A Randomized, Double-Blind, Placebo-Controlled Trial of CVN424 in Early Parkinson's Disease
Phase: PHASE2
Conditions: Parkinson's Disease
Sponsor: Cerevance Beta, Inc.

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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Page 1 of 92 
Title Page 
Protocol Title: 
A Randomized, Double-Blind, Placebo-Controlled 
Trial of CVN424 in Early Parkinson’s Disease 
Protocol Number: 
CVN424-203 
Compound: 
CVN424 
Indication: 
Parkinson’s Disease 
Study Phase: 
Phase 2b 
Short Title: 
Early Parkinson’s Disease Monotherapy with 
CVN424 
Manufacturer: 
Patheon, Milton Park, United Kingdom 
Sponsor  
Sponsor Name: 
Cerevance Beta, Inc. 
Legal 
Registered 
Address: 
One Marina Park Drive Suite 1410  
Boston, MA 02210  
United States 
Regulatory Agency Identifier 
Number(s): 
Registry 
Identifier 
Number 
NCT 
NCT06006247 
EudraCT 
Not Applicable 
Other 
Not Applicable 
Protocol Version and Date: 
Document Version 
Date 
Original (v1.0) 
22 June 2023 
Amendment 1 (v2.0) 
17 January 2024 
 
Amendment 2 (v3.0) 
10 July 2024 
 
CONFIDENTIALITY NOTICE 
The information contained in this protocol and all other information relevant to CVN424 are the 
confidential and proprietary information of Cerevance Beta, Inc. and, except as may be required 
by federal, state, or local laws or regulation, may not be disclosed to others without the prior 
written permission of Cerevance Beta, Inc. 
 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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SPONSOR SIGNATORY 
Protocol Number: CVN424-203 
Protocol Title:  
A Randomized, Double-Blind, Placebo-Controlled Trial of CVN424 in Early Parkinson’s 
Disease 
 
I, the undersigned, have approved of the clinical trial protocol with the date of 10 July 2024. 
 
, MD 
Medical Officer 
 
  
 
 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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Page 3 of 92 
INVESTIGATOR AGREEMENT 
Protocol Number: CVN424-203 
Protocol Title:  
A Randomized, Double-Blind, Placebo-Controlled Trial of CVN424 in Early Parkinson’s 
Disease 
 
I have read the protocol, including all appendices, and I agree that it contains all the necessary 
information for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein, in compliance with current Good Clinical Practice (GCP) standards as defined 
by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use (ICH) Guideline for GCP, all applicable national, state, and local laws and 
regulations, and the applicable Institutional Review Board/Independent Ethics Committee 
(IRB/IEC) and other institutional requirements.  
I will provide all study personnel under my supervision copies of the protocol and any 
amendments, and access to all information provided by Cerevance Beta, Inc. or specified 
designees. I will discuss the material with them to ensure that they are fully informed about 
Cerevance Beta, Inc., understand this study, and are able to comply. 
 
______________________________  __________________________ 
Principal Investigator Name (printed)  Signature 
______________________________ 
Date 
 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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Table of Contents 
Title Page ........................................................................................................................................1 
SPONSOR SIGNATORY .............................................................................................................2 
INVESTIGATOR AGREEMENT ...............................................................................................3 
Table of Contents ...........................................................................................................................4 
List of Tables ..................................................................................................................................8 
List of Figures .................................................................................................................................9 
List of Abbreviations ...................................................................................................................10 
1. 
Protocol Summary ........................................................................................................13 
1.1. 
Synopsis ..........................................................................................................................13 
1.2. 
Schema ............................................................................................................................22 
1.3. 
Schedule of Assessments (SoA) .....................................................................................23 
2. 
Introduction ...................................................................................................................27 
2.1. 
Study Rationale ...............................................................................................................27 
2.2. 
Background .....................................................................................................................27 
2.2.1. 
Disease Background........................................................................................................27 
2.2.2. 
Investigational Product Background: CVN424 ..............................................................28 
2.3. 
Benefit/Risk Assessment ................................................................................................33 
2.3.1. 
Risk Assessment .............................................................................................................33 
2.3.2. 
Benefit Assessment .........................................................................................................33 
2.3.3. 
Overall Benefit Risk Conclusion ....................................................................................34 
3. 
Objectives, Endpoints, and Estimands .......................................................................35 
4. 
Study Design ..................................................................................................................37 
4.1. 
Overall Design ................................................................................................................37 
4.1.1. 
Study Duration for an Individual Subject .......................................................................38 
4.1.2. 
Number of Subjects.........................................................................................................38 
4.1.3. 
Number of Sites ..............................................................................................................38 
4.2. 
Scientific Rationale for Study Design ............................................................................38 
4.3. 
Justification for Dose ......................................................................................................39 
4.4. 
End of Study Definition ..................................................................................................39 
4.5. 
End of Treatment Definition ...........................................................................................39 
5. 
Indication & Study Population ....................................................................................40 
5.1. 
Inclusion Criteria ............................................................................................................40 
5.2. 
Exclusion Criteria ...........................................................................................................40 
5.3. 
Prohibited Medications and Lifestyle Considerations ....................................................42 
5.3.1. 
Study Drug and Meals Considerations ...........................................................................43 
5.3.2. 
Study Drug Interruption or Suspension ..........................................................................43 
5.3.3. 
Alcohol ............................................................................................................................43 
5.3.4. 
Activity ...........................................................................................................................43 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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5.4. 
Screen Failures ................................................................................................................43 
6. 
Investigational Product and Concomitant Therapy ..................................................45 
6.1. 
Investigational Product Dispensation, Dosing and Regimen..........................................45 
6.2. 
Investigational Product Assignment, Storage, and Accountability ................................46 
6.2.1. 
Investigational Product Storage ......................................................................................46 
6.2.2. 
Investigational Product Assignment Procedure ..............................................................46 
6.2.3. 
Investigational Product Accountability...........................................................................46 
6.3. 
Randomization and Blinding ..........................................................................................47 
6.3.1. 
Breaking the Blind ..........................................................................................................47 
6.4. 
Study Drug Compliance..................................................................................................48 
6.5. 
Treatment of Overdose ...................................................................................................49 
6.6. 
Prior and Concomitant Therapy ......................................................................................49 
6.6.1. 
Rescue Medicine .............................................................................................................50 
7. 
Discontinuation of Study Drug and Subject Early 
Termination/Discontinuation or Withdrawal ............................................................51 
7.1. 
Discontinuation of Study Drug .......................................................................................51 
7.2. 
Subject Early Termination/Discontinuation/Withdrawal From the 
Study ...............................................................................................................................51 
7.3. 
Lost to Follow-up............................................................................................................52 
8. 
Study Assessments and Procedures.............................................................................53 
8.1. 
General Assessments ......................................................................................................53 
8.1.1. 
Medical History ..............................................................................................................53 
8.1.2. 
Prior Therapy ..................................................................................................................53 
8.1.3. 
Demographics .................................................................................................................53 
8.2. 
Efficacy Assessments .....................................................................................................53 
8.2.1. 
Movement Disorders Society – Unified Parkinson's Disease 
Rating Scale (MDS-UPDRS) ..........................................................................................54 
8.2.2. 
Clinical Global Impression of Severity Scale (CGI-S) ...................................................54 
8.2.3. 
Patient Global Impression of Severity Scale (PGI-S) .....................................................54 
8.2.4. 
Epworth Sleepiness Scale (ESS) .....................................................................................54 
8.2.5. 
Non-Motor Symptoms Scale (NMSS) for Parkinson's Disease ......................................55 
8.2.6. 
Parkinson's Disease Sleep Scale (PDSS-2) .....................................................................55 
8.2.7. 
Starkstein Apathy Scale (SAS) .......................................................................................55 
8.2.8. 
Exploratory Efficacy Assessments .................................................................................55 
8.3. 
Safety Assessments .........................................................................................................58 
8.3.1. 
Physical and Neurological Examinations .......................................................................58 
8.3.2. 
Vital Signs .......................................................................................................................59 
8.3.3. 
Electrocardiograms (ECGs) ............................................................................................59 
8.3.4. 
Modified Hoehn and Yahr Scale.....................................................................................59 
8.3.5. 
Montreal Cognitive Assessment (MoCA) ......................................................................60 
8.3.6. 
The Beck Depression Inventory-II (BDI-II) ...................................................................60 
8.3.7. 
The Columbia Suicide Severity Rating Scale (C-SSRS) ................................................60 
8.3.8. 
Clinical Safety Laboratory Tests ....................................................................................61 
8.3.9. 
Pregnancy Testing ...........................................................................................................61 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs), and 
Other Safety Reporting ...................................................................................................61 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................62 
8.4.2. 
Method of Detecting AEs and SAEs ..............................................................................62 
8.4.3. 
Follow-up of AEs and SAEs ...........................................................................................62 
8.4.4. 
Regulatory Reporting Requirements for SAEs ...............................................................63 
8.4.5. 
Pregnancy ........................................................................................................................63 
8.4.6. 
Adverse Events of Special Interest .................................................................................64 
8.5. 
Pharmacokinetics, Metabolite, and
...............................................................65 
8.5.1. 
Pharmacokinetic, Metabolite, and 
Sample Collection ..................................65 
8.5.2. 
Bioanalytical Methods ....................................................................................................65 
8.5.3. 
Pharmacokinetic Parameters ...........................................................................................65 
9. 
Statistical Considerations .............................................................................................66 
9.1. 
Sample Size Determination ............................................................................................66 
9.2. 
Populations For Analyses ...............................................................................................66 
9.3. 
Statistical Analyses .........................................................................................................67 
9.3.1. 
Efficacy Endpoint Analysis ............................................................................................67 
9.3.2. 
Tolerability and Safety Analysis .....................................................................................68 
9.3.3. 
Data Monitoring Committee ...........................................................................................69 
10. 
Supporting Documentation and Operational Considerations ..................................70 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................70 
10.1.1. Regulatory and Ethical Considerations ...........................................................................70 
10.1.2. Financial Disclosure........................................................................................................70 
10.1.3. Informed Consent Process ..............................................................................................71 
10.1.4. Data Protection................................................................................................................71 
10.1.5. Committees Structure......................................................................................................72 
10.1.6. Dissemination of Clinical Study Data.............................................................................72 
10.1.7. Data Quality Assurance ..................................................................................................72 
10.1.8. Source Documents ..........................................................................................................73 
10.1.9. Study Termination ..........................................................................................................73 
10.1.10. Publication Policy ...........................................................................................................74 
10.1.11. Sample Storage and Destruction .....................................................................................74 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................76 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .........................................................78 
10.3.1. Definition of AE .............................................................................................................78 
10.3.2. Definition of SAE ...........................................................................................................79 
10.3.3. Recording and Follow-up of AE and/or SAE .................................................................80 
10.3.4. Reporting of SAEs ..........................................................................................................83 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ..........................................................84 
10.4.1. Definitions.......................................................................................................................84 
10.4.2. Contraception Guidance..................................................................................................85 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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10.5. 
Appendix 5: Country-specific Requirements .................................................................87 
10.6. 
Appendix 6: Protocol Amendment History ....................................................................88 
11. 
References ......................................................................................................................91 
 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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List of Tables 
Table 1-1. 
Schedule of Assessments ...................................................................................... 23 
Table 3-1. 
Objectives and Endpoints ..................................................................................... 35 
Table 5-1. 
Prohibited Medications and Dietary Products ...................................................... 42 
Table 6-1. 
Study Arms ........................................................................................................... 45 
Table 8-1. 
Collection of Blood Samples for PK Analysis ..................................................... 65 
Table 10-1. 
Protocol-required Laboratory Tests ...................................................................... 76 
 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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List of Figures 
Figure 1. 
Study Schema........................................................................................................ 22 
Figure 2. 
Beacon Dreem EEG Schema ................................................................................ 58 
Figure 3. 
Parameters for Sample Size and Power Calculations ........................................... 66 
 
