Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Presentation (March 2024)
35 slides from Praxis Precision Medicines's investor presentation, Mar 5, 2024
Slide 1: Corporate Overview March 2024
CORPORATE OVERVIEW March 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: Four pillars guide how we develop medicines
3 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 4: Praxis is positioned to bring more innovation to patients
4 4 >$7B 4 2 2026 Praxis is positioned to bring more innovation to patients Assets in clinical trials Commercial opportunity across the portfolio Trial readouts in next twelve months Discovery platforms to optimize drug development Cash runway into
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 PHASE TWO *PRAX-020 (KCNT1) is a research collaboration with UCB +PRAX-080 (PCDH19 ), PRAX-090 (SYNGAP1) & PRAX-100 (SCN2A-LoF) ASOs are a collaboration with The Florey Institute of Neuroscience and Mental Health PRECLINICAL PHASE ONE PHASE THREEPLATFORM PRAX-020* KCNT1 PRAX-050 Undisclosed PRAX-0
Slide 7: Cerebrum Small Molecule Platform
7 CEREBRUM SMALL MOLECULE PLATFORM
Slide 8: Ulixacaltamide Milestones
8 Ulixacaltamide Milestones 1H 2024: Enrollment complete 2H 2024: Topline results 2025: File NDA
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 SOURCE: Vetterick, C., Lyons, K.E., Matthews, L.G. et al. The Hidden Burden of Disease and Treatment Experiences of Patients with Essential Tremor: A Retrospective Claims Data Analysis. Adv Ther (2022)
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 • Improvement based on regaining function • Each point reduction provides benefit to a patient • ADL asse
Slide 11: Essential1 Phase 2b set foundation for the Essential3 Phase 3 program
11 • Alignment with FDA on dose and primary endpoint • Phase 3 program design structured around the patient needs • Robust recruitment strategy Essential1 Phase 2b set foundation for the Essential3 Phase 3 program Sets up a clear path to registration • Strong efficacy signal with robust endpoint (mA
Slide 12: Majority of patients achieved at least a 3-point change in mADL11 at 8 weeks
12 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 13: Adding ulixacaltamide benefited more patients on propranolol
13 25% 48% 0% 10% 20% 30% 40% 50% Week 8 Propanolol + Placebo Propanolol + 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 weeks
Slide 14: Essential3: An innovative Phase 3 program
14 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 15: Essential3 Program is well powered
15 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 16: Path to success
16 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 17: PRAX-628 Milestones
17 PRAX-628 Milestones 1Q 2024: Topline results of Phase 2a PPR 2H 2024: Initiate Phase 2b in focal epilepsy
Slide 18: Praxis epilepsy portfolio targets significant unmet need
18 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 19: PRAX-628: Precision medicine therapeutic for Focal Epilepsy
19 Differentiated Profile Goal: Preferential action against neuronal hyperexcitability PRAX-628: Precision medicine therapeutic for Focal Epilepsy Next generation, functionally selective small molecule targeting the hyperexcitable states of sodium channels in the brain, with the potential to address
Slide 20: PRAX-628 shows a differentiated pre-clinical profile
20 PRAX-628 shows a differentiated pre-clinical profile Protected index measured as tolerability / efficacy (TD50 / ED50) 1. https://praxismedicines.com/wp-content/uploads/2023/12/Anderson_AES2023_Predictive-Validity_Poster_Final.pdf; 2 Praxis data on file 3. https://praxismedicines.com/wp-content/u
Slide 21: PRAX-628 has unprecedented margins over best-in-class ASMs
21 PRAX-628 has unprecedented margins over best-in-class ASMs based on MES efficacy and clinical tolerability in humans 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 predic
Slide 22: Phase 1 study demonstrated brain activity and rapid therapeutic concentrations
22 0 5 23 0 4 8 12 16 20 24 Cenobamate XEN1101 PRAX-628 Phase 1 study demonstrated brain activity and rapid achievement of therapeutic concentrations - 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 • Composite endpoint from qEEG showed separation of drug versus pla
Slide 23: PRAX-628 has presented an ideal precision ASM profile through Phase 1
23 PRAX-628 has presented an ideal precision ASM profile through Phase 1 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 provide maximum effect Rapidly achieve
Slide 24: PRAX-628 Photo Paroxysmal Response (PPR) study
24 The Phase 2 PRAX-628 Photo Paroxysmal Response (PPR) study will provide insight into efficacy and inform dose selection for pivotal studies 1 Source: First Pub: C.D. Binnie Electroencephalography and clinical neurophysiology A, 1986, 63, 35-41; LEV paper: DGA Kasteleijn-Nolst Trenité Epilepsy Res
Slide 25: PRAX-562 Milestones
25 PRAX-562 Milestones Mid-2024: Topline results in Phase 2 EMBOLD Study
Slide 26: PRAX-562 potential first- and best-in-class small molecule for DEEs
26 Preclinical and emerging clinical data demonstrate PRAX-562 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 potent
Slide 27: PRAX-562 Phase 1 summary
27 PRAX-562 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 PRAX-562 and oxcarbazepine led to additive sodium blocking ef
Slide 28: PRAX-562 Phase 2 EMBOLD study topline data expected mid-2024
28 PRAX-562 Phase 2 EMBOLD study topline data expected in mid-2024 + Participants receive either 0.5 mg/kg/day PRAX-562 QD for 16 weeks or 0.5 mg/kg/day PRAX-562 QD for 12 weeks & matching placebo QD for 4 weeks. Participants in the PRAX-562/placebo arm will receive placebo for 4 consecutive weeks d
Slide 29: Elsunersen (PRAX-222) Solidus ASO Platform
29 Elsunersen (PRAX-222) SOLIDUS ASO PLATFORM
Slide 30: Elsunersen specifically designed for SCN2A GoF patients
30 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 form of epilepsy some
Slide 31: Significant reduction in seizures observed for SCN2A patients
31 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 32: What to expect from Praxis during 2024
32 What to expect from Praxis during 2024 1H2024 2H24PLATFORM CEREBRUM SMALL MOLECULE PLATFORM SOLIDUS ASO PLATFORM PRAX-562 Phase 2 EMBOLD Study Topline Results DEEs PRAX-628 Phase 2 PPR study Topline Results Focal Epilepsy Ulixacaltamide Phase 3 Complete Enrollment Essential Tremor Elsunersen Regu
Slide 33: Dare for More
DARE FoR MORE’
Slide 34: Appendix
34 Appendix
Slide 35: Essential1 Phase 2b study evaluating ulixacaltamide for essential tremor
35 Essential1 Phase 2b study evaluating the efficacy and safety of ulixacaltamide for essential tremor DBLI = double blind lead-in, OLE = open label extension ClinicalTrials.gov NCT05021991 Safety Follow-up Essential 1 Study: Weeks: 1–8 ulixacaltamide Placebo Or DBLI Weeks 9–14 OLE Week 15+ Ulixa Pl
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