Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Presentation (February 2022)
48 slides from Praxis Precision Medicines's investor presentation, Feb 28, 2022
Slide 1: Corporate Overview February 2022
PAGE 1CONFIDENTIAL C O R P O R A T E OVERVIEW F E B R U A R Y 2 0 2 2
Slide 2: Forward-looking statements
PAGE 2CONFIDENTIAL 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 statemen
Slide 3: A patient-guided CNS company developing new classes of treatments
PAGE 3CONFIDENTIAL A PATIENT-GUIDED CNS COMPANY D E V E L O P I N G N E W C L A S S E S O F T R E A T M E N T S Inspired By Human Genetics & The Biology Of Epilepsy
Slide 4: Targeting common and rare diseases connected by neuronal imbalance
PAGE 4CONFIDENTIAL Targeting Common & Rare Diseases Connected By Neuronal Imbalance The biology of epilepsy offers insights into brain function for CNS disorders Targets Elucidated By Genetics SCN1A SCN9A SCN10A SCN11A CACNA1A KCNA1 SLC1A3 SETX RFC1 DRD3 HTT FMR1 OPA1 SYNGAP1 SHANK3 CDKL5 DNM1 UNC79
Slide 5: Praxis is built on four key pillars
PAGE 5CONFIDENTIAL Development informed by TRANSLATIONAL TOOLS Targets identified through GENETICS Clinical development paths to POC RIGOROUS and EFFICIENT Development strategies are PATIENT-GUIDED Praxis is built on four key pillars
Slide 6: Broad portfolio of highly differentiated programs across multiple CNS disorders
PAGE 6CONFIDENTIAL Broad portfolio of highly differentiated programs across multiple CNS disorders PRECLINICAL PHASE 1 PHASE 2 REGISTRATIONAL ENABLINGPROGRAMMECHANISM OF ACTIONFRANCHISE * SCN2A-LOF, SYNGAP1 & PCDH19 ASOs are a collaboration with The Florey Institute PRAX-114 Phase 2 trial for ET, PR
Slide 7: Upcoming catalysts throughout portfolio in 2022
PAGE 7CONFIDENTIAL PROGRAM Q4 2022Q1 2022 Q3 2022 Q2 2022 INDICATION Upcoming catalysts throughout portfolio in 2022 PRAX-562 PRAX-114 PRAX-944 Initiate Phase 2 Trial DEEs MDD PTSD ET PD Phase 2b Essential1 Study Topline Initiate Phase 2 Trial ET Phase 2 ToplinePRAX-114 PRAX-944 PSYCHIATRY MOVEMENT
Slide 8: Dare for More
PAGE 8CONFIDENTIAL DARE for MORE
Slide 9: Psychiatry: PRAX-114 key upcoming milestones
PAGE 9CONFIDENTIAL PSYCHIATRY PRAX-114 GABAA Receptor PAM Depression Post-traumatic Stress Disorder 2Q 2022 Ph 2/3 Monotherapy MDD Aria Study Topline MID-2022 Ph 2 MDD Dose-Ranging Acapella Study Topline 2H 2022 Ph 2 PTSD Topline KEY UPCOMING MILESTONES
Slide 10: Major depressive disorder is a growing and debilitating disorder with substantial unmet need
PAGE 10CONFIDENTIAL Major depressive disorder is a growing and debilitating disorder with substantial unmet need despite numerous treatment options Source: Rush et al 2006, Masand et al 2003, Kupfer et 2005, DSM-5 2013, ExpressScripts MDD Report 2020 MAJOR DEPRESSIVE DISORDER (MDD) ~19 million Ameri
Slide 11: Preference for extrasynaptic GABAA receptors
PAGE 11CONFIDENTIAL Preference for extrasynaptic GABAA receptors has the potential of marked antidepressant effect with an improved tolerability profile GABA: Gamma-aminobutyric acid; GABAA PAMs: GABAA receptor positive allosteric modulators Potentiation Fold Potentiation α4β3δ: extrasynaptic GABAA
Slide 12: Extrasynaptic GABAA preference allows high GABAergic activation with improved tolerability
