Praxis Precision Medicines, Inc. · NASDAQ:PRAX
Praxis Precision Medicines — Investor Day (December 2021)
71 slides from Praxis Precision Medicines's investor day presentation, Dec 17, 2021
Slide 1: Movement Disorder Day
Movement Disorder Day FRIDAY, DECEMBER 17, 2021
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: Agenda
3 — Praxis - A Leader in CNS & Movement Disorders — Essential Tremor (ET) - More Than Tremor — Daring for More for People Living with ET — Daring for More Beyond ET — Praxis - The Year Ahead — Q&A DECEMBER 17, 2021 PRAXIS 2021 MOVEMENT DISORDER DAY
Slide 4: Today's Speakers
4 NICOLE SWEENY Chief Commercial Officer BERNARD RAVINA Chief Medical Officer TIM KELLY Chief Financial Officer MARCIO SOUZA President & Chief Executive Officer Today’s Speakers
Slide 5: Praxis – A Leader in CNS and Movement Disorders
5 Praxis – A Leader in CNS and Movement Disorders
Slide 6: Mission: delivering life-altering treatments for CNS disorders
6 The needs of patients with CNS disorders are devastatingly urgent. Our mission is to help patients by delivering life-altering treatments faster and more effectively than has ever been done before — and to do it again and again.
Slide 7: Praxis is built on four key pillars
7 Praxis is built on four key pillars Development informed by TRANSLATIONAL TOOLS Targets identified through GENETICS Clinical development paths to POC RIGOROUS and EFFICIENT Development strategies are PATIENT-GUIDED
Slide 8: Three distinct franchises primed for growth in 2022
8 THREE DISTINCT FRANCHISES PRIMED FOR GROWTH IN 2022 PSYCHIATRY MOVEMENT DISORDERS RARE DISEASE
Slide 9: Pipeline across psychiatry, movement disorders, rare diseases
9 PSYCHIATRY MOVEMENT DISORDERS RARE DISEASES >$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
Slide 10: Movement Disorder franchise focus for 2022
10 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 Demonstrate well- tolerat
Slide 11: Essential Tremor (ET) – More Than Tremor
11 Essential Tremor (ET) – More Than Tremor
Slide 12: Medications developed specifically for Essential Tremor patients
12 Medications developed specifically for Essential Tremor patients
Slide 13: Medication approved for ET based on a 2-week study of nine patients
13 Medication approved for Essential Tremor over 50 years ago based on a 2-week study of nine patients
Slide 14: Million people in the US need better options
14 Million people in the US with daily symptoms of Essential Tremor need better and more options
Slide 15: DARE for MORE
15 DARE for MORE
Slide 16: Why Essential Tremor matters
16 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) (P.231, C.1, PH.1
Slide 17: ET burden of disease extends beyond the tremor
17 Social embarrassed by their tremor1,2 Mood symptoms of social isolation, depression, and anxiety1-5 Self feel negative about themselves1 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;1
Slide 18: Current management of ET is based on trial and error
18 OR Current management of ET is based on trial and error Pharmacologic initiation As needed Chronic PHARMACOLOGIC TREATMENT IS DETERMINED BY: • severity of tremor • body part affected • occupation of the patient • degree of disability • comorbidities SOURCE: 1 WELTON , ESSENTIAL TREMOR NATURE REVI
Slide 19: As needed treatment options offer minimal utility
19 As needed treatment options offer minimal utility As needed CURRENT MANAGEMENT • Alcohol use 10-15 min before event • Propranolol one hour before event SOURCE: 1 WELTON , ESSENTIAL TREMOR NATURE REVIEWS (2021) (P.1)
Slide 20: Chronic use options increase tolerability concerns
20 Chronic use options increase tolerability concerns Chronic CURRENT MANAGEMENT • Propranolol • Primidone • Topiramate SOURCE: 1 WELTON , ESSENTIAL TREMOR NATURE REVIEWS (2021) (P.1)
Slide 21: What have we learned?
What have we learned?
