Praxis Precision Medicines, Inc. (Praxis), a clinical-stage biopharmaceutical company, engages in the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance.
The company is applying genetic insights to the discovery and development of therapies for neurological disorders through two proprietary platforms, using its understanding of shared biological targets and circuits in the brain. Cerebrum, the company’s small molecule pl...
Praxis Precision Medicines, Inc. (Praxis), a clinical-stage biopharmaceutical company, engages in the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance.
The company is applying genetic insights to the discovery and development of therapies for neurological disorders through two proprietary platforms, using its understanding of shared biological targets and circuits in the brain. Cerebrum, the company’s small molecule platform, utilizes deep understanding of neuronal excitability and neuronal networks and applies a series of computational and experimental tools to develop orally available precision therapies.
Solidus, the company’s antisense oligonucleotide, or ASO, platform, is an efficient, targeted precision medicine discovery and development engine anchored on a proprietary, computational methodology. The company's platforms utilize a deliberate, pragmatic, and patient-guided approach, leveraging a suite of translational tools, including novel transgenic and predictive translational animal models and electrophysiology markers, to enable an efficient path to proof-of-concept in patients. Through this approach, the company has established a diversified, multimodal central nervous system (CNS) portfolio with four clinical-stage product candidates across movement disorders and epilepsy.
Cerebrum (smafm)
The company has built Cerebrum, enabled by innovative computational and experimental tools, to discover and develop first- and best-in-class CNS small molecule therapies. The company’s world-class ion channel discovery science team, along with external collaborators, accelerate its ability to create and execute novel screening cascades for its selected genetic targets. Fundamental to advancement of candidates are its multiscale disease models that link genetic cause to network function to elucidate novel drivers of disease phenotype. The company employs translational biomarkers such as quantitative electroencephalography, or qEEG, to guide dose selection, with the goal of improving probability of success in the clinic. The precision application of its candidates is guided by genomics and informatics to identify, stratify and activate patients for trial recruitment and execution. To date, Cerebrum has generated three clinical stage product candidates, ulixacaltamide (formerly known as PRAX-944), vormatrigine (formerly known as PRAX-628) and relutrigine (formerly known as PRAX-562), as well as PRAX-020 which has been in-licensed by UCB Biopharma SRL, or UCB. Cerebrum has the potential to continue delivering first- and best-in-class orally available therapies for genetic CNS targets.
Solidus (ASO platform)
The company has built Solidus to discover and develop first- and best-in-class ASOs with high probability of advancement into the clinic. Solidus is enabled by its proprietary, computational workflow to discover ASOs with desired drug-like properties to optimize for up/down-regulation, avoidance of toxic motifs and optimization of binding affinity and specificity. Led by the company’s clinical-stage product candidate, elsunersen (formerly known as PRAX-222), Solidus has also generated three novel ASOs with preclinical proof of mechanism that it expects to nominate development candidates for in 2025 — PRAX-080 targeting PCDH19-related developmental epilepsy; PRAX-090 targeting SYNGAP1 loss-of-function, or LoF, mutation driven developmental epilepsy; and PRAX-100 targeting SCN2A LoF mutations, the predominant genetic link to de novo autism spectrum disorders. The platform is uniquely positioned to continue discovering and advancing other new ASOs for novel genetic CNS targets.
Strategy
The company leverages the genetics of epilepsy as a gateway for CNS drug discovery and development. Recent investigations have led to the identification of over 900 genes that are causal or risk factors for different forms of epilepsy, providing the field with an outsized understanding of epilepsy genetics relative to other diseases, such as Alzheimer’s disease, amyotrophic lateral sclerosis or ALS, and many others.
The company’s collaborators include world-renowned research groups and drug developers, clinical research organizations (CROs), innovative patient mapping database companies, experts in translational tools, next-generation drug delivery technology companies, and others.
Clinical Stage Programs
The company has advanced four product candidates to the clinical stage, including three small molecules through the Cerebrum platform and one antisense oligonucleotide (ASO) through the Solidus platform:
Ulixacaltamide for Essential Tremor
The company's most advanced program, ulixacaltamide, is a differentiated and highly selective small molecule inhibitor of T-type calcium channels in Phase 3 clinical development for the treatment of Essential Tremor (ET). Additionally, the company has an exclusive collaboration and license agreement with Tenacia Biotechnology (Shanghai) Company, Ltd., a China-based portfolio company of Bain Capital, to develop and commercialize ulixacaltamide for the treatment of ET in China, Hong Kong, Macau, and Taiwan. Ulixacaltamide has the potential to be developed for other indications, including Parkinson’s disease.
