Longboard Pharmaceuticals Announces Positive Topline Data from a Phase 1 Clinical Study Evaluating Central Nervous System Pharmacokinetics and Pharmacodynamics of LP352 in Healthy Volunteers

06 Dec 2022
pipelinereview.com
Phase 1Clinical ResultLicense out/in
LA JOLLA, CA, USA I December 05, 2022 I Longboard Pharmaceuticals, Inc. (Nasdaq: LBPH), a clinical-stage biopharmaceutical company focused on developing novel, transformative medicines for neurological diseases, today 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.
"We are excited to share data from our 102 study, the first known of its kind for a 5-HT2 receptor agonist5-HT2 receptor agonist, to further elucidate the potentially best-in-class profile of LP352. We believe the results of this study are encouraging as orally administered LP352 plasma and CSF PK concentration increased in a dose-dependent and consistent manner, a clear indicator that LP352 is crossing the blood brain barrier. Furthermore, the observation of demonstrated effects on qEEG activity within the first few doses and after continuous dosing suggests that LP352 engaged neurotransmitter systems and altered the EEG spectrum. We are pleased to see favorable safety and tolerability results in this study, consistent with previous work we have conducted," stated Dr. Randall Kaye, Longboard’s Chief Medical Officer. "We anticipate sharing additional data to substantiate our belief that LP352 has the potential to be a safer and more efficacious treatment of seizures in a broad range of developmental and epileptic encephalopathies (DEEs), and we look forward to providing updates on the ongoing Phase 1b/2a PACIFIC study as they become available."
Study Design & Objectives:
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.
qEEG Results:
Serial EEGs were taken at Days -1, 1, 3 & 10, and Day 16 (at trough). LP352 demonstrated early qEEG changes within the first few doses. LP352 also demonstrated sustained, dose-dependent effects on qEEG activity after continuous dosing, thus indicating receptor engagement. LP352 engaged neurotransmitter systems and altered the EEG spectrum.
Safety / Tolerability Findings:
Favorable safety and tolerability across both cohorts were observed, with AEs generally consistent with previous clinical studies of LP352.
About LP352
LP352 is an oral, centrally acting 5-HT2C superagonist in development for the potential treatment of seizures associated with developmental and epileptic encephalopathies (DEEs) such as Dravet syndrome, Lennox-Gastaut syndrome (LGS), tuberous sclerosis complex (TSC), CDKL5 deficiency disorder (CDD)CDKL5 deficiency disorder (CDD), and other epileptic disorders. LP352 is designed to modulate GABA and, as a result, suppress the central hyperexcitability that is characteristic of seizures. LP352 has no detected activity at the 5-HT2B and 5-HT2A receptor subtypes. 5-HT2B and 5-HT2A receptor agonism have been associated with significant adverse side effects. LP352 has novel chemistry and attributes. It was designed to be more specific and selective for the 5-HT2C receptor subtype, giving it the potential to reduce seizures in patients with DEEs while overcoming the known or perceived safety limitations of available drugs in the 5-HT2 class. LP352 is currently being evaluated in an ongoing Ph 1b/2a clinical trial (the PACIFIC Study) in participants with DEEs, with data expected in the second half of 2023, as well as in additional supportive studies.
Longboard Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on developing novel, transformative medicines for neurological diseases. Longboard is working to advance a portfolio of centrally acting product candidates designed to be highly selective for specific G protein-coupled receptors (GPCRs). Longboard’s small molecule product candidates are based on more than 20 years of GPCR research. Longboard is evaluating LP352, an oral, centrally acting 5-hydroxytryptamine 2C (5-HT2C) receptor superagonist, with no detected activity at the 5-HT2B and 5-HT2A receptor subtypes. LP352 is currently being evaluated in a Phase 1b/2a clinical trial, the PACIFIC Study, and being developed for the potential treatment of seizures associated with a broad range of developmental and epileptic encephalopathies (DEEs). Longboard is also evaluating LP659, a centrally acting, sphingosine-1-phosphate (S1P) receptor subtypes 1 and 5 modulator, in development for the potential treatment of multiple neurological diseases. Longboard holds rights to other product candidates, including LP143 and nelotanserin, through a License Agreement with Arena Pharmaceuticals, Inc.
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