Slide 22: The ET market today: immediate addressable U.S. market
22 The ET market today: immediate addressable U.S. market COMPREHENSIVE CLAIMS ANALYSIS 2019 SNAPSHOT Patients are coping with Treatment Burden Patients are coping with Disease Burden ~1M patients On-treatment ~1M patients Not on-treatment SOURCE: US CLAIMS DATA FROM THE COMPILE DATABASE FROM 2015-2
Slide 23: Equilibrium between patients who discontinue and initiate treatment
23 Currently, there is an equilibrium between patients who discontinue treatment and those who initiate treatment ~1M patients On-treatment ~1M patients Not on-treatment Each year 200K patients discontinue treatment SOURCE: US CLAIMS DATA FROM THE COMPILE DATABASE FROM 2015-2019; PRIMARY MARKET RESE
Slide 24: Patients not on treatment could rejoin the on-treatment pool
24 Patients not on treatment could (re)join the on-treatment pool which increases treatment utilization SOURCE: US CLAIMS DATA FROM THE COMPILE DATABASE FROM 2015-2019; PRIMARY MARKET RESEARCH AND PRAXIS INTERNAL MODELING AND PROJECTIONS ~1M patients On-treatment Increase treatment use ~1M patients
Slide 25: Newly diagnosed patients initiate treatment earlier
25 Newly diagnosed patients initiate treatment earlier which increases the total addressable patient market Each year 200K new patients are diagnosed Potential to expand on-treatment patients to 2M SOURCE: US CLAIMS DATA FROM THE COMPILE DATABASE FROM 2015-2019; PRIMARY MARKET RESEARCH AND PRAXIS IN
Slide 26: 3M Total Addressable Market; $4B+ US ET market
26 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 THAT 50% OF DIAG
Slide 27: Praxis treatments let patients fit the right therapy to their needs
27 Praxis treatments will allow patients to fit the right therapy to their needs to realize improved outcomes • Patients will initiate ET treatment sooner • Patients will treat as needed • Patients will maintain ET therapy + As needed Chronic PRAX-114 PRAX-944
Slide 28: Longer-term opportunity extends into the undiagnosed
28 Longer-term opportunity extends into capturing the undiagnosed 3M Total Addressable Market 7M US Prevalence Disease awareness Earlier adoption of treatment in disease course Access Multiple effective, well-tolerated therapies PRIMARY MARKET RESEARCH AND PRAXIS INTERNAL MODELING AND PROJECTIONS
Slide 29: Daring for More for People Living with Essential Tremor
29 Daring for More for People Living with Essential Tremor
Slide 30: Tackling Movement Disorders through two mechanisms of action
30 Tackling Movement Disorders through two mechanisms of action GABAA RECEPTORST-TYPE CALCIUM CHANNELS CEREBELLO-THALAMO-CORTICAL (CTC) CIRCUIT PRAX-944 PRAX-114
Slide 31: Tackling Movement Disorders through two mechanisms of action
31 Tackling Movement Disorders through two mechanisms of action GABAA RECEPTORST-TYPE CALCIUM CHANNELS CEREBELLO-THALAMO-CORTICAL (CTC) CIRCUIT PRAX-944 PRAX-114
Slide 32: T-type calcium channel mutations linked to familial ET
32 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 channels are gatekee
Slide 33: EEG biomarker of T-type calcium channels: sigma frequency
33 • Sigma frequency (10-14 Hz) occurs during NREM sleep • Thought to be generated by thalamic-cortical pathways • Reduced with Cav3.3 knock-out of T-type Calcium Channels EEG biomarker of T-Type calcium channels: sigma frequency SOURCE: ASTORI, PNAS, 2011.
Slide 34: PRAX-944 reduced rat harmaline-induced tremor and sigma band EEG
34 PRAX-944 dose-dependently reduced rat harmaline-induced tremor and sigma band EEG Rat harmaline-induced tremor Free Plasma (NM) Tremor Reduction EEG Change Strong preclinical correlation between EEG change and tremor reduction SOURCE: Puryear, et al – CNS Summit 2021, PRAXIS DATA ON FILE *statist
Slide 35: PRAX-944 is a differentiated, selective T-type calcium channel blocker
35 HIGHLY POTENT ON ALL 3 ISOFORMS HIGHLY SELECTIVE NO ACTIVE METABOLITES PRAX-944 is a differentiated, selective T-Type calcium channel blocker SOURCE: PRAXIS DATA ON FILE
Slide 36: Predictable PK and extensive safety data
36 Predictable PK Wide dosing range up to 120mg Flexibility in titration Extensive safety and PK data from > 165 Healthy Volunteers SAFETY SUMMARY • Studied multiple IR, MR formulations • Most common AEs included: – CNS: dizziness, headache, euphoric mood, illusion, disturbed attention – GI: nausea
