Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Presentation (August 2022)
30 slides from Praxis Precision Medicines's investor presentation, Aug 8, 2022
Slide 1: Corporate Overview August 2022
CORPORATE OVERVIEW August 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 KCNA1 SLC1A3 SETX RFC1 CACNA1G GABRB3 KCN1A SCN8A SCN2A DRD3 HTT FMR1 OPA1 SYNGAP1 SHANK3 TPH2 FKBP2 HTR2A CDKL5 DNM1 UNC79 TRIM3 PCDH19 CACNA1A EPILEPSYMOVEMENT
Slide 4: Pipeline across movement disorders, epilepsy and psychiatry
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 FOCUS AREA PRAX-114 MDD *PRAX-222
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 into 1Q24
6 CASH RUNWAY into 1Q24 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 two key therapeutic franchises DATA RICH 2022 Topline results from four Phase 2 or registr
Slide 7: Milestone rich 2H 2022
7 Milestone rich 2H 2022 FOCUS AREA PROGRAM INDICATION Q2 2022 Q3 2022 Q4 2022 MOVEMENT DISORDERS PRAX-944 PRAX-944 ET PD INITIATE PHASE 2 TRIAL PHASE 2A PART B TOPLINE PHASE 2B ESSENTIAL1 STUDY TOPLINE PSYCHIATRY MDDPRAX-114 PHASE 2 ACAPELLA STUDY TOPLINE PHASE 2/3 ARIA STUDY TOPLINE X EPILEPSY P
Slide 8: Movement disorders: PRAX-944 key upcoming milestones
8 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 2H 2022 Initiate PRAX-944 Ph 2 PD Trial KEY UPCOMING MILESTONES PRAX-944 Phase 2a Part B topline results disclosed in May 2022 4Q 2022
Slide 9: At Praxis, we DARE for MORE for people living with essential tremor
9 At Praxis, we DARE 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 10: $4B+ US essential tremor market
10 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 11: T-type calcium channels are gatekeepers of neuronal firing patterns
11 T-Type calcium channels are gatekeepers of neuronal firing patterns in the CTC circuit 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 Dee
Slide 12: PRAX-944 is a differentiated, selective T-type calcium channel blocker
12 PRAX-944 is a differentiated, selective T-type calcium channel blocker Source: Praxis Data on file Highly selective for T- type calcium channels Potential for effectiveness across range of neuronal activity levels Highly potent across all three T-type isoforms
Slide 13: Wide dosing range and modified release formulation for PRAX-944
13 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 CMAX Source
Slide 14: Modified ADLs in randomized withdrawal
14 MODIFIED ADLs IN RANDOMIZED WITHDRAWAL MEAN % CHANGE FROM DAY 42 Marked functional benefit observed in patients treated with PRAX-944, while withdrawal of PRAX-944 results in regression to baseline severity MODIFIED ADLs IN OPEN LABEL MEAN % CHANGE FROM BASELINE *Nominal p-value based on ANCOVA S
Slide 15: Safety summary
15 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 16: Key PRAX-944 development questions in ET
16 Key PRAX-944 development questions in ET PRAX-944-221 Phase 2a Part B PRAX-944-222 Phase 2b Essential1 Study (ongoing) PRAX-944 Phase 3 (planned for 2023) Tolerability of PRAX-944 in ET and clear evidence of effect Efficacy, safety and tolerability of once-daily daytime treatment of 60 mg or 100
Slide 17: PRAX-944 Phase 2b Essential1 study design
17 Source: clinicaltrials.gov/ct2/show/NCT05021991 PRAX-944 Phase 2b Essential1 study topline results expected 4Q22 *Composite sum of items 1 to 11 of TETRAS-ADL subscale and items 6 (bilateral) and 7 of TETRAS-PS; modified ADL score is calculated as the sum of all 13 items and ranges from 0 to 42 c
Slide 18: T-type calcium channels in Parkinson's disease
18 T-type Calcium Channels modulate the motor circuit in Parkinson’s disease and overlap with target for Deep Brain Stimulation Mcgregor mm, nelson ab. Neuron. 2019. Doi:10.1016/j.Neuron.2019.03.004 Tai c-h et al. J clin invest. 2011. Doi:10.1172/jci46482 THALAMO-CORTICAL PATHWAY IMBALANCE IN PD STN
Slide 19: Blocking T-type calcium channels improves motor function in Parkinson's model
19 Blocking T-type calcium channels with Ni2+ improves motor function in burst firing model of movement deficit in Parkinson’s disease Pan et al (2016) j clin invest doi: 10.1172/jci88170 BURST FIRING IN STN OF 6-OHDA PARKINSON’S MODEL BLOCK OF BURST FIRING IMPROVES MOVEMENT IN 6-OHDA PARKINSON’S MO
Slide 20: PRAX-944 Phase 2 Parkinson's disease study design
20 CLINICAL MEASUREMENTS: Motor function KEY QUESTION: Does PRAX-944 demonstrate motor improvement in patients? PRAX-944 Phase 2 Parkinson’s disease study expected to initiate 2H22 Safety Follow Up PRAX-944 Titration 5 mg to 100 mg DAY 1-49 DAY 50-77 PRAX-944 Titration Maintenance DAY 78-84 PLACEBO
Slide 21: Epilepsy key upcoming milestones
21 2Q 2022 PRAX-562 Ph 1 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 ASO) PRAX-080 (P
Slide 22: Three key imperatives guide our epilepsy portfolio build
22 Three key imperatives guide our epilepsy portfolio build *PRAX-222 in collaboration with Ionis Pharmaceuticals, Inc. and RogCon, Inc.. PCDH19 (PRAX-080), SYNGAP1(PRAX-090), SCN2A-LOF(PRAX-100) ASOs are a collaboration with The Florey Institute of Neuroscience and Mental Health. TARGET ID BY POLYG
Slide 23: Precision medicines for 25,000+ rare epilepsy patients
23 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 24: PRAX-562 first- and best-in-class NaV blocker for DEEs
24 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 with potential for superior sa
Slide 25: Comparison of potency and selectivity
25 % INHIBITION OF hNaV1.6 PERSISTENT INa 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 Lamotrigine Cenobamate PRAX-56
Slide 26: Mechanistic hypothesis translates to a wide therapeutic index in vivo
26 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 27: PRAX-562 completely blocks seizures in SCN2A and SCN8A GoF mouse models
27 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 28: PRAX-562 Phase 1 study summary
28 PRAX-562 Phase 1 study summary • PRAX-562 was well-tolerated in Part A of the study, with no clinically significant safety findings. The majority of TEAEs were considered mild to moderate in both Part A and Part B of the study. • Co-administration of supra-therapeutic doses of PRAX-562 and oxcarb
Slide 29: Three epilepsy drugs in clinic by end of 2022
29 PRAX-222 (SCN2A) PRAX-562 (SCN2A, SCN8A, TSC) PRAX-628 (FOCAL EPILEPSY) Three epilepsy drugs in clinic by end of 2022 Initiate Seamless Study: 2H22* Initiate Phase 2 Study: 2H22 Initiate Phase 1 Study: 4Q22 PRAX-222 and PRAX-562 received Orphan Drug Designations for severe pediatric epilepsy indi
Slide 30: DARE for MORE
DARE for MORE™
Praxis Precision Medicines — Investor Presentation (August 2022) on 6ix