Praxis Precision Medicines, Inc. provided an update on its portfolio and planned key milestones in 2024: Topline results of PRAX-628 in Phase 2a PPR study in the first quarter of 2024, followed by the expected initiation of the Phase 2b study in focal epilepsy in 2024; Topline results for both Phase 3 studies evaluating ulixacaltamide in essential tremor in the second half of 2024; Complete regulatory interactions to advance elsunersen (PRAX-222) towards a pivotal study for the treatment of SCN2A gain-of-function (GOF) developmental epilepsies; Topline results of the Phase 2 EMBOLD study of PRAX-562 in SCN2A and SCN8A developmental epilepsies in the first half of 2024. PRAX-628 for Focal Epilepsy · Praxis made strong progress in developing PRAX-628 for focal epilepsy, which affects over 1 million Americans. Initial data from PRAX-628 show it has a good tolerability profile, a potentially wide therapeutic index and reaching efficacious concentrations within 24 hours.

(poster [2]) · Praxis is conducting a Phase 2a PPR study to evaluate the efficacy of PRAX-628 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. This approach has been validated with several approved and new therapies.

A preliminary analysis of the 15 mg cohort showed that this cohort exceeds the expectations in terms of drug activity. The full data set will be disclosed after completion of the ongoing 45 mg cohort and full analysis of the Study. In 2023, Praxis disclosed results from a Phase 1 dose escalation study of PRAX-628 in healthy volunteers: · PRAX-628 was generally well-tolerated at all tested doses.

Pharmacokinetic data demonstrated dose-dependent exposure supporting once-daily dosing without titration to achieve potentially therapeutically effective drug concentration levels. (press release [3]) · Further analysis of patients in the Phase 1 study using qEEG data showed a pharmacodynamic effect at all dose levels and was significantly different from placebo. (poster [4]) Ulixacaltamide for Essential Tremor Essential tremor affects up to seven million people in the United States with action tremors that impact daily living, and there are currently no drugs specifically designed for essential tremor.

Enrollment in Essential3 remains on track, with plans to complete in the first half of 2024 and topline results expected in the second half of 2024, supporting a planned New Drug Application (NDA) submission in 2025. Key elements of the Essential3 registrational program are: · Two simultaneous Phase 3 trials, including a 12-week, parallel design study and a 12-week randomized withdrawal study for stable responders · Using the modified Activities of Daily Living 11 (mADL11) as a primary endpoint · In the Phase 2 Essential1 study, mADL11 produced a consistent and meaningful response in ulixacaltamide when compared to placebo after 8 weeks of treatment (p=0.042, nominal) · Using a single 60 mg dose in the Phase 3 trials · Safety database for a NDA by ICH guidelines requiring 300 patients with six-months of exposure and 100 patients with one-year of exposure · On January 5, 2024, Praxis announced a partnership with Tenacia Biotechnology to develop and commercialize ulixacaltamide in Greater China (press release [5]) Elsunersen (PRAX-222) for SCN2A Gain-of-Function Developmental Epilepsies SCN2A developmental and epileptic encephalopathy (SCN2A-DEE) is a debilitating and fatal monogenic epilepsy disorder caused by variants in the SCN2A gene. More than 70% of early-onset SCN2A-DEE patients live with uncontrolled seizures, and approximately 75% live with severe intellectual disability with patients rarely surviving beyond their teenage years.

In December 2023 at the American Epilepsy Society annual conference, Praxis shared data from Part 1 of the EMBRAVE study, where four patients were dosed once a month for a four-month period (poster [6]) · Patients showed a 43% median reduction in seizures from baseline · Patients showed a 48% increase in seizure-free days from baseline · There were no drug-related treatment-emergent adverse events or serious adverse events · Praxis has an upcoming meeting with the FDA to discuss next steps in developing elsunersen PRAX-562 for SCN2A and SCN8A Developmental Epilepsies Praxis continues to progress PRAX-562 as a unique sodium channel modulator targeting developmental and epileptic encephalopathies (DEEs). Praxis expects topline results from the EMBOLD study in pediatric patients with SCN2A-DEE and SCN8A-DEE in the first half of 2024.