Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Presentation (May 2022)
35 slides from Praxis Precision Medicines's investor presentation, May 9, 2022
Slide 1: Corporate Overview May 2022
© CORPORATE OVERVIEW May 2022
Slide 2: Forward-looking statements
2 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 current beliefs, expectatio
Slide 3: Developing New Classes of Treatments Inspired by the Genetics of Epilepsy
3 Developing New Classes of Treatments INSPIRED BY THE GENETICS OF EPILEPSY PSYCHIATRY GABRB3 KCNT1 SCN1A CACNA1A KCN1A SLC1A3 SETX RFC1 CACNA1G GABRB3 KCN1A SCN8A SCN2A DRD3 HTT FMR1 OPA1 SYNGAP1 SHANK3 TPH2 FKBP2 HTR2A CDKL5 DNM1 UNC79 TRIM3 PCDH19 CACNA1A EPILEPSY MOVEMENT
Slide 4: Targeting diseases connected by neuronal imbalance across three franchises
4 MOVEMENT DISORDERS EPILEPSY PSYCHIATRY PRECLINICAL IND / PHASE ONE PHASE TWO REGISTRATION ENABLING PRAX-562 DEEs PRAX-020 KCNT1 PRAX-628 Focal Epilepsy PRAX-080 (ASO) PCDH19 PRAX-090 (ASO) SYNGAP1 PRAX-100 (ASO) SCN2A LoF PRAX-030 Undisclosed PRAX-050 Undisclosed PRAX-114 Essential Tremor PRAX-944
Slide 5: Praxis is built on four key pillars
5 Praxis is built on four key pillars DEVELOPMENT INFORMED BY TRANSLATIONAL TOOLS TARGETS IDENTIFIED THROUGH GENETICS CLINICAL DEVELOPMENT PATHS TO POC ARE RIGOROUS & EFFICIENT DEVELOPMENT STRATEGIES ARE PATIENT-GUIDED
Slide 6: Cash runway, deep early-stage pipeline, data rich 2022
6 CASH RUNWAY to advance each program through value inflecting milestones DEEP EARLY- STAGE PIPELINE Enables continuous advancement of new programs MULTI-BILLION DOLLAR REVENUE POTENTIAL from each of three therapeutic franchises DATA RICH 2022 Topline results from six Phase 2 or registrational studi
Slide 7: Six phase 2 or registrational topline readouts in 2022
7 Six phase 2 or registrational topline readouts in 2022 PRAX-114 Phase 2/3 Aria Study topline results expected in June 2022; PRAX-944 Phase 2a Part B topline results disclosed in May 2022 FOCUS AREA PROGRAM INDICATION Q2 2022 Q3 2022 Q4 2022 EPILEPSY MOVEMENT DISORDERS PSYCHIATRY MDD PTSD PRAX-114
Slide 8: Psychiatry: PRAX-114 key upcoming milestones
8 PSYCHIATRY PRAX-114 GABAA Receptor PAM Depression Post-traumatic Stress Disorder JUNE 2022 Ph 2/3 Monotherapy MDD Aria Study Topline 3Q 2022 Ph 2 MDD Dose-Ranging Acapella Study Topline 2H 2022 Ph 2 PTSD Topline KEY UPCOMING MILESTONES
Slide 9: PRAX-114 is a novel GABAA-PAM suited to unmet needs in MDD
9 PRAX-114 is a novel GABAA-PAM ideally suited to address the unmet needs of patients living with major depressive disorder Source: Rush et al 2006, Masand et al 2003, Kupfer et 2005, DSM-5 2013, ExpressScripts MDD Report 2020 UNMET NEEDS Low response rate >50% of treated patients fail first line tr
Slide 10: PRAX-114 shows 10.5-fold greater potentiation of extrasynaptic GABAA receptors
10 POTENTIATION FOLD POTENTIATION PRAX-114 SHOWS 10.5-FOLD GREATER POTENTIATION OF EXTRASYNAPTIC THAN SYNAPTIC GABAA RECEPTORS Preference for extrasynaptic GABAA receptors has the potential of marked antidepressant effect with an improved tolerability profile Source: Praxis Data on file α4β3δ: extra
Slide 11: Phase 2a combined HAM-D monotherapy and adjunctive results
11 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) -16.6 (5.23) -12.2 (7.02) PRAX-114 Phase 2a: rapid, marked & durable improvement i
Slide 12: PRAX-114 monotherapy MDD Phase 2/3 Aria Study design
12 PRAX-114 monotherapy MDD Phase 2/3 Aria Study completed; topline data expected June 2022 +PRAX-114 administered in tablet formulation clinicaltrials.gov/ct2/show/NCT04832425; https://theariastudy.com/ Ph 2/3 1:1 RANDOMIZED PLACEBO CONTROLLED IN MONOTHERAPY MDD 216 participants 1 2 3 4 5 6 PRAX-11