 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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List of Abbreviations  
ADL 
Activities of Daily Living 
AE(s) 
adverse event(s) 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC(0-x) 
area under the plasma concentration-time curve from time 0 to x; 
where x = 6 hours or 96 hours 
AV 
atrioventricular 
β-HCG 
beta human chorionic gonadotropin 
BDI 
Beck Depression Inventory 
CBD 
cannabidiol 
CFR 
Code of Federal Regulations 
CGI 
Clinical Global Impression  
CGI-S 
Clinical Global Impression of Severity Scale 
CIOMS 
Council for International Organizations of Medical Sciences  
CI 
confidence interval 
Cmax 
maximum plasma drug concentration 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CMH 
Cochran–Mantel–Haenszel 
CNS 
central nervous system 
COMT 
catechol-O-methyl transferase  
COVID-19 
coronavirus disease 2019 
CS 
Compound Symmetry 
CSTC 
cortico-striato thalamo-cortical 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CYP 
Cytochrome P450 
DET 
detection 
DHTs 
Digital Health Technologies 
EAC 
Enrollment Authorization Committee 
ECG(s) 
electrocardiogram(s) 
eCRF(s) 
electronic Case Report Form(s) 
eGFR 
estimated glomerular filtration rate 
EEG 
electroencephalogram 
ESS 
Epworth Sleepiness Scale 
ET 
early termination 
FDA 
(US) Food and Drug Administration 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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GPR6 
G protein-coupled receptor 6 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HDPE 
high-density polyethylene 
HIV 
human immunodeficiency virus 
HPLC-MS/MS 
High-Performance Liquid Chromatography – Tandem Mass 
Spectrometry 
HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
IDN 
identification 
IDSSTS 
International Digit Symbol Substitution Test – Symbols 
IEC(s) 
Independent Ethics Committee(s) 
IND 
investigational new drug 
IRB(s) 
Institutional Review Board(s) 
IRT 
interactive response technology 
ISLT 
International Shopping List Test 
ISRL 
International Shopping List Test – Delayed Recall 
ITT 
Intention-to-Treat 
K2EDTA 
dipotassium ethylene diamine tetraacetic acid 
LS 
least squares 
MAOB 
Monoamine Oxidase B 
MAR 
Missing at Random 
MDS-UPDRS 
Movement Disorder Society – Unified Parkinson’s Disease Rating 
Scale 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intention-to-Treat 
MMRM 
Mixed Model for Repeated Measures 
MMSE 
Mini-Mental State Examination 
MNAR 
Missing Not at Random 
MoCA 
Montreal Cognitive Assessment  
MSNs 
medium spiny neurons 
NMSS 
Non-Motor Symptoms Scale 
ONB 
One Back 
PD 
Parkinson’s Disease 
PD-PROP™ 
Parkinson’s Disease Patient Report of Problems 
PDSS 
Parkinson’s Disease Sleep Scale 
PGI 
Patient Global Impression 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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PGI-S 
Patient Global Impression of Severity 
PK 
pharmacokinetic(s) 
PWB-PROP™ 
Personal Wellbeing Patient Report of Problems 
QC 
quality control 
QTcB 
QT interval corrected using Bazett’s formula 
QTcF 
QT interval corrected using Fridericia’s formula 
RF 
radiofrequency 
SAE(s) 
serious adverse event(s) 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SE 
standard error 
SoA 
schedule of assessments 
TEAE(s) 
treatment emergent adverse event(s) 
ULN 
upper limit of normal 
US(A) 
United States (of America) 
WOCBP 
woman of childbearing potential 
 
 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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1. 
Protocol Summary 
1.1. 
Synopsis 
Protocol Title: 
A Randomized, Double-Blind, Placebo-Controlled Trial of CVN424 in Early Parkinson’s 
Disease 
Brief Title: 
Early Parkinson’s Disease Monotherapy with CVN424 
Indication: 
Parkinson’s Disease 
Rationale: 
This study will examine the potential of CVN424 to improve motor and non-motor functions in 
individuals with early untreated Parkinson’s Disease (PD).  
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
Primary Efficacy Endpoint 
To determine the effect of CVN424 on 
motor features of early, untreated subjects 
with Parkinson’s Disease (PD) 
Change from Baseline to Week 12 on the 
Movement Disorder Society – Unified 
Parkinson’s Disease Rating Scale (MDS-UPDRS) 
Part II + Part III (Motor Aspects of Experiences 
of Daily Living + Motor Examination) between 
CVN424 150 mg and placebo 
Secondary 
Secondary Endpoints 
To further define the effects of CVN424 
on motor and non-motor clinical features, 
function, and quality of life in PD 
Change from Baseline to Week 12 in the 
following endpoints, arranged in hierarchical 
order: 
 
• MDS-UPDRS Part III 
• Clinical Global Impression of Severity Scale 
(CGI-S)  
• Patient Global Impression of Severity Scale 
(PGI-S)  
• MDS-UPDRS Part II  
• MDS-UPDRS Part I  
• Epworth Sleepiness Scale (ESS)  
• Non-motor Symptoms Scale (NMSS)  
• Sum of MDS-UPDRS of Parts I, II, and III  

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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• Parkinson’s Disease Sleep Scale (PDSS-2)  
To assess the safety and tolerability of 
CVN424 in the PD population  
• Incidence and temporal profile of treatment 
emergent adverse events (TEAEs), evaluated 
by type/nature, severity/intensity, seriousness, 
and relatedness  
• Incidence of related TEAEs of moderate or 
severe intensity  
• Incidence of TEAEs leading to withdrawal of 
study drug  
• Incidence of serious adverse events (SAEs)  
• Changes in physical examination, vital signs 
(blood pressure and heart rate), 
electrocardiogram (ECG), laboratory values, 
and Columbia Suicide Severity Rating 
Scale (C-SSRS)  
• Incidence and timing of abuse-related adverse 
events (AEs)  
• Occurrence of withdrawal symptoms recorded 
at the follow-up visit  
• Percentage of completers  
Exploratory 
Exploratory Endpoints 
To describe the effects of CVN424 on 
motor performance, function, cognition, 
and sleep with other exploratory endpoints  
Change from Baseline to Week 12 in the 
following endpoints: 
 
• Modality Virtual Assessment  
• CogState digital cognitive battery  
• Schwab and England Activities of Daily 
Living (ADL)  
• Starkstein Apathy Scale  
• Electroencephalogram (EEG) derived sleep 
metrics  
• PD-PROP™ and PWB-PROP™ 
• Pharmacokinetics (PK) 
Overall Design: 
This is a Phase 2b multicenter, 12-week, randomized, parallel-group, double-blind, 
placebo-controlled clinical trial of CVN424 150 mg in early, untreated PD. It will evaluate 
CVN424 150 mg once a day against placebo. 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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There will be 7 in-person visits:  
• Screening (Visit 1)  
• Baseline/Randomization (Visit 2)  
• Week 2 (Visit 3)  
• Week 4 (Visit 4)  
• Week 8 (Visit 5)  
• Week 12/Early Termination Visit (Visit 6)  
• Week 14/Safety Follow-up Visit (Visit 7)  
After signing the informed consent form (ICF) and after all Screening procedures have been 
performed, subjects will be reviewed by an Enrollment Authorization Committee (EAC) for 
determination of eligibility and suitability for participation. Candidates may complete the 
screening visit in more than one day. Eligible subjects will be randomized in a 1:1 ratio to 
CVN424 150 mg or placebo at the Baseline Visit. Treatment will be initiated during the Baseline 
Visit. The study drug will be self-administered once daily at a consistent time in the morning and 
taken with food. The food taken with study drug may be a snack or typical morning meal and 
should include fat in its content (e.g., buttered toast, peanut butter on crackers, an egg, cream 
cheese on a bagel, full fat yogurt or milk).. 
At Baseline (Visit 2), the primary endpoint (sum of Movement Disorder Society – Unified 
Parkinson’s Disease Rating Scale [MDS-UPDRS] Part II + Part III), other secondary 
endpoints (Clinical Global Impression of Severity Scale [CGI-S], Patient Global Impression of 
Severity Scale [PGI-S], MDS-UPDRS Part I, Epworth Sleepiness Scale [ESS], Non-motor 
Symptom Scale [NMSS], Parkinson’s Disease Sleep Scale [PDSS-2]), and exploratory 
endpoints (Parkinson’s Disease Patient Report of Problems [PD-PROP™] and Personal 
Wellbeing Patient Report of Problems [PWB-PROP™]) will be assessed.  
In-person clinic visits at Week 2, Week 4, Week 8, and Week 12 will assess both the primary 
and secondary endpoints, including exploratory endpoints, per the Schedule of 
Assessments (SoA).  
Telephone visits will be conducted at Week 6 and Week 10 for safety and to check that Modality 
assessments have been completed. 
Remote data collection between clinic visits will be conducted using the following technologies:  
• Beacon Dreem overnight electroencephalogram (EEG): a wearable device that collects EEG 
signals to measure sleep metrics. This optional activity will be collected up to 3 consecutive 
nights before or after specified in-person clinic visits, per the SoA (see Section 8.2.8.4). 
Subjects who opt out of the Beacon Dreem EEG collection can continue their study 
participation in other study activities. 
o Modality Assessments: an audio-visual conversational technology to conduct 
customizable video interviews with subjects designed to test various aspects of their 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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speech, visuo-motor, prosodic (stress and intonation patterns), cognitive, and linguistic 
function. They include PD-PROP™, PWB-PROP™, and Schwab and England Activities 
of Daily Living (ADL) scale to enquire about specific problems and symptoms they are 
experiencing in daily and social activities. Subjects interact with a virtual agent using a 
web browser on any device of their choice. Subjects will be asked to complete the 
assessments at home (approximately 1-2 days prior to clinic visit). The assessments 
should take about 30 minutes to complete. Subjects who cannot complete all of the 
exploratory endpoint assessments, but who otherwise remain eligible for the study, can 
continue their participation (see Section 8.2.8.1). If a subject needs help to troubleshoot 
technical issues, their personal email ID will be shared with Modality. QC will be done 
by Modality staff who will review audio/video files throughout the conduct of the trial.  
• Adverse events, concomitant medications, vital signs, safety laboratory parameters, and 
electrocardiogram (ECG) data will be collected and assessed throughout the study per the 
SoA. 
Brief Summary: 
The purpose of this study is to measure effect on motor features with CVN424 tablets compared 
to placebo in early, untreated PD and to evaluate the potential of CVN424 to improve motor and 
non-motor functions in subjects with early PD who are not taking dopaminergic or anti-PD 
therapies. 
Study details include: 
The study duration will be up to approximately 18 weeks. 
The screening period duration will be up to 4 weeks. 
The treatment duration will be up to 12 weeks, with a 2-week safety follow-up period. 
The visit frequency will be every 2 weeks. 
Number of Subjects: 
Approximately 62 subjects will be enrolled and will be randomized in a 1:1 ratio to either 
CVN424 150 mg or placebo.  
Eligibility Criteria: 
Inclusion Criteria:  
1. Diagnosis of PD consistent with United Kingdom Brain Bank and Movement Disorder 
Society Research Criteria for the Diagnosis of PD; must include bradykinesia with sequence 
effect, and motor asymmetry if no PD-type rest tremor. 
2. Not receiving anti-parkinsonian therapy, and not expecting to require it for the duration of 
the study. 
3. Men or women of all races who are at least 30 years at Screening. 
4. Modified Hoehn and Yahr ≤ 2.5 at Screening. 
5. Montreal Cognitive Assessment (MoCA) ≥ 26. 

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Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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6. Freely ambulatory at time of Screening (with/without assistive device). 
7. Female subjects of childbearing potential and male subjects with female partners of 
childbearing potential must agree to either remain abstinent or use adequate and reliable 
contraception throughout the study and at least 30 days after the last dose of study drug has 
been taken.  
8. Able and willing to give written (signed and dated) informed consent approved by an 
institutional review board, and to comply with scheduled visits, treatment plan, laboratory 
tests, and other study-related procedures to complete the study. 
9. Approved as an appropriate and suitable candidate by the EAC. 
Exclusion Criteria: 
1. Diagnosis of secondary or atypical parkinsonism. 
2. Diagnosis of parkinsonian motor signs or symptoms ≥ 4 years before Screening Visit. 
3. Previous surgical procedure for PD. 
4. Prior treatment with a dopamine agonist, levodopa, monoamine oxidase B (MAOB) 
inhibitor, or adenosine A2A receptor antagonists for more than 28 total days prior to 
screening. Additional exclusionary parameters around PD treatment include: 
• Treatment with a dopamine agonist within 14 days of Screening. 
• Treatment with a MAOB inhibitor within 90 days of Screening. 
5. Current use of any antipsychotic, metoclopramide, or reserpine. If previously used, this may 
not have been within 28 days of Screening or 5 elimination half-lives (whichever one is 
longer). 
6. Current use of potent Cytochrome P450 (CYP) 3A4/5 inhibitors or inducers. 
7. Clinically significant orthostatic hypotension. 
8. Clinically significant hallucinations requiring antipsychotic use. 
9. Known autoimmune, malignancy (except basal cell carcinoma), or hematologic disease (prior 
or current) likely to interfere with the safe participation of the subject or interfere with 
assessment of safety or efficacy based on the opinion of the investigator and the medical 
monitor. 
10. Any clinically significant medical, surgical, or psychiatric abnormality that, in the judgment 
of the Investigator, is likely to interfere with study compliance, the safe participation of the 
subject, or the assessment of safety or efficacy. 
11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 
2 times the upper limit of normal (ULN), and total bilirubin greater than 1.5 times ULN. 
Subjects with Gilbert’s syndrome may have direct bilirubin measured and would be eligible 
for this study provided that direct bilirubin is ≤ 1.5 times ULN. 

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Protocol Date and Version: 10 July 2024; v3.0 
 
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12. Significant renal impairment as determined by eGFR using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) equation of ≤ 50 mL/min. 
13. Subject has an ECG, prior documentation history, or clinical evidence of potentially unstable 
heart disease, including, but not limited to the following: 
a. QTcF > 470 msec for female subjects; > 450 msec for male subjects 
b. Complete right or left bundle branch block 
c. Myocardial infarction within 1 year prior to screening, unstable angina within 6 
months, or a current concern for symptomatic ischemic heart disease in the opinion of 
the investigator 
d. Clinically significant atrial or ventricular dysrhythmia; the heart must be in 
predominantly normal sinus rhythm 
e. Second- or third-degree atrioventricular (AV) block 
f. NYHA Class II or higher congestive heart failure 
g. Clinically significant cardiomyopathy or cardiac structural abnormality, in the 
opinion of the investigator 
h. Any other cardiac condition that the Investigator feels may predispose the subject to 
ischemia or arrhythmia 
14. Current (or within past 12 months) diagnosis or history of substance abuse (excluding 
nicotine or caffeine) by Diagnostic and Statistical Manual of Mental Disorders 5 criteria. 
15. Positive urine drug screen for tetrahydrocannabinol or any drugs that may affect subject 
safety or interfere with efficacy assessments. 
16. Medical or recreational use of marijuana within 2 months of the Screening Visit. Use of 
cannabidiol (CBD) is prohibited after the Screening Visit and throughout the study. 
17. Currently active major depression as determined by Beck Depression Inventory-II (BDI-II) 
score of > 19. 
18. Active suicidal ideation within 1 year prior to Screening Visit as determined by a positive 
response to Question 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS). 
19. Currently lactating or pregnant, or planning to become pregnant during the study. 
20. Current participation in another investigational clinical study and/or receipt of any 
investigational drug within 90 days prior to Screening. 
21. Prior use of CVN424 investigational product. 
22. Positive test for coronavirus disease 2019 (COVID-19). A subject who tests positive for 
COVID-19 will be eligible to be rescreened once result is negative. 
23. Positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis 
C virus (HCV) consistent with current infection. 

