Longboard Pharmaceuticals Stock

Longboard Pharmaceuticals, Inc. operates as a clinical-stage biopharmaceutical company.

The company focuses on developing novel, transformative medicines for neurological diseases.

The company's small molecule product candidates were discovered out of the same platform at Arena that represents a culmination of more than 20 years of world-class G protein-coupled receptors (GPCR) research. The company focuses on developing the following product candidates in its pipeline:

LP352, an oral, centrally acting, 5-hydroxytryptamine 2C receptor subtype (5-HT2C) superagonist, in a Phase 1b/2a clinical trial (the PACIFIC Study) expected to evaluate 50 participants ages 12 to 65 years old with developmental and epileptic encephalopathies (DEEs), which may include Dravet syndrome, Lennox-Gastaut syndrome (LGS), tuberous sclerosis complex (TSC), CDKL5 deficiency disorder (CDD), SCN2A-related disorders, among others, with study enrollment expected to be completed in the first half of 2023 and topline data expected in the second half of 2023; and

LP659, a centrally acting, sphingosine-1-phosphate (S1P) receptor subtypes 1 and 5 (S1P1,5) modulator, for which the company anticipates initiating a Phase 1 clinical study in healthy volunteers in the first half of 2023 and anticipate topline single ascending dose (SAD) data in the second half of 2023.

LP352, the company's most advanced product candidate, is a potential best-in-class serotonin receptor agonist anti-seizure medication (ASM) for DEEs. LP352 had shown no measurable impact on 5-HT2B and 5-HT2A receptor subtypes in preclinical studies as of December 31, 2022. 5-HT2B and 5-HT2A receptor agonism have been associated with significant adverse side effects, including valvular heart disease and pulmonary arterial hypertension in the case of the 5-HT2B receptor, and euphoria, hallucination, and dissociation in the case of the 5-HT2A receptor. LP352 has the potential to be a clinically differentiated 5-HT2C superagonist for patients with DEEs, a group of severe early-childhood onset epilepsies characterized by refractory seizures and developmental delay and/or regression.

The company is also developing LP659, a centrally acting, S1P1,5 receptor modulator for which aberrant modulation has been shown to be involved in a wide range of neurological diseases. Based on its novel chemistry, potential for high selectivity for specific subtypes of GPCRs and favorable blood-brain-barrier penetration, LP659 has the potential to address multiple inflammatory neurological conditions. LP659 was designed by Arena to have more optimized pharmacology and pharmacokinetics (PK) for its intended S1P receptor subtypes, compared to other known compounds.

Pipeline

The company's product candidates are targeted towards specific G protein-coupled receptors (GPCRs). The company's GPCR product candidates are designed to increase the likelihood of the desired pharmacology and pharmacokinetics (PK) and minimize the risk of off-target effects.

LP352

The company is developing LP352, an oral, centrally acting, 5-HT2C superagonist for DEEs and other epileptic disorders. LP352 is the only 5-HT2C receptor agonist being dose optimized specifically for DEEs, a group of severe early-childhood onset epilepsies characterized by refractory seizures and developmental delay and/or regression. These diseases are often progressive and resistant to treatment. DEEs encompass a diverse range of over 25 syndromes, of which only four have FDA-approved therapies. LP352 could be a treatment for individuals with DEEs where no options are available and a potentially safer, more efficacious, easy to add-on treatment option for individuals with syndromes where therapies are inadequate.

LP352 selectively targets the 5-HT2C receptor, which has been shown to upregulate the release of gamma-aminobutyric acid (GABA), a principal neurotransmitter in the brain. This release of GABA increases the threshold for neuronal hyperexcitability, and decreases the likelihood of seizure occurrences. LP352 has the mechanistic potential to reduce seizures in a broad number of DEEs.

The company initiated its first clinical trial in patients with DEEs (the PACIFIC Study) in the first quarter of 2022. It plans to evaluate 50 patients, ages 12 to 65 years old, with a range of DEEs, across sites in the United States and Australia. Topline data is expected in the second half of 2023. In addition, the company has conducted multiple Phase 1 clinical trials in healthy volunteers with LP352, and will continue to conduct such trials to further explore the potential of LP352.

