Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Presentation (November 2024)
46 slides from Praxis Precision Medicines's investor presentation, Nov 6, 2024
Slide 1: Corporate Overview November 2024
CORPORATE OVERVIEW November 2024 ®
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: Praxis is positioned to bring more innovation to patients
3 4 >$9B 5 2 2027 Praxis is positioned to bring more innovation to patients Assets in late stage Commercial opportunity across the portfolio High value clinical readouts within the next eighteen months 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 for defined patient populations
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: Four clinical stage assets and multitude of early-stage programs
6 Program Pre clin Ph 1 Ph 2 Ph 3 Upcoming Catalyst Ulixacaltamide Essential Tremor ESSENTIAL3 Study1 placebo controlled Q1 2025 interim for Study 1 ESSENTIAL3 Study 2 randomized withdrawal Vormatrigine Focal Onset Seizures & Generalized Epilepsy EMPOWER observational study Enrolling RADIANT open la
Slide 7: Cerebrum Small Molecule Platform
7 CEREBRUM SMALL MOLECULE PLATFORM
Slide 8: Ulixacaltamide Milestones
8 Ulixacaltamide Milestones Q1 2025: Study 1 interim analysis 2025: NDA filling
Slide 9: Essential tremor market is significantly underserved and ready for disruption
9 Essential tremor market is significantly underserved and ready for disruption $4bn+ US ET Market 1. Louis ED, Ottman R. Tremor Other Hyperkinet Mov (N Y). 2014;4:259. 2. Elble RJ. Curr Neurol Neurosci Rep. 2013 Jun;13(6):353. 3. Putzke JD, et al. J Neurol Neurosurg Psychiatry. 2006 Nov;77(11):1235
Slide 10: Modified Activities of Daily Living 11 (mADL11) as Primary Endpoint
10 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 11: Surveys of >400 ET patients highlight hidden burden of ET
11 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 12: US neurologists emphasize the need for more effective treatments in ET
12 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 13: Essential1 Phase 2b study set foundation for Essential3 Phase 3 program
13 • Alignment with FDA on dose and primary endpoint • Phase 3 program design structured around patient needs • Robust recruitment strategy Essential1 Phase 2b study set foundation for the Essential3 Phase 3 program Sets up a clear path to registration • Strong efficacy signal with robust endpoint (
Slide 14: Using Essential1 to define clinical meaningfulness in essential tremor
14 Using Essential1 to define clinical meaningfulness in essential tremor MSD=Meaningful Score Difference, PGI-C = Patient Global Impression of Change 8 6 4 2 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -20 • Patient response on mADL11 endpoint was well-correlated to PGI-C response • Aligned with recently iss
Slide 15: Majority of patients achieved at least a 3-point change in mADL11 at 8 weeks
15 31% 55% 64% 0% 10% 20% 30% 40% 50% 60% 70% PLACEBO ULIXACALTAMIDE ULIXACALTAMIDE MAINTAINED Majority of patients achieved at least a 3-point change in mADL11 at 8 weeks Durable response in extension study patients who continued through 14 weeks Results from Essential1 study measuring participants
Slide 16: Adding ulixacaltamide benefitted more patients on propranolol
16 25% 48% 0% 10% 20% 30% 40% 50% Week 8 PROPRANOLOL + PLACEBO PROPRANOLOL + ULIXACALTAMIDE Adding ulixacaltamide benefitted more patients on propranolol Results from Essential1 study showing % of participants on stable propranolol dose achieving meaningful change at 8 weeks based on a meaningful sc
Slide 17: Essential3: An innovative Phase 3 program
17 Essential3: An innovative Phase 3 program that optimizes all aspects of study conduct 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 Ulixacalt
Slide 18: Essential3 Program is well powered
18 Essential3 Program is well powered Study Study 1 – Parallel Design Study 2 – Randomized Withdrawal Participants 400 200 Primary endpoint and power mADL11 Change from Baseline to Week 12 between ulixacaltamide and placebo 90% power to detect difference Difference in maintenance of response rate du
Slide 19: Path to success