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Protocol Date and Version: 10 July 2024; v3.0 
 
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Summary of Statistical Considerations: 
Sample Size Determination: 
A sample size of approximately 62 subjects with a 1:1 randomization to CVN424 150 mg or 
placebo will provide 75% power to detect a difference of 5 or more points for the sum of 
MDS-UPDRS Parts II and III, assuming a standard deviation (SD) of 8, two-sided alpha of 0.10, 
and a 10% dropout rate. 
The effect size of 5 points for Parts II + III is felt to reflect a meaningful threshold that, if 
achieved, would be comparable to other effective PD medications at 12 weeks (pramipexole, 
levodopa). 
Statistical Analysis Methods: 
The statistical analysis plan (SAP) will be finalized prior to database lock and unblinding of the 
study data and it will include a more technical and detailed description of the statistical analyses 
that will be performed. 
All data analyses will be performed using at least one of the following analysis sets: 
Safety Analysis Set 
Includes all subjects who have received at least 1 dose of study 
drug. All safety population analyses will be based on the treatment 
the subject received. Subjects in this analysis set will be used for 
demographic, baseline characteristics, and safety analyses. 
Modified Intention To 
Treat (mITT) 
Includes all subjects who are randomized, and administered study 
drug, classified according to treatment received, and have at least 
one post-baseline evaluation of efficacy endpoints.  
Intention-to-Treat (ITT) 
Set 
Includes all randomized subjects. 
Completer Set 
Includes all subjects who completed all study treatment for 
12 weeks. 
Pharmacokinetic (PK) 
Analysis Set 
Includes all subjects who received at least 1 dose of study drug 
and have at least 1 measurable plasma concentration. 
Per Protocol Set 
Includes all subjects who completed the study and who received 
all study treatment and have no significant protocol deviations. All 
significant protocol deviations will be assessed, and a decision will 
be made on a case-by-case basis whether to exclude subjects from 
the Per Protocol analysis set prior to breaking the blind. All per 
protocol analyses will be based on the treatment the subject 
received. This set will be used as a sensitivity analysis for primary 
and secondary efficacy outcomes. 
 
 

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Efficacy Endpoint Analysis: 
Each efficacy endpoint (primary and secondary) will include a comparison of CVN424 versus 
placebo. The overall Type I error rate within the family of efficacy endpoints will be maintained 
by using Hochberg’s step-up method to maintain alpha while comparing CVN424 to placebo. 
Efficacy endpoints will be evaluated in a hierarchical manner. 
The primary estimand will be defined as follows:  
Population:  
Subjects with PD as defined by inclusion/exclusion 
criteria and are in the mITT population 
Variable:  
The primary endpoint is the change from Baseline to 
Week 12 in the MDS-UPDRS Part II + Part III 
score (Motor Aspects of Experiences of Daily 
Living + Motor Examination)  
Intercurrent Events and Proposed 
Strategy:  
Treatment Discontinuation: Hypothetical Strategy  
Initiation of Parkinsonian medication for treatment 
of motor features: Hypothetical Strategy 
Population Level Summary: 
Treatment difference of the least-squares mean 
change from Baseline to Week 12 in the 
MDS-UPDRS Part II + Part III score (Motor 
Aspects of Experiences of Daily Living + Motor 
Examination) between placebo and CVN424 groups 
 
Efficacy endpoints will be analyzed in the mITT population using a Mixed Model for Repeated 
Measures (MMRM) with no imputation. This will include response data from each post-baseline 
visit based on the mITT population. The baseline score will be included as a covariate as well as 
the treatment group (150 mg CVN424 or placebo), visits, interaction between treatment group 
and visit, as fixed factors in the MMRM. The difference between CVN424 versus placebo at the 
final visit will be estimated from the MMRM. An unstructured covariance matrix will be used 
initially, and if it fails to converge, a Compound Symmetry (CS) or an AR (1) matrix shall be 
employed, in that order. 
Sensitivity analyses for efficacy endpoints will be conducted on the Intention-to-Treat (ITT) set 
with the multiple imputation method, both assuming that data are missing at random (MAR) and 
missing not at random (MNAR). Missing not at random analyses will include tipping point and 
jump-to-reference (placebo) assumptions. Further sensitivity analysis will be conducted on the 
completer and per-protocol set with MMRM. 
Categorical secondary efficacy endpoints (proportion of subjects improving based on CGI-S or 
PGI-S) will be analyzed in the mITT population using the Cochran–Mantel–Haenszel (CMH) 
test. This test will include the frequency and percentage of proportions for each group, along 
with their respective 95% confidence interval (CI). Additionally, the difference in proportions 
between the treatment groups, along with its CI, will be calculated. As a sensitivity analysis, a 
GLIMMIX model that can incorporate all response data from each post-baseline visit into the 
analysis will be employed. The model will include the treatment group, visit, interaction between 

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Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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treatment groups and visit. An unstructured covariance structure will be used for the repeated 
measures. The odds ratio for the treatment difference, 95% CI for the odds ratio, and p-value will 
be provided. 
Tolerability and Safety Analysis: 
Tolerability will be assessed by comparing percentages of premature drug and study 
discontinuations in the treatment groups (CVN424 versus placebo).  
Treatment emergent adverse events (TEAEs) will be coded according to the Medical Dictionary 
for Regulatory Activities (MedDRA) and summarized by treatment group, organ class and 
preferred term, and duration. Further summaries will be done by seriousness, severity, 
relationship to study treatment and dose at the time of onset. Safety endpoints will be 
summarized with descriptive statistics. 
Data Monitoring Committee: 
No data monitoring committee will be appointed for this study. 
 

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1.2. 
Schema 
Figure 1. Study Schema 
 
MDS-UPRDS = Movement Disorder Society – Unified Parkinson’s Disease Rating Scale; TC = telephone call; QD = once a day. 
 

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1.3. 
Schedule of Assessments (SoA) 
Table 1-1. Schedule of Assessments 
Study Period 
SCR 
Treatment Period 
SFUa 
Study Day/Week 
(Day -28 to 0) 
Baseline 
Week 2 (± 1 
day) 
Week 4 
(± 1 
day) 
Week 6 
Week 8 
(± 1 day) Week 10  
Week 12/ETb 
(± 1 day) 
Week 14c 
Visit Number 
1 
2 
3 
4 
TC1 
5 
TC2 
6 
7 
General and Safety Assessments 
Informed consent 
X 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
X 
 
 
 
 
 
 
 
Enrollment 
Authorization 
Committee Review 
X 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsd 
X 
X 
X 
X 
 
X 
 
X 
X 
Height and weighte 
X 
 
 
 
 
 
 
X 
X 
AE/SAE collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG  
X 
X 
X 
X 
 
X 
 
X 
Xf 
Physical 
examination 
X 
 
 
 
 
 
 
X 
Xf 
Neurological 
examination 
X 
 
 
 
 
 
 
X 
Xf 
Laboratory Assessments (refer to Table 10-1) 
Clinical 
Laboratory Testsg 
X 
 
 
X 
 
X 
 
X 
Xf 
Urine Drug Screen 
X 
X 
 
 
 
 
 
 
 
Pregnancy testh 
X 
X 
 
X 
 
X 
 
X 
X 

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Study Period 
SCR 
Treatment Period 
SFUa 
Study Day/Week 
(Day -28 to 0) 
Baseline 
Week 2 (± 1 
day) 
Week 4 
(± 1 
day) 
Week 6 
Week 8 
(± 1 day) Week 10  
Week 12/ETb 
(± 1 day) 
Week 14c 
Visit Number 
1 
2 
3 
4 
TC1 
5 
TC2 
6 
7 
Plasma 
Pharmacokinetics; 
 
Study-specific Assessments 
MDS-UPDRS Part 
I 
 
X 
X 
X 
 
X 
 
X 
X 
MDS-UPDRS Part 
II 
X 
X 
X 
X 
 
X 
 
X 
X 
MDS-UPDRS Part 
III 
X 
X 
X 
X 
 
X 
 
X 
X 
CGI-Sj 
 
X 
X 
X 
 
X 
 
X 
 
PGI-Sk 
 
X 
X 
X 
 
X 
 
X 
 
ESS 
 
X 
X 
X 
 
X 
 
X 
 
NMSS 
 
X 
 
X 
 
X 
 
X 
 
PDSS-2 
 
X 
 
X 
 
X 
 
X 
 
Starkstein Apathy 
Scale 
 
X 
 
X 
 
X 
 
X 
 
Modified Hoehn 
and Yahr Scale 
X 
 
 
 
 
 
 
 
 
MoCA 
X 
 
 
 
 
 
 
 
 
BDI-II 
X 
 
 
 
 
 
 
 
 
C-SSRS 
("Lifetime”) 
X 
 
 
 
 
 
 
 
 
C-SSRS (“Since 
Last Visit”) 
 
X 
X 
X 
 
X 
 
X 
X 
Modality 
Assessmentsl 
 
X 
X 
X 
X 
X 
X 
X 
X 

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Protocol Date and Version: 10 July 2024; v3.0 
 
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Study Period 
SCR 
Treatment Period 
SFUa 
Study Day/Week 
(Day -28 to 0) 
Baseline 
Week 2 (± 1 
day) 
Week 4 
(± 1 
day) 
Week 6 
Week 8 
(± 1 day) Week 10  
Week 12/ETb 
(± 1 day) 
Week 14c 
Visit Number 
1 
2 
3 
4 
TC1 
5 
TC2 
6 
7 
Schwab and 
England ADL (by 
subject) 
 
X 
 
X 
 
X 
 
X 
 
PD-PROP™ and 
PWB-PROP™ 
 
X 
 
 
 
 
 
X 
X 
Cogstate Cognitive 
Computerized 
Battery 
Assessmentsm 
X 
X 
 
 
 
X 
 
X 
X 
Dreem Overnight 
EEGn 
 
X 
 
X 
 
 
 
X 
X 
Study Intervention 
In Clinic Study 
Drug Dosing 
 
X 
 
 
 
 
 
 
 
Study Drug 
Compliance and 
Accountability 
 
 
X 
X 
 
X 
 
X 
 
Study Drug 
Dispensationo 
 
X 
X 
X 
 
X 
 
 
 
ADL = Activities of Daily Living; AE = adverse event; BDI-II = Beck Depression Inventory-II; CGI-S = Clinical Global Impression Scale—Severity; C-SSRS = Columbia 
Suicide Severity Rating Scale; ECG = electrocardiogram; EEG = electroencephalogram; ESS = Epworth Sleepiness Scale; ET = early termination; MDS-UPDRS = Movement 
Disorder Society – Unified Parkinson’s Disease Rating Scale; MoCA = Montreal Cognitive Assessment; NMSS = Non-motor Symptoms Scale; PD-PROP™ = Parkinson’s 
Disease Patient Report of Problems; PDSS = Parkinson’s Disease Sleep Scale; PGI-S = Patient Global Impression Scale—Severity; PWB-PROP™ = Personal Wellbeing Patient 
Report of Problems; RF = radiofrequency; SAE = serious adverse event; SCR = Screening; SFU = safety follow-up; TC = telephone call. 
a 
Unscheduled visits may be conducted at any time for any reason. 
b 
If a subject discontinues the study prematurely, the Week 12 procedures should be conducted. 
c 
To occur approximately 14 days after Visit 6 (± 1 day). 
d 
Vital signs include blood pressure and pulse rate (pre-dose and 1 hour after dosing), respiration, and body temperature. Refer to Section 8.3.2 for details. Blood pressure will 
be measured after at least 5 minutes supine and again within 1 to 3 minutes of standing. Study personnel will carefully monitor subjects for signs of orthostatic hypotension 
within 3 minutes of standing up from a supine position. 
e 
Height at Screening only. 
f 
To be collected only if there were abnormalities at Week 12 requiring follow-up. 

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g 
Refer to Table 10-1 for a list of all hematology, clinical chemistry, and urinalysis tests to be performed. Coagulation tests will be performed only at Screening. 
h 
For women of childbearing potential, serum pregnancy test at Screening (central laboratory), and urine pregnancy tests at all other indicated visits (on site). Refer to 
Section 8.3.9 for details. 
i 
Plasma pharmacokinetic samples to be collected pre-dose and at 4 hours post dose at Baseline/Visit 2 and at a single timepoint after the last administered dose (which may be 
the day before or on the day of visit) at Weeks 4, 8, and 12/Visits 4, 5, and 6. Time of administration of last administered dose must be recorded accurately to enable 
pharmacokinetic (PK) sample time assignment. At the same time that PK sample is collected, a blood sample for metabolite and
will also be collected.. Refer to 
Section 8.5 for details. 
j 
CGI-S should be completed following the MDS-UPDRS by the same rater to assure that the CGI-S rater has spent some time with the subject just prior to that rating. 
k 
PGI -S may benefit by occurring immediately following the MDS-UPDRS so that the subject has clearly in mind any symptoms they may experience that will be more 
evident after going through the MDS-UPDRS assessment. 
l 
Modality assessments are to be conducted remotely, not during clinic visits (approximately 1-2 days prior to clinical visit). If a subject needs help to troubleshoot technical 
issues, their personal email ID will be shared with Modality. QC will be done by Modality staff who will review audio/video files throughout the conduct of the trial. Subjects 
who are unable to complete the Modality assessments can continue their study participation. 
m 
Cogstate Computerized Battery testing will be conducted twice at screening for familiarization. 
n 
Beacon Dreem Overnight electroencephalogram recording is optional and will occur up to 3 consecutive nights prior to randomization (Baseline) and Week 14 (Visit 7) visits, 
as well as immediately following Week 4 (Visit 4) and Week 12 (Visit 6) visits. Refer to Section 8.2.8.4 for details. 
o 
Subject will be supplied with CVN424 for self-administered, at-home dosing. 
 

