Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Presentation (August 2024)
38 slides from Praxis Precision Medicines's investor presentation, Aug 13, 2024
Slide 1: Corporate Overview August 2024
CORPORATE OVERVIEW August 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 >$7B 5 2 2027 Praxis is positioned to bring more innovation to patients Assets in late stage in 2024 Commercial opportunity across the portfolio 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 Q4 2024 interim, 2H 2024 topline results ESSENTIAL3 Study 2 randomized withdrawal PRAX-628 Focal Onset Seizures & Generalized Epilepsy EMPOWER observational study Q3 2024 begin en
Slide 7: Cerebrum Small Molecule Platform
7 CEREBRUM SMALL MOLECULE PLATFORM
Slide 8: Ulixacaltamide Milestones
8 Ulixacaltamide Milestones Q4 2024: Interim analysis of Essential3 Study 1 2H 2024: Topline results for Essential 3 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. GHOSH (2016) (P.231, C.1, PH.1, L.1-2), 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):1235-7. 4. Vetterick, C., Lyons
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 • Improvement based on regaining function • ADL assess
Slide 11: Essential1 Phase 2b study set foundation for the Essential3 Phase 3 program
11 • 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 12: Using Essential1 to define clinical meaningfulness in essential tremor
12 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 13: Majority of patients achieved at least a 3-point change in mADL11 at 8 weeks
13 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 14: Adding ulixacaltamide benefited more patients on propranolol
14 25% 48% 0% 10% 20% 30% 40% 50% Week 8 PROPRANOLOL + PLACEBO PROPRANOLOL + ULIXACALTAMIDE Adding ulixacaltamide benefited more patients on propranolol with > 3-point improvement Results from Essential1 study showing % of participants on stable propranolol dose achieving meaningful change at 8 week
Slide 15: Essential3: An innovative Phase 3 program
15 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 Placebo Study 2: Randomized Withdrawal Study Ulixacaltamide R
Slide 16: Essential3 Program is well powered
16 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 17: Path to success
17 Path to success De-risked Trial design based on key learnings from Essential1 Regulatory alignment based on successful End-of-Phase 2 meeting Efficient Focused execution Single protocol: Optimized screening, enrollment, analysis Streamlined Design Decentralized study to expand reach and reduce st
Slide 18: PRAX-628 Milestones
18 PRAX-628 Milestones Q3 2024: Begin enrolling EMPOWER observational study 2H 2024: Begin enrolling RADIANT open label study Q4 2024: Begin enrolling POWER1 registrational study 1H 2025: Begin enrolling POWER2 registrational study 1H 2025: Topline results for RADIANT 2H 2025: Topline results for PO
Slide 19: Praxis epilepsy portfolio targets significant unmet need
19 The Praxis epilepsy portfolio targets significant unmet need in both the common and rare epilepsy markets >$3B+ US Common and Developmental Epilepsy Market Opportunity 3.5M US Prevalence for Common Epilepsy 14K+ US Prevalence for Rare Epilepsies covered by Praxis’ Portfolio1 1 SCN2A Gof, SCN2A Lo
Slide 20: PRAX-628: Precision medicine therapeutic for focal onset seizures and generalized epilepsy
20 Differentiated Profile Goal: Preferential action against neuronal hyperexcitability PRAX-628: 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 brain
Slide 21: PRAX-628 shows a differentiated pre-clinical profile
21 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 PRAX-628 shows a differentiated pre-clinical profile Protective index (PI) measured as tolerability / efficacy (TD50 / ED50); MES = maximal electroshock seizure 1. ht
Slide 22: PRAX-628 has unprecedented margins over best-in-class ASMs
22 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 PRAX
Slide 23: Phase 1 study demonstrated brain activity and rapid achievement of therapeutic concentrations
23 - 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 PRAX-628 • Composite endpoint from qEEG showed separation of drug versus placebo in the SAD and MAD cohorts • Difference between PRAX-628 and placebo significant for all
Slide 24: Phase 2 PPR study demonstrated proof of concept
24 • 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 25: PRAX-628 presents an ideal precision ASM profile
25 PRAX-628 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 well
Slide 26: PRAX-628 ENERGY program
26 PRAX-628 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 efficacy PO
Slide 27: EMPOWER Observational Study to better understand patient journey
27 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 28: RADIANT Phase 2 open label study
28 • Measuring seizure frequency, seizure freedom, safety and pharmacokinetics • Will allow the evaluation of PRAX-628 in a broader population, including generalized epilepsy • Initiate in 2H 2024 with topline results in 1H 2025 RADIANT Phase 2 open label study to evaluate safety and efficacy in foc
Slide 29: Proposed study designs for POWER1 and POWER2
29 Proposed study designs for POWER1 and POWER2 6 weeks, 30mg 12 weeks placebo • Screening • Observation • Randomization POWER1, n= 200 Safety follow-up • POWER1 to initiate Q4 2024 with topline readout 2H 2025 • POWER2 to initiate in 1H 2025 6 weeks, 20 mg POWER2, n= 300 • Screening • Observation •
Slide 30: Relutrigine (PRAX-562) Milestones
30 Relutrigine (PRAX-562) Milestones Q3 2024: Topline results in Phase 2 EMBOLD Study
Slide 31: Relutrigine potential first- and best-in-class small molecule for DEEs
31 Preclinical and emerging clinical data demonstrate relutrigine has the potential to be a first- and best-in-class small molecule for DEEs Superior selectivity for disease-state NaV channel hyperexcitability Convenient auto-titration regimen with stable PK Unprecedented therapeutic window with pot
Slide 32: Relutrigine Phase 1 summary
32 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 33: Relutrigine Phase 2 EMBOLD study topline data expected Q3 2024
33 Relutrigine Phase 2 EMBOLD study topline data expected in Q3 2024 + Participants receive either 0.5 mg/kg/day relutrigine QD for 16 weeks or 0.5 mg/kg/day relutrigine QD for 12 weeks & matching placebo QD for 4 weeks. Participants in the relutrigine/placebo arm will receive placebo for 4 consecut
Slide 34: EMBOLD is the tip of the iceberg for relutrigine in broader DEE population
34 EMBOLD is the tip of the iceberg for the potential of relutrigine in broader DEE population SCN2A, SCN8A EMBOLD study Potential future development Many DEEs already use sodium channel blockers Broad applicability for relutrigine in genetic driver with high seizure burden >100k patients High Seizu
Slide 35: Elsunersen (PRAX-222) Solidus ASO Platform
35 Elsunersen (PRAX-222) SOLIDUS ASO PLATFORM
Slide 36: Elsunersen specifically designed for SCN2A GoF patients
36 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 37: Significant reduction in seizures observed for SCN2A patients
37 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
Slide 38: - DARE -oR MORE
- DARE -oR MORE
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