Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — International Epilepsy Congress (IEC) 2025
13 slides from Praxis Precision Medicines's conference presentation, August 2025
Slide 1: PAC-GEN: Establishing the Predictive Validity of Preclinical Seizure Models in Generalized Epilepsies
PAC-GEN: Establishing the Predictive Validity of Preclinical Seizure Models in Generalized Epilepsies Lyndsey Anderson, PhD Director, in Vivo Pharmacology
Slide 2: Conflict of Interest
Conflict of Interest Lyndsey Anderson is a current employee of Praxis Precision Medicines and is a Praxis shareholder. 2
Slide 3: Innovative epilepsy treatments needed faster and more than ever
Innovative epilepsy treatments needed faster and more than ever ~50 MILLION PEOPLE Focal onset seizures and generalized epilepsy worldwide are affected by epilepsy account for >90% of epilepsy cases in adults and children A significant number of patients remain Central to the development of novel AS
Slide 4: Praxis Analysis of Concordance (PAC) Framework
Praxis Analysis of Concordance (PAC) Framework The PAC framework was implemented to assess the translational concordance between preclinical and clinical ASM response across the clinical epilepsy spectrum for 32 FDA-approved ASMs in the United States Anderson et al 2025 Epilepsia, https://doi.org/10
Slide 5: Preclinical ASM Response
potent anticonvulsant (PI>10) anticonvulsant (P12- 10) anticonvulsant butimpaired (<2) unknown rmixedresults no effect(PI<1) roconvulsant Preclinical ASM Response Generalized Seizure Models Focal Seizure Models Status GAERS or Hr GHz ‘Systemic Hippocampal Amygdals Comeal Hippocampal Amygdala uG- MES
Slide 6: Calculation of Translational Concordance
Calculation of Translational Concordance • A unified scoring matrix was developed to assign translational concordance between preclinical and clinical ASM response • Individual ASM concordance scores were calculated, summed and normalized to generate a global translational concordance score • Data d
Slide 7: Clinical ASM Response
^ denotes significant safety issues marked efficacy perceived / common monotherapy moderate efficacy perceived / alternative monotherapy Clinical ASM Response antiseizure (documented reduction and/or freedom) add-on unknown / not typically used mixed results not effective contraindicated Generalized
Slide 8: PAC Framework Identifies Differential Translational Concordance Between Preclinical Models and Generalized Epilepsy Types
PAC Framework Identifies Differential Translational Concordance Between Preclinical Models and Generalized Epilepsy Types 8
Slide 9: PAC-FOS: Vormatrigine exceeds thresholds needed to advance development
PAC-FOS: Vormatrigine exceeds thresholds needed to advance development Vormatrigine Results Protective index (PI) measured as tolerability / efficacy (TD50 / ED50); MES = maximal electroshock seizure Bialer et al 2024 Epilepsia; Anderson et al 2025 Epilepsia, https://doi.org/10.1111/epi.18592 9
Slide 10: Vormatrigine effect in RADIANT: Best-in-Disease Efficacy
P196 Vormatrigine effect in RADIANT: Best-in-Disease Efficacy Wilcoxon sign test p<0.05 in all weeks and overall; LOESS: Locally weighted plot smoothing 10
Slide 11: Conclusions
Conclusions • Findings from this study extend our insights into the predictive validity of commonly used seizure models across the spectrum of human epilepsies. • Notably, we demonstrate differential translational concordance between preclinical seizure models and generalized epilepsy types, as well
Slide 12: Thank You
Thank You Connect with us Questions? Booth #435 lyndsey@praxismedicines.com praxismedicines.com @PraxisMedicines Praxis Precision Medicines praxismedicines Scan to view full presentation listing from Praxis at IEC 2025 12
Slide 13: Example
Focal Onset MES Seizures MES m m FOS Ethosuximide Methsuximide 1 1 Individual ASM concordance scores for Example mouse MES to FOS Cav channels Zonisamide 1 Gabapentin 1 Pregabalin 0.75 GAERS or GAERS or WAG/Rij Absence WAG/Rij Carbamazapine 1 r Absence Cenobamate 1 1 na Eslicarbazepine Acetate 1 1 F
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