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2. 
Introduction 
Parkinson’s Disease (PD) is an adult-onset, progressive neurodegenerative disorder. While it has 
been traditionally regarded as a movement disorder, based on the hallmark features of tremor, 
bradykinesia and rigidity, it also includes a wide range of non-motor manifestations. Although 
currently available therapies can provide symptomatic relief mainly for motor symptoms, an 
effective treatment that could target both motor and non-motor symptoms across the disease 
stages remains a high unmet need (The American Parkinson Disease Association, 2023). 
2.1. 
Study Rationale 
Previous clinical studies, including a Phase 1 safety and pharmacokinetic (PK) study performed 
in 64 healthy volunteers (Study CVN424-101; NCT03657030), a relative bioavailability study 
conducted in 32 healthy volunteers (Study CVN424-102; NCT05635461), and a Phase 2a study 
as an adjunctive treatment in 136 PD subjects (Study CVN424-201; NCT04191577) support the 
use of the selected dose level of CVN424 in this study. The dose of 150 mg per day is expected 
to provide a potentially therapeutic level of G protein-coupled receptor 6 (GPR6) occupancy in 
brain tissue even at its steady state-nadir plasma concentration. Data from the completed Phase 1 
and 2 studies show that CVN424 150 mg is safe and well tolerated in both healthy volunteers 
and individuals with PD taking anti-PD medications. No changes in vital signs or laboratory 
values of clinical significance were observed following CVN424 dosing. 
In the Phase 2a study of CVN424 in subjects with PD and motor fluctuations 
(Study CVN424-201; NCT04191577), CVN424 150 mg demonstrated significant reduction in 
OFF time. Overall, the rates of treatment emergent adverse events (TEAEs) were low compared 
to other dopaminergic medications. Common dopaminergic TEAEs occurred at low rates, many 
in 1 or no subjects. There were no treatment-related severe adverse events (AEs) or serious 
adverse events (SAEs). The discontinuation rate due to TEAEs was low. These findings support 
continuing the development of CVN424 for the treatment of PD. 
The present study will examine the potential of CVN424 to improve motor and non-motor 
functions in individuals with early PD not taking dopaminergic or anti-PD therapies. Thus, this 
study will provide evidence for further pursuing the development of CVN424 for the broader 
treatment of motor and non-motor symptoms of PD.  
2.2. 
Background 
2.2.1. 
Disease Background  
Parkinson’s disease is a progressive neurodegenerative disorder of the nervous system involving 
the gradual loss of dopaminergic neurons in the substantia nigra pars compacta that project to the 
striatum (Wichmann et al, 2011). There are estimated to be approximately 1 million individuals 
in the United States of America (USA) and > 10 million worldwide living with PD (The 
American Parkinson Disease Association, 2023). The clinical hallmark of the disease is the 
motor features of tremor, bradykinesia, rigidity, and postural instability. However, several 
non-motor symptoms, which could include hyposmia, apathy, depression, anxiety, pain, fatigue, 

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Protocol Date and Version: 10 July 2024; v3.0 
 
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sleep disorders, autonomic dysfunction, and impairment in executive functions can be frequently 
identified in virtually all subjects even in the earlier stages (Pont-Sunyer et al, 2015; 
Zis et al, 2015). Clinically manifested PD is preceded by a potentially long prodromal period 
when non-motor symptoms of extra-nigral degeneration are present. Currently, establishment of 
prodromal symptoms has no clinical implications, although better understanding of the 
prodromal phase will probably have consequences when disease-modifying treatments become 
available. At present, no therapy can slow down or arrest the progression of PD but informed by 
new insights in genetic causes and mechanisms of neuronal death, several promising strategies 
are being tested for disease-modifying potential (Bloem et al, 2021). 
Levodopa is the most effective medication therapy in the treatment of PD and is eventually 
needed by all patients as the disease progresses. With time, due to non-physiologic, fluctuating, 
striatal dopamine levels induced by intermittent oral dosing, the usually consistent benefit of 
levodopa gradually becomes variable (motor fluctuations) and abnormal movements can develop 
(dyskinesias) (Olanow et al, 2020). Most patients will eventually experience these motor 
complications as their disease progresses. Current treatments for motor fluctuations include 
levodopa dosage changes and addition of medications that supplement dopaminergic tone 
(dopamine agonists) or delay the breakdown of dopamine (catechol-O-methyl 
transferase [COMT] inhibitors or monoamine oxidase B [MAOB] inhibitors). Apomorphine 
rescue, levodopa gel delivered to the small intestine, and deep brain stimulation may also be 
employed. The efficacy and tolerability of these approaches varies considerably, underscoring 
the need for new treatments that promote consistent motor benefit (Gustavsson et al, 2011). 
GPR6 is an orphan G-protein coupled receptor that is selectively expressed in the brain and is a 
non-dopaminergic target for the treatment of PD. In the brain, GPR6 is predominantly localized 
in the striatopallidal medium spiny neurons (MSNs) that also express dopamine D2 receptors 
(Brice et al, 2021; Lein et al, 2007; Margolin et al, 2022). GPR6 is a constitutively expressed and 
active G-coupled receptor that functionally opposes the Gi-coupled D2 receptors in indirect 
MSNs. Due to progressive loss of dopaminergic innervation, GPR6 is thought to drive the 
hyperactivity of the indirect pathway, likely responsible for several of the clinical features of PD. 
Inhibition of GPR6 using an inverse agonist is predicted to exert anti-parkinsonian effects by 
reducing the overactivity of striatopallidal output neurons in the indirect pathway without 
activating the dopamine D1-receptor-expressing MSNs of the direct (striatonigral) pathway.  
For this reason, CVN424, a potent and selective inverse agonist of GPR6, has therapeutic 
promise to modify the function of pathways relevant in PD pathogenesis in a way that can 
benefit individuals with PD across stages of disease progression as either monotherapy or 
adjunctive therapy.  
2.2.2. 
Investigational Product Background: CVN424 
Human Studies with CVN424 
Three studies have been completed with CVN424 in human subjects:  

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The first study was a Phase 1 single and multiple ascending dose study, with evaluation of food 
effect bioavailability of CVN424 (Study CVN424-101; NCT03657030). This first-in-human 
safety and tolerability study of CVN424 was conducted in 64 healthy male and female 
volunteers; the study findings are summarized in the Investigator’s Brochure (IB). In brief, 
CVN424 was safe and well-tolerated when administered to healthy subjects as a single oral dose 
of between 1 mg and 225 mg or when administered as 7 daily oral doses of between 25 mg and 
150 mg. Study drug-related AEs were reported by 2 of 40 subjects (5.0%) overall in the single 
dose cohorts (feeling hot; headache). Study drug-related AEs were reported by 2 of 24 subjects 
(8.3%) overall in the multiple-dose cohorts (dysphagia; chills). With one exception, all AEs were 
mild in severity; dysphagia of moderate severity led to treatment discontinuation in one subject 
after their third daily dose (75 mg).  
There were no severe or serious AEs, and all AEs resolved by the end of the study. 
Administration of the first dose of CVN424 was associated with an elevation in group mean and 
median body temperature. These changes were detectable at 1 hour post-dose (the earliest 
scheduled post-dose assessment), increased further by 6 hours post-dose, and spontaneously 
returned to baseline by 24 hours post-dose. The increases tended to be larger at higher doses but 
did not appear to be strictly dose proportional. A trend of increased heart rate while standing was 
also observed with a similar time course and relationship to dosage. These trends were not 
considered clinically significant, and no individual vital sign measurement was reported as an 
AE. In the multiple-dose cohorts, elevations in body temperature and heart rate were observed 
only after the first dose of CVN424; this was not observed following subsequent doses. No other 
trends in vital sign measurements were noted. No treatment-related trends were observed in the 
clinical laboratory results or 12-lead electrocardiogram (ECG) measurements.  
In this healthy volunteer study, CVN424 in suspension was rapidly absorbed after oral 
administration in the fasted state; peak plasma concentration was usually attained between 1- and 
3-hours post-dose (median 1.5 hours). When CVN424 was administered after a meal, the peak 
plasma concentration was delayed and decreased, while total exposure was minimally increased, 
compared to the same dose level administered under fasted conditions. With repeated once-daily 
dosing, trough plasma concentrations usually reached a steady-state level by Day 4, with a 
terminal elimination half-life of approximately 33 hours. Accordingly, the PK profile of 
CVN424 in suspension formulation is considered appropriate for once daily oral dosing, with or 
without food.  
The second healthy volunteer study (Study CVN424-102; NCT05635461) was performed to 
determine the relative bioavailability of 150 mg CVN424 administered in a single dose of 
suspension formulation compared to a 150 mg tablet, and to evaluate the food effect 
bioavailability of the 150 mg tablet. The study was conducted in 32 healthy male and female 
subjects. The results of the study showed that CVN424 in an oral tablet formulation administered 
in the fed state has similar exposure (area under the plasma concentration-time curve from time 
0 to 96 hours [AUC0-96h]) to CVN424 suspension administered in the fasted state. While 
maximum plasma drug concentration (Cmax) in the tablet-fed conditions was 15% lower than that 
in the suspension-fasted conditions, for a drug administered for a chronic condition with efficacy 
believed to be driven by duration of exposure, the extent of exposure (AUC parameter) is the 

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most clinically relevant, and therefore the tablet-formulation administered under fed conditions is 
considered appropriate for clinical use.  
No SAEs were reported in this study. Of the 88 reported TEAEs, 84 events were mild, and 
4 events were moderate in severity; 65 events were considered by the Investigator to be related to 
study product. One subject (1%) was discontinued due to an unrelated TEAE (asymptomatic 
coronavirus disease 2019 [COVID-19]). One subject experienced a laboratory-described TEAE 
(asymptomatic bacteriuria) during study period 2 that was determined to be not related to study 
drug; the same subject was discontinued from study in study period 3 due to an 
out-of-reference-range laboratory result in a different parameter (low hemoglobin). All TEAEs 
had resolved without sequelae by the end of the study. There were a few abnormal findings 
across all treatment periods in the clinical laboratory, vital signs, orthostatic vital signs, 12-lead 
ECG, and physical examination assessments; however, these were generally minor and did not 
present any obvious trends. Mean vital sign and orthostatic response results, including body 
temperature and heart rate, remained within normal limits at all post-dose time points across all 3 
treatment periods. No signal in increased suicidal ideation or behavior, as assessed by the 
Columbia Suicide Severity Rating Scale (C-SSRS), was observed throughout the study. 
In a 27-day, Phase 2a study of CVN424 in subjects diagnosed with PD with motor fluctuations 
(Study CVN424-201; NCT04191577), 136 subjects were enrolled and included in the primary 
efficacy analysis and safety analysis set. After the Screening visit, subjects were randomized in a 
1:1:1 ratio into 1 of 3 study groups to receive once-daily low-dose (50 mg) CVN424, high-dose 
(150 mg) CVN424, or matching placebo on Day 0/Visit 1. Subjects not randomized to placebo, 
initiated treatment with 50 mg CVN424 on Day 1 (Visit 2) to allow for baseline assessments on 
Day 0. Thereafter, the low-dose group continued to receive 50 mg per day, while the high-dose 
cohort increased their dosage to 150 mg CVN424 per day, beginning on Day 8 ± 2 days (Visit 3) 
and continued this dose thereafter. The study drug was self-administered each morning on an 
outpatient basis as an oral suspension. Efficacy and safety evaluations were made throughout the 
study and follow-up safety and efficacy assessments occurred on Day 35/Visit 7, approximately 
7 days after the final study drug dose. The primary endpoints for the study were safety and 
tolerability, and the primary efficacy endpoint was OFF time per day.  
In this study, exposure to CVN424 increased with dose level from 50 to 150 mg. The increase in 
exposure with dose was slightly less than dose proportional. After CVN424 50 mg dosing, there 
was a trend for higher exposure in female subjects compared with male subjects. There were no 
apparent differences between female subjects and male subjects after CVN424 150 mg dosing, 
and PK parameters were comparable. After CVN424 50 mg dosing, Cmax and area under the 
plasma concentration-time curve from time 0 to 6 hours (AUC0-6h) were slightly higher in the 
group of subjects with a weight of less than the median weight, compared with the group of 
subjects with a weight of greater than or equal to the median weight. Exposure parameters were 
generally comparable between weight groups after CVN424 150 mg dosing. 
There was a higher incidence of TEAEs and treatment-related TEAEs among subjects treated 
with CVN424 (both dose groups) compared to placebo. Overall, there was a higher incidence of 
TEAEs in the CVN424 150 mg dose group than in the CVN424 50 mg group; however, 

