Company: LBRX
Filing Date: 2025-07-23
Form Type: DRS/A
Source: 0000950123-25-006557
Chunk: 170

Company: LB PHARMACEUTICALS INC
Filing Date: 2025-07-23
Form: DRS/A
Chunk 170
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of schizophrenia. Despite amisulpride’s efficacy and tolerability profile, it has not received regulatory approval in the United States for the treatment of any neuropsychiatric disorders, including schizophrenia, because the development and
regulatory requirements of the FDA were incompatible with patent coverage on the drug.

The modifications we incorporated into LB-102 were designed to improve the tolerability and efficacy profile of amisulpride by addressing its shortcomings, such as limited blood-brain barrier, or BBB, permeability and dosing frequency. Enhanced BBB
permeability was expected to improve the potency of the molecule with respect to dopamine receptor binding and enable the use of lower doses compared with amisulpride. The use of lower doses was hypothesized to improve the tolerability profile. We
also aimed to create a new chemical entity with strong composition of matter intellectual property protection. We believe that the methylation of amisulpride addresses these design goals, and we aimed to demonstrate in our clinical trials that LB-102’s

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improved BBB penetration would confer benefits over amisulpride and other antipsychotic drugs, including lower dosing levels, a wider therapeutic window, improved tolerability, and less frequent
once-daily dosing. Use of lower doses may also improve the feasibility of developing an LAI formulation.

Because amisulpride was used as
the starting point in the creation of LB-102, we have conducted preclinical head-to-head studies with the compound to determine
superiority as well as to assess whether the clinical development path of amisulpride may provide a risk-mitigated path for our development of LB-102. We have not conducted head-to-head clinical trials to date comparing LB-102 to amisulpride; however, our
head-to-head preclinical studies that compared amisulpride to LB-102 in animal models of schizophrenia demonstrated that LB-102 had equivalent or better results than similar doses of amisulpride and that LB-102 bound similarly to the dopamine Dand D receptors, with a K (inhibition constant) of 0.82 nM compared to amisulpride’s reported K of 1.1 nM, and had a similar affinity for the 5-HT7 receptor with a K of 31 nM compared to
amisulpride’s reported K of 44 nM. Our Phase 1 trials in healthy volunteers showed that LB-102 was generally well-tolerated, and in our Phase 1b