Slide 37: PRAX-944 modified release enables once daily daytime dosing
37 PRAX-944 modified release is optimized to enable once daily daytime dosing with a well-tolerated safety profile SOURCE: PRAXIS STUDY-944-105; PRAXIS DATA ON FILE 0 5 10 15 20 25 30 35 40 45 50 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 ) Time (h) Mean concentration-time profiles a
Slide 38: PRAX-944 showed robust PK:PD relationship
38 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 STUDY-944-105; PRAXIS
Slide 39: Key PRAX-944 development questions in ET
39 Key PRAX-944 development questions in ET PRAX-944-221 Phase 2a 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 Demonstrate efficacy and sa
Slide 40: Study design
40 Study 221 design DAYS 1-14 Safety Follow- up Screening/ Baseline PART A DAYS 15-21 Part A data shared previously 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 Period at High Do
Slide 41: Clinical measures used in Study 221
41 • TETRAS Upper Limb – Performance Scale Examples of clinical measures used in Study 221 • TETRAS Activities of Daily Living (ADL) 4 3.5 3 2.5 2 1.5 Barely Visible = 1 No Tremor = 0 < 1 cm 1-3 cm 3-5cm 5-10 cm 10-20 cm >20cm POURING A GLASS OF WATER 4 Cannot pour 3 Must use two hands or use other
Slide 42: PRAX-944-221 current patient disposition
42 PRAX-944-221 PART A PART B Current patient disposition All discontinuations included in safety data set ^ Discontinuation with evaluable post dose efficacy Discontinued (4): Protocol violation/AE 20mg (2/3) ^Withdrew Day 21, AE/40mg (1) Enrolled and dosed (7) Completed Per Protocol (6) Discontinu
Slide 43: Study demographics representative of the ET population
43 Study 221 demographics representative of the ET population BASELINE DEMOGRAPHICS PART A (N = 7) PART B (N = 12) OVERALL (N = 19) Age, mean (range) 68 (58-75) 59 (43-75) 62 (43-75) Disease Duration, mean (range) 42 (14-57) 32 (11-52) 36 (11-57) Gender (Male/Female) (n, %) 5 / 2 (71%/29%) 11 /1 (92
Slide 44: TEAEs are mild to moderate
44 TEAEs are mild to moderate and consistent with safety profile for the program NUMBER OF PARTICIPANTS WITH CNS RELATED TREATMENT EMERGENT ADVERSE EVENTS * Preferred Term Part A Part B Any TEAE** 6 10 Dizziness 4 3 Headache 3 1 Cognitive disorder 3 Fatigue 2 Insomnia 2 Paraesthesia 2 PRELIMINARY DA
Slide 45: TEAEs leading to down-titration or discontinuation
45 TEAEs leading to dose down-titration or discontinuation were mild- moderate TEAEs ASSOCIATED WITH STUDY DRUG DISCONTINUATION IN 5 PARTICIPANTS* Preferred Term Part A Part B Anxiety 1 Cognitive disorder 2 Confusional state 1 Disturbance in attention 1 Dizziness 1 Hallucinations 1 TEAEs LEADING TO
Slide 46: Preliminary Part B data: modified ADL by baseline CUL score
46 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 ITEM; % CHANGE CALCU
Slide 47: Preliminary Part B data: TETRAS CUL and TETRAS ADL
47 Preliminary Part B data: TETRAS CUL and TETRAS ADL PRELIMINARY DATA AS OF 10-DEC-2021 CUTOFF; ONGOING CLINICALTRIALS.GOV/CT2/SHOW/NCT05021978 *PART B PATIENT 1 DISCONTINUED AFTER DAY 21 ASSESSMENT. % C H A N G E I N T E T R A S C U L 80% 60% 40% 20% 0% -20% -40% -60% 80% 60% 40% 20% 0% -20% -40%
Slide 48: Preliminary data: PRAX-944-221 TETRAS CUL
48 PART B PARTICIPANTSPART A PARTICIPANTS Preliminary data: PRAX-944-221 TETRAS CUL PRELIMINARY DATA AS OF 10-DEC-2021 CUTOFF; ONGOING CLINICALTRIALS.GOV/CT2/SHOW/NCT05021978 *PART B PATIENT 1 DISCONTINUED AFTER DAY21 ASSESSMENT; FINAL DOSE LEVEL NOTED IN CHART % C H A N G E I N T R E M O R A M P L
Slide 49: Key learnings from Part A/Part B and implications
49 Key learnings from Part A/Part B: implications to Essential1 and program PRAX-944-221 Phase 2a Part B PRAX-944-222 Phase 2b Essential1 Study • Safety and tolerability • Efficacy: consistency, plausibility, magnitude, dose response • Titration: planning 5-100 mg, increase weekly • Dose: parallel d
Slide 50: Moving towards more objective assessments for clinical endpoints
50 Physician-observed ADLs TETRAS UL Self-reported ADL Objective tremor measurement Moving towards more objective assessments for clinical endpoints Real-time observation of activities: • Pouring water • Dressing Sensor-based tremor assessment + Patients asked to recall ability to perform ADLs 4 3.5
Slide 51: Testing innovative, objective ways of measuring tremor
51 We are testing innovative, objective ways of measuring tremor Forward Hand Extension