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treatment-related TEAEs had a similar incidence in the 50 mg and 150 mg CVN424 dose groups. 
There were no treatment-related SAEs in this study. One SAE, an event of cardiac arrest in 
1 (2.1%) subject in the CVN424 150 mg group, leading to study drug discontinuation and death, 
was reported as unrelated to study treatment.  
Overall, the most common TEAEs (preferred terms) were headache (1 [2.3%] subject, 
1 [2.2%] subject, and 4 [8.5%] subjects in the placebo, CVN424 50 mg, and CVN424 150 mg 
groups, respectively) and nausea (1 [2.3%] subject, 2 [4.4%] subjects, and 3 [6.4%] subjects in 
the placebo, CVN424 50 mg, and CVN424 150 mg groups, respectively). Overall, 
treatment-related TEAEs were more common in the CVN424 groups than in the placebo group 
(9.1%, 17.8%, and 19.1% of subjects in the placebo, CVN424 50 mg, and CVN424 150 mg 
groups, respectively). Nausea was the most common treatment-related TEAE, with a total of 
4 (2.9%) subjects experiencing 5 treatment-related events (0 [0%] subjects, 2 [4.4%] subjects, 
and 2 [4.3%] subjects in the placebo, CVN424 50 mg, and CVN424 150 mg groups, 
respectively). Hallucinations, somnolence, confusion, orthostatic hypotension, and dyskinesia 
were each observed in fewer than 2 CVN424-treated subjects. Overall, approximately 67% of 
treatment-related TEAEs were mild in severity; the remainder were moderate in severity. There 
was no severe treatment-related TEAEs. There was a higher incidence of moderate 
treatment-related TEAEs in the CVN424 150 mg group (8.5%) than in the CVN424 50 mg 
(2.2%) and placebo groups (4.5%). Overall, 6 (4.4%) subjects discontinued study drug due to a 
TEAE: 2 (4.5%), 1 (2.2%), and 3 (6.4%) subjects in the placebo, CVN424 50 mg, and CVN424 
150 mg groups, respectively. Of the 4 subjects who received CVN424, 2 subjects (1 each in the 
CVN424 50 mg and 150 mg groups) discontinued the study drug due to nausea.  
During the study, no medically significant treatment-related TEAEs (as defined in the protocol) 
occurred. There were no notable changes in laboratory parameters, physical examinations, 
ECGs, and Beck Depression Inventory-II (BDI-II) scores during the study. However, subjects 
receiving CVN424 did experience transient increases in blood pressure and pulse rate on Day 1 
and Day 8. Treatment with CVN424 did not impact impulsivity as assessed by the Questionnaire 
for Impulsive-Compulsive Disorders, with the exception of sex on Day 15. No statistically 
significant correlations were identified between 3-hour post-dose CVN424 concentration and 
ECG or vital signs parameters on Days 1 and 8 for the 50 mg or 150 mg dose levels.  
Treatment with CVN424 was associated with a statistically significant and clinically meaningful 
improvement (relative to placebo) in OFF time with the 150 mg dose at Day 27 in the Primary 
Efficacy Analysis Set. On Day 27, the least squares (LS) mean (± standard error [SE]) for 
average daily hours of OFF time for the CVN424 150 mg vs placebo comparison was -
1.30 (± 0.56) h; p = 0.0418 (Dunnett) and p = 0.0225 (Mixed Model for Repeated Measures 
[MMRM]). The CVN424 50 mg vs placebo comparison was not statistically significant at 
Day 27 (p = 0.3302 [Dunnett]; p = 0.1985 [MMRM]). At Day 27, the LS mean (± SE) for the 
combined CVN424 vs placebo comparison was -1.02 (± 0.50) h; p = 0.0410 (MMRM). Analysis 
of the Secondary Efficacy Analysis Set and a sensitivity analysis yielded results similar to the 
Primary Efficacy Analysis Set. Treatment with CVN424 50 mg and CVN424 150 mg was 
associated with a non-statistically significant numerical increase in ON time without troublesome 
dyskinesia on Day 15 and Day 27 vs placebo. ON time with troublesome dyskinesia was 

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generally constant throughout the course of the trial; changes from baseline to Day 27 were less 
than 12 minutes of worsening. In the CVN424 150 mg group, ON time with dyskinesia was 
generally constant throughout the study; the increase from baseline was less than 6 minutes on 
Day 27. Treatment with CVN424 50 mg and CVN424 150 mg was associated with an increase in 
ON time on Day 15 and Day 27; however, the differences between the CVN424 groups and 
placebo were not statistically significant.  
Treatment with CVN424 did not demonstrate significant benefit on Movement Disorder 
Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I, Part III, or Part IV 
scores. The 150 mg dose was associated with a numerical improvement on the MDS-UPDRS 
Part II scores (motor experiences of daily living) vs placebo, but the difference compared to 
placebo did not reach statistical significance due to the small size of the study. Treatment with 
CVN424 did not demonstrate significant benefit on the Clinical Global Impression (CGI) Scale 
or the Patient Global Impression (PGI) scores. On Day 15 and Day 27, numerically higher 
percentages of CVN424-treated subjects were considered CGI and PGI responders compared 
with the placebo group, but these differences did not reach statistical significance. Treatment 
with CVN424 150 mg led to numeric improvement in the Epworth Sleepiness Scale (ESS) scores 
from baseline, with numerical improvement compared to placebo on Days 15, 27, and 
35 (statistically significant difference on Day 15 only). 
Cerevance Beta Inc. conducted additional post-hoc analyses on the PD diary data, conforming to 
the Food and Drug Administration (FDA) standardized analysis for the PD diary. The PD diary 
was normalized to a 16-hour waking day, required 44/48 entries per day, required having both 
days of diaries, and only included subjects with at least one post-baseline data point. This post-
hoc analysis was first conducted for the full analysis set and confirmed the result of the primary 
analysis, with greater numeric improvement compared to placebo on the reduction in OFF time 
(CVN424 150 mg had a 1.45-hour benefit compared to placebo; nominal p=0.01) and 
improvement in ON time without troublesome dyskinesia (CVN424 had a 0.96-hour benefit 
compared to placebo; p = 0.098). ON time with troublesome dyskinesia was comparable to the 
primary analysis. A second post-hoc analysis was conducted using FDA standards for the PD 
diary analysis, excluding subjects with a Baseline OFF time of 2-3 hours. Previous studies in PD 
subjects with motor fluctuations, with drugs proven effective, have demonstrated that subjects 
with 2-3 hours of OFF time are less likely to demonstrate change for clinical trials in PD subjects 
with motor fluctuations and will be the cutoff for the adequate and well-controlled trial of 
CVN424 in PD subjects with motor fluctuations. This analysis showed a more robust effect of 
CVN424 on reduction in OFF time (1.78-hour improvement vs placebo for the 150 mg dose; 
nominal p = 0.005) and improvement in ON time without troublesome dyskinesia (1.30-hour 
improvement vs placebo for the 150 mg dose; nominal p = 0.042). ON time with troublesome 
dyskinesia was similar to the primary analysis.  
CVN424 is expected to be a pharmacological treatment for PD subjects, as monotherapy or 
adjunctive to dopaminergic therapy, to elicit sustained improvement of motor activity with a 
reduced risk of troublesome dyskinesia compared with dopaminergic therapies. As a novel, 
first-in-class, non-dopaminergic drug for the symptomatic treatment of PD, CVN424 may prove 
useful for treatment of PD. 

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A detailed description of the chemistry, pharmacology, efficacy, and safety of CVN424 is 
provided in the IB. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of CVN424 may be found in the IB.  
2.3.1. 
Risk Assessment 
Overall, CVN424 was safe and well-tolerated in Phase 1 and Phase 2 studies in both healthy 
volunteers and subjects with PD with motor complications. There were no treatment-related 
SAEs, and one severe AE was reported in the CVN424 150 mg group as well as the placebo 
groups. Overall, discontinuation due to AEs has occurred at low rates. There was a very low 
prevalence of known dopaminergic AEs with CVN424 (ie, nausea, vomiting, somnolence, 
dizziness, orthostatic hypotension, hallucinations). In the first-in-human Phase 1 study in healthy 
volunteers, mild and non-clinically significant increases in heart rate and temperature were seen 
with the first dose but did not persist with subsequent dosing. These changes were not observed 
in the Phase 2 study in PD subjects with motor fluctuations. One subject in the Phase 2 PD study 
experienced a cardiovascular SAE resulting in death on Day 2 of study treatment (50 mg dose), 
which was determined to be not related to study drug as the subject had a recent history of active 
coronary artery disease. 
2.3.2. 
Benefit Assessment 
Data from the Phase 2a study in subjects with PD with motor fluctuations demonstrated that 
CVN424 improved motor fluctuations compared to placebo. There were significant and 
clinically meaningful improvements in OFF time compared to placebo with numeric 
improvement in ON time without troublesome dyskinesia. Additional post-hoc analyses 
supported an even more robust effect on motor fluctuations. Additionally, CVN424 
demonstrated signs of improvement in activities of daily living (ADL), overall function and 
statistically significant improvement in daytime alertness compared to placebo measured with 
the ESS. The latter finding is consistent with a direct effect of CVN424 rather than lack of off 
target dopaminergic effects since it was observed with the higher dose of CVN424. In addition, it 
is possible that the improvement of the ESS score may also reflect an improvement of 
cortico-striato-thalamo-cortical (CSTC) connectivity. Basal ganglia and CSTC pathways appear 
involved in the modulation of sleep (Hasegawa et al, 2020). Abnormal and impaired CSTC 
connectivity is involved in the pathophysiology of apathy, fatigue, and cognitive deficits and it 
has also been linked to excessive daytime sleepiness in PD (Gong et al, 2020; Zi et al. 2022). In 
support of this hypothesis are the findings that CVN424 improves behavior in an animal model 
of anhedonia, most likely decreasing the activity of the indirect pathway and thus improving 
ventral striatum-prefrontal cortex connectivity. Overall based on preclinical data as well as the 
previous study in PD subjects, there is reason to hypothesize that CVN424 can have 
anti-parkinsonian benefits in early PD patients. 

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2.3.3. 
Overall Benefit Risk Conclusion 
Overall, based on data to date, the benefit/risk is favorable for CVN424 which has been 
generally safe and well-tolerated. The safety profile has the potential to be differentiated from 
other anti-PD drugs that affect the dopaminergic system but causing lower rates of 
well-established dopaminergic AEs. Additionally, rates of discontinuation due to AEs appear 
lower than with other dopaminergic treatments. Preliminary signs of efficacy are clinically 
meaningful, especially in the setting of lower rates of dopaminergic AEs. As this drug is still 
early in development, this study will have safety assessments of ECGs, clinical laboratory, 
C-SSRS, and collection of AEs over time to evaluate for any potential safety finding. 
Considering the measures taken to minimize risk to subjects participating in this study, the 
potential risks identified in association with CVN424 are justified by the anticipated benefits that 
may be afforded to patients with PD. 
 

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3. 
Objectives, Endpoints, and Estimands 
Table 3-1. Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
Primary Efficacy Endpoint 
To determine the effect of CVN424 on 
motor features of early, untreated subjects 
with Parkinson’s Disease (PD) 
Change from Baseline to Week 12 on the 
Movement Disorder Society – Unified 
Parkinson’s Disease Rating Scale (MDS-UPDRS) 
Part II + Part III (Motor Aspects of Experiences 
of Daily Living + Motor Examination) between 
CVN424 150 mg and placebo 
Secondary 
Secondary Endpoints 
To further define the effects of CVN424 
on motor and non-motor clinical features, 
function, and quality of life in PD 
Change from Baseline to Week 12 in the 
following endpoints, arranged in hierarchical 
order: 
 
• MDS-UPDRS Part III  
• Clinical Global Impression of Severity Scale 
(CGI-S)  
• Patient Global Impression of Severity Scale 
(PGI-S)  
• MDS-UPDRS Part II  
• MDS-UPDRS Part I  
• Epworth Sleepiness Scale (ESS)  
• Non-motor Symptoms Scale (NMSS)  
• Sum of MDS-UPDRS of Parts I, II, and III  
• Parkinson’s Disease Sleep Scale (PDSS-2)  
To assess the safety and tolerability of 
CVN424 in the PD population 
• Incidence and temporal profile of treatment 
emergent adverse events (TEAEs), evaluated 
by type/nature, severity/intensity, seriousness, 
and relatedness  
• Incidence of related TEAEs of moderate or 
severe intensity  
• Incidence of TEAEs leading to withdrawal of 
study drug  
• Incidence of serious adverse events (SAEs) 

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• Changes in physical examination, vital signs 
(blood pressure and heart rate), 
electrocardiogram (ECG), laboratory values, 
and Columbia Suicide Severity Rating Scale 
(C-SSRS)  
• Incidence and timing of abuse-related adverse 
events (AEs)  
• Occurrence of withdrawal symptoms recorded 
at the follow-up visit  
• Percentage of completers  
Exploratory 
Exploratory Endpoints 
To describe the effects of CVN424 on 
motor performance, function, cognition, 
and sleep with other exploratory endpoints 
Change from Baseline to Week 12 in the 
following endpoints:  
 
• Modality Virtual Assessment  
• CogState digital cognitive battery  
• Schwab and England Activities of Daily 
Living (ADL)  
• Starkstein Apathy Scale  
• Electroencephalogram (EEG) derived sleep 
metrics  
• PD-PROP™ and PWB-PROP™ 
• Pharmacokinetics (PK) 
 

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4. 
Study Design 
4.1. 
Overall Design 
This is a Phase 2b multicenter, 12-week, randomized, parallel-group, double-blind, 
placebo-controlled clinical trial of CVN424 150 mg in early, untreated PD. 
There will be 7 in-person visits and 2 telephone visits (see Schema in Section 1.2): 
Screening (V1) 
 
Week 8 (V5) 
Baseline/Randomization (V2) 
 
Week 10 (TC2) 
Week 2 (V3) 
 
Week 12/Early Termination Visit (V6) 
Week 4 (V4) 
 
Week 14/Safety Follow-up Visit (V7) 
Week 6 (TC1) 
 
 
TC = telephone call; V = visit. 
 
