Company: LBRX
Filing Date: 2025-08-22
Form Type: S-1
Source: 0001193125-25-186467
Chunk: 209

Company: LB PHARMACEUTICALS INC
Filing Date: 2025-08-22
Form: S-1
Chunk 209
---

schizophrenia doses to keep D receptor occupancy at a level that lowers the potential for EPS yet high enough for antidepressant benefit. This is the dosing model that was used by Vraylar and
Latuda, both of which are approved for schizophrenia and bipolar depression. In contrast, Caplyta, another drug approved for use in both schizophrenia and bipolar depression, utilized the same dose in both indications, in part because of its low
rates of EPS. In selecting doses for our Phase 2 trial, we are blending these two paradigms. We plan to initiate all patients on half the lowest dose used in our acute schizophrenia trial (25 mg). Importantly, we believe that results of our Phase 2
acute schizophrenia trial, which demonstrated <1% EPS and no sedation even at 50 mg, provide us an opportunity to explore that dose in bipolar depression similar to Caplyta, which used a single dose across both indications. All patients
randomized to receive LB-102 will begin treatment at 25 mg for the first three weeks of the trial. At the end of Week 3, if a patient has not improved based on a protocol guided set of specific items in the
Clinical Global Impression-Bipolar Illness, or CGI-BP, scale and the patient is tolerating the drug, the dose of LB-102 will be increased in this patient to 50 mg for
the remaining three weeks of the trial, subject to an allowance for up to one dose reduction for safety reasons. 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. The primary endpoint is expected to be MADRS-10 and will compare all LB-102 treated patients regardless of the dose received versus placebo. Secondary
endpoints are

147

expected to include MADRS-6, CGI-BP-S, cognition, anhedonia, as well as
safety and tolerability. We have designed this trial to highlight what we believe will be differentiating attributes of LB-102 in bipolar depression. Specifically, we are targeting competitive MADRS-10 versus other approved agents, improved tolerability as evidenced by lower rates of sedation and gastrointestinal side effects compared with other approved agents, a rate of EPS consistent with or lower than
what we observed in our schizophrenia Phase