19 Path to success De-risked Trial design based on key learnings from Essential1 Regulatory alignment based on successful End-of-Phase 2 meeting High Quality and Efficient Focused execution Single protocol: Optimized screening, enrollment, analysis Decentralized study to expand reach and reduce stud
Slide 20: Vormatrigine (PRAX-628) Milestones
20 Vormatrigine (PRAX-628) Milestones 1H 2025: Topline results for RADIANT 1H 2025: Begin enrolling POWER2 2H 2025: Topline results for POWER1
Slide 21: Praxis epilepsy portfolio targets significant unmet need in common and rare epilepsy
21 The Praxis epilepsy portfolio targets significant unmet need in both the common and rare epilepsy markets >$2.5B+ US Common Epilepsy Market Opportunity 3.5M US Prevalence for Common Epilepsy Praxis Epilepsy Portfolio Vormatrigine
Slide 22: Vormatrigine: Precision medicine therapeutic for focal onset seizures and generalized epilepsy
22 Differentiated Profile Goal: Preferential action against neuronal hyperexcitability Vormatrigine: Precision medicine therapeutic for focal onset seizures and generalized epilepsy Next generation, functionally selective small molecule targeting the hyperexcitable states of sodium channels in the b
Slide 23: Vormatrigine shows a differentiated pre-clinical profile
23 0.1 1 10 100 0 25 50 75 100 Dose (mg/kg) Pe rc en t p ro te ct ed PRAX-628 Cenobamate Lamotrigine XEN1101 Carbamazepine NBI-921352 Vormatrigine shows a differentiated pre-clinical profile Protective index (PI) measured as tolerability / efficacy (TD50 / ED50); MES = maximal electroshock seizure P
Slide 24: Vormatrigine has unprecedented margins over best-in-class ASMs
24 Source: Praxis data on file (Ph1 study), Cenobamate Cmax: >46,100 ng/mL, 400 mg Cmax (Vernillet et al 2020), XEN1101 Cmax: >107 ng/mL (Phase 1 data) x MES EC50 = multiple of predicted human EC50 based on the rodent MES model; IEC2023_628-SAD-MAD 4.8 2.5 5.0 15.0 CENOBAMATE 400mg XEN1101 25mg vorm
Slide 25: Phase 1 study demonstrated brain activity and rapid achievement of therapeutic concentrations
25 - 5 10 15 20 25 0 1 2 3 4 5 6 7 8 QE EG C OM PO SI TI VE C HA NG E HOURS POST DOSE 0 5 23 0 4 8 12 16 20 24 Cenobamate XEN1101 vormatrigine • Composite endpoint from qEEG showed separation of drug versus placebo in the SAD and MAD cohorts • Difference between vormatrigine and placebo significant
Slide 26: Phase 2 PPR study demonstrated proof of concept
26 • 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 27: Vormatrigine presents an ideal precision ASM profile
27 Vormatragine presents an ideal precision ASM profile https://praxismedicines.com/wp-content/uploads/2023/12/Kahlig_AES2023_628-In-Vivo_Poster_Final.pdf https://praxismedicines.com/wp-content/uploads/2023/09/IEC2023_628-SAD-MAD.pdf Ability to significantly exceed therapeutic concentrations while w
Slide 28: Vormatrigine ENERGY program to demonstrate efficacy
28 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 29: EMPOWER Observational Study to better understand patient journey
29 EMPOWER Observational Study to better understand patient journey In partnership with The Epilepsy Study Consortium (TESC) PA TI EN T PA TH W AY Multi-channel engagement of epilepsy patients to EMPOWER Patient consented and provides core medical data Patient is given a seizure diary/epilepsy track
Slide 30: RADIANT Phase 2 open label study
30 • Measuring seizure frequency, seizure freedom, safety and pharmacokinetics • Will allow the evaluation of vormatrigine in a broader population, including generalized epilepsy • Topline results in 1H 2025 RADIANT Phase 2 open label study to evaluate safety and efficacy in focal onset or generaliz
Slide 31: Proposed study designs for POWER1 and POWER2
31 Proposed study designs for POWER1 and POWER2 6 weeks, 30mg 12 weeks placebo • Screening • Observation • Randomization POWER1, n= 200 Safety follow-up • POWER1 initiated in Q4 2024 with topline readout 2H 2025 • POWER2 to initiate in 1H 2025 6 weeks, 20 mg POWER2, n= 300 • Screening • Observation
Slide 32: Relutrigine (PRAX-562) Milestones
32 Relutrigine (PRAX-562) Milestones 2H 2024: EMBOLD Cohort 2 enrolling 1H 2025: Initiate EMERALD study
Slide 33: Relutrigine is poised to disrupt the DEE market
