Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Presentation (May 2021)
31 slides from Praxis Precision Medicines's investor presentation, May 11, 2021
Slide 1: Corporate Overview May 2021
PAGE 1CONFIDENTIAL C O R P O R A T E OVERVIEW M a y 2 0 2 1
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 inspired by human genetics
PAGE 3CONFIDENTIAL A P A T I E N T - G U I D E D C N S C O M P A N Y DEVELOPING NEW CLASSES OF TREATMENTS INSPIRED BY HUMAN GENETICS
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: Broad portfolio of highly differentiated programs across multiple CNS disorders
PAGE 5CONFIDENTIAL Broad portfolio of highly differentiated programs across multiple CNS disorders REGISTRATIONAL ENABLINGDISCOVERY PRECLINICAL PHASE 1 PHASE 2 Figures represent est. worldwide prevalence PROGRAMMECHANISM OF ACTION PRAX-944 PRAX-114 PSYCHIATRY Nav1.2 downregulation SCN2A PRAX-562 PRA
Slide 6: Leveraging genetics to efficiently translate insights into therapies
PAGE 6CONFIDENTIAL Leveraging genetics to efficiently translate insights into therapies 0401 02 03 Targets identified through genetics Efficient, rigorous clinical development paths to PoC Patient-guided development strategies Translational tools to inform development 01 02 03 04
Slide 7: Substantial potential for value creation across the portfolio
PAGE 7CONFIDENTIAL 1H 2022 MID 2021 2H 2021 2H 2022 PRAX-114 Phase 2a PMD Topline PRAX-114 Phase 2/3 Monotherapy MDD Aria Study Topline PRAX-114 Phase 2 Adjunctive MDD Topline PRAX-944 Phase 2a ET Topline PRAX-944 Initiate Phase 2 Randomized Controlled ET Trial PRAX-562 Initiate Phase 2 Adult Cephal
Slide 8: PRAX-114 GABAA receptor PAM upcoming milestones
PAGE 8CONFIDENTIAL GABAA Receptor PAM PRAX-114 PSYCHIATRY & MOVEMENT DISORDERS UPCOMING MILESTONES Depression Post-traumatic Stress Disorder Essential Tremor MID 2021 Initiate Ph 2 Adjunctive MDD Trial 2H 2021 Ph 2a PMD Topline 2H 2021 Initiate Ph 2 PTSD Trial 2H 2021 Initiate Ph 2 ET Trial 1H 2022
Slide 9: ~19 million Americans affected by MDD
PAGE 9CONFIDENTIAL ~19 million Americans and an estimated 300 million people worldwide affected by MDD 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-5 201
Slide 10: Preference for extrasynaptic GABAA receptors may give antidepressant effect with improved tolerability
PAGE 10CONFIDENTIAL 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 11: Extrasynaptic GABAA preference allows high GABAergic activation with improved tolerability
PAGE 11CONFIDENTIAL 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 12: Effect of high-fat meal on pharmacokinetics
PAGE 12CONFIDENTIAL Effect of high-fat meal on pharmacokinetics *Definition of food effect from FDA guidance - Assessing the Effects of Food on Drugs in INDs and NDAs Significant increase with food* No food Effect* Significant decrease with food* PRAX-114 Cmax PRAX-114 AUC0-t 0.0 0.5 1.0 1.5 2.0 PRA
Slide 13: Phase 2a MDD HAM-A and HAM-D results
PAGE 13CONFIDENTIAL Phase 2a MDD combined* HAM-A anxiety and HAM-D insomnia item results Phase 2a MDD combined* HAM-D monotherapy & adjunctive results Visit HAM-D Monotherapy Mean (SD) N=11 HAM-D Adjunctive Mean (SD) N=35 Day 1 (BL) 25.2 (1.94) 24.7 (2.94) Day 8 (CFB) -17.5 (4.95) -13.5 (7.99) Day 1
Slide 14: Estimated somnolence rate of approximately 10% for 40 mg tablet
PAGE 14CONFIDENTIAL 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 S o m n o le n c e A E % 60 mg Daytime/Nighttime 0 10 20 30 40 50 60 60 mg N
Slide 15: PRAX-114 monotherapy MDD Aria Study topline data expected 1H 2022
PAGE 15CONFIDENTIAL PRAX-114 monotherapy MDD 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 28 PRIMARY ENDPOINT HAM-D17 at Day 15 ~200 Subjects First of two registra
Slide 16: PRAX-114 has broad potential in psychiatry and movement disorders
PAGE 16CONFIDENTIAL PRAX-114 has broad potential in psychiatry and movement disorders Post-traumatic Stress Disorder is a debilitating psychiatric disorder that leads to social, occupational and interpersonal dysfunction Profound unmet need, meaningful link to PRAX-114 MOA, and complementarity to MD
Slide 17: PRAX-944 T-type calcium channel inhibitor upcoming milestones
PAGE 17CONFIDENTIAL T-Type calcium channel inhibitor PRAX-944 MOVEMENT DISORDERS UPCOMING MILESTONES Mid 2021 Ph2a ET Topline Essential Tremor Parkinson’s Disease 2H 2021 Initiate Ph2 Randomized Controlled ET Trial 1H 2022 Initiate Ph2 PD Trial 2H 202 Ph2 Randomized Controlled ET Topline