Slide 52: Key PRAX-944 development questions in ET
52 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 Demonstrate efficacy
Slide 53: Daring for More for People Living with ET: PRAX-114
53 Daring for More for People Living with ET: PRAX-114
Slide 54: Tackling Movement Disorders through two neuronal systems
54 Tackling Movement Disorders through two neuronal systems GABAA RECEPTORST-TYPE CALCIUM CHANNELS CEREBELLO-THALAMO-CORTICAL (CTC) CIRCUIT PRAX-944 PRAX-114
Slide 55: Central role of extrasynaptic GABAA receptors in tremor
55 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 ExtrasynapticWith Extrasynaptic α4β3δ %* α1β2γ2 % α4β3δ/ α1
Slide 56: Targeting doses that activate the system without sedation
56 Targeting doses that activate the system without expected sedation KEY LEARNINGS: • β–Power of ~1.3 corresponds to efficacy in harmaline tremor model with PRAX-114 • In HV studies β–Power achieved with 10-20mg at Cmax • This dose range showed no AE of somnolence or sedation with day- time dosing
Slide 57: PRAX-114 ET Phase 2 study design
57 PRAX-114 ET Phase 2 study initiated 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 PERIOD 2 PERIOD 3 Was
Slide 58: Praxis treatments allow patients to fit the right therapy
58 Praxis treatments will allow patients to fit the right therapy to their needs to realize improved outcomes • Patients will initiate ET treatment sooner • Patients will treat as needed • Patients will maintain ET therapy As needed Chronic PRAX-114 PRAX-944 +
Slide 59: Daring for More Beyond ET
59 Daring for More Beyond ET
Slide 60: Why Parkinson's disease matters
60 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/UNDERSTANDING-PARKIN
Slide 61: Current treatment adds to the burden of Parkinson's disease
61 Current treatment adds to the burden of Parkinson’s disease Progressive & debilitating High treatment burden Inconsistent therapeutic effect over time SOURCE: 1. PRIMARY MARKET RESEARCH, 2. THE VOICE OF THE PATIENT, PARKINSON’S DISEASE PUBLIC MEETING: SEPTEMBER 22, 2015, REPORT DATE: APRIL 2016
Slide 62: Limitations of dopaminergic therapy
62 Limitations of dopaminergic therapy Dopamine promotes movement Dopamine related motor and non- motor complications PRAX-944 has potential to be a non-dopaminergic therapy for Parkinson’s disease
Slide 63: T-type calcium channels modulate the motor circuit in Parkinson's
63 T-type Calcium Channels modulate the motor circuit in Parkinson’s disease and overlap with target for Deep Brain Stimulation Thalamo-Cortical Pathway Imbalance in PDThalamo-Cortical Pathway STN-Healthy STN-PD MCGREGOR MM, NELSON AB. NEURON. 2019. DOI:10.1016/J.NEURON.2019.03.004 TAI C-H ET AL. J
Slide 64: Blocking T-type calcium channels improves motor activity in 6-OHDA model
64 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 CLIN INVEST DOI: 1
Slide 65: PRAX-944 in Parkinson's disease - study design
65 PRAX-944 in Parkinson’s disease - study design 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 50-77 PRAX-944 Titration Maintenance DAY 78-84 PLACEBO PLACEBO 2:1 Randomizat
Slide 66: Daring for More: The Year Ahead
66 Daring for More The Year Ahead
Slide 67: 3M Total Addressable Market; $4B+ US ET market
67 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 THAT 50% OF DIAG
Slide 68: Upcoming catalysts for Movement Disorders in 2022
68 PROGRAM Q4 2022Q1 2022 Q3 2022 Q2 2022 INDICATION Upcoming catalysts for Movement Disorders in 2022 PRAX-944 PD PRAX-114 ET PRAX-944 ET Phase 2b Essential1 Study Topline Phase 2a Part B Randomized Withdrawal Topline Phase 2 Topline Initiate Phase 2 Trial MOVEMENT DISORDERS Phase 2 Trial Phase 2b
Slide 69: Upcoming catalysts throughout portfolio in 2022
69 PSYCHIATRY MOVEMENT DISORDERS RARE DISEASES 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 SUNCT/SUNA/TN DEEs MDD PTSD ET PD Phase 2 Topline Phase 2 Acapella Study Topline Phase 2/3 Aria Study Top
Slide 70: Upcoming portfolio events in 1H 2022
70 PSYCHIATRY DAY • PRAX-114: Major Depressive Disorder • PRAX-114: Post Traumatic Stress Disorder RARE DISEASE DAY • PRAX-562: Cephalgias and DEEs • PRAX-222: SCN2A-DEE • Preclinical Portfolio - KCNT1 - SYNGAP1 - PCDH19 - SCN2A (LoF) Upcoming portfolio events in 1H 2022
Slide 71: DARE for MORE
71 DARE for MORE
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