Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Presentation (October 2025)
55 slides from Praxis Precision Medicines's investor presentation, Oct 21, 2025
Slide 1: Corporate Overview October 2025
CORPORATE OVERVIEW October, 2025 ®
Slide 2: Forward-looking statements
2 This presentation may contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations, and financial conditions, including but not limited to express or implied statements regarding the current beliefs, expectatio
Slide 3: Positioned to bring innovation to patients with CNS disorders
3 4 4 2 2028 Positioned to bring innovation to patients with CNS disorders Assets in late stage Clinical readouts in next 4 quarters Discovery platforms to optimize drug development Cash runway into
Slide 4: Four pillars guide how we develop medicines
4 GENETICS Focus on therapeutic targets identified through human genetics TRANSLATIONAL TOOLS Translational tools validate potential of target and product candidate and can provide early proof of biology EFFICIENT & RIGOROUS Efficient, rigorous clinical development paths to proof- of-concept in huma
Slide 5: Two platforms to generate optimized therapies
5 Two platforms to generate optimized therapies * Relutrigine has received Breakthrough Therapy Designation (BTD), Orphan Drug Designation (ODD) and Rare Pediatric Disease (RPD) designation from the FDA, and ODD from the European Medicines Agency (EMA) for the treatment of SCN2A and SCN8A-DEE and RP
Slide 6: Pipeline and upcoming catalysts
6 PROGRAM PRE CLINICAL PHASE ONE PHASE TWO PHASE THREE UPCOMING CATALYST Cerebrum SMALL MOLECULE PLATFORM Vormatrigine Focal Onset Seizures & Generalized Epilepsy EMPOWER observational study Ongoing RADIANT Phase 2 Full cohort topline results Q4 2025 POWER1 Phase 2/3 Finalize study in Q4 2025 POWER2
Slide 7: Movement Disorders: Ulixacaltamide
MOVEMENT DISORDERS: Ulixacaltamide
Slide 8: No specific drugs approved for essential tremor
8 No specific drugs developed for ET currently approved An estimated 7 million people in the U.S. live with ET
Slide 9: Surveys of ET patients highlight hidden burden of ET
9 Surveys of >400 ET patients across the US highlight ongoing hidden burden of ET and associated challenges in managing everyday life Praxis data on file. The Essential Tremor Patient Research was conducted by Fuel Insights (www.fuelinsights.com) from June-July 2024. Two separate surveys were comple
Slide 10: US neurologists emphasize need for more effective treatments
10 US neurologists emphasize the need for more effective treatments and the importance of patient-physician dialogue in ET Praxis data on file. The Essential Tremor HCP Research was conducted by Fuel Insights (www.fuelinsights.com) in April 2024. The survey was fielded at the American Academy of Neu
Slide 11: Precision modulation of tremor circuits through T-type calcium channels
11 Precision modulation of tremor circuits through T-type calcium channel modulation Targeting T-type Ca²⁺ channels offers circuit-level normalization Aberrant T-type calcium channel activity in the cerebello- thalamo-cortical circuit drives essential tremor Images from Matthews et al. Ann Clin Tran
Slide 12: Essential3 is the first successful program in essential tremor
12 Essential3 is the First Successful Program in Essential Tremor Several important clinical questions answered successfully and support NDA filing Hypothesis 1 Study 1 Parallel-group design (PD) Hypothesis 2 Study 2 Blinded Stable-responder, randomized withdrawal design (RW) Hypothesis 3 Studies 1+
Slide 13: Essential3: An ambitious and innovative Phase 3 program
13 Essential3: An ambitious and innovative Phase 3 program Blinded randomization 2:1 (Study 1: Study 2) occurred following completion of screening Blinded randomization 1:1 (Ulixacaltamide: Placebo) for treatment arm allocation in Study 1 and for treatment arm allocation of Responders into the rando
Slide 14: Study 1 baseline demographics
14 Study 1 Baseline demographics - mITT ULIXACALTAMIDE (N = 199) PLACEBO (N = 233) Age, Mean (SD) 67.9 (9.1) 68.9 (8.1) Gender, Male/Female % 57.3% / 42.7% 56.7% / 43.3% Race, White/Other % 98.5% / 1.5% 95.7% / 4.3% Years since ET Onset, Mean (Median) 29.8 (26.0) 31.1 (27.0) ET symptoms worsened ove
Slide 15: Study 1 primary and key secondary endpoints met