Ulixacaltamide Phase 3 Essential3 Program
Essential3 is a decentralized, Phase 3, multi-study, clinical trial evaluating the safety and efficacy of 60 mg of ulixacaltamide in ET. The trial includes two separate and simultaneous Phase 3 pivotal studies — a 12-week parallel design, placebo-controlled study (N=400), or Study 1, and a 12-week randomized withdrawal study (N=200), or Study 2 — with all participants undergoing one screening process and a long-term safety study, or LTSS. The study uses the modified Activities of Daily Living 11, or mADL11, as the primary endpoint. A pre-planned interim analysis of Study 1 was conducted in the first quarter of 2025.
Essential1 study
The Essential1 study was a multi-center, randomized, double-blind, placebo-controlled, dose-range finding Phase 2b clinical trial evaluating the efficacy, safety and tolerability of once-daily treatment of ulixacaltamide compared to placebo after 56 days in participants with moderate-to-severe ET. Topline results for the Phase 2b Essential1 study were announced in the first quarter of 2023. Results of the Essential1 study informed the design of the Phase 3 Essential3 program.
ENERGY Program
The company’s ENERGY program for vormatrigine aims to generate efficacy, safety and PK data to serve as the basis of regulatory registrations globally. The program consists of four studies — EMPOWER, RADIANT, POWER1 and POWER2.
EMPOWER Observational Study
EMPOWER is an observational study in partnership with the Epilepsy Study Consortium that aims to better characterize seizure burden. The company begins enrolling patients in 2024, and it expects to generate standardized, longitudinal data to support planned interventional trials and deepen its understanding of patient experiences with epilepsy. Preliminary findings from EMPOWER revealed a significant disease burden compounded by persistent, uncontrolled and often untracked seizures alongside profound psychosocial impact.
RADIANT Phase 2 Study
The company has initiated RADIANT, a Phase 2 open-label study to evaluate PK, safety and efficacy of vormatrigine in up to 50 patients with FOS or generalized epilepsy. Patients will be treated with a 30 mg dose over an 8-week period to evaluate the impact of vormatrigine on seizure burden. The company anticipates topline results by mid-year 2025.
POWER1 and POWER 2 Phase 2/3 Registrational Studies
POWER1 and POWER2 are two 12-week Phase 2/3 studies in patients with FOS to evaluate the efficacy of vormatrigine. The company has initiated and plan to enroll approximately 250 patients in POWER1, which is assessing adjunctive treatment that allows dosing of vormatrigine on top of one to three antiseizure medications. POWER1 is a parallel-arm study, comparing a treatment arm of 20 mg for six weeks followed by 30 mg for six weeks versus a placebo arm for 12 weeks. The company anticipates topline results in the second half of 2025. POWER2 will be a multi-arm, 12-week registrational study for vormatrigine, and it expects to begin enrollment of the study in the second half of 2025.
Phase 2a Photo-Paroxysmal Response study
The company conducted a Phase 2a Photo-Paroxysmal Response, or PPR, study to evaluate the efficacy and safety of vormatrigine across two cohorts, dosed at 15 mg and 45 mg. PPR studies measure EEG signatures after intermittent photic stimulation and are widely used as a marker of anti-seizure efficacy and to aid in dose determination.
Vormatrigine Phase 1 studies
The company has conducted Phase 1 healthy volunteer studies of vormatrigine to evaluate the tolerability, PK, PD and food effect of vormatrigine across single and multiple ascending dose cohorts and first announced topline results in the second quarter of 2023.
Phase 2 EMBOLD study
The EMBOLD study is a randomized, double-blind, placebo-controlled Phase 2 clinical trial evaluating the safety, tolerability, efficacy (motor seizure frequency) and PK of relutrigine in pediatric participants aged 2 to 18 years with DEEs, followed by an open-label extension, or OLE. The company announced topline results of the first cohort of the EMBOLD study (n=16) in the third quarter of 2024.