Slide 13: PRAX-114 program leverages best practices in conduct of MDD trials
13 • 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 1: Sonawalla SB, Rosenbaum JF. Plac
Slide 14: HAM-D placebo change trends in MDD trials
14 HAM-D+ placebo change trends toward 6-8 points reduction at 2 weeks in MDD trials +Based on HAM-D or conversion of MADRS to HAM-D (Leucht et al. 2017, Table 2) *Bubble size correlates to N population size -13-12-11-10-9-8-7-6-5-4-3-2-10 Sage-217: Phase 3 Mountain - 2019 Sage-217: Phase 3 Waterfal
Slide 15: GABA pathway dysfunction and PTSD symptoms
15 DYSFUNCTION OF GABA PATHWAY IS ASSOCIATED WITH CHRONIC STRESS AND SYMPTOMS OF PTSD PRAX-114 has broad potential in psychiatry disorders such as PTSD POST- TRAUMATIC STRESS DISORDER (PTSD) Post-traumatic Stress Disorder is a debilitating psychiatric disorder that leads to social, occupational and
Slide 16: PRAX-114 PTSD Phase 2/3 study design
16 PRAX-114 40 MG + 40 OR 60 MG PRAX-114 PTSD Phase 2 topline data expected 2H22 +PRAX-114 administered in tablet formulation clinicaltrials.gov/ct2/show/NCT04969510 Ph 2/3 1:1 RANDOMIZED PLACEBO CONTROLLED IN PTSD ~80 participants 1 2 3 4 5 6WEEK OUTPATIENT NIGHTLY DOSING FOLLOW-UP+ PLACEBO PRIMARY
Slide 17: Movement disorders: key upcoming milestones
17 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 PRAX-114 GABAA Receptor PAM Essential Tremor 2H 2022 PRAX-114 Ph 2 ET Topline KEY UPCOMING MILESTONES PRAX-944 Phase 2a Part B topline r
Slide 18: Daring for more for people living with essential tremor
18 Daring for more for people living with essential tremor 0 medications developed specifically for ET & only 1 medication approved for ET >50 years ago ~50% of patients that seek treatment discontinue medication due to limited efficacy & poor tolerability
Slide 19: Capturing the $4B+ US essential tremor market
19 3M Total Addressable Market Our focus is on elevating the standard of care to capture the $4B+ US ET market Source: Primary market research and praxis internal modeling and projections 1. Claims analysis indicates that 50% of diagnosed patients are on treatment; 2. Based on minimum of range for n
Slide 20: Praxis treatments could allow patients to fit the right therapy to their needs
20 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+ CEREBELLO-THALAMO-CORTICAL (CTC) CIRCUIT GABAA RECEPTO
Slide 21: Wide dosing range and modified release formulation for PRAX-944
21 Wide dosing range and modified release formulation for PRAX-944 may support improved tolerability & efficacy profile Source: Praxis Data on file 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 (n g/ m L) Time (h) SUSTAINED EXPOSURE WITH BLUNTED MR CMAXPREDICT
Slide 22: Modified ADLs in randomized withdrawal
22 MODIFIED ADLs IN RANDOMIZED WITHDRAWAL MEAN % CHANGE FROM DAY 42 Marked functional benefit observed while on PRAX-944 in Part B of Phase 2a study while withdrawal results in regression to baseline severity MODIFIED ADLs IN OPEN LABEL MEAN % CHANGE FROM BASELINE *Nominal p-value based on ANCOVA So
Slide 23: Safety summary: PRAX-944 Part B Phase 2a
23 SAFETY SUMMARY PRAX-944 was generally well tolerated in Part B of Phase 2a study 1 Participant had a pre-existing condition which was unrelated to study drug and required a medical procedure 2 One severe AE of essential tremor reported while on placebo following withdrawal of PRAX-944; all other
Slide 24: PRAX-114 and extrasynaptic GABAA receptors in tremor
24 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 on file Without E