15 Study 1 - Primary and all key secondary efficacy endpoints met -4.3 -1.7 p < 0.0001 ULIXACALTAMIDE (n=199) PLACEBO (n=233) LS means for the mADL11 were estimated using a mixed model for repeated measures with treatment group, visit (categorical), treatment-by-visit interaction, randomization stra
Slide 16: Study 1 rapid and consistent response over weeks
16 Study 1 - Rapid and consistent response over 12 weeks
Slide 17: Study 1 efficacy robust across subgroups
17 Study 1 efficacy – Robust response across subgroups
Slide 18: Study 1 efficacy remains significant under extreme scenarios
18 Study 1 Efficacy remains significant under extreme scenarios LS means for the mADL11 were estimated using a mixed model for repeated measures with treatment group, visit (categorical), treatment-by-visit interaction, randomization strata (IT status, propranolol use, family history of ET), and bas
Slide 19: Clinical meaningfulness with mADL11 and ADL
19 Study 1 –Clinical meaningfulness with mADL11 and ADL -4.3 -1.7 p < 0.0001 ULIXACALTAMIDE (n=199) PLACEBO (n=233) LS means for the mADL11 were estimated using a mixed model for repeated measures with treatment group, visit (categorical), treatment-by-visit interaction, randomization strata (IT sta
Slide 20: Study 2 RW baseline demographics
20 Study 2 – RW baseline demographics – stable-responders BLINDED LEAD-IN ULIXACALTAMIDE ULIXACALTAMIDE STABLE RESPONDERS Age, Mean (SD) 67.9 ( 7.9) 67.3 (8.4) Gender, Male/Female % 51.8% / 48.2% 55.0% / 45.0% Race, White/Other % 96.3% / 3.7% 95.0% / 5.0% Years since ET Onset, Mean (Median) 28.7 (25
Slide 21: Study 2 primary and first secondary endpoint met
21 Study 2 efficacy - Primary and first secondary endpoint met 55% 33% p=0.037 ULIXACALTAMIDE (n=40) PLACEBO (n=40) OR=2.7 (1.06-6.92) For primary endpoint, odds ratio, 95% confidence interval, and p-value were obtained from a logistic regression model including treatment group as the main effect an
Slide 22: Hypothesis 3 combined efficacy analysis
22 -4.3 -1.7 p < 0.0001 ULIXACALTAMIDE (n=390) PLACEBO (n=233) Primary Endpoint mADL11 CFB to Day 56 Hypothesis 3– Day 56 Parallel-group combined efficacy analysis
Slide 23: Hypothesis 4 combined efficacy analysis
23 -4.2 -1.7 p < 0.0001 ULIXACALTAMIDE (n=191) PLACEBO (n=233) Primary Endpoint mADL11 CFB to Day 56 Hypothesis 4– Day 56 Parallel-group combined efficacy analysis
Slide 24: Safety across studies remains consistent
24 • No change in overall safety profile and no new signals identified • Most common TEAEs (≥10%) in participants treated with ulixacaltamide were constipation, dizziness, euphoric mood, brain fog, headache, paraesthesia and insomnia. • Discontinuations were primarily due to AEs, with most common du
Slide 25: Essential3 study disposition
25 Essential3 Program: Study 1 and Study 2 disposition Study 1 Enrolled/ITT: All randomized participants Study 2 Enrolled: All randomized participants Safety: All participants who received at least one dose of study drug Study 1 mITT: All randomized participants who received at least one dose and ha
Slide 26: Safety population overview of AEs
26 Safety population – Overview of AEs OVERVIEW OF ADVERSE EVENTS STUDY 1 STUDY 2 ULIXACALTAMIDE (N = 233) PLACEBO (N = 234) ULIXACALTAMIDE (N = 231) Participants with any TEAE 221 (94.9%) 177 (75.6%) 209 (90.5%) Participants with: Mild TEAEs 98 (42.0%) 89 (38.0%) 87 (37.7%) Moderate TEAEs 109 (46.8
Slide 27: Safety population most common TEAEs
27 Safety population - Most common TEAEs TREATMENT EMERGENT ADVERSE EVENTS ≥10% OF PATIENTS STUDY 1 STUDY 2 Preferred Term ULIXACALTAMIDE (N = 233) PLACEBO (N = 234) ULIXACALTAMIDE (N = 231) Constipation 57 (24.5%) 16 (6.84%) 68 (29.4%) Dizziness 56 (24.0%) 27 (11.5%) 59 (25.5%) Euphoric mood 30 (12
Slide 28: Epilepsy
EPILEPSY
Slide 29: Praxis epilepsy portfolio targets significant unmet need and market opportunity
29 The Praxis Epilepsy portfolio targets significant unmet need and market opportunity in the common and rare epilepsy markets Program US Prevalence US Market Opportunity Vormatrigine Sodium channel modulator 3.5M Common Epilepsy >$2.5B Relutrigine Sodium channel modulator >200k Developmental Epilep
Slide 30: Focal epilepsy is a serious condition with inadequate options