LP659

The company is developing LP659, a centrally acting, S1P1,5 receptor modulator for inflammatory neurological conditions. LP659 was designed for optimized pharmacology, PK and engagement of S1P1,5, which may lead to improved efficacy and safety. LP659 was designed to avoid the negative effects connected to the receptor subtypes 2 and 3, which may be associated with more serious, off-target cardiac, pulmonary, and cancer-related effects. LP659 rapidly reduced circulating lymphocytes, which returned to baseline after its clearance. LP659 has high oral bioavailability with a direct impact on central nervous system (CNS) glial cell S1P receptors. The company anticipates initiating a Phase 1 clinical trial in healthy volunteers for LP659 in the first half of 2023. Topline SAD data is expected in the second half of 2023.

Strategy

The key elements of the company's strategy are to advance its lead program LP352 through clinical development and approval in DEEs; continue preclinical development of LP659, an S1P1,5 receptor modulator, across a range of neurological diseases and progress into clinical development; identify additional product candidates, including those that the company holds rights to, and expands candidates into additional neurological diseases; and explore strategic collaborations to maximize the value of the company's product candidates.

Product Candidates

LP352, An Oral, Centrally Acting, 5-HT2C Superagonist

The company is developing LP352, an oral, centrally acting, 5-HT2C superagonist for DEEs and other epileptic disorders. LP352 is designed to selectively target 5-HT2C, which has been shown to upregulate the release of GABA, a principal inhibitory neurotransmitter in the brain. The release of GABA increases the threshold for neuronal hyperexcitability and decreases the likelihood of seizure occurrence. LP352 has the mechanistic potential to reduce the frequency of seizures in Dravet syndrome and LGS, as well as a broader epilepsy population. The company has conducted multiple clinical trials in healthy volunteers with LP352. The company initiated the PACIFIC Study in patients with DEEs in the first quarter of 2022 and expect to have topline data in the second half of 2023.

LP352 in Epilepsies

LP352 is an oral, centrally acting, 5-HT2C superagonist. As a 5-HT2C superagonist, LP352 is designed to modulate GABA inhibition and as a result, suppress the hyperexcitability that is characteristic of seizures. Based on its potential mechanism of action, LP352 has the potential to reduce the frequency of seizures in Dravet syndrome, LGS, and across a broad range of refractory epilepsies. 5-HT2C agonism has shown clinical benefit in epilepsy patients, however, available 5-HT2 agonists have been associated with significant adverse events (AEs). LP352 was discovered at Arena, and was developed to be the next-generation to lorcaserin. LP352 has novel chemistry and attributes, and was designed with the goal of being a safer, more effective 5-HT2C superagonist. The company holds worldwide rights to LP352 through the Arena License Agreement.

The company has shown LP352 to be a superagonist in a dynamic mass redistribution assay measuring a holistic integrated cellular response to lorcaserin, serotonin and LP352. This assay demonstrated that, as the concentration of LP352 increases, the cellular response is greater than the endogenous ligand serotonin and considerably more than lorcaserin.

LP352 Clinical Development

Phase 1 Clinical Trial SAD-MAD

LP352 was evaluated in a multi-part Phase 1 clinical trial in healthy volunteers. This was a randomized, double-blind, placebo-controlled, parallel-group trial that included a SAD portion (with and without food effect) and a MAD portion (with and without dose titration). Safety and tolerability were evaluated throughout the clinical trial, and blood sampling and urine samples for PK analysis were also collected. LP352 was administered as a capsule formulation. The Phase 1 clinical trial enrolled 83 healthy participants.

SAD Results: LP352 was observed to be generally well-tolerated, and AEs were consistent with events observed with other centrally acting 5-HT2C agonists. In the SAD and food effect portions of the clinical trial, LP352 demonstrated favorable PK and pharmacodynamic effects (with target plasma exposure (minimum serum concentration) measured based on prolactin levels), including dose-dependent PK properties with proportional increases in AUC and Cmax.