33 >$500M US Market Opportunity * Poke G, Stanley J, Scheffer IE, Sadleir LG. Epidemiology of Developmental and Epileptic Encephalopathy and of Intellectual Disability and Epilepsy in Children >100k Developmental Epilepsies with high seizure burden using sodium channel blockers* >$2B+ Opportunity fo
Slide 34: Relutrigine potential first- and best-in-class small molecule for DEEs
34 Superior selectivity for disease-state NaV channel hyperexcitability Unprecedented therapeutic window with potential for superior safety and efficacy Generally well-tolerated with mostly mild to moderate AEs, no drug-related SAEs and no relutrigine dose reduction required Demonstrated robust seiz
Slide 35: Relutrigine Phase 1 summary
35 Relutrigine Phase 1 summary Source: Praxis data on file; https://investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-provides-corporate-update-and-5 * Co-administration of supra-therapeutic doses of relutrigine and oxcarbazepine led to additive sodium block
Slide 36: Relutrigine Phase 2 EMBOLD study design and endpoints
36 KEY ENDPOINTS: • Incidence and severity of treatment-emergent adverse events (TEAEs) • Change from baseline in monthly (28-day) motor seizure frequency • Seizure freedom achieved for a 4-week period • Clinical and Caregiver Global Impression of Improvement and Severity Relutrigine Phase 2 EMBOLD
Slide 37: Relutrigine demonstrated robust reduction in motor seizures
37 Relutrigine demonstrated robust reduction in motor seizures and unprecedented seizure-free status per 28-day period *Percent reduction derived from log-transformed placebo-adjusted relutrigine effect **Assessment of motor seizures over the controlled plus open-label periods through August 21, 202
Slide 38: Relutrigine patients demonstrated significant improvement in motor seizures
38 -90% -80% -70% -60% -50% -40% -30% -20% -10% 0% Relutrigine patients demonstrated significant improvement over the short and long-term in motor seizures Long-term extension data for 8 patients with data available for at least one 28-day period as of August 21, 2024 Placebo (n=7) -1.6% Relutrigine
Slide 39: Meaningful impact in days without motor seizures
39 Meaningful and consistent impact in days without motor seizures for relutrigine treated patients * Inclusive of OLE period 3 3 20 46 0 5 10 15 20 25 30 35 40 45 50 Baseline all Placebo Relutrigine Relutrigine Double-Blind Treatment Period All drug periods* Mean of longest period without seizures
Slide 40: Relutrigine treatment led to disease modifying impact
40Clinical 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 41: SCN2A and SCN8A are the tip of the iceberg across other DEEs
41 SCN2A and SCN8A are the tip of the iceberg in addressing the significant unmet needs across the spectrum of other DEEs *Based on PubMed Search of DEEs that could use SCBs to treat focal seizures when they presented. >$500m peak revenue Low tolerability and inadequate response >70% DEE patients tr
Slide 42: Regulatory agency input and next steps
42 Regulatory agency input • EMBOLD registrational Cohort 2 initiated • Leveraging EMBOLD successful study design Next steps Initiated EMBOLD cohort 2 registrational trial for SCN2A and 8A, begin enrollment for EMERALD trial in 1H 2025 2H 2024 1H 2025 Initiate EMERALD Trial 1:1 Randomization N=80 (S
Slide 43: Elsunersen (PRAX-222) Solidus ASO Platform
43 Elsunersen (PRAX-222) SOLIDUS ASO PLATFORM
Slide 44: Elsunersen specifically designed for SCN2A GoF patients
44 Elsunersen specifically designed for SCN2A GoF patients DISEASE OVERVIEW • Epilepsy and developmental impairment before the age of 16 years occurs in 1 in 340 children • The majority of these cases result from sporadic de novo genetic variation • In both de novo and familial forms of epilepsy som
Slide 45: Significant reduction in seizures observed for SCN2A patients
45 Significant reduction in seizures observed for SCN2A patients Data from Part 1 of EMBRAVE Study, https://praxismedicines.com/wp-content/uploads/2023/12/Frizzo_AES2023_EMBRAVE_Poster_Final.pdf -39% -43% Im pr ov em en t Mean Median 52% 48% Mean Median Im pr ov em en t • No TEAEs or SAEs considered
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