms, including cognitive impairment associated with the
disease.

Planned Phase 2 Trial of LB-102in Bipolar Depression

We are planning to initiate a Phase 2 trial of LB-102 in participants with depressive episodes
associated with bipolar 1 disorder or bipolar depression in the first quarter of 2026, which, if positive, could potentially support a regulatory pathway along with an additional Phase 3 trial for the treatment of bipolar depression as a
monotherapy. We plan to report topline data for this trial in the first quarter of 2028 and, subject to positive results from that trial, meet with the FDA to discuss trial results at an end-of-Phase 2 meeting thereafter. The Phase 2 trial is designed to be an outpatient, two-arm, double-blinded, placebo-controlled, oral, once-daily fixed-flexible dose
of LB-102 in patients with depressive episodes associated with bipolar 1 disorder, with six-week treatment duration. We plan to enroll approximately 320 patients and
conduct this trial entirely in the United States at approximately 30 sites. Patients will be randomized in a 1:1 ratio to LB-102 or placebo. Across most atypical antipsychotics, bipolar depression doses are
usually approximately 50% lower than schizophrenia doses to keep D receptor occupancy at a level that lowers the potential for EPS yet high enough for antidepressant