MAD Results: LP352 demonstrated dose- and exposure-dependent increases of prolactin, suggesting proof of central 5-HT2C receptor engagement, as well as dose-dependent increases in exposure (Cmax and AUCtau). The safety and tolerability of titrating LP352 was also examined.

Other Phase 1 Clinical Trials

In December 2022, the company announced topline data from cohorts 1 and 2 of a Phase 1 clinical trial assessing CNS PK/PD parameters in healthy adult male and female participants. In these cohorts LP352 exhibited a strong correlation between plasma and cerebrospinal fluid (CSF) PK concentration, which increased in a dose-dependent and consistent manner. In these cohorts LP352 also demonstrated early quantitative electroencephalogram (qEEG) changes and sustained effects on qEEG activity after continuous dosing in a dose-dependent manner indicating receptor engagement, and favorable safety and tolerability results were observed, with AEs generally consistent with previous clinical studies.

The company is conducting and plans to conduct additional Phase 1 clinical trials with LP352 to further characterize and differentiate LP352.

The PACIFIC Study - a Phase 1b/2a Clinical Trial of LP352 in Patients with DEEs

The PACIFIC Study is a Phase 1b/2a safety, tolerability and exploratory efficacy clinical trial of LP352. This is a randomized double-blind placebo-controlled trial. The company plans to enroll 50 participants ages 12-65 with a variety of treatment resistant motor seizures and seizure disorders that fall into the category of DEEs. The PACIFIC Study was initiated in the first quarter of 2022, with completion of enrollment expected in the first half of 2023 and topline data expected in the second half of 2023.

LP659, A Centrally Acting, S1P1,5 Modulator

The company is developing LP659, a centrally acting, S1P1,5 receptor modulator for inflammatory neurological conditions. LP659 was designed to have optimized pharmacology, PK and engagement of S1P1,5, which may lead to improved efficacy and safety. LP659 was designed to avoid the negative effects connected to the receptor subtypes 2 and 3, which may be associated with more serious, off-target cardiac, pulmonary, and cancer-related effects. The company anticipates initiating a Phase 1 clinical study in healthy volunteers in the first half of 2023 and expects topline SAD data in the second half of 2023.

LP659 in Neurological Diseases

LP659 acts as a S1P1 and S1P5 receptor subtypes modulator with no observed impact on S1P2 or S1P3 and has been selectively developed to cross the blood-brain barrier and target neurological diseases. In addition to its receptor subtype selectivity, LP659 has demonstrated rapid onset and offset of action (in preclinical models), with a low half-maximal inhibitory concentration in plasma (IC50 approximately 25 ng/ml in rat) to inhibit entrance of lymphocytes into blood.

LP659 was designed to avoid the negative effects connected to the receptor subtypes 2 and 3, which may be associated with more serious, off-target cardiac, pulmonary, and cancer-related effects. While initial studies have shown that LP659 is efficacious in reducing the development and severity of disease in a widely accepted model of demyelinating disease (e.g., multiple sclerosis), the company has not finalized a target indication as it sees potential for a selective S1P1 receptor modulator to treat a spectrum of inflammatory neurological conditions.

Other Compounds

The company has a license to certain compounds, including LP143, a centrally acting, full cannabinoid type 2 receptor (CB2) agonist, and compounds targeting the 5-HT2A receptor, including nelotanserin.

License Agreement with Arena

The Arena License Agreement was originally entered into in October 2020 and amended in January 2022 and again in September 2022. Pursuant to the Arena License Agreement, Arena Pharmaceuticals, Inc. (Arena) granted the company an exclusive, royalty bearing, sublicensable, worldwide license under certain know-how and patents of Arena to LP352 for any use in humans, LP659 for the treatment of developmental, degenerative and autoimmune disease, disorders or conditions of the CNS or peripheral nervous system in humans and LP143 and certain 5-HT2A compounds for the treatment of CNS indications (excluding the treatment, prevention or amelioration of pain or any gastrointestinal, non-CNS autoimmune or cardiovascular disorder) in humans (pharmaceutical products containing any such compounds, Licensed Products). Arena further granted the company a covenant not to sue under any patents or certain information of Arena with respect to each Licensed Product in its respective field. Arena retained the exclusive right to use the licensed intellectual property to develop, make or use intermediates, pro-drugs and metabolites related to the LP352, LP659, LP143 and 5-HT2A compounds to exploit Arena's etrasimod, lorcaserin, olorinab, or temanogrel products, in any dosage strength or formulation, and the company granted Arena a covenant not to sue with respect to such activities under certain of its intellectual property related to such compounds and the Licensed Products.