Slide 25: PRAX-114 ET Phase 2 study design
25 PRAX-114 ET Phase 2 study designed to evaluate safety, tolerability, PK and efficacy of daytime dosing Safety Follow Up PRAX-114 10, 20 mg or PLACEBO PERIOD 1 PERIOD 2 PERIOD 3 Washout PRAX-114 10, 20 mg or PLACEBO PRAX-114 10, 20 mg or PLACEBO 1:1:1 Randomization Washout STUDY DESIGN: RANDOMIZED
Slide 26: Epilepsy: key upcoming milestones
26 2Q 2022 PRAX-562 Ph 1 ASSR Biomarker Topline 2H 2022 Initiate PRAX-562 Ph 2 DEE Trial 2H 2022 Initiate PRAX-222 Seamless SCN2A-DEE Trial KEY UPCOMING MILESTONESEPILEPSY PRAX-562 (DEEs) PRAX-222 (SCN2A-GOF ASO) PRAX-020 (KCNT1) PRAX-628 (Focal Epilepsy) PRAX-100 (SCN2A-LOF ASO) PRAX-090 (SYNGAP1 A
Slide 27: Three key imperatives guide our epilepsy portfolio build
27 Three key imperatives guide our epilepsy portfolio build TARGET ID BY POLYGENIC RISK VARIANTS SMALL MOLECULE TARGETS IDENTIFIED THROUGH GENETICS PRAX-562 SMALL MOLECULE PCDH19* ASO SCN2A-LOF * ASO KCNT1 INHIB. SMALL MOLECULE PRAX-628 SMALL MOLECULE SYNGAP1* ASO PRAXIS-030 SMALL MOLECULE PRAX-222*
Slide 28: First and best-in-class precision medicines for 25,000+ rare epilepsy patients
28 Delivering first and best-in-class precision medicines for 25,000+ rare epilepsy patients LGS: Lennox-Gastaut Syndrome; TSC: Tuberous Sclerosis Complex Source: Ambit Genetic Testing and Claims Data Analysis; EvaluatePharma; Sanders S. J. et al. Trends Neurosci. (2018); Wolff M. et al Brain (2017)
Slide 29: Unmet need in the $3B+ US common epilepsy market
29 >1M w/ Refractory Seizures We aim to address unmet need in the $3B+ US common epilepsy market Source: CDC, EvaluatePharma; Tang F. et al. Front. Neurol. (2017) 3.5M US Prevalence $3B+ US Common Epilepsy Market Opportunity
Slide 30: PRAX-562 first- and best-in-class NaV blocker for DEEs
30 Preclinical and emerging clinical data demonstrate PRAX-562 will be a first- and best-in-class NaV blocker for DEEs Superior selectivity for disease-state NaV channel hyperexcitability Convenient auto-titration regimen with stable PK Unprecedented therapeutic window translating to superior safety
Slide 31: Comparison of potency and selectivity
31 % INHIBITION OF hNaV1.6 PERSISTENT INa (SAME DATA AS ON PRIOR SLIDE) COMPARISON OF POTENCY AND SELECTIVITY Broader in vitro panel indicates PRAX-562 has best-in-class preferences *solubility concerns 0.01 0.1 1 10 100 1000 10000 0 20 40 60 80 100 Concentration (µM) % In hi bi tio n Carbamazepine
Slide 32: Wide therapeutic index in vivo
32 MES EFFICACY sLMA TOLERABILITY Veh 10 20 40 0 10000 20000 30000 40000 50000 60000 70000 To ta l D Is ta nc e Tr av el le d (m m ) ** ** Veh 0.3 1 3 10 0 20 40 60 M ES La te nc y (s ec ) ** ** Our mechanistic hypothesis translates to a wide therapeutic index in vivo Therapeutic Index (TI) = TC50 /
Slide 33: PRAX-562 blocks seizures in SCN2A and SCN8A GoF mouse models
33 IN VIVO POC IN SCN2A SPONTAEOUS SEIZURES1 IN VIVO POC IN SCN8A AUDIOGENIC EVOKED SEIZURES2 PRAX-562 completely blocks seizures in SCN2A and SCN8A GoF mutation mouse models 1 PRAX-562 inhibition of spontaneous seizures in Q54 GoF mice. 2 PRAX-562 inhibition of audiogenic seizures in N1768D D/+ mic
Slide 34: Three epilepsy drugs in clinic by end of 2022
34 PRAX-222 (SCN2A) PRAX-562 (SCN2A, SCN8A, TSC) PRAX-628 (FOCAL EPILEPSY) Three epilepsy drugs in clinic by end of 2022 Initiate Seamless Study: 2H2022* Initiate Phase 2 Study: 2H22 Initiate Phase 1 Study: 4Q22 PRAX-222 and PRAX-562 received Orphan Drug Designations for severe pediatric epilepsy in
Slide 35: DARE for MORE
DARE for MORE™
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