PAGE 12CONFIDENTIAL Extrasynaptic GABAA preference allows PRAX-114 the potential to achieve high-levels of GABAergic activation with improved tolerability PRAX-114 shows robust qEEG signal and target activation No MTD identified up to 80mg Tolerability profile maintained throughout dose escalation E
Slide 13: Effect of high-fat meal on pharmacokinetics
PAGE 13CONFIDENTIAL Effect of high-fat meal on pharmacokinetics *FDA Guidance for Industry: Food-Effect Bioavailability and Fed Bioequivalence Studies Increase in exposure with food* No food Effect* Decrease in exposure without food* PRAX-114 Cmax PRAX-114 AUC0-t 0.0 0.5 1.0 1.5 2.0 PRAX-114 Cmax PR
Slide 14: Phase 2a HAM-A and HAM-D results
PAGE 14CONFIDENTIAL Phase 2a combined* HAM-A anxiety and HAM-D insomnia item results Phase 2a combined* HAM-D monotherapy & adjunctive results Visit HAM-D Monotherapy Mean (SD) N=14 HAM-D Adjunctive Mean (SD) N=38 Day 1 (BL) 25.2 (1.82) 24.7 (2.90) Day 8 (CFB) -17.6 (4.77) -13.4 (7.94) Day 15 (CFB)
Slide 15: Estimated somnolence rate of approximately 10% for 40 mg tablet
PAGE 15CONFIDENTIAL Estimated somnolence rate of approximately 10% for 40 mg tablet (1.7x beta power) administered at nighttime Low rates of somnolence with PRAX-114 at targeted exposure level β-EEG Multiple 2.1 2.1 1.7 1.7 So m no le nc e AE % 60 mg Daytime/Nighttime Phase 2a Part A (N=13) 0 10 20
Slide 16: PRAX-114 clinical program leverages best practices in MDD trials
PAGE 16CONFIDENTIAL • Integration of a placebo control reminder script for patients at every visit • Inclusion of the AiCure smartphone-based adherence monitoring system with structured site intervention 3 PRAX-114 clinical program leverages best practices in conduct of MDD trials OPTIMIZED TRIAL DE
Slide 17: PRAX-114 monotherapy MDD Phase 2/3 Aria Study
PAGE 17CONFIDENTIAL PRAX-114 monotherapy MDD Phase 2/3 Aria Study topline data expected 2Q 2022* Ph 2/3 1:1 RANDOMIZED PLACEBO CONTROLLED IN MONOTHERAPY MDD 1 2 3 4 5 6 -114 40 mg+ PLACEBO WEEK KEY SECONDARY ENDPOINT HAM-D17 at Day 29 PRIMARY ENDPOINT HAM-D17 at Day 15 ~200 participants First of two
Slide 18: PRAX-114 MDD Phase 2 Acapella Study
PAGE 18CONFIDENTIAL PRAX-114 MDD Phase 2 Acapella Study topline data expected mid-year 2022 Ph 2 RANDOMIZED PLACEBO CONTROLLED DOSE-RANGING IN MDD 1 2 3 4 5 6 -114 60 mg PLACEBO WEEK KEY SECONDARY ENDPOINT HAM-D17 at Day 29 PRIMARY ENDPOINT HAM-D17 at Day 15 ~125 participants Dose-ranging study to e
Slide 19: PRAX-114 has broad potential in psychiatry disorders such as PTSD
PAGE 19CONFIDENTIAL PRAX-114 has broad potential in psychiatry disorders such as PTSD POST- TRAUMATIC STRESS DISORDER (PTSD) Dysfunction of GABA pathway is associated with chronic stress and symptoms of PTSD 1 2 Post-traumatic Stress Disorder is a debilitating psychiatric disorder that leads to soci
Slide 20: Dosing started in PRAX-114 PTSD Phase 2 study
PAGE 20CONFIDENTIAL Dosing has started in PRAX-114 PTSD Phase 2 study Ph 2 1:1 RANDOMIZED PLACEBO CONTROLLED IN PTSD 1 2 3 4 5 6 -114 40 mg + WEEK PRIMARY ENDPOINT CAPS-5 Total Score at Day 29 ~80 participants To evaluate safety, tolerability and efficacy of PRAX-114 for treatment of adults with PTS
Slide 21: Movement disorders: key upcoming milestones
PAGE 21CONFIDENTIAL MOVEMENT DISORDERS PRAX-944 T-Type Calcium Channel Inhibitor Essential Tremor Parkinson’s disease 2Q 2022 PRAX-944 Ph 2a ET Part B Randomized Withdrawal Topline 2Q 2022 Initiate PRAX-944 Ph 2 PD Trial KEY UPCOMING MILESTONES 2H 2022 PRAX-944 Ph 2b ET Essential1 Study ToplinePRAX-
Slide 22: Movement disorder franchise focus for 2022
PAGE 22CONFIDENTIAL Movement Disorder franchise focus for 2022 PRAX-944: for Essential Tremor Identify dose for registrational study Essential1 Study Topline Data: 2H2022 PRAX-944: for Parkinson’s disease Demonstrate motor improvement Initiate Ph2 Study 2Q2022 PRAX-114: for Essential Tremor Demonstr
Slide 23: Why essential tremor matters
PAGE 23CONFIDENTIAL Why Essential Tremor matters Most common movement disorder ~7x the prevalence of Parkinson’s disease1 Daytime action tremor that primarily affects the hands3,4 ~ 50% of patients have a family history2,3 Heterogeneous condition with progressive disability3 SOURCE: 1. GHOSH (2016)
Slide 24: ET burden of disease extends beyond the tremor
PAGE 24CONFIDENTIAL ET burden of disease extends beyond the tremor 1. LOUIS ED, ET AL. PARKINSONISM RELAT DISORD. 2015;21(7):729-735. 2. HOLDING SJ, ET AL. CHRONIC ILLN. 2015 MAR;11(1):69-71. 3.SHALASH AS, ET AL. TREMOR OTHER HYPERKINET MOV (N Y). 2019;9. 4. JANICKI SC,ET AL. THER ADV NEUROL DISORD.
Slide 25: Capturing the $4B+ US ET market
PAGE 25CONFIDENTIAL 3M Total Addressable Market Our focus is on elevating the standard of care to capture the $4B+ US ET market 7M US Prevalence 1.5M Total Treated Market1 $4B+ US ET Market Opportunity2 PRIMARY MARKET RESEARCH AND PRAXIS INTERNAL MODELING AND PROJECTIONS 1. CLAIMS ANALYSIS INDICATES
Slide 26: Praxis treatments could allow patients to fit the right therapy to their needs
PAGE 26CONFIDENTIAL Praxis treatments could allow patients to fit the right therapy to their needs to realize improved outcomes • Patients could initiate ET treatment sooner • Patients could treat as needed • Patients could maintain ET therapy As needed Chronic PRAX-114 PRAX-944 +
Slide 27: Tackling movement disorders through two mechanisms of action
PAGE 27CONFIDENTIAL Tackling Movement Disorders through two mechanisms of action GABAA RECEPTORS T-TYPE CALCIUM CHANNELS CEREBELLO-THALAMO-CORTICAL (CTC) CIRCUIT PRAX-944PRAX-114
Slide 28: T-type calcium channel mutations genetically linked to familial ET
PAGE 28CONFIDENTIAL Mutations in T-type calcium channels (TTCC) are genetically linked to familial ET TTCC drive burst firing in the CTC circuit Burst firing in the CTC circuit correlated with tremor in patients with ET and PD Deep Brain Stimulation reduces burst firing and tremor T-Type calcium cha
Slide 29: PRAX-944 designed for once daily dosing and well-tolerated safety profile
PAGE 29CONFIDENTIAL PRAX-944 is designed to enable once daily dosing and a well-tolerated safety profile Sustained exposure with blunted MR Cmax allows for potential of sustained efficacy and improved tolerability 0 5 10 15 20 25 30 35 40 45 50 0 6 12 18 24 PR AX -9 44 P la sm a Co nc en tr at io n
Slide 30: PRAX-944 showed robust PK:PD relationship to guide dosing
PAGE 30CONFIDENTIAL KEY TAKEAWAYS • Dose-dependent reduction in sigma-band power • Effect observed over >20x dose range • Provides confidence that PRAX-944 is reaching functionally relevant brain concentrations and targets PRAX-944 showed robust PK:PD relationship to guide dosing SOURCE: PRAXIS STUD
Slide 31: Enrollment completed in PRAX-944 Phase 2a ET study
PAGE 31CONFIDENTIAL Enrollment completed in PRAX-944 Phase 2a ET study DAYS 1-14 Safety Follow- up Screening/ Baseline PART A DAYS 15-21 Completed Open-Label Titration of PRAX-944 up to 40 mg CLINICALTRIALS.GOV/CT2/SHOW/NCT05021978 *Topline results expected in May 2022 DAYS 29-42 1:1 RANDOMIZATION O
Slide 32: Phase 2a ET Part A shows dose dependent reduction in tremor amplitude
PAGE 32CONFIDENTIAL Percent change in TETRAS score (N=6)Change from baseline in TETRAS score (N=6) PRAX-944 Phase 2a ET Part A data shows dose dependent reduction in tremor amplitude ON TREATMENT WASHOUT PERFORMANCE SCALE (PS) UPPER LIMB (UL) PERFORMANCE SCALE (PS) UPPER LIMB (UL) ON TREATMENT WASHO
Slide 33: Preliminary Part B data: TETRAS CUL and ADL
PAGE 33CONFIDENTIAL Preliminary Part B data: TETRAS Combined Upper Limb (CUL) and TETRAS Activities of Daily Living (ADL) Preliminary data as of 10-Dec-2021 cutoff; ongoing CLINICALTRIALS.GOV/CT2/SHOW/NCT05021978 * 8 of 12 patients enrolled and dosed completed per protocol ; Part B Patient 1 discont
Slide 34: Preliminary Part B data: modified ADL by baseline CUL score
PAGE 34CONFIDENTIAL Preliminary Part B data: modified ADL by baseline CUL score PRELIMINARY DATA AS OF 10-DEC-2021 CUTOFF; ONGOING CLINICALTRIALS.GOV/CT2/SHOW/NCT05021978; *PART B PATIENT 1 DISCONTINUED AFTER DAY 21 ASSESSMENT; **PART B PATIENT 2 DAY 42 – MODIFIED ADL INCLUDED MISSING DATA FOR ONE I
Slide 35: PRAX-944 ET Phase 2b Essential1 Study
PAGE 35CONFIDENTIAL Dose-ranging study to evaluate safety, tolerability and efficacy of PRAX-944 for treatment of adults with ET KEY INCLUSION CRITERIA Ages 18 or older Diagnosis of ET for at least 3 years TETRAS UL score ≥10 TOPLINE DATA EXPECTED 2H22Randomized, double-blind, placebo-controlled stu
Slide 36: PRAX-114: central role of extrasynaptic GABAA receptors in tremor
PAGE 36CONFIDENTIAL α4β3δ %* α1β2γ2 % α4β3δ/ α1β2γ2 300% 29% 10.5 PRAX-114: Evidence suggests central role of extrasynaptic GABAA receptors targeting tremor pathophysiology Α4Β3Δ: EXTRASYNAPTIC GABAA RECEPTOR; Α1Β2Γ2: SYNAPTIC GABAA RECEPTOR; * EQUIVALENT OF FULL GABA ACTIVATION SOURCE: PRAXIS DATA
Slide 37: PRAX-114 ET Phase 2 study of daytime dosing
PAGE 37CONFIDENTIAL PRAX-114 ET Phase 2 study designed to evaluate safety, tolerability, PK and efficacy of daytime dosing KEY QUESTION: Is there a dose that enables reduction in tremor without somnolence or sedation? TOPLINE DATA: 2H2022 Safety Follow Up PRAX-114 10, 20 mg or PLACEBO PERIOD 1 PERIO
Slide 38: PRAX-944 potential non-dopaminergic therapy for Parkinson's disease
PAGE 38CONFIDENTIAL PRAX-944 has potential to be a non-dopaminergic therapy for motor function for Parkinson’s disease patients Dopamine promotes movement Dopamine related motor and non- motor complications
Slide 39: Why Parkinson's disease matters
PAGE 39CONFIDENTIAL Why Parkinson’s disease matters? Affects ~1 million people in the US, with 85% of patients treated pharmacologically Progressive disability motor and non-motor symptoms Incidence is age related. Average age of onset is early 60s. High risk in men. 1. HTTPS://WWW.PARKINSON.ORG/UND
Slide 40: Blocking T-type calcium channels improves motor activity in Parkinson's model