The company will assign to Arena new intellectual property developed by it related to such compounds. The company has sole responsibility over development, regulatory and commercialization activities for the Licensed Products in the applicable fields, as well as commercial manufacture and supply therefor. In September 2022, the company provided Arena a right of first negotiation, for a specified period of time, to acquire certain development and commercial rights to LP659 products subject to Arena and the company mutually agreeing on terms. This right of first negotiation is triggered by the company's announcing Phase 2 clinical results relating to an LP659 product for an indication that was not in the original field of the license or if the company otherwise intend to commence discussions or negotiations to license or partner rights to LP659 in such field.

Intellectual Property

As of February 1, 2023, the company held an exclusive, worldwide license to issued and pending patent claims for compositions of matter and certain methods of treatment using LP352 in several jurisdictions, including issued patents in the United States, Europe (17 countries), China, Japan, India, Russia, South Korea, Australia, Mexico, New Zealand, and Israel; and pending applications in Brazil, Canada, and Macao. The terms of these patents (and applications, if issued) are capable of continuing into 2036, without taking into account any patent term adjustment or extension regimes of any country (e.g., up to five additional years in certain jurisdictions if maximum PTE or SPC applies) or any additional term of exclusivity the company might obtain by virtue of later filed patent applications. For example, the company exclusively licenses pending patent claims directed to methods of dosing LP352 in a later patent application having a term capable of continuing into 2043 in certain jurisdictions, without taking into account any applicable patent term adjustment or extension.

As of February 1, 2023, the company held an exclusive, worldwide license to issued and pending patent claims for compositions of matter and certain methods of treatment using LP659 in several jurisdictions, including issued patents in the United States, Europe (39 countries), Brazil, China, Japan, Canada, Russia, South Korea, Australia, Mexico, South Africa, New Zealand, Singapore, Israel. The terms of these patents (and applications, if issued) are capable of continuing into 2029, without taking into account any patent term adjustment or extension regimes of any country (e.g., up to five additional years in certain jurisdictions if maximum PTE or SPC applies) or any additional term of exclusivity the company might obtain by virtue of later filed patent applications. For example, the company exclusively licenses patent claims for compositions of matter and certain methods of treatment using salt and crystalline forms of LP659 in several jurisdictions, including issued patents in the United States and 10 countries in Europe. The terms of these patents are capable of continuing into 2031 in certain jurisdictions, without taking into account any patent term adjustment or extension.

The company is a party to a license agreement with Arena under which it is granted intellectual property rights to know-how that are important to its business. The company has licensed know-how related to the Licensed Products (including LP352, LP659, LP143 and certain 5-HT2A compounds) in all countries around the world from Arena. The Arena License Agreement imposes various development, regulatory and/or commercial diligence obligations, payment of royalties, including a mid-single digit royalty on net sales of Licensed Products of LP352, and a low-single digit royalty on net sales of all other Licensed Products, by its company, its affiliates or its sublicensees, subject to standard reductions, and other obligations.

Sales and Marketing

The company intends to build a commercial infrastructure to support sales of any of its approved products. The company expects to manage sales, marketing and distribution through internal resources and third-party relationships.

Research and Development

The company's research and development expenses were $34.6 million for the year ended December 31, 2022.

Government Regulation and Product Approval

Product candidates that the company develops must be approved by the U.S. Food and Drug Administration (FDA), before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in foreign countries.

History

Longboard Pharmaceuticals, Inc. was founded in 2020. The company was incorporated in state of Delaware in 2020.