Core Insights - The FDA has approved changes to the EMBRAVE3 trial design, converting it to a single-arm, baseline-controlled study for the treatment of SCN2A developmental and epileptic encephalopathy (DEE) with elsunersen [1][2] - Enrollment in the EMBRAVE3 trial is accelerating, with topline results expected in 2026 [1][2] - Elsunersen is an antisense oligonucleotide targeting SCN2A gene expression, showing promise in reducing seizures and improving symptoms in preclinical models [3][5] Group 1: EMBRAVE3 Trial Updates - The EMBRAVE3 study will now enroll 30 patients instead of the previously planned 40, with all patients receiving elsunersen from the start [5] - The primary analysis will focus on the change from baseline in countable motor seizures [5] - The ongoing EMBRAVE study (Part A) has enrolled 9 patients, with topline results expected in the first half of 2026 [1][5] Group 2: Elsunersen Overview - Elsunersen is designed to selectively decrease SCN2A gene expression, addressing the underlying cause of early-onset SCN2A DEE [3] - In vitro studies have shown a reduction in SCN2A gene expression and protein levels, while in vivo studies demonstrated significant reductions in seizures and improved survival in SCN2A mouse models [3] - Elsunersen has received Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA, as well as similar designations from the European Medicines Agency [3] Group 3: Company Background - Praxis Precision Medicines is focused on developing therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance [4] - The company utilizes genetic insights to create therapies for both rare and prevalent neurological disorders through its proprietary platforms [4]

Core Insights - Praxis Precision Medicines is advancing its clinical programs in developmental and epileptic encephalopathies (DEEs), highlighting significant opportunities in this field [2][5] - The company is focusing on two main therapeutic candidates: Relutrigine and Elsunersen, both showing promising results in clinical studies [5][8] Relutrigine - Relutrigine has demonstrated a mean seizure reduction of approximately 90% from baseline after 11 months of patient dosing in the EMBOLD study [5] - The EMBOLD study is expected to provide topline results by the first half of 2026, with a registrational study (EMERALD) planned to start in mid-2025, targeting a US market potential of at least $3 billion [5][7] - Relutrigine is a first-in-class small molecule that selectively inhibits persistent sodium current, showing dose-dependent inhibition of seizures in various DEE mouse models [7] Elsunersen - Elsunersen is an antisense oligonucleotide (ASO) targeting SCN2A gain-of-function mutations, with significant seizure reduction observed in clinical studies [8] - The EMBRAVE3 trial is set to enroll patients aged 2-18, with plans for treatment initiation from birth, reflecting the early onset of SCN2A DEE [5][8] - The global market potential for Elsunersen is estimated at $1 billion, based on a target population of approximately 5,000 patients [5] Pipeline and Future Developments - Praxis plans to nominate a development candidate for its early-stage ASO program PRAX-100, targeting SCN2A loss-of-function mutations, by mid-2025 [11] - The company is also on track to nominate development candidates for PRAX-080 and PRAX-090 by the end of 2025, focusing on PCDH19 and SYNGAP1 mutations respectively [11] - The company is leveraging its proprietary platforms, Cerebrum™ and Solidus™, to develop therapies for CNS disorders [9]