Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Presentation (May 2025)
41 slides from Praxis Precision Medicines's investor presentation, May 2, 2025
Slide 1: Corporate Overview May 2025
CORPORATE OVERVIEW May, 2025 ®
Slide 2: Forward-looking statements
2 Forward-looking statements 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
Slide 3: Positioned to bring innovation to patients with CNS disorders
3 4 6 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 CEREBRUM SMALL MOLECULE PLATFORM Cerebrum utilizes deep understanding of neuronal excitability and neuronal networks and applies a series of computational and experimental tools to develop orally available precision therapies SOLIDUS ANTISENSE OLIGONUCLEOTIDE (ASO) PLATFORM Solidus is an efficient
Slide 6: Praxis pipeline and upcoming catalysts
6 Program Pre clin Ph 1 Ph 2 Ph 3 Upcoming Catalyst Vormatrigine Focal Onset Seizures & Generalized Epilepsy EMPOWER observational study Ongoing RADIANT open label Topline results by mid-2025 POWER1 Phase 2/3 2H 2025 topline results POWER2 Phase 2/3 2H 2025 begin enrollment Relutrigine DEEs EMBOLD C
Slide 7: Epilepsy
EPILEPSY
Slide 8: Praxis Epilepsy portfolio targets significant unmet need and market opportunity
8 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 Epileps
Slide 9: Vormatrigine presents an ideal precision ASM profile
9 Significantly more potent than competitive molecules in highly translatable pre-clinical models Rapidly achieves therapeutic concentrations after once-daily dose with no food effect Ability to significantly exceed therapeutic concentrations while well tolerated Proof of concept achieved in epileps
Slide 10: Vormatrigine has differentiated potency in the MES model
10 0.1 1 10 100 0 25 50 75 100 Dose (mg/kg) P e rc e n t p ro te ct e d PRAX-628 Cenobamate Lamotrigine XEN1101 Carbamazepine NBI-921352 Protective index (PI) measured as tolerability / efficacy (TD50 / ED50); MES = maximal electroshock seizure; Praxis data on file; Bialer et al 2024 Epilepsia Sourc
Slide 11: Phase 2 vormatrigine PPR study demonstrated proof of concept
11 • Patients must demonstrate PPR response during screening and baseline to be evaluable • Response Assessment • Partial: Reduction, other than to zero, in the number of generalized PPR events at any assessment period vs baseline • Complete: Reduction to zero in the number of generalized PPR events
Slide 12: Vormatrigine ENERGY program to demonstrate efficacy
12 Vormatrigine ENERGY program to demonstrate efficacy and bring an improved therapy to focal and generalized epilepsy patients • Registry to help epilepsy patients track their seizures • In partnership with The Epilepsy Study Consortium POWER1 designed to maximize opportunity to demonstrate efficac
Slide 13: EMPOWER Observational Study to better understand patient journey
13 EMPOWER Observational Study to better understand patient journey In partnership with The Epilepsy Study Consortium (TESC) P A T IE N T P A T H W A Y Multi-channel engagement of epilepsy patients to EMPOWER Patient consented and provides core medical data Patient is given a seizure diary/epilepsy
Slide 14: RADIANT Phase 2 open label study
14 • Measuring seizure frequency, seizure freedom, safety and pharmacokinetics • Will allow the evaluation of vormatrigine in a broader population, including generalized epilepsy • Topline results by mid-year 2025 RADIANT Phase 2 open label study to evaluate safety and efficacy in focal onset or gen
Slide 15: Pivotal POWER1 study enrolling and POWER2 to initiate in 2H 2025
15 Pivotal POWER1 study enrolling and POWER2 to initiate in 2H 2025 6 weeks, 30mg 12 weeks placebo • Screening • Observation • Randomization POWER1, n= ~250 Safety Follow-up • POWER1 topline readout 2H 2025 • Design for POWER2 to be finalized reflecting results from RADIANT study 6 weeks, 20 mg POWE
Slide 16: Relutrigine: Potential for class leading efficacy and tolerability
16 Demonstrated robust seizure reduction and unprecedented seizure-free status per 28-day period Superior selectivity for hyperactive NaV channels, a known cause of seizure manifestation in all DEEs regardless of etiology Generally well-tolerated with mostly mild to moderate AEs, no drug-related SAE
Slide 17: Broad applicability across multiple etiologies
17 • All genetically driven DEEs result in hyperactivation of sodium channels, manifesting in epilepsy syndromes • Relutrigine’s mechanism of action is to target hyperactive NaV channels to address the neuronal hyperexcitability driving seizures • Targeting the root cause of DEE symptomology allows
Slide 18: Consistent efficacy in diverse number of DEE models
18 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 19: Current US DEE market is over 200,000 patients
19 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 20: EMBOLD Cohort 1 study design
20 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 21: EMBOLD Cohort 1 results: sustained seizure reduction