After signing the informed consent form (ICF) and after all Screening procedures have been 
performed, subjects will be reviewed by an Enrollment Authorization Committee (EAC) for 
determination of eligibility and suitability for participation. Candidates may complete the 
screening visit in more than one day. Eligible subjects will return for the Baseline Visit and 
assessments will be performed per the Schedule of Assessments (SoA) (see Section 1.3). 
Subjects will be randomized in a 1:1 ratio to CVN424 150 mg or placebo at the Baseline Visit. 
Treatment will be initiated during the Baseline Visit. The study drug will be self-administered 
once daily at a consistent time in the morning and taken with food. The food taken with study 
drug may be a snack or typical morning meal and should include fat in its content (e.g., buttered 
toast, peanut butter on crackers, an egg, cream cheese on a bagel, full fat yogurt or milk). 
At Baseline (Visit 2), the primary endpoint (sum of MDS-UPDRS Part II + Part III), other 
secondary endpoints (Clinical Global Impression of Severity Scale [CGI-S], Patient Global 
Impression of Severity Scale [PGI-S], MDS-UPDRS Part I, ESS, NMSS, PDSS-2), and 
exploratory endpoints (PD-PROP™ and PWB-PROP™) will be assessed. 
In-person clinic visits at Week 2, Week 4, Week 8, and Week 12 will assess the primary and 
secondary endpoints as well as exploratory endpoints per the SoA (see Section 1.3). Telephone 
visits will be conducted at Week 6 and Week 10 for safety, and to check that Modality 
assessments have been completed. 
Remote data collection between clinic visits will be conducted using the following technologies: 
• Beacon Dreem overnight EEG: a wearable device that collects EEG signals to measure 
sleep metrics. This optional activity will be collected up to 3 consecutive nights before or 
after specified in-person clinic visits, per the SoA (see Section 1.3). Subjects who opt out 
of the Beacon Dreem EEG collection can continue their study participation in other study 
activities. 

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o Modality Assessments: an audio-visual conversational technology to conduct 
customizable video interviews with subjects. Subjects will interact with a virtual agent 
using a web browser on the device of their choice to complete assessments designed to 
test various aspects of their speech, visuo-motor, prosodic (stress and intonation patterns), 
cognitive, and linguistic function. This will also include Parkinson’s Disease Patient 
Report of Problems (PD-PROP™), Personal Wellbeing Patient Report of Problems 
(PWB-PROP™) and Schwab and England ADL to enquire about specific problems and 
symptoms they are experiencing in daily and social activities. Subjects will be asked to 
complete the assessments at home (approximately 1-2 days prior to clinic visit). The 
assessments should take about 30 minutes to complete. Subjects who cannot complete all 
of the exploratory assessments, but who otherwise remain eligible for the study, can 
continue their participation. If a subject needs help to troubleshoot technical issues, their 
personal email ID will be shared with Modality. QC will be done by Modality staff who 
will review audio/video files throughout the conduct of the trial. 
• Adverse events (AEs), concomitant medications, vital signs, safety laboratory parameters, 
and ECG data will be collected and assessed throughout the study per the SoA (see 
Section 1.3). 
• Subjects will return for a safety follow-up visit two weeks after Visit 6 (ie, last day of study 
drug dosing). Subjects will complete assessments per the SoA (see Section 1.3). 
4.1.1. 
Study Duration for an Individual Subject 
The study duration for an individual subject will be up to 18 weeks and will include an eligibility 
screening period of up to 4 weeks, treatment duration of up to 12 weeks, and 2 weeks of safety 
follow-up.  
4.1.2. 
Number of Subjects 
Approximately 62 subjects will be enrolled into the study with a 1:1 randomization to CVN424 
or placebo.  
4.1.2.1. 
Replacement of Subjects 
Subjects who withdraw or discontinue early from the study may be replaced at the Sponsor’s 
discretion. 
4.1.3. 
Number of Sites 
Approximately 25 sites in the USA. 
4.2. 
Scientific Rationale for Study Design 
Previous clinical studies, including two Phase 1 studies in healthy volunteers and a Phase 2a 
study as an adjunctive treatment in subjects with PD and motor fluctuations, support the use of 
CVN424 in this study. Data from these studies showed that CVN424 150 mg was safe and well 
tolerated in both healthy volunteers and individuals with PD taking anti-PD medications. No 
changes in vital signs or laboratory values of clinical significance were observed following 

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Protocol Date and Version: 10 July 2024; v3.0 
 
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CVN424 dosing. In the Phase 2a study, CVN424 150 mg demonstrated significant reduction in 
OFF time. 
This study will examine the potential of CVN424 to improve motor and non-motor functions in 
individuals with early PD not taking dopaminergic or anti-PD therapies, to provide the evidence 
for further pursuing the development of CVN424 for the broader treatment of the motor and 
non-motor symptoms of PD. 
For further details, see Background – Section 2.2. 
4.3. 
Justification for Dose 
The dose of CVN424 that will be administered in this study (150 mg per day) is expected to 
provide a high level of GPR6 occupancy in brain tissue even at its steady-state nadir plasma 
concentration, which is predicted to achieve potentially therapeutic concentrations of drug 
exposure. CVN424 150 mg tablets will be administered orally, once a day,  in the morning with a 
snack or typical morning meal, which should include fat in its content.. 
In the healthy volunteer study CVN424-102 (Study CVN424-102; NCT05635461), oral 
administration of 150 mg CVN424 tablets under fed conditions (approximately 30% fat content) 
resulted in an approximately 62% increase in overall exposure (AUCs) and a 204% increase in 
peak exposure (Cmax) of plasma CVN424 compared to 150 mg CVN424 tablets given under 
fasted conditions. These results indicate that a high-fat, high-calorie meal increases both the 
extent and peak exposures of CVN424 tablets in plasma. 
4.4. 
End of Study Definition 
A subject is considered to have completed the study if he or she has completed all scheduled 
visits of the study, including the 2-week safety follow-up period (Week 14; refer to the SoA, 
Section 1.3). 
4.5. 
End of Treatment Definition 
A subject is considered to have completed treatment if he or she has completed 12 weeks of 
treatment with once daily dosing with CVN424 150 mg or placebo tablets. 

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5. 
Indication & Study Population 
Before any study-specific activities/procedures, the appropriate written informed consent must 
be obtained (see Section 10.1.3). Prospective approval of protocol deviations to recruitment and 
enrollment criteria, also known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Subjects are eligible to be included in the study only if all of the following criteria apply: 
1. Diagnosis of PD consistent with United Kingdom Brain Bank and Movement Disorder 
Society Research Criteria for the Diagnosis of PD; must include bradykinesia with sequence 
effect, and motor asymmetry if no PD-type rest tremor. 
2. Not receiving anti-parkinsonian therapy, and not expecting to require it for the duration of 
the study. 
3. Men or women of all races who are at least 30 years at Screening. 
4. Modified Hoehn and Yahr ≤ 2.5 at Screening. 
5. Montreal Cognitive Assessment (MoCA) ≥ 26. 
6. Freely ambulatory at time of Screening (with/without assistive device). 
7. Female subjects of childbearing potential and male subjects with female partners of 
childbearing potential must agree to either remain abstinent or use adequate and reliable 
contraception throughout the study and at least 30 days after the last dose of study drug has 
been taken. 
8. Able and willing to give written (signed and dated) informed consent approved by an 
institutional review board, and to comply with scheduled visits, treatment plan, laboratory 
tests, and other study-related procedures to complete the study. 
9. Approved as an appropriate and suitable candidate by the EAC. 
5.2. 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
1. Diagnosis of secondary or atypical parkinsonism. 
2. Diagnosis of parkinsonian motor signs or symptoms ≥ 4 years before Screening Visit. 
3. Previous surgical procedure for PD. 
4. Prior treatment with a dopamine agonist, levodopa, MAOB inhibitor, or adenosine A2A 
receptor antagonists for more than 28 total days prior to screening. Additional exclusionary 
parameters around PD treatment include: 
• Treatment with a dopamine agonist within 14 days of Screening. 
• Treatment with a MAOB inhibitor within 90 days of Screening. 

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5. Current use of any antipsychotic, metoclopramide, or reserpine. If previously used, this may 
not have been within 28 days of Screening or 5 elimination half-lives (whichever one is 
longer). 
6. Current use of potent Cytochrome P450 (CYP) 3A4/5 inhibitors or inducers. 
7. Clinically significant orthostatic hypotension. 
8. Clinically significant hallucinations requiring antipsychotic use. 
9. Known autoimmune, malignancy (except basal cell carcinoma), or hematologic disease (prior 
or current) likely to interfere with the safe participation of the subject or interfere with 
assessment of safety or efficacy based on the opinion of the investigator and the medical 
monitor. 
10. Any clinically significant medical, surgical, or psychiatric abnormality that, in the judgment 
of the Investigator, is likely to interfere with study compliance, the safe participation of the 
subject or the assessment of safety or efficacy. 
11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 
2 times the upper limit of normal (ULN), and total bilirubin greater than 1.5 times ULN. 
Subjects with Gilbert’s syndrome may have direct bilirubin measured and would be eligible 
for this study provided that direct bilirubin is 1.5 times ULN. 
12. Significant renal impairment as determined by eGFR using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) equation of ≤ 50 mL/min. 
13. Subject has and ECG, prior documented history, or clinical evidence of potentially unstable 
heart disease, including, but not limited to the following: 
a. QTcF > 470 msec for female subjects; > 450 msec for male subjects 
b. Complete right or left bundle branch block 
c. Myocardial infarction within 1 year prior to screening, unstable angina within 6 months, 
or a current concern for symptomatic ischemic heart disease in the opinion of the 
investigator 
d. Clinically significant atrial or ventricular dysrhythmia; the heart must be in 
predominantly normal sinus rhythm 
e. Second- or third-degree atrioventricular (AV) block 
f. NYHA Class II or higher congestive heart failure 
g. Clinically significant cardiomyopathy or cardiac structural abnormality, in the opinion of 
the investigator 
h. Any other cardiac condition that the Investigator feels may predispose the subject to 
ischemia or arrhythmia 
14. Current (or within past 12 months) diagnosis or history of substance abuse (excluding 
nicotine or caffeine) by Diagnostic and Statistical Manual of Mental Disorders 5 criteria. 
15. Positive urine drug screen for tetrahydrocannabinol or any drugs that may affect subject 
safety or interfere with efficacy assessments. 

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16. Medical or recreational use of marijuana within 2 months of the Screening Visit. Use of 
cannabidiol (CBD) is prohibited after the Screening Visit and throughout the study. 
17. Currently active major depression as determined by BDI-II score of > 19.  
18. Active suicidal ideation within 1 year prior to Screening Visit as determined by a positive 
response to Question 4 or 5 on the C-SSRS. 
19. Currently lactating or pregnant, or planning to become pregnant during the study. 
20. Current participation in another investigational clinical study and/or receipt of any 
investigational drug within 90 days prior to Screening. 
21. Prior use of CVN424 investigational product. 
22. Positive test for COVID-19. A subject who tests positive for COVID-19 will be eligible to be 
rescreened once result is negative. 
23. Positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis 
C virus (HCV) consistent with current infection. 
5.3. 
Prohibited Medications and Lifestyle Considerations 
Use of the agents in Table 5-1 (prescription or nonprescription) is prohibited from the time 
points specified until completion of all study activities. 
The following medications are not prohibited prior to or during the study but should only be used 
if medically necessary because they may theoretically diminish CVN424 bioavailability:  
• Proton pump inhibitors (eg, omeprazole, pantoprazole, lansoprazole)  
• Histamine H2-receptor antagonists (eg, cimetidine, ranitidine, famotidine, nizatidine) 
• Antacids taken within 4 hours of dosing 
Use of CBD is prohibited after the Screening Visit and throughout the study. 
All concomitant medications, including proton pump inhibitors and H2-receptor antagonists, will 
be documented in the electronic Case Report Form (eCRF). Subjects will be instructed not to 
take any new medications without first consulting with the Investigator or their delegate. 
Table 5-1. Prohibited Medications and Dietary Products 
Within 28 days prior to randomization or 5 elimination half-lives, whichever is longer 
• Antipsychotics: Both typical and atypical antipsychotics, including, but not limited to: 
aripiprazole, fluphenazine, haloperidol, perphenazine, pimozide, thiothixene, 
trifluoperazine, loxapine, molindone, chlorpromazine, mesoridazine, thioridazine, 
clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and pimavanserin. 
• Other: metoclopramide, prochlorperazine, promethazine  

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• Nutraceuticals (eg, St. John’s wort, ginseng, kava, Ginkgo Biloba, Chinese herbs, and 
melatonin) 
• Mucuna Pruriens 
• Amphetamines 
• Known strong inhibitors/inducers of cytochrome P-450 3A4/5, including rifampin, 
clarithromycin, ketoconazole, and itraconazole [CYTOCHROME P450 DRUG 
INTERACTION TABLE (iu.edu)]. 
5.3.1. 
Study Drug and Meals Considerations 
Subjects will be dispensed study drug to be administered at home. The study drug should be 
taken once daily at a consistent time in the morning and taken with food. The food taken with 
study drug may be a snack or typical morning meal and should include fat in its content (e.g., 
buttered toast, peanut butter on crackers, an egg, cream cheese on a bagel, full fat yogurt or 
milk). 
5.3.2. 
Study Drug Interruption or Suspension 
Study drug may be temporarily suspended based on investigator judgement (eg, in response to a 
clinically significant adverse event suspected to be related to the study drug) and only after 
consultation with the Medical monitor.  
A suspension may happen once during the study and should not exceed 10 days in duration. 
If a participant cannot successfully resume investigational drug after suspension, they will 
discontinue study drug but may remain in the study for continued assessment. 
5.3.3. 
Alcohol 
Subjects must abstain from regular alcohol consumption exceeding 7 drinks/week for female 
subjects and 14 drinks/week for male subjects (1 drink = 5 ounces [150 mL] of wine or 
12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor). 
5.3.4. 
Activity 
Subjects must abstain from strenuous exercise for 24 hours before each blood collection for 
clinical laboratory tests. 
5.4. 
Screen Failures 
Screen failures are defined as subjects who consented to participate in the clinical trial but do not 
meet eligibility criteria and cannot be randomized in the study. Minimal information to be 
collected for screen failure documentation includes demography, reason for screen failure 
details, and eligibility criteria. 

