Company: LBRX
Filing Date: 2025-08-22
Form Type: S-1
Source: 0001193125-25-186467
Chunk: 193

Company: LB PHARMACEUTICALS INC
Filing Date: 2025-08-22
Form: S-1
Chunk 193
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 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). Compared to
other commonly prescribed antipsychotic drugs, both LB-102 and amisulpride have weaker binding to other off-target CNS receptors that are commonly associated with
adverse side effects such as anxiety, weight gain, or metabolic syndrome such as 5HT2C.

In Vivo Activity of LB-102is Similar to Amisulpride

We evaluated LB-102
in the Locomotor Activity, or LMA, rat model of hyperactivity, often used to predict clinical activity in treating positive symptoms of schizophrenia. In the LMA, rats dosed with amphetamine alone displayed hypermobility, while rats additionally
dosed with antipsychotic drugs showed more normal, calmer activity.

LB-102 had equivalent or
better results than similar doses of amisulpride in the LMA model of hyperactivity. In our head-to-head preclinical rat model of cognition, the Novel Object Recognition
model, and in a mouse model of stereotypy or excessive repetition, the Apomorphine Induced Climbing model, we observed that the effects of treatment with LB-102 were statistically indistinguishable from that
of amisulpride.

Brain Penetration and Dopamine Receptor Occupancy of LB-102

The ability of LB-102 to cross the BBB was estimated using a standardin vitro membrane
permeability assay. In this assay, the permeability of LB-102 was approximately 200-fold greater than that of amisulpride.

Anin vivohead-to-head study in mice using positron
emission tomography, or PET, demonstrated that at a dose of 100 mg/kg of both LB-102 and amisulpride, LB-102 had greater dopamine receptor occupancy in the brain
than amisulpride, as shown below. We believe these results supported dosing LB-102 at much lower levels than amisulpride to achieve the desired effect on symptoms of schizophrenia.

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LB-102reduced the binding of a dopamine receptor PET ligand in the brain by two-foldcompared to amisulpride. More faint luminescence represents greater dopamine receptor occupancy. %ID/g represents the percent injected dose per gram.