21 -90% -80% -70% -60% -50% -40% -30% -20% -10% 0% 0 1 2 3 4 5 8 11 M e d ia n S e iz u re R e d u c ti o n Months of exposure EMBOLD Cohort 1 results: sustained seizure reduction with continued exposure on top of SOC *Inclusive of open-label extension period as of April 24, 2025 Praxis Data on File
Slide 22: EMBOLD Cohort results: sustained seizure-free periods
22 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 23: Relutrigine treatment led to disease modifying impact
23Clinical Global Impression of Improvement and Caregiver Global Impression of Improvement assessed at Week-16 visit 57% 71% 43% 29% 69% 62% 31% 23% 0% 10% 20% 30% 40% 50% 60% 70% 80% Alertness Seizure Severity and Intensity Communication Disruptive Behavior Clinician Caregiver Relutrigine treatment
Slide 24: EMBOLD Cohort 2 designed as a pivotal study
24 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 25: Relutrigine's clinical profile expanding with EMERALD study
25 Relutrigine’s clinical profile expanding with EMERALD study Large, unmet needBroad biologic rationale Clinical proof of concept data
Slide 26: EMERALD targets phenotypic DEEs regardless of etiology
26 Phenotypically defined, etiology agnostic DEEs EMERALD targets phenotypic DEEs regardless of etiology Placebo Daily dose, 16 weeks 1:1 Randomization N=160 Relutrigine Daily dose, 16 weeks • No titration period • Once-daily, oral-dose Key Inclusion Criteria • Ages ≥2 and ≤65 years • Has a document
Slide 27: Elsunersen is the first drug designed for SCN2A GoF DEE
27 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 28: Precision targeting of SCN2A GoF patients positions elsunersen
28 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 29: EMBRAVE Part 1 showed clinically meaningful seizure reduction
29 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 30: Ongoing EMBRAVE Part A supports registrational package
30 • Starting dose of 1 mg with optional dose escalation up to 8 mg based on individual tolerability at each dose • Enrollment expected to complete by mid-year Ongoing EMBRAVE Part A supports registrational package *option to increase to n=16 Sham procedure every 4 weeks for 24 weeks • 3:1 Randomiza
Slide 31: EMBRAVE3 registrational trial
31 EMBRAVE3 registrational trial GoF=gain-of-function 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 a
Slide 32: Extending treatment to birth: age-based coverage in EMBRAVE3
32 • Cohort 1 results will support registration • Cohort 2 and 3 will allow for label expansion to patients at birth • Same inclusion criteria and endpoints as Cohort 1 Extending treatment to birth: systematic age-based coverage in EMBRAVE3 Elsunersen Screening and Baseline N=5 TREATMENT EXTENSION E
Slide 33: Complementary development of elsunersen and relutrigine
33 Relutrigine Small molecule Elsunersen ASO Complementary development of elsunersen and relutrigine targeting both the genetic driver and downstream network dysfunction in SCN2A GoF DEE=developmental & epileptic encephalopathy, GoF=gain-of-function Elsunersen targets root genetic cause of disease R
Slide 34: Solidus pre-clinical portfolio on-track for clinical trials in 2026
34 Solidus pre-clinical portfolio on-track for clinical trials in 2026 ASO=antisense oligonucleotide, DEE=developmental and epileptic encephalopathy, LoF=loss-of-function PRAX-80 PRAX-90 PRAX-100 Indication PCDH19 Clustering Epilepsy: X-linked mosaic expression disorder with early-onset clustered se
Slide 35: Movement Disorders
MOVEMENT DISORDERS
Slide 36: Surveys of >400 ET patients highlight hidden burden of ET
36 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 compl
Slide 37: US neurologists emphasize need for more effective treatments in ET
37 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 38: Two Phase 3 studies measuring Activities of Daily Living
38 Speaking Dressing Using Keys Hygiene Pouring Working Writing Drinking from a glass Feeding with a spoon Carrying food trays, plates or similar items Overall disability with most affected task Each point reduction provides benefit to a patient’s ability to perform regular activities • Improvement
Slide 39: Essential3: An innovative Phase 3 program
39 Essential3: An innovative Phase 3 program Single Recruiting Expert Review for Eligibility Screening Blinded Study Randomization Study 1: Placebo-controlled Parallel Group Study Ulixacaltamide, 60 mg Placebo Study 2: Randomized Withdrawal Study Ulixacaltamide, 60 mg Randomization 60 mg Placebo Lon
Slide 40: Praxis pipeline and upcoming catalysts
40 Program Pre clin Ph 1 Ph 2 Ph 3 Upcoming Catalyst Vormatrigine Focal Onset Seizures & Generalized Epilepsy EMPOWER observational study Ongoing RADIANT open label Topline results by mid-2025 POWER1 Phase 2/3 2H 2025 topline results POWER2 Phase 2/3 2H 2025 begin enrollment Relutrigine DEEs EMBOLD
Slide 41: ~ DARE }0R MORE
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