Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — American Epilepsy Society 2023 Annual Meeting
13 slides from Praxis Precision Medicines's conference presentation, Nov 4, 2023
Slide 1: Kristopher Kahlig, PhD, Praxis Precision Medicines
Kristopher Kahlig, PhD Praxis Precision Medicines 4 November 2023 Image Courtesy of Nashville Convention & Visitors Corp.
Slide 2: Disclosure
• Kris Kahlig is a current employee of Praxis Precision Medicines and is a Praxis stockholder American Epilepsy Society | 2023 Annual Meeting | Orlando, FL | #AES2023 2
Slide 3: Objectives: differentiating features of PRAX-628
• Understand key differentiating features of PRAX-628 relative to - Approved sodium channel blockers (SCBs) - Molecules in development for adult Focal Onset Seizure American Epilepsy Society | 2023 Annual Meeting | Orlando, FL | #AES2023 3
Slide 4: Developing treatments inspired by the genetics of epilepsy
Developing treatments inspired by the genetics of epilepsy ENABLED BY TWO PLATFORMS CEREBRUM™ SOLIDUS™ SMALL MOLECULE PLATFORM ANTISENSE OLIGONUCLEOTIDE (ASO) PLATFORM Ulixacaltamide (PRAX-944) Elsunersen PRAX-090 PRAX-020 (PRAX-222) PRAX-562 PRAX-030 PRAX-080 PRAX-100 PRAX-628 PRAX-050 Cerebrum™ ut
Slide 5: Focal epilepsy background
Defined as epilepsy that originates in one side or Most common type of epilepsy in adults and area of the brain and affects one side of the body children - occurs in 60% of epilepsy cases ~ 50% have family history but genetics is Most common age of onset is in the first year not well understood of l
Slide 6: Preferential action against hyperexcitability
Preferential Action Against Hyperexcitability Biophysical “Levers” to Achieve Preferential Action untreated epileptic A. Reduce pro-excitatory channel function range • Inhibit persistent current ideal drug B. Dynamic block of channels during high NEURAL ACTIVITY activity • Inhibit voltage dependent
Slide 7: Preclinical profile of PRAX-628 suggests broad, potent anticonvulsant activity
Complete protection from MES-induced Significant reduction of 6-Hz induced Significant reduction of PTZ-induced tonic hindlimb extension psychomotor seizures clonic seizures ED50 0.42 mg/kg ED50 1.9 mg/kg ED50 2.6 mg/kg Preclinical profile of PRAX-628 suggests broad, potent anticonvulsant activity A
Slide 8: ED50 for PRAX-628 approximately 10x lower than standard of care
The ED50 value for PRAX-628 is approximately 10x lower than standard of care ASMs Carbamazepine Lamotrigine Cenobamate XEN1101 NBI-921352 PRAX-628 Carbamazepine Cenobamate Lamotrigine XEN1101 NBI-921352 ED50 values (mg/kg) 0.42 5.4 4.1 3.8 3.9 82 © 2023 Praxis Precision Medicines, Inc. American Epil
Slide 9: Combining MES and human safety studies for predictive translation
Combining MES and human safety studies for predictive translation High efficacy FOLD CHANGE IN EFFICACIOUS HUMAN EXPOSURE Tolerability limit Efficacy range “Maximal electroshock seizure (MES) is an experimental paradigm 1X LO HIGH Low efficacy that induces synchronous neural discharges in the brain
Slide 10: Clinically tolerated exposures
Clinically tolerated exposures No Clinical Tolerability Concerns MULTIPLE OF MES EC50 TOLERATED CLINICALLY Additional tolerated Cenobamate 4.8x Exposures with Clinical Toxicity margin for and Tolerability Concerns PRAX-628 XEN1101 2.5x PRAX-628 >15.5x* Cenobamate Cmax: >46,100 ng/mL, 400 mg Cmax (Ve
Slide 11: PRAX-628 focal epilepsy summary
Superior selectivity for hyperexcitable state of sodium channels in the brain associated with disease PRAX-628 Unprecedented therapeutic window could translate to Focal Epilepsy superior safety and efficacy Small Molecule qEEG analysis confirms CNS activity for clinical doses above 5mg See poster 3.
Slide 12: Additional Praxis Posters at the Scientific Sessions
Additional Praxis Posters at the Scientific Sessions • Lyndsey Anderson • Karl Hansen PRAX-628 is a Next Generation, Functionally Selective Small • Steven Petrou Molecule with Potent Anti-Seizure Activity and Potential as • Marcio Souza Best-in-Class Treatment for Focal Epilepsy • Nicole Hawkins Pos
Slide 13: AES 2023 Annual Meeting
AES 2023. ANNUAL _ MEETING
Praxis Precision Medicines — American Epilepsy Society 2023 Annual Meeting on 6ix