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Subjects who do not meet the criteria for participation in this trial (screen failure) may be 
rescreened if the reason for screen failure has resolved. Rescreened subjects must be assigned a 
new subject identification number. A subject can be rescreened no more than 2 times.  

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6. 
Investigational Product and Concomitant Therapy 
The CVN424 150 mg tablet drug product is a film-coated, immediate release tablet. The 
formulation is comprised of drug substance, CVN424, compendial excipients (mannitol, 
microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon 
dioxide, and magnesium stearate) and film-coating (Opadry®). 
The matching placebo tablet components are microcrystalline cellulose, mannitol, magnesium 
stearate, and film-coating (Opadry®). 
CVN424 150 mg tablets and matching placebo are packaged and labeled using the 
randomization code. Each bottle of study drug will be labeled in English and the language 
appropriate to the investigational site. Label text will be approved according to the Sponsor’s 
procedures. Bottles will be labeled with pertinent study information and caution statements in 
accordance with regulatory requirements. 
Refer to the Pharmacy Manual for more detailed information regarding the storage, preparation, 
destruction, and administration of each treatment. 
6.1. 
Investigational Product Dispensation, Dosing and Regimen 
The Investigator or Investigator’s designee will instruct each subject (and their home caregiver, 
where applicable) on the dosing regimen. Study drug will be dispensed as 30 count tablets in 
properly labeled high-density polyethylene (HDPE) bottles.  
The study drug will be self-administered once daily at a consistent time in the morning and taken 
with food. The food taken with study drug may be a snack or typical morning meal and should 
include fat in its content (e.g., buttered toast, peanut butter on crackers, an egg, cream cheese on 
a bagel, full fat yogurt or milk).. 
The planned study arms and dose levels are provided in Table 6-1. 
Table 6-1. Study Arms 
FDA = US Food and Drug Administration. 
Arm Title 
Study Drug 
Placebo 
Arm Type 
CVN424 150 mg per day 
Matching Placebo  
Arm Description 
31 subjects receive 1 tablet 
(150 mg) per day 
31 subjects receive 1 tablet 
per day 
Associated Product 
Labels 
Each label will include the protocol number; unique bottle 
identification number; contents; route of administration; storage 
conditions; directions for use; FDA Caution Statement; Sponsor 
name, address and phone number; and a space for the sites to 
record the date dispensed, subject identification number and 
subject initials 

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No dosage adjustments are anticipated in this study.  
In the event a subject misses taking a dose of study drug at the scheduled time, the subject should 
take that dose as soon as they remember, but no later than 6 hours beyond the scheduled time of 
administration. If it is greater than 6 hours beyond the scheduled dose, the subject should be 
instructed to skip that dose and resume dosing at the next regularly scheduled time. 
6.2. 
Investigational Product Assignment, Storage, and Accountability 
6.2.1. 
Investigational Product Storage 
All study drug stored at the investigative site must be kept in an appropriate, limited-access, 
secure storage location until it is used or returned to the Sponsor or designee for destruction. All 
study drug must be stored under the conditions specified on the label and remain in the original 
container until dispensed. Store the CVN424 150 mg tablets at controlled room temperature, 
59°F to 77°F (15°C to 25°C).  
6.2.2. 
Investigational Product Assignment Procedure 
Randomization assignments will be generated using an online interactive response technology 
(IRT) system. All randomization information is accessible only by authorized study personnel. 
Study drug will be dispensed to subjects as tablets in properly labeled, capped bottles. 
6.2.3. 
Investigational Product Accountability 
Only subjects enrolled in the study may receive study drug, and only authorized site staff may 
supply or administer study drug. All study drug must be stored in a secure, environmentally 
controlled, and monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the Investigator and authorized site staff. The Investigator must 
maintain records of all study drug delivery to the site, site inventory used by each subject, and 
returned to the Sponsor or designee. The Investigator, institution, or the head of the medical 
institution (where applicable) is responsible for study drug accountability, reconciliation, and 
record maintenance (ie, receipt, reconciliation, and final disposition records). 
Drug supplies will be counted and reconciled at the site before being returned to the Sponsor or 
designee or before a site follows institutional policies for destruction. 
Upon receipt of the study drug, the Investigator or designee must verify the contents of the 
shipments against the packing list and ensure the quantity is correct and received within the 
labeled storage conditions. The Investigator must maintain 100% accountability for all study 
drug received and dispensed during their full participation in the study. Proper drug 
accountability includes, but is not limited to: 
• Frequently verifying that actual inventory matches documented inventory; verifying that all 
bottles used are documented accurately on the log; and verifying that required fields are 
completed accurately and legibly. 

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If any dispensing errors or discrepancies are discovered, the Sponsor must be notified 
immediately. 
The Investigator or designee must record the current inventory of all study drug on a 
Sponsor-approved drug accountability log. The following information will be recorded at a 
minimum: protocol number and title, name of Investigator, site identifier and number, 
description of study drug, retest/expiry date, and amount dispensed, including the initials of the 
person dispensing and receiving the study drug.  
Subjects will return their bottles of study drug, whether empty or unused, at each in-person clinic 
study visit. The Investigator or designee must record the number of empty and unused bottles 
returned. 
During the study, the assigned monitor will perform clinical study material accountability and 
reconciliation before clinical study materials are returned to the Sponsor or its designee for 
destruction. The Investigator will retain the original documentation regarding clinical study 
material accountability, return, and/or destruction, and copies will be sent to the Sponsor or 
designee. 
The Investigator will be notified of any expiry date or retest date extension of clinical study drug 
during the study conduct.  
Refer to the Pharmacy Manual for more detailed information regarding the storage, preparation, 
destruction, and administration of each treatment. 
6.3. 
Randomization and Blinding 
Subjects who continue to meet all the inclusion criteria and do not meet any of the exclusion 
criteria at the Baseline visit will be randomly assigned in a 1:1 ratio to CVN424 150 mg or 
placebo once daily using an online IRT system.  
This is a double-blind study. All individuals involved in the conduct of the study, including 
subjects, Investigators, site staff, clinical research organization personnel, and Sponsor study 
personnel, will remain blinded to treatment assignments and dose throughout the study. The 
randomization schedule will not be released until all subjects have completed the study and the 
database has been locked.  
At all times, study personnel will attempt to safeguard the integrity of the blind to minimize bias 
in the conduct of the study. If the Investigator or site study staff becomes aware of a subject’s 
study treatment assignment, efforts should be made to not disclose assignments to other study 
staff, subjects, or their caregivers. 
6.3.1. 
Breaking the Blind 
Breaking the blind should not occur, except in the case of a medical emergency if specific 
emergency treatment or course of action would be determined by knowing the treatment 

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assignment of the subject. If possible, the Investigator should discuss the situation with the 
medical monitor before breaking the blind. 
If an Investigator needs to know a subject’s treatment assignment for a medical emergency, the 
Investigator may access this information via the IRT system.  
If the blind is broken for an individual subject, the Sponsor should be informed as soon as 
possible. The date and reason for the unblinding must be documented in the subject’s source 
documentation and eCRF. Any documentation indicating the subject’s treatment assignment 
must be retained with the subject’s source documents in a secure manner (ie, sealed envelope) so 
as not to unblind the treatment assignment to other site or Sponsor personnel. 
If the blind is broken for a subject, the decisions to continue or discontinue study drug and 
whether the subject is asked to continue or discontinue the study will be based on the nature of 
the medical emergency as judged by the Investigator in consultation with the medical monitor, 
and not necessarily because the study blind was broken (although this may be a factor in the 
decisions). 
When an AE is an unexpected, related SAE, the blind will be broken by the Sponsor only for that 
specific subject. The blind will be maintained for persons responsible for the ongoing conduct of 
the study and those responsible for data analysis and interpretation of results at the conclusion of 
the study. Unblinded information will only be accessible to those who need to be involved in the 
safety reporting to health authorities and an Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC). Investigators will receive only blinded information unless unblinded 
information is judged necessary for safety reasons. 
6.4. 
Study Drug Compliance 
Study drug will first be administered while subjects are at the clinical site (at the Baseline Visit). 
Subsequent doses will be self-administered at home. The date and time of each observed dose 
will be recorded in the source documents and in the eCRFs.  
Treatment compliance will be assessed at each study visit as indicated in the SoA (see 
Section 1.3). Subjects will be instructed to bring all used/unused study drug bottles to each study 
visit. To assess subjects’ compliance with study drug, manual tablet counts of study drug will be 
performed. At each visit, subjects will return all used/unused study drug bottles to the site, 
whether empty or full, for assessment of treatment compliance. 
Overall, treatment noncompliance is defined as taking ≤ 80% or ≥ 120% of the planned study 
drug during a treatment period. 
If a subject is found to be noncompliant with dosing, the Investigator will discuss the reasons for 
the noncompliance and then counsel the subject on the need to remain compliant.  

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Subjects who are significantly noncompliant may be discontinued from the study. A subject will 
be considered significantly noncompliant if the subject intentionally missed more than 20% of 
study drug during the study.  
An inventory of the study drug dispensed will be performed by the site staff or pharmacist and 
recorded onto the Drug Accountability Log. 
6.5. 
Treatment of Overdose 
An overdose is defined as a known deliberate or accidental administration of investigational 
study drug, to or by a study subject, at a dose above that which is assigned to that individual 
subject according to the study protocol. For this study, any dose of CVN424 greater than 300 mg 
within a 24-hour time period will be considered an overdose. 
All cases of overdose (with or without associated AEs) will be documented on an Overdose page 
of the eCRF. Cases of overdose without manifested signs or symptoms are not considered AEs. 
AEs associated with an overdose will be documented on AE eCRF(s). 
Serious adverse events (SAEs) associated with overdose should be reported according to the 
procedure outlined in Sections 8.4.4 and 10.3.4, Reporting of SAEs. 
In the event of an overdose, supportive measures should be employed as needed, eg, 
administration of supportive therapy as dictated by the subject’s clinical status, and initiation of 
additional clinical monitoring. 
In the event of an overdose, the Investigator should evaluate the subject to determine, in 
consultation with the medical monitor, if possible, whether study drug should be interrupted, 
closely monitor the subject for any AE/SAE and laboratory abnormalities, obtain a plasma 
sample for PK analysis within 4 days from the date of the last dose of study drug if requested by 
the medical monitor (determined on a case-by-case basis), and document the quantity of the 
excess dose as well as the duration of the overdose. 
6.6. 
Prior and Concomitant Therapy 
Concomitant medications are any drug given in addition to the study drug. These may be 
prescribed by a physician or over the counter.  
At each study visit, subjects will be asked whether they have taken any medication other than the 
study drug (used from the signing of the ICF through the end of the study), and all medication, 
including vitamin supplements, over-the-counter medications, and oral herbal preparations, must 
be recorded in the eCRF. Documentation will include generic medication name, dose, unit, 
frequency, route of administration, start and end dates, and reason for use. 
Subjects must abstain from taking prescription or nonprescription drugs (including vitamins, 
recreational drugs, and dietary or herbal supplements) as specified in Table 5-1 within 28 days or 
5 elimination half-lives (whichever is longer) before the start of study drug until completion of 
the follow-up visit. Proton pump inhibitors, histamine H2-receptor antagonists and antacids 

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(taken within 4 hours of dosing) are not prohibited prior to or during the study but should only be 
used if medically necessary because they may theoretically diminish CVN424 bioavailability. 
Subjects will be instructed not to take any new medications without first consulting with the 
Investigator or their delegate. 
Paracetamol/Acetaminophen, at doses of ≤ 2 g/day, is permitted for use any time during the 
study, under the supervision of the Investigator. Other concomitant medications may be 
considered on a case-by-case basis by the Investigator, in consultation with the medical monitor, 
if required.  
Anti-parkinsonian medications: Subjects can be enrolled in the study if they are not receiving 
anti-parkinsonian medications at the time of screening and if they are not expected to require 
symptomatic treatment for the entire length of the study. If medically necessary, subjects may 
need to begin medications to treat the motor symptoms of PD during the study. This is not 
actively encouraged, but is permitted in the judgment of the subject, Investigator, and in 
consultation with the medical monitor. Subjects who start PD medication will be taken off study 
drug, followed for safety, and complete study activities as best as possible. 
6.6.1. 
Rescue Medicine 
Not applicable. 