Elsunersen for SCN2A-DEE
Elsunersen is a clinical-stage ASO designed to down-regulate NaV1.2 expression, an effect that has demonstrated disease-modifying activity in animal models of SCN2A epileptic encephalopathy. In transgenic mice carrying a human SCN2A GoF mutation, the company observed a significant, dose-dependent reduction in seizures and increased survival of mice treated with a mouse ASO that is designed to down-regulate SCN2A. The survival benefit from the ASO was maintained with repeat dosing. The company also observed survival benefits following administration of a mouse ASO to a group of mice after onset of disease and around the time of onset of mortality. Elsunersen has received ODD and RPD from the FDA, and ODD and PRIority MEdicines, or PRIME, designation from the EMA for the treatment of SCN2A-DEE.
The company is continuing to evaluate elsunersen in the second cohort of the EMBRAVE study in Brazil, and plan to initiate EMBRAVE3, a Phase 3 registrational study, by mid-year 2025.
EMBRAVE study
Part 1 of the EMBRAVE study was a 21-week open-label cohort in which participants received elsunersen for up to 13 weeks, designed to determine the safety and tolerability of intrathecal delivery of elsunersen. No treatment-related adverse events (AEs) or serious adverse events (SAEs) were observed. Additionally, patients reported a marked reduction in seizures and an increase in seizure-free days. The company is enrolling patients in the second cohort of the EMBRAVE study in Brazil, where it is evaluating the safety and efficacy of elsunersen versus a sham procedure, and anticipates topline results in the first half of 2026.
EMBRAVE3 study
The company plans to initiate EMBRAVE3, a global, 24-week, double-blind, sham procedure-controlled clinical trial to assess the efficacy, safety, tolerability, and pharmacokinetics (PK) of elsunersen by mid-year 2025. It expects this to be a registrational trial consisting of three cohorts. Cohort 1 will enroll approximately 40 patients between 2 and 18 years of age experiencing at least four motor seizures during a four-week baseline period. The primary endpoint will assess the change in seizure frequency.
Competition
The company’s competitors fall primarily into the following groups of treatment:
Approved therapies for ET, such as propranolol, and off-label therapies, such as primidone.
Sodium channel blocker or similar ion channel-targeting programs in development for common epilepsies, including those of SK-Pharma, Xenon Pharmaceuticals, and Biohaven Pharmaceuticals, as well as other programs in clinical development targeting other mechanisms of action, including those from Lundbeck and Stoke Therapeutics, and approved therapies, including other existing ion channel blockers.
Intellectual Property
T-type Calcium Channel Blockers
The company owns fourteen patent families directed to T-type Calcium channel blockers. One patent family discloses and claims compositions of matter of certain T-type calcium channel modulators, including ulixacaltamide. This patent family has issued in many major pharmaceutical markets and is pending in others and expires in 2029. A second patent family is directed to certain pharmaceutical formulations of ulixacaltamide and methods of use in treating disorders such as essential tremor. Three U.S. patents have issued in this patent family, and expire in 2040, and this family remains pending in multiple jurisdictions of potential commercial interest. A third family is directed to titration methods of using ulixacaltamide and expires in 2041. A fourth patent family is directed to certain analog compounds of ulixacaltamide and expires in 2040. A fifth patent family is directed to the adjunctive use of a beta blocker and/or certain anticonvulsants with ulixacaltamide and expires in 2043. A sixth patent family is directed to a dosage form of ulixacaltamide and expires in 2044. A seventh patent family is directed to salt forms of ulixacaltamide and expires in 2044. An eighth patent family is directed to crystalline forms of ulixacaltamide and expires in 2044. A ninth patent family is directed to methods of treatment using ulixacaltamide and expires in 2044. A tenth patent family is directed to methods of treatment using ulixacaltamide and expires in 2044. The remaining patent families are directed to other TTCC blockers of various core structures and methods of use in treating diseases such as movement disorders, which expire in 2039 and 2040.
