Praxis Precision Medicines Highlights 2025 Corporate Strategy and Business Priorities

Three blockbuster-potential assets in late-stage clinical trials and four pivotal readouts expected in 2025; anticipate four commercial assets by 2028

Study 1 of Essential3 program for ulixacaltamide in essential tremor $(ET)$ on track for Q1 2025 interim analysis; NDA filing for ulixacaltamide expected in 2025

Enrollment in EMBOLD study of relutrigine cohort 2 is on track; targeting NDA filing in 2026

Vormatrigine ENERGY program advancing with read-outs of RADIANT in first half of 2025 and POWER1 by year-end 2025

UCB has exercised its option to license KCNT1 small molecule candidate for global development and commercialization

Cash and investments $470 million at the end of 2024 support runway into 2028

BOSTON, Jan. 12, 2025 (GLOBE NEWSWIRE) -- Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system $(CNS)$ disorders characterized by neuronal excitation-inhibition imbalance, today highlighted its portfolio progress and provided its business priorities for 2025.

"2024 was a landmark year for Praxis with positive topline results from the Phase 2 photoparoxysmal response (PPR) trial of vormatrigine that led to initiating our ENERGY program in common epilepsies. Additional highlights this year were the unprecedented efficacy in cohort 1 of the EMBOLD study of relutrigine in developmental and epileptic encephalopathies (DEEs), followed by the initiation of the registrational cohort 2, and the continued overwhelming interest in the Essential3 program. Together, this progress has led to three blockbuster programs in late stage, with the potential for four product launches between 2026 and 2028," said Marcio Souza, president and chief executive officer.

Mr. Souza continued, "We are now well positioned for a readout-rich 2025, with results anticipated for ulixacaltamide in the Essential3 program in ET followed by our first NDA filing, as well as topline results for vormatrigine from the RADIANT study in focal onset seizures $(FOS.AU)$ and generalized epilepsy, and the POWER1 study in FOS. We are also thrilled to have received a third rare pediatric drug designation (RPDD) for relutrigine in Dravet Syndrome, and with strong interest in cohort 2 of the EMBOLD study, we expect to file the NDA in 2026. With regulatory feedback on the elsunersen program, we expect to initiate the pivotal trial in the first half of 2025. We are sufficiently funded to advance all programs through their topline readouts, with runway into 2028. We look forward to providing a thorough update across our portfolio at the planned Investor R&D Day in the second quarter of 2025."

Portfolio updates and anticipated milestones

Cerebrum$(TM)$ Small Molecule Platform

Ulixacaltamide for Essential Tremor

ET is an inadequately managed, undertreated and high burden disease with a prevalence of seven million patients in the U.S. The Essential3 program includes two Phase 3, registrational studies: Study 1 is a parallel design, placebo-controlled study (N=400) and Study 2 is a randomized withdrawal study (N=200). Since beginning recruitment in November 2023, over 100,000 patients have demonstrated interest in participating in the study.

   -- A pre-planned interim analysis of Study 1 is anticipated in the first 
      quarter of 2025. 
 
   -- At the time of the interim analysis update, Praxis will provide further 
      detail on timing for the full readouts of Study 1 and Study 2. 
 
   -- Praxis anticipates filing the NDA for ulixacaltamide in 2025. 
 
   -- Following positive results from Essential3, the Company plans to 
      re-initiate a study of ulixacaltamide in Parkinson's disease, where there 
      is significant and unmet need for non-dopaminergic treatment options. 

Vormatrigine (PRAX-628) for Common Epilepsies (Focal Onset Seizures and Generalized Epilepsy)

An estimated 3.5 million people in the U.S. suffer from common epilepsies. Sodium channel therapy is the cornerstone of treatment for patients with epilepsy yet currently approved drugs have significant safety and efficacy limitations. Vormatrigine is the most potent sodium-channel modulator ever designed to precisely target the hyperexcitable state of sodium-channels in adult common epilepsies.

   -- In recently completed Phase 1 studies, vormatrigine continued to 
      demonstrate an ideal profile with strong competitive differentiation. 
      Full results will be shared at an upcoming medical conference and 
      highlights include: 
 
          -- Results from an additional 45 mg multiple ascending dose $(MAD.AU)$ 
             cohort showed a dose proportional increase in exposure with 
             excellent tolerability, similar to the 20 and 30 mg MAD cohorts 
             completed previously. 
 