30 Focal epilepsy is a serious medical condition with inadequate therapeutic options impacting approximately 3M patients in the US 1. Praxis Claims Analysis on File 2024. FOS patient cohort (n = 440k) ASM: Anti-Seizure Medication Patients need a new therapy: • That is tolerable so they adhere and ca
Slide 31: Vormatrigine is poised to transform the epilepsy landscape
31 Vormatrigine is poised to quickly transform the epilepsy landscape Sources: -AAN 2023 Poster - PRAX-628: A Novel Sodium Channel Blocker with Greater Potency and Activity Dependence Compared to Standard of Care; Kahlig, K., Chapman, M., Petrou, S. -AAN 2024 Poster - First-in-human Phase 1 Clinical
Slide 32: Vormatrigine development program
32 Vormatrigine development program to demonstrate efficacy and bring an improved therapy to focal and generalized epilepsy patients Registry to help epilepsy patients track their seizures POWER1 pivotal study Evaluate efficacy, safety and extensive PK in broader epilepsy patients EMPOWER POWER1 POW
Slide 33: RADIANT study: best-in-class execution in epilepsy
33 Proven recruitment engine -> scalable across the ENERGY program Best-in-disease efficacy Full dataset for focal and generalized expected by Q4 ~75 patients* Foundation of the safety database and generalized proof-of- concept 61 patients dosed to date**99 Patients Screened RADIANT study: Best-in-c
Slide 34: RADIANT Phase 2 showed disease-leading efficacy
34 • 8-week RADIANT results de-risks efficacy for POWER1 and POWER2 12- week studies • Full cohort for RADIANT, including generalized patients, to be shared at 2025 AES RADIANT Phase 2 study showed disease-leading efficacy 8-week study with focal patients showed a 56% median seizure reduction from b
Slide 35: First cohort of RADIANT provides confidence for ENERGY program
35 First cohort of RADIANT provides confidence and opportunity for ENERGY program Radiant cohort 1 results De-risks the 12-week pivotal POWER-1 and POWER-2 studies Full cohort for RADIANT to be shared at AES in December, including generalized patients • Can support go/no-go for generalized pivotal s
Slide 36: Pivotal POWER1 and POWER2 study designs
36 Pivotal POWER1 study completing end of 2025, POWER2 enrollment complete 2H 2026 6 weeks, 30mg 12 weeks placebo • Screening • Observation • Randomization Safety Follow-up • Both studies expected to support NDA submission • Range of doses in POWER2 based off PK/PD analysis to optimize efficacy oppo
Slide 37: POWER3 monotherapy study design
37 • Key study aspects: • Refractory epilepsy with 1-2 current ASMs • Initiate vormatrigine while titrating off current regimen over 4 weeks • Details to follow after protocol finalization POWER3 designed to demonstrate the potential of vormatrigine as a stand-alone agent, expect to initiate 1H 2026
Slide 38: Relutrigine: potential for class leading efficacy and tolerability
38 Relutrigine: Potential for class leading efficacy and tolerability AE=adverse event, DEE=developmental & epileptic encephalopathy, NaV=voltage-gated sodium channel, SAE=serious adverse event Relutrigine Oral suspension, no titration, once daily administration Formulated for pediatric use Small mo
Slide 39: Differentiated profile enabling wide therapeutic index
39 Differentiated profile enabling wide therapeutic index Praxis data on file hNav=human voltage-gated sodium channel, µM = micromolar, TI=therapeutic index Relutrigine Carbamazepine LamotrigineCo nc en tr at io n to a ch ie ve 5 0% in hi bi tio n, µ M ) .1 1 10 100 1000 Narrow margin between blocki
Slide 40: Relutrigine's potential for broad applicability across etiologies
40 • All genetically driven DEEs result in hyperactivation of sodium channels, manifesting in epilepsy syndromes • Relutrigine’s mechanism of action targets hyperactive NaV channels addressing the neuronal hyperexcitability driving seizures • Targeting the root cause of DEE symptomology allows for b
Slide 41: Consistent efficacy in diverse DEE models
41 Consistent efficacy in diverse number of DEE models Praxis data on file, Anderson LL, et al. Epilepsia. 2014;55(5):1274-83., Baker EM, et al. Epilepsia. 2018;59(60):1166-76.; Anderson LL, et al. Sci Rep. 2017;7(1):1682., Johnson JP, et al. Elife. 2022:11:e72468., Hawkins NA, et al. Ann Clin Trans
Slide 42: Current US DEE market is over 200,000 patients
42 Current US DEE market is over 200,000 patients Expected to increase in coming years as care and diagnosis improve Poke G, et al. Neurology. 2023;100(13)e.1363-75., Lopez-Rivera JA, et al. Brain.2020;143(4):1099-1105., Wu YW, et al. Pedatrics.2015;136(5):e1310-15., Scheffer IE, et al. Nat Rev Dis
