Longboard Pharmaceuticals, Inc. announced positive topline results from a Phase 1 clinical study evaluating the central nervous system (CNS) pharmacokinetics (PK) and pharmacodynamics (PD) of LP352, an oral, centrally acting 5-HT2C superagonist, in healthy volunteers. The primary objectives of this open-label, Phase 1 study are to assess the CNS PK and PD of orally administered LP352 in healthy adult male and female participants (n=10 in each Cohort). Objectives include the characterization of plasma and CSF PK, the characterization of safety and tolerability of doses with titration and taper, and the assessment of the PK-PD relationships between plasma and CSF exposure, and PD endpoints of safety and efficacy, including quantitative electroencephalogram (qEEG) endpoints.

Data being shared today relate to two doses (Cohort 1 = 6 mg and Cohort 2 = 12 mg) of LP352 three times daily (TID) that were tested over a 16-day period in addition to a screening and follow-up period. Additional cohorts of the study are ongoing. Plasma samples were obtained on Day 1 through Day 11 (and during taper), measuring maximum concentration (Cmax), time of peak plasma concentration (Tmax), and area under the curve (AUCtau).

Serial CSF samples were taken on Day 11 at multiple timepoints. At steady state, LP352 12 mg TID mean concentrations exceeded the Ki value for 5-HT2C activity throughout the dosing interval. The vast majority of participants in Cohort 2 achieved plasma and CSF levels above the relevant Ki throughout the dosing period at steady state.

LP352 exhibited a strong correlation between plasma and CSF PK concentration, which increased in a dose-dependent and consistent manner.