14 slides from Praxis Precision Medicines's conference presentation, September 2026
Slide 1: POWER1 – A Double-Blind, Randomized, Multicenter Registrational Study of Vormatrigine
POWER1 – A Double-Blind, Randomized, Multicenter Registrational Study Evaluating the Efficacy and Safety of Vormatrigine in Adults with Focal Onset Seizures Orrin Devinsky, MD Praxis Precision Medicines, Boston, MA, USA Disclosure: Orrin Devinsky is a current employee of Praxis Precision Medicines a
Slide 2: Innovative Epilepsy Treatments Needed Faster and More Than Ever
Innovative Epilepsy Treatments Needed Faster and More Than Ever Seizures and their frequency ~50 MILLION PEOPLE FOS accounts for the majority of are directly related to QoL and worldwide are affected by epilepsy epilepsy cases in adults outcomes in epilepsy patients A significant number of patients
Slide 3: Vormatrigine: Functionally Selective Sodium Channel Modulator
Vormatrigine: Functionally Selective Sodium Channel Modulator in Development for Focal Onset Seizures and Generalized Epilepsy Significantly more potent than competitive molecules in Vormatrigine highly translatable pre-clinical models Focal and generalized Rapidly achieves therapeutic concentration
Slide 4: Phase 2/3 Clinical Findings POWER1 Study
PHASE 2/3 CLINICAL FINDINGS POWER1 STUDY Vormatrigine is an investigational drug and has not been approved by any regulatory body for use. 4
Slide 5: POWER1 Phase 2/3 Study Design
POWER1 Phase 2/3 Study Design Primary Endpoint • Percent change in monthly (28 days) focal 6 weeks, 20 mg, QD 6 weeks, 30 mg, QD seizure frequency from Baseline to Treatment Period Key Secondary Efficacy Endpoint 12 weeks placebo • Proportion of subjects experiencing a ≥50% reduction in monthly (28
Slide 6: Participant Disposition
Participant Disposition Screened for Eligibility (N=561) Excluded (N=306) 251 Eligibility criteria not met 16 Withdrawal of consent 26 Other 7 Investigator decision 6 Lost to follow-up Randomized (N=255) Placebo (N=128) Vormatrigine (N=127) • Safety population (N=128) • Safety population (N=127) • C
Slide 7: Participant Demographics and Baseline Characteristics
Participant Demographics and Baseline Characteristics Placebo Vormatrigine (N=128) (N=127) Age, years Mean (SD) 40.5 (13.3) 40.7 (13.0) Sex M, F 63, 65 54, 73 # Background ASMs Mean (SD) 2.3 (0.7) 2.4 (0.7) Sodium Channel Blocker 111 (86.7%) 114 (89.8%) SV2A 51 (39.8%) 53 (41.7%) Concomitant ASM* GA
Slide 8: Primary Endpoint Not Met
Primary Endpoint Not Met Percent Change in Monthly (28-Day) Focal Seizure Frequency • Primary endpoint % change from baseline in 28-day seizure frequency not met (p=0.28) -27.7% -10.8% 10% • Seizure reduction was more pronounced during the second half of the study on the higher p-value: 0.28 30 mg d
Slide 9: Key Secondary Endpoint Nominally Met Significance
Key Secondary Endpoint Nominally Met Significance RR 50%, Odds Ratio = 1.85 (p=0.0355) Vormatrigine, 30 mg period Vormatrigine, 20 mg period Placebo, overall 12 weeks 80% 60% achieving threshold (%) Proportion of patients 40% 20% 0% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% 55% 60% 65% 70% 75% 80% 8
Slide 10: Key Learnings from POWER1: Drivers of Vormatrigine Treatment Effect
Key Learnings from POWER1: Drivers of Vormatrigine Treatment Effect Fewer than 2 SCBs (n=83) High-performing sites (n=89) 30 mg period (Post-Switch) (n=116) % change +/- 95 CI 10 10
Slide 11: Drivers of Vormatrigine Treatment Effect: Site Performance
Drivers of Vormatrigine Treatment Effect: Site Performance High performing sites – more participants, fewer discontinuations Group Patients (N) Per Site (N) Disc. (%) High-performing 175 5.3 7% Other 78 2.7 18% Overall 10% 11 11
Slide 12: Safety Summary
Safety Summary Placebo (N=128) VORMATRIGINE (N=127) • Vormatrigine was generally well-tolerated; AE-related Discontinuation due to TEAE 1 (0.8) 12 (9.4) discontinuations were <10% Participants with ≥1 TEAE 69 (53.9) 104 (81.9) Serious AEs (SAEs) 2 (1.6) 5 (3.9) • Most common TEAEs Drug-related TEAE
Slide 13: POWER1 Study Summary
POWER1 Study Summary • The study did not meet its primary endpoint of reduction in monthly focal seizure frequency from baseline at Week 12. • The study nominally met the secondary endpoint, with a significant number of patients achieving ≥50% reduction in seizure frequency. • Seizure reduction duri
Slide 14: Acknowledgements
Acknowledgements William Martins1, Karl Hansen2, Michael Steidle2, Orrin Devinsky2,3, Henry Jacotin2, Dharit Patel2, Noam Epstein2, Steven Petrou2, Marcio Souza2, Giovanni Assenza4, Cristine Cukiert5, Ana Gonçalves6, Pedro Kowacs7, Lucia Marques8, Bashar Mohsen9, Marcin Nastaj10, Manuel Toledo11, Fe