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7. 
Discontinuation of Study Drug and Subject Early 
Termination/Discontinuation or Withdrawal 
7.1. 
Discontinuation of Study Drug 
Subjects who discontinue from study drug will be followed up for safety. Remaining study 
assessments and procedures should be completed as indicated by the SoA (see Section 1.3). 
7.2. 
Subject Early Termination/Discontinuation/Withdrawal From the 
Study 
Subjects are free to voluntarily withdraw from the study at any time upon request. The 
Investigator may remove a subject from the study if, in the Investigator’s opinion, it is not in the 
best interest of the subject to continue the study. Subjects may be early terminated/discontinued 
due to the following (not inclusive): 
• Occurrence of AE(s): Clinical or laboratory events that, in the medical judgement of the 
Investigator, are grounds for discontinuation of the subject from the study. 
• Protocol deviation: The subject failed to adhere to protocol requirements. Unless either the 
Investigator or medical monitor considers that continuation in the study may pose a safety 
risk to the subject, the subject may continue in the study. The protocol deviation will be 
documented in the subject's source documentation and eCRF. 
• Withdrawal of consent: The subject provides a verbal or written request to withdraw from the 
study and withdraws consent to ensure that data collected up to the time of study withdrawal 
can be used for analysis. 
• Physician decision. 
• Lost to follow-up: A subject will be considered lost to follow-up if the subject repeatedly 
fails to return for scheduled visits and is unable to be contacted by the study site after 
multiple attempts (at least 3 times). Several attempts to contact the subject will be made by 
study staff and documented in the subject’s source documentation. The date that the subject 
is considered lost to follow-up and the reason for the subject’s subsequent discontinuation 
from the study will be documented in the subject’s source documentation and eCRF.  
• Voluntary withdrawal from the study: The subject verbalizes or states in writing their desire 
to withdraw from the study. Data already collected remains as part of the study. The reason 
for withdrawal, if provided, should be recorded in the eCRF. 
Note: Attempts should be made to determine the underlying reason for the withdrawal, and, 
where possible, the primary underlying reason should be recorded (eg, withdrawal due to an 
AE; withdrawal due to relocation). 
• The Sponsor decides to terminate the study. 

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If a subject discontinues the study at any time after enrollment, but prior to the final scheduled 
study visit, the Investigator will promptly notify the Sponsor and make every effort to have the 
subject complete the safety follow-up assessment (ie, early termination (ET) assessments 
indicated in SoA [see Section 1.3]) as soon as feasible after discontinuation. Subjects who 
discontinue from the study early will be asked to return for an Early Termination Visit. The date 
of and reason for the subject’s discontinuation from the study will be documented in the 
subject’s source documentation and eCRF. All data collected up to the time of early termination 
will be used for final analyses, unless the subject withdraws consent to use the study data. 
All subjects who discontinue the study with ongoing clinically significant clinical or laboratory 
findings will be followed until the finding is resolved or deemed medically stable by the 
Investigator in consultation with the medical monitor. 
Subjects who are lost to follow-up or discontinue the study early may be replaced if deemed 
necessary by the Sponsor. 
7.3. 
Lost to Follow-up 
If a subject fails to return for clinic visits, every attempt must be made to make contact.  
The site will attempt to contact the subject and reschedule the missed visit as soon as possible, 
counsel the subject on the importance of maintaining the assigned visit schedule and assess if the 
subject wishes to and/or should continue in the study. 
Before a subject is deemed lost to follow-up, the Investigator or designee will make every effort 
to regain contact with the subject (where possible, 3 telephone calls and, if necessary, a certified 
letter to the subject’s last known mailing address or local equivalent methods). These contact 
attempts should be documented in the subject’s medical record or study file.  
If the investigative site is not able to reach or make contact with the subject or caregiver, he or 
she will be considered to have been lost to follow-up. 
 

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8. 
Study Assessments and Procedures 
Study procedures and their timing are summarized in the SoA (see Section 1.3). Protocol waivers 
or exemptions are not allowed. 
Immediate safety concerns should be discussed with the Sponsor immediately upon occurrence 
or awareness to determine if the subject should continue or discontinue study drug. 
Adherence to the study design requirements, including those specified in the SoA (see 
Section 1.3), is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria. The Investigator will maintain a screening log to record details of all 
subjects screened and to confirm eligibility or record reasons for screening failure, as applicable. 
Safety/laboratory/analyte results that could unblind the study will not be reported to investigative 
sites or other blinded personnel until the study has been unblinded. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. 
8.1. 
General Assessments 
8.1.1. 
Medical History 
The Investigator or designee will collect a complete medical history that started prior to 
screening through time of signing of informed consent. Medical history will include information 
on the subject’s concurrent medical conditions. All findings will be recorded in the medical 
history eCRF. The current severity grade will be collected for each condition that has not 
resolved. 
8.1.2. 
Prior Therapy 
Prior therapies that were being taken/used from 28 days (90 days for MAOB inhibitors) prior to 
enrollment through the first dose of investigational product, will be collected. 
For prior PD therapies, collect therapy name, dose, unit, frequency, start date, and stop date. For 
all other prior therapies, collect therapy name, start, and stop date. 
8.1.3. 
Demographics 
Demographic data will be collected at Screening, and will include sex, age, race, and ethnicity. 
The data will be collected to study their possible association with subject safety and treatment 
effectiveness.  
8.2. 
Efficacy Assessments 
Planned timepoints for all efficacy assessments are provided in the SoA (see Section 1.3). 

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8.2.1. 
Movement Disorders Society – Unified Parkinson's Disease Rating Scale 
(MDS-UPDRS)  
The MDS-UPDRS (Goetz et al, 2008) is a comprehensive 50-question assessment of both motor 
and non-motor symptoms associated with PD. It features sections that require independent 
completion by people with PD and their caregivers, as well as sections to be completed by an 
approved rater. At each site, the same rater should perform all MDS-UPDRS assessments 
throughout the study, as best  possible. 
• Part I: Non-motor Aspects of Experiences of Daily Living. This has 13 items and is further 
grouped into two parts: 
o Part IA has items associated with behaviors that are assessed and completed by the rater 
based on information provided by the subject and caregiver. 
o Part IB is self-administered and completed by the subject with or without assistance or 
input from the caregiver, but independently of the rater. 
Responses to both IA and IB can be reviewed by the rater to ensure information accuracy and/or 
provide additional information or clarification of the test items, if necessary. 
o Part II: Motor Aspects of Experiences of Daily Living. This part has 13 items. It is a 
self-administered questionnaire completed by the subject, which can be reviewed by the 
Investigator to ensure all responses are completed.  
o Part III: Motor Examination. This part of the MDS-UPDRS has 18 items evaluating the 
motor signs of PD (bradykinesia, tremor, rigidity, hand and leg movements, gait, balance, 
etc.).  
• Part IV: Motor Complications. Part IV data will not be collected and used in the trial.  
It is estimated that the MDS-UPDRS would take around 30 minutes to complete.  
8.2.2. 
Clinical Global Impression of Severity Scale (CGI-S)  
The CGI-S (Padhi and Fineberg, 2010) is a 7-point scale, with the severity of illness scale using 
a range of responses from 1 (normal/not at all ill) to 7 (amongst the most severely ill patients). 
This requires the clinician to rate the severity of the patient's illness at the time of assessment, 
relative to the clinician's past experience with patients who have the same diagnosis.  
8.2.3. 
Patient Global Impression of Severity Scale (PGI-S)  
The PGI-S is a subject-completed assessment rating PD severity on a scale of 1 to 5 with 1 being 
none and 5 being very severe. 
8.2.4. 
Epworth Sleepiness Scale (ESS) 
The ESS (Johns, 1992) is a subject self-administered questionnaire with 8 questions. 
Respondents are asked to rate, on a 4-point scale (0 to 3: would never doze, slight chance of 
dozing, moderate chance of dozing, and high chance of dozing), their usual chances of dozing off 
or falling asleep while engaged in eight different activities, such as sitting and reading, watching 
television, sitting inactive in a public place, etc. Most people engage in those activities at least 

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occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores) can 
range from 0 to 24. The higher the ESS score, the higher that person’s average sleep propensity 
in daily life, or their ‘daytime sleepiness’. The questionnaire takes no more than 2 to 3 minutes to 
answer. 
8.2.5. 
Non-Motor Symptoms Scale (NMSS) for Parkinson's Disease  
The NMSS for Parkinson's Disease (Chaudhuri et al, 2007) is a 30-item rater-based scale to 
assess the frequency and severity of NMSS in patients across all stages of PD. The NMSS 
measures the severity and frequency of non-motor symptoms across 9 dimensions 
(cardiovascular, including falls, sleep/fatigue, mood/cognition, perceptual 
problems/hallucinations, attention/memory, gastrointestinal, urinary, sexual function, and 
miscellany). Responses are to quantify symptoms according to severity (using a scale of 0 to 3) 
and frequency (using a scale of 0 to 4). It is completed by a rater. 
8.2.6. 
Parkinson's Disease Sleep Scale (PDSS-2) 
The PDSS-2 (Trenkwalder et al, 2011) is a 15-item subject-reported outcome measure to assess 
nocturnal disturbances in PD. It is a 5-point frequency scale (from “very often” [0] to 
“never” [4]), with a total score ranging from 0 to 60, where higher scores indicate greater 
impairment.  
8.2.7. 
Starkstein Apathy Scale (SAS) 
The SAS is based on the construct of apathy proposed by Marin (Starkstein et al, 1992), 
characterized as the absence or lack of feeling, emotion, interest, or motivation. The Starkstein 
scale standardized Marin's construct into a set of criteria, based on the presence of diminished 
goal-directed behavior and diminished goal-directed cognition. The scale comprises 14 questions 
in which the respondent self-rates on a 4-point scale, ranging from "Not at all", "Slightly", 
"Some", and "A Lot". Ratings are a score from 3 to 0 for questions 1-8, and from 0 to 3 for 
questions 9-14, producing a total score out of 42. A score above 14 is usually considered the 
more severe level of apathy. 
8.2.8. 
Exploratory Efficacy Assessments 
8.2.8.1. 
The Modality System  
The Modality System is an artificial intelligence interface that collects information about clinical 
performance. Subjects will communicate with a virtual agent via web browser on an electronic 
device. This virtual agent will interview them and give instructions for simple tasks to test 
various aspects of their speech, visuo-motor, prosodic (stress and intonation patterns), cognitive, 
and linguistic function. It includes the PD-PROP™ and PWB-PROP™ to enquire about specific 
problems and symptoms individuals are experiencing in daily and social activities. It is estimated 
these tasks will take about 30 minutes to complete. 
Modality assessments will be conducted at home by the subject 1 to 2 days prior to the clinic 
visit. If a subject needs help to troubleshoot technical issues, their personal email ID will be 
shared with Modality. QC will be done by Modality staff, who will review audio/video files 

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throughout the conduct of the trial. Subjects who cannot complete all of the Modality 
assessments, but who otherwise remain eligible for the study, can continue their study 
participation. 
8.2.8.1.1. The Parkinson’s Disease Patient Report of Problems (PD-PROP™) 
The PD-PROP™ is a series of open-ended questions that asks individuals with PD to rank, in 
their own words, without restriction of content or length, up to 5 PD-related bothersome 
problems and their related effects on daily functioning. 
8.2.8.1.2. Personal Wellbeing Patient Report of Problems (PWB-PROP™) 
The PWB-PROP™ is a series of open-ended questions that asks individuals with PD to rank, in 
their own words, without restriction of content or length, up to 5 PD-related bothersome 
problems related to their day-to-day life or personal wellbeing, such as personal, family, 
financial, social, or other aspects and their related effects on daily functioning. 
8.2.8.2. 
Schwab and England Activities of Daily Living Scale (ADL) 
The Schwab and England ADL scale (Schwab and England, 1968) estimates the abilities of 
individuals living with a disease relative to a completely independent situation. Scores range 
from 100%, which indicates a completely independent individual; 70% is not completely 
independent and may have more difficulty with activities which may take 3 to 4 times as 
long (eg, may take large part of day for chores); 40% is very dependent and can assist with all 
chores but can manage few alone; and zero percent which indicates an individual who is no 
longer functioning. 
8.2.8.3. 
Cogstate Digital Cognitive Testing Battery 
The Cogstate Computerized Testing Battery will be conducted twice at screening to familiarize 
the subject with the procedure. 
Cogstate Digital Cognitive Testing Battery are computerized cognitive assessments of attention, 
executive function, verbal learning, and memory. Cogstate Digital Cognitive Testing Battery will 
occur at the timepoints specified in the SoA (see Section 1.3). The Cogstate Digital Cognitive 
Testing Battery implemented for this study includes the following tests: 
8.2.8.3.1. Detection (DET; Psychomotor Function)  
The DET test is a measure of psychomotor function and uses a well-validated simple reaction 
time paradigm with playing card stimuli. In this test, the playing cards all depict the same joker. 
The subject is asked to press the Yes key as soon as the card in the center of the screen turns face 
up. The software measures the speed and accuracy of each response.  
Duration of Test: 3 minutes. 
8.2.8.3.2. Identification (IDN; Attention)  
The IDN test is a measure of visual attention and uses a well-validated choice reaction time 
paradigm with playing card stimuli. In this test, the playing cards are all either red or black 
jokers. The subject is asked whether the card displayed in the center of the screen is red. The 

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subject responds by pressing the Yes key when the joker card is red and the No key when it is 
black. The software measures the speed and accuracy of each response.  
Duration of Test: 4 minutes. 
8.2.8.3.3. One Back (ONB; Working Memory)  
The ONB test is a measure of working memory and uses a well-validated n-back paradigm with 
playing card stimuli. In this test, the playing cards are identical to those found in a standard deck 
of 52 playing cards (without the joker cards). The subject is asked whether the card displayed in 
the center of the screen is the same as the card presented immediately previously.  
The subject responds by pressing the Yes or No key. Since no card has been presented yet on the 
first trial, a correct first response is always No. The software measures the speed and accuracy of 
each response.  
Duration of Test: 5 minutes. