Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Presentation (January 2022)
53 slides from Praxis Precision Medicines's investor presentation, Jan 10, 2022
Slide 1: Corporate Overview January 2022
PAGE 1 CONFIDENTIAL CORPORATE OVERVIEW JANUARY 2 0 2 2 PAGE 1
Slide 2: Forward-looking statements
PAGE 2 CONFIDENTIAL 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 stateme
Slide 3: A patient-guided CNS company developing new classes of treatments inspired by human genetics
PAGE 3 CONFIDENTIAL PAGE 3 A P A T I E N T - GUIDED CNS COMPANY DEVELOPING NEW CLASSES OF TREATMENTS INSPIRED BY HUMAN GENETICS
Slide 4: Targeting common & rare diseases connected by neuronal imbalance
PAGE 4 CONFIDENTIAL 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 UNC7
Slide 5: Praxis is built on four key pillars
PAGE 5 CONFIDENTIAL 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 PAGE 5
Slide 6: Broad portfolio of highly differentiated programs across multiple CNS disorders
PAGE 6 CONFIDENTIAL Broad portfolio of highly differentiated programs across multiple CNS disorders REGISTRATIONAL ENABLING DISCOVERY PRECLINICAL PHASE 1 PHASE 2 Figures represent est. worldwide prevalence PAGE 6 PROGRAM MECHANISM OF ACTION PRAX-944 PRAX-114 PSYCHIATRY Nav1.2 downregulation SCN2A PR
Slide 7: Three distinct franchises primed for growth in 2022
PAGE 7 CONFIDENTIAL >$1B Potential Revenue >$1B Potential Revenue >$1B Potential Revenue PRAX-114 MDD Ph 2a PRAX-114 PTSD Ph 2 PRAX-114 MDD Ph 2/3 PRAX-944 ET Ph 2a PRAX-944 ET Essential1 Ph 2b PRAX-562 Ph 1 PRAX-562 Ph 2 SUNCT/ SUNA/TN PRAX-222 Preclinical KCNT1 Discovery SCN2A LOF PCDH19 SYNGAP1 2
Slide 8: Upcoming catalysts throughout portfolio in 2022
PAGE 8 CONFIDENTIAL PROGRAM Q4 2022 Q1 2022 Q3 2022 Q2 2022 INDICATION Upcoming catalysts throughout portfolio in 2022 PRAX-562 PRAX-114 PRAX-944 Initiate Phase 2 Trial SUNCT/SUNA/TN DEEs MDD PTSD ET PD Phase 2 Topline Phase 2 Acapella Study Topline Phase 2/3 Aria Study Topline Phase 2b Essential1 S
Slide 9: Dare for More
PAGE 9 CONFIDENTIAL PAGE 9 DARE for MORE
Slide 10: Psychiatry: PRAX-114 key upcoming milestones
PAGE 10 CONFIDENTIAL PSYCHIATRY PAGE 10 PRAX-114 GABAA Receptor PAM Depression Post-traumatic Stress Disorder 1H 2022 Ph 2/3 Monotherapy MDD Aria Study Topline 1H 2022 Ph 2 MDD Dose-Ranging Acapella Study Topline 2H 2022 Ph 2 PTSD Topline KEY UPCOMING MILESTONES
Slide 11: Major depressive disorder is a growing and debilitating disorder with substantial unmet need
PAGE 11 CONFIDENTIAL 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 Amer
Slide 12: Preference for extrasynaptic GABAA receptors
PAGE 12 CONFIDENTIAL 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 13: Extrasynaptic GABAA preference allows high GABAergic activation with improved tolerability
PAGE 13 CONFIDENTIAL 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
Slide 14: Effect of high-fat meal on pharmacokinetics
PAGE 14 CONFIDENTIAL 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 P
Slide 15: PRAX-114 Phase 2a: rapid and marked improvement in depression scores
PAGE 15 CONFIDENTIAL 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 16: Estimated somnolence rate of approximately 10% for 40 mg tablet at nighttime
PAGE 16 CONFIDENTIAL 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 Somnolence AE % 60 mg Daytime/Nighttime Phase 2a Part A (N=13) 0 10 20 30 4
Slide 17: PRAX-114 clinical program leverages best practices in conduct of MDD trials
PAGE 17 CONFIDENTIAL • 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 D
Slide 18: PRAX-114 monotherapy MDD Phase 2/3 Aria Study
PAGE 18 CONFIDENTIAL PRAX-114 monotherapy MDD Phase 2/3 Aria Study topline data expected 1H 2022 Ph 2/3 1:1 RANDOMIZED PLACEBO CONTROLLED IN MONOTHERAPY MDD 1 2 3 4 5 6 -114 40 mg tablet PLACEBO WEEK KEY SECONDARY ENDPOINT HAM-D17 at Day 29 PRIMARY ENDPOINT HAM-D17 at Day 15 ~200 participants First
Slide 19: PRAX-114 MDD Phase 2 Acapella Study
PAGE 19 CONFIDENTIAL PRAX-114 MDD Phase 2 Acapella Study topline data expected 1H 2022 Ph 2 RANDOMIZED PLACEBO CONTROLLED PRIMARILY IN ADJUNCTIVE MDD 1 2 3 4 5 6 -114 60 mg tablet PLACEBO WEEK KEY SECONDARY ENDPOINT HAM-D17 at Day 29 PRIMARY ENDPOINT HAM-D17 at Day 15 ~125 participants Dose-ranging
Slide 20: PRAX-114 has broad potential in psychiatry disorders: PTSD
PAGE 20 CONFIDENTIAL PRAX-114 has broad potential in psychiatry disorders 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 social, occupati
Slide 21: Enrollment has started for PRAX-114 PTSD Phase 2 study
PAGE 21 CONFIDENTIAL Enrollment has started for PRAX-114 PTSD Phase 2 study Ph 2 1:1 RANDOMIZED PLACEBO CONTROLLED IN PTSD 1 2 3 4 5 6 -114 40 mg tablet WEEK PRIMARY ENDPOINT CAPS-5 Total Score at Day 29 ~80 participants To evaluate safety, tolerability and efficacy of PRAX-114 for treatment of adul
Slide 22: Movement Disorders: PRAX-944 and PRAX-114 key upcoming milestones
PAGE 22 CONFIDENTIAL PAGE 22 MOVEMENT DISORDERS PRAX-944 T-Type Calcium Channel Inhibitor Essential Tremor Parkinson’s disease 1H 2022 PRAX-944 Ph 2a ET Part B Randomized Withdrawal Topline 1H 2022 Initiate PRAX-944 Ph 2 PD Trial KEY UPCOMING MILESTONES 2H 2022 PRAX-944 Ph 2b ET Essential1 Study Top
Slide 23: Movement Disorder franchise focus for 2022
PAGE 23 CONFIDENTIAL 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 1H2022 PRAX-114: for Essential Tremor Demonst
Slide 24: Why Essential Tremor matters
PAGE 24 CONFIDENTIAL 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 25: ET burden of disease extends beyond the tremor
PAGE 25 CONFIDENTIAL 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 26: Capturing the $4B+ US ET market
PAGE 26 CONFIDENTIAL 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 INDICATE
Slide 27: Praxis treatments could allow patients to fit the right therapy to their needs
PAGE 27 CONFIDENTIAL 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 28: Tackling movement disorders through two mechanisms of action
PAGE 28 CONFIDENTIAL Tackling Movement Disorders through two mechanisms of action GABAA RECEPTORS T-TYPE CALCIUM CHANNELS CEREBELLO-THALAMO-CORTICAL (CTC) CIRCUIT PRAX-944 PRAX-114
Slide 29: T-type calcium channels linked to familial ET and CTC circuit burst firing
PAGE 29 CONFIDENTIAL 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 ch
Slide 30: PRAX-944 designed for once daily dosing and well-tolerated safety profile
PAGE 30 CONFIDENTIAL 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 PRAX - 944 Plasma Concentration (ng/mL) T
Slide 31: PRAX-944 showed robust PK:PD relationship to guide dosing
PAGE 31 CONFIDENTIAL 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 STU
Slide 32: PRAX-944 Phase 2a ET study design
PAGE 32 CONFIDENTIAL PRAX-944 Phase 2a ET study design 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 DAYS 29-42 1:1 RANDOMIZATION Open-Label Titration of PRAX-944 up to 120 mg Stable Pe
Slide 33: PRAX-944 Phase 2a ET Part A data shows dose dependent reduction in tremor amplitude
PAGE 33 CONFIDENTIAL 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 WAS
Slide 34: Preliminary Part B data: TETRAS CUL and ADL
PAGE 34 CONFIDENTIAL 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 discon
Slide 35: Key PRAX-944 development questions in ET
PAGE 35 CONFIDENTIAL Key PRAX-944 development questions in ET PRAX-944-221 Phase 2a Part B PRAX-944-222 Phase 2b Essential1 Study PRAX-944 Phase 3 Tolerability of PRAX-944 in ET and sufficient evidence of effect Dose ranging safety, tolerability, and efficacy to support dose selection for Phase 3 De
Slide 36: PRAX-944 ET Phase 2b Essential1 Study
PAGE 36 CONFIDENTIAL 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 2H22 Randomized, double-blind, placebo-controlled s
Slide 37: Movement Disorder franchise focus for 2022
PAGE 37 CONFIDENTIAL 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 1H2022 PRAX-114: for Essential Tremor Demonst
Slide 38: PRAX-114: central role of extrasynaptic GABAA receptors in tremor
PAGE 38 CONFIDENTIAL 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 39: PRAX-114 ET Phase 2 study designed to evaluate daytime dosing
PAGE 39 CONFIDENTIAL 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 PERI
Slide 40: Movement Disorder franchise focus for 2022
PAGE 40 CONFIDENTIAL 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 1H2022 PRAX-114: for Essential Tremor Demonst
Slide 41: Why Parkinson's disease matters
PAGE 41 CONFIDENTIAL 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/UN
Slide 42: PRAX-944 potential non-dopaminergic therapy for Parkinson's motor function
PAGE 42 CONFIDENTIAL 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 43: Blocking T-type calcium channels improves motor activity in Parkinson's model
PAGE 43 CONFIDENTIAL 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
Slide 44: PRAX-944 Parkinson's disease study design
PAGE 44 CONFIDENTIAL PRAX-944 study to evaluate motor function in Parkinson’s disease patients expected to initiate in 1H22 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-
Slide 45: Rare Diseases: PRAX-562 and PRAX-222 key upcoming milestones
PAGE 45 CONFIDENTIAL PAGE 45 RARE DISEASES PRAX-562 Persistent Sodium Channel Blocker Adult Cephalgias Pediatric Epilepsies (DEEs) PRAX-222 (ASO) Nav1.2 downregulation SCN2A-DEE 1H 2022 PRAX-562 Ph 1 ASSR Biomarker Topline 1H 2022 Initiate PRAX-562 Ph 2 DEE Trial 1H 2022 Initiate PRAX-222 Ph 1/2/3 S
Slide 46: PRAX-562: block of persistent sodium current reduces neuronal hyperexcitability
PAGE 46 CONFIDENTIAL 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 hyperexcitabi
Slide 47: PRAX-562 potential in SUNCT, SUNA and trigeminal neuralgia
PAGE 47 CONFIDENTIAL PRAX-562 has broad potential in rare CNS conditions Source: Eltze et al. 2013 ; Howell et al 2018 SUNCT, SUNA AND TRIGEMINAL NEURALGIA (TN) SUNCT, SUNA & TN are devastating headache disorders with limited treatment options 1 2 SUNCT and SUNA Cephalgias are devastating primary he
Slide 48: PRAX-562 potential in developmental and epileptic encephalopathy
PAGE 48 CONFIDENTIAL PRAX-562 has broad potential in rare CNS conditions 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 feature of man
Slide 49: PRAX-562 protects mice from seizure with a wide therapeutic window
PAGE 49 CONFIDENTIAL 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 E
Slide 50: PRAX-562 reduces seizures in genetic pediatric epilepsy animal models
PAGE 50 CONFIDENTIAL 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 grante
Slide 51: PRAX-562 development strategy in rare cephalgias and pediatric epilepsies
PAGE 51 CONFIDENTIAL PRAX-562 development strategy in rare cephalgias and pediatric epilepsies OBJECTIVE Identify PoC and safety in SUNCT/SUNA & Trigeminal Neuralgia while continuing efforts to expand to rare pediatric epilepsies PHASE 1 HEALTHY VOLUNTEERS SAD/MAD, ASSR Biomarker, Food Effect PHASE
Slide 52: PRAX-222 expected to initiate registrational first-in-patient trial in 1H22
PAGE 52 CONFIDENTIAL PRAX-222 is expected to initiate seamless, registrational first-in-patient trial in 1H22 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 expressio
Slide 53: Upcoming catalysts throughout portfolio in 2022
PAGE 53 CONFIDENTIAL PROGRAM Q4 2022 Q1 2022 Q3 2022 Q2 2022 INDICATION Upcoming catalysts throughout portfolio in 2022 PRAX-562 PRAX-114 PRAX-944 Initiate Phase 2 Trial SUNCT/SUNA/TN DEEs MDD PTSD ET PD Phase 2 Topline Phase 2 Acapella Study Topline Phase 2/3 Aria Study Topline Phase 2b Essential1
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