          -- A Phase 1 food effect study demonstrated that food intake does not 
             affect vormatrigine absorption and therefore there is no need to 
             take vormatrigine with food, which increases flexibility in dosing 
             and ease of use. 
 
   -- Praxis continues to make progress on the ENERGY program to advance 
      vormatrigine through efficacy and registrational trials. 
 
          -- The EMPOWER observational study, in partnership with the Epilepsy 
             Study Consortium, is aiming to better characterize seizure burden 
             started enrolling patients in 2024 and has enrolled over 2,000 
             patients. Early results were shared during the Praxis scientific 
             exhibit at the December 2024 American Epilepsy Society $(AES)$ 
             Annual Meeting. The RADIANT Phase 2 study for FOS and generalized 
             epilepsy is currently enrolling patients, with topline results 
             expected in the first half of 2025. RADIANT is an open-label study 
             recruiting up to 50 patients with FOS or generalized epilepsy, who 
             will be treated with a 30 mg dose over an 8-week period to 
             evaluate the impact of vormatrigine on seizure burden. 
 
          -- Enrollment for the POWER1 Phase 2/3 registrational study in 
             patients with treatment resistant FOS is progressing as planned, 
             with topline results anticipated in the second half of 2025. 
             POWER1 is assessing adjunctive treatment, allowing dosing of 
             vormatrigine on top of 1 to 3 antiseizure medications (ASMs), and 
             aims to enroll approximately 250 patients in a parallel-arm study, 
             comparing a treatment arm of 20 mg for 6 weeks followed by 30 mg 
             for 6 weeks versus a placebo arm for 12 weeks. 
 
          -- POWER2 will be the second registrational study for vormatrigine 
             and is expected to begin enrollment in the second half of 2025 as 
             a three-arm, 12-week study. 
 
   -- Praxis continues to evaluate the potential for expansion of one of its 
      highly functionally selective compounds into pain indications. The 
      program will be discussed at Praxis' planned R&D Day in the second 
      quarter of 2025. 

Relutrigine (PRAX-562) for Developmental and Epileptic Encephalopathies

DEEs cover a wide range of genetically and phenotypically defined epileptic conditions that are often characterized by onset of seizures at or shortly after birth and occur in approximately 200,000 patients in the U.S. Relutrigine is a sodium channel modulator with therapeutic potential across developmental epilepsies. Relutrigine is currently being evaluated in the EMBOLD study in SCN2A and SCN8A DEEs, with future plans for the EMERALD study in a broader, pan-DEE patient population.

   -- In cohort 1 of the EMBOLD study assessing relutrigine versus placebo in 
      SCN2A gain-of-function (GoF) and SCN8A patients, relutrigine showed 
      unparalleled results, with an update on the open-label extension (OLE) 
      shared at the 2024 AES Annual Meeting . Key results included: 
 
          -- 46% placebo-adjusted reduction in monthly motor seizures from 
             baseline over a 16-week period. 
 
          -- Patients continuing into the ongoing OLE (n=13) saw a 77% 
             reduction in motor seizures from baseline through nine months of 
             treatment. 
 
          -- Over 30% of patients (n=5) achieved seizure freedom status while 
             on relutrigine. 
 
          -- Patients achieving seizure freedom had a median of 46 days of 
             seizure freedom, inclusive of OLE period, compared to 3 days at 
             baseline. 
 
          -- Meaningful gains observed in alertness, communication and seizure 
             severity suggest relutrigine has a disease modifying effect. 
 
          -- Relutrigine was generally well-tolerated with no drug-related 
             serious adverse events or dose reductions required. 
 
   -- EMBOLD is currently enrolling 80 patients with SCN2A and SCN8A DEEs in 
      registrational cohort 2, with topline results anticipated in the first 
      half of 2026, to be followed by an NDA filing later in 2026. 
 
   -- In December 2024, Praxis received RPDD for relutrigine for Dravet 
      Syndrome. This is the third RPDD for relutrigine, in addition to SCN2A 
      and SCN8A DEEs. 
 
   -- Praxis remains on track to initiate the EMERALD registrational study in 
      the first half of 2025. 
 
   -- At the 2024 AES Annual Meeting, Praxis shared an update for an emergency 
      use patient with extended benefit achieved after receiving relutrigine 

Solidus(TM) Antisense Oligonucleotide $(ASO)$ Platform

Elsunersen (PRAX-222) for early-seizure-onset SCN2A-DEE

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January 12, 2025 21:00 ET (02:00 GMT)