PAGE 40CONFIDENTIAL Blocking T-type Calcium Channels improves motor activity in 6-OHDA model of Parkinson’s disease Burst firing in STN of 6-OHDA Parkinson’s model BURST FIRING IN STN OF 6-OHDA PARKINSON’S MODEL BLOCK OF BURST FIRING IMPROVES MOVEMENT IN 6-OHDA PARKINSON’S MODEL PAN ET AL (2016) J C
Slide 41: PRAX-944 Parkinson's disease study expected to initiate in 2Q22
PAGE 41CONFIDENTIAL PRAX-944 study to evaluate motor function in Parkinson’s disease patients expected to initiate in 2Q22 CLINICAL MEASUREMENTS: Motor function KEY QUESTION: Does PRAX-944 demonstrate motor improvement in patients? Safety Follow Up PRAX-944 Titration 5 mg to 100 mg DAY 1-49 DAY 50-7
Slide 42: Epilepsy: key upcoming milestones
PAGE 42CONFIDENTIAL EPILEPSY PRAX-562 PRAX-222 ASO 2Q 2022 PRAX-562 Ph 1 ASSR Biomarker Topline 2Q 2022 Initiate PRAX-562 Ph 2 DEE Trial 2Q 2022 Initiate PRAX-222 Seamless SCN2A-DEE Trial KEY UPCOMING MILESTONES PRAX-020 PRAX-628 SCN2A-LOF ASO SYNGAP1 ASO PCDH19 ASO
Slide 43: PRAX-562: block of persistent sodium current reduces neuronal hyperexcitability
PAGE 43CONFIDENTIAL PRAX-562: Block of persistent sodium current can reduce neuronal hyperexcitability and impact multiple disease states Standard sodium channel blockers target peak sodium current and disrupt AP, leading to side effects Modulation of persistent sodium current reduces hyperexcitabil
Slide 44: PRAX-562 has broad potential in rare CNS conditions such as DEEs
PAGE 44CONFIDENTIAL PRAX-562 has broad potential in rare CNS conditions such as DEEs Source: Eltze et al. 2013 ; Howell et al 2018 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY (DEE) DEE is a group of monogenic disorders with severe seizure, developmental delay & high mortality rate 1 2 A pathologic fe
Slide 45: PRAX-562 protects mice from seizure with a wide therapeutic window
PAGE 45CONFIDENTIAL PRAX-562 mediated persistent current block protects mice from seizure with a wide therapeutic window in-vivo PRAX-562 shows robust anti-seizure activity without impairment of locomotor activity TD50: 44 mg/kg CD-1 mice; (n=12/group) ED50: 2 mg/kg Veh 1 0.3 1 3 10 0 20 40 60 M ES
Slide 46: PRAX-562 reduces seizures in genetic pediatric epilepsy animal models
PAGE 46CONFIDENTIAL Treatment with PRAX-562 has shown significant reduction of seizures in genetic pediatric epilepsy animal models PRAX-562 elicited dose-dependent prevention of seizures in SCN2A* mouse model PRAX-562 elicited dose-dependent prevention of seizures in SCN8A* mouse model *FDA granted
Slide 47: PRAX-222 expected to initiate seamless trial for SCN2A-DEE in 2Q22
PAGE 47CONFIDENTIAL PRAX-222 is expected to initiate seamless trial for SCN2A-DEE in 2Q22 PRAX-222: ASO to treat SCN2A GoF Epilepsy • Severe early onset epilepsy estimated to affect thousands of patients worldwide • Antisense oligonucleotide (ASO) to down-regulate SCN2A expression Increased Survival
Slide 48: Upcoming catalysts throughout portfolio in 2022
PAGE 48CONFIDENTIAL PROGRAM Q4 2022Q1 2022 Q3 2022 Q2 2022 INDICATION Upcoming catalysts throughout portfolio in 2022 PRAX-562 PRAX-114 PRAX-944 Initiate Phase 2 Trial DEEs MDD PTSD ET PD Phase 2b Essential1 Study Topline Initiate Phase 2 Trial ET Phase 2 ToplinePRAX-114 PRAX-944 PSYCHIATRY MOVEMENT
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