Persistent Sodium Current Blockers
The company owns fifteen patent families directed to persistent sodium current blockers, including a patent family that relates to relutrigine and vormatrigine, two additional patent families that relate to relutrigine, and the remaining patent families relate to other persistent sodium current blockers. One patent family discloses and claims certain persistent sodium current blockers, including relutrigine and vormatrigine, and methods of use in treating diseases such as epilepsy (including pediatric epilepsy), as well as migraine and pain. In this patent family, relutrigine is covered by a patent that has granted in the United States, and patent applications pending in other potentially commercially relevant jurisdictions, which expire in 2039. In this same patent family, vormatrigine is covered by two granted U.S. patents that will expire in 2039. A second family discloses other persistent sodium current blockers and generically claims relutrigine, as well as methods of treating diseases such as pediatric epilepsy. This patent family is pending in multiple jurisdictions and expires in 2037. A third family is directed to pharmaceutical formulations of relutrigine, methods of use in treating diseases, such as pediatric epilepsy, cephalgia, short-lasting unilateral neuralgiform headache attacks with conjunctival injection, or SUNCT, and tearing and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms, or SUNA, and methods of making relutrigine, and expires in 2040. The remaining patent families are directed to other persistent sodium current blockers of various core structures and methods of use in treating diseases such as pediatric epilepsy, expiring between 2037 and 2043.
SCN2A Downregulation
The company has exclusively in-licensed three patent families directed to its SCN2A program. Two of these patent families are owned by RogCon, Inc., and disclose and claim certain ASOs targeting SCN2A and methods of use in treating diseases such as epilepsy, including epilepsy having certain SCN2A mutations. One patent family is pending in the United States and expires in 2038. A second patent family is directed to methods of treating SCN1A encephalopathy using ASOs targeting SCN2A and expires in 2039.
The other in-licensed patent family is owned by Ionis Pharmaceuticals, Inc., and is directed to compositions of matter of elsunersen. This family expires in 2041 and one U.S. patent has issued in this family.
The company owns seven patent families directed to its elsunersen program. The first has claims directed to a method of treating SCN2A gain of function neurological diseases using certain ASOs. This patent family is pending in the United States and expires in 2041. The second is directed to methods of treating SCN2A-related disorders using SCN2A inhibitors and expires in 2043. The third is directed to methods of treating SCN2A-related disorders using SCN2A inhibitors and expires in 2044. The fourth is directed to compositions and methods for treating SCN2A disorders and expires in 2039. The fifth is directed to methods for detecting if a subject with an SCN2A disorder has a gain of function mutation and expires in 2039. The sixth is directed to oligonucleotides targeting SCN2A retained introns and expires in 2039. The seventh is directed to compositions and methods for treating disorders associated with loss-of-function mutations in SCN2A and expires in 2041.
KCNT1 Blockers
The company owns twelve patent families directed to KCNT1 blockers. These patent families disclose and claim small molecule KCNT1 blockers and methods of use in treating diseases, such as epilepsy, including epilepsy having certain KCNT1 mutations, and expire between 2040 and 2043.
GABAA receptor positive allosteric modulators
The company owns four patent families directed to GABAA receptor positive allosteric modulators. One patent family discloses and claims salts and polymorphs of PRAX-114. Two patents are granted in the United States, which expire in 2039. A second patent family is directed to alternative salt forms of PRAX-114, and a U.S. patent has issued, which expires in 2042. Other patent applications cover methods of use in treating diseases (including the use of combination formulations), such as epilepsy, musculoskeletal conditions, motor disorder, or essential tremor, which expire from 2042 to 2043.
PCDH19
The company owns one patent family directed to compositions and methods for the treatment of PCDH19 related disorders, which expires in 2042.
SYNGAP
The company owns one patent family directed to compositions and methods for the treatment of disorders associated with loss-of-function mutations in SYNGAP1, which expires in 2041.
License Agreements
License Agreement with RogCon
In September 2019, the company and RogCon, Inc., or RogCon, entered into a Cooperation and License Agreement, or the RogCon Agreement, to collaborate on the development of ASOs for the treatment of epilepsy caused by mutations of the SCN2A gene. RogCon had an existing collaboration arrangement with Ionis Pharmaceuticals, Inc., or Ionis, and as a result, the company and Ionis negotiated a Research Collaboration, Option and License Agreement, or the Ionis Agreement, (described below) in order to complete the license agreement with RogCon.
Ionis Collaboration Agreement
In September 2019, the company and Ionis entered into the Ionis Agreement to discover and develop ASOs to treat forms of epilepsy caused by mutations of the SCN2A gene. Pursuant to the Ionis Agreement, the company and Ionis each conducted certain research activities, and Ionis was responsible for identifying a development candidate and conducting an IND-enabling toxicology study. The design of the IND-enabling toxicology study was prepared and mutually agreed to by the company and Ionis.
History
Praxis Precision Medicines, Inc. was incorporated in 2015.