Slide 18: ET is the most common movement disorder
PAGE 18CONFIDENTIAL ET is the most common movement disorder PRAX-944 is a selective T-type calcium channel inhibitor for the treatment of Essential Tremor Up to 7 million patients in the U.S. 1-2% of the world population lives with essential tremor 80% estimated discontinuation rate for available th
Slide 19: Evidence supporting key role of T-type calcium channels in ET
PAGE 19CONFIDENTIAL Large body of clinical, preclinical and human genetic evidence supporting key role of T-type calcium channels in ET T-Type calcium channels are gatekeepers of neuronal firing patterns T-type calcium channels drive burst firing in the cerebello-thalamo-cortical (CTC) circuit Mutat
Slide 20: PRAX-944 designed for once daily dosing and well-tolerated safety profile
PAGE 20CONFIDENTIAL 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 20 40 60 80 100 120 0 6 12 18 24 P la s m a C o n c e n tr a ti o n ( n g /m L ) Tim
Slide 21: PRAX-944 shows significant pharmacodynamic effect on sigma band EEG power
PAGE 21CONFIDENTIAL PRAX-944 shows significant pharmacodynamic effect on sigma band EEG power during NREM sleep* PK-PD analysis suggests that doses of PRAX-944 of up to ~120 mg/day may drive additional pharmacodynamic effect • NREM sigma EEG biomarker is relevant to T-type calcium channel inhibitor
Slide 22: Phase 2a ET Part A shows dose dependent reduction in tremor amplitude
PAGE 22CONFIDENTIAL Percent change in tremor amplitude (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 W
Slide 23: Archimedes spiral data indicates functional improvement
PAGE 23CONFIDENTIAL PRAX-944 phase 2a ET Part A Archimedes spiral data indicates functional improvement PRAX-944 Archimedes spiral*Change from baseline in TETRAS score (N=6) TETRAS ARCH. SPIRALS (AS) Site Rating BASELINE Day 1 DAY 7 20 mg SS DAY 14 40 mg SS DAY 21 Washout Day 7 20 mg Day 14 40 mg Da
Slide 24: PRAX-944 phase 2a ET Part B clinical trial design
PAGE 24CONFIDENTIAL PART B: Open-label titration & randomized withdrawal study — Up to 12 patients, up to 120 mg PRAX-944 phase 2a ET Part B clinical trial design PRAX-944 PLACEBO Safety Follow-up Randomized Withdrawal (Days 43-56) Days 29-42Days 1-28 1:1 Randomization Open-Label Titration of PRAX-9
Slide 25: PRAX-562 persistent sodium channel blocker upcoming milestones
PAGE 25CONFIDENTIAL Persistent Sodium Channel Blocker PRAX-562 RARE DISEASES UPCOMING MILESTONES Mid 2021 Ph 1 Safety, Tolerability & PK 2H 2021 Initiate Ph 2 Adult Cephalgia Trial Adult Cephalgias Pediatric Epilepsies (DEEs) 1H 2022 Initiate Ph 2 DEE Trial
Slide 26: Block of persistent sodium current can reduce neuronal hyperexcitability
PAGE 26CONFIDENTIAL 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 hyperexcitability withou
Slide 27: PRAX-562 has broad potential in rare CNS conditions
PAGE 27CONFIDENTIAL PRAX-562 has broad potential in rare CNS conditions SUNCT and SUNA Cephalgias are devastating primary headaches highly responsive to IV sodium channel blockers Source: Eltze et al. 2013 ; Howell et al 2018 SUNCT, SUNA & TN are devastating headache disorders with limited treatment
Slide 28: PRAX-562 protects mice from seizure with a wide therapeutic window
PAGE 28CONFIDENTIAL 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 S
Slide 29: PRAX-562 reduces seizures in genetic pediatric epilepsy animal models
PAGE 29CONFIDENTIAL 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 30: PRAX-562 development strategy in headache and pediatric epilepsies
PAGE 30CONFIDENTIAL PRAX-562 development strategy in headache and pediatric epilepsies OBJECTIVE Identify PoC and safety in SUNCT/SUNA & Trigeminal Neuralgia headaches while continuing efforts to expand to rare pediatric epilepsies PHASE 1 HEALTHY VOLUNTEERS SAD/MAD, ASSR Biomarker, Food Effect SUNC
Slide 31: Substantial potential for value creation across the portfolio
PAGE 31CONFIDENTIAL 1H 2022 MID 2021 2H 2021 2H 2022 PRAX-114 Phase 2a PMD Topline PRAX-114 Phase 2/3 Monotherapy MDD Aria Study Topline PRAX-114 Phase 2 Adjunctive MDD Topline PRAX-944 Phase 2a ET Topline PRAX-944 Initiate Phase 2 Randomized Controlled ET Trial PRAX-562 Initiate Phase 2 Adult Cepha
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