Slide 43: EMBOLD Cohort 1 study design
43 KEY ENDPOINTS: • Incidence and severity of treatment- emergent adverse events (TEAEs) • Change from baseline in monthly motor seizure frequency • Length of seizure freedom achieved over a 28-day period • Clinical and Caregiver Global Impression of Improvement and Severity EMBOLD Cohort1 study des
Slide 44: EMBOLD Cohort 1 sustained seizure reduction
44 -90% -80% -70% -60% -50% -40% -30% -20% -10% 0% 0 1 2 3 4 5 8 11 M ed ia n Se iz ur e Re du ct io n Months of exposure • *Inclusive of open-label extension period as of April 24, 2025 • Praxis Data on File • AE=adverse event, SAE=serious adverse event, SOC = standard of care EMBOLD Cohort 1 resul
Slide 45: EMBOLD sustained seizure-free periods
45 EMBOLD Cohort 1 results: sustained seizure-free periods reflect both clinical and daily life improvements *Inclusive of open-label extension period at data cutoff as of April 24, 2025 Praxis Data on File 3 3 26 35 43 50 55 63 67 0 10 20 30 40 50 60 70 80 Relutrigine arm Placebo arm Month 1 Month
Slide 46: Relutrigine treatment led to disease modifying impact
46 Relutrigine treatment led to disease modifying impact Meaningful gains in overall well-being of patients, despite severity and historical lack of improvement with available treatments Clinical Global Impression of Improvement and Caregiver Global Impression of Improvement assessed at Week-16 visi
Slide 47: EMBOLD Cohort 2 designed as pivotal study
47 KEY ENDPOINTS: • Change from baseline in monthly motor seizure frequency • Length of seizure freedom achieved over a 28-day period • Incidence and severity of treatment- emergent adverse events (TEAEs) • Clinical and Caregiver Global Impression of Improvement and Severity EMBOLD Cohort 2 is desig
Slide 48: Relutrigine's clinical profile expanding with EMERALD study
48 Relutrigine’s clinical profile expanding with EMERALD study Large, unmet needBroad biologic rationale Clinical proof of concept data
Slide 49: EMERALD targets phenotypic DEEs regardless of etiology
49 EMERALD targets phenotypic DEEs, regardless of etiology Key Inclusion Criteria • Ages ≥2 and ≤65 years • Has a documented diagnosis of a developmental and epileptic encephalopathy in childhood • Has 4 or more countable motor seizures during the 28-day observation period Treatment • Relutrigine or
Slide 50: Elsunersen is the first drug designed for SCN2A GoF DEE
50 Designed to selectively decrease SCN2A gene expression Significant reduction in seizures achieved in SCN2A GoF patients No adverse events related to the study were considered treatment-emergent or serious Orphan Drug Designation (ODD) and Rare Pediatric Disease (RPD) designation from the FDA, and
Slide 51: Precision targeting of SCN2A GoF patients
51 Precision targeting of SCN2A GoF patients positions elsunersen as a potential disease-modifying therapy ASO=antisense oligonucleotide, DEE=developmental & epileptic encephalopathy, NaV=voltage-gated sodium channel DISEASE STATE: EXCESSIVE SCN2A ACTIVITY ASO TREATED: NORMALIZED SCN2A ACTIVITY • SC
Slide 52: EMBRAVE Part 1 showed clinically meaningful seizure reduction
52 KEY ENDPOINTS: • Incidence and severity of treatment-emergent adverse events (TEAEs) • Change from baseline in monthly (28-day) motor seizure frequency SAFETY: • No TEAEs or SAEs considered related to study drug • All TEAEs recovered/resolved EMBRAVE Part 1 showed clinically meaningful seizure re
Slide 53: Ongoing EMBRAVE Part A supports registrational package
53 • Starting dose of 1 mg with optional dose escalation up to 8 mg based on individual tolerability at each dose • Topline results expected 1H 2026 • *Option to increase to n=16 Ongoing EMBRAVE Part A supports registrational package Sham procedure every 4 weeks for 24 weeks • 3:1 Randomization Ages
Slide 54: EMBRAVE3 registrational trial
54 EMBRAVE3 registrational trial Cohort 1: ages >2-18 yrs (n=40) Sham procedure every 4 weeks for 24 weeks 1:1 Randomization Elsunersen 1 mg every 4 weeks for 24 weeks Open Label Extension Key Inclusion Criteria • Documented SCN2A GoF variant with seizures prior to 3 months of age • Between the ages
Slide 55: - DARE -oR MORE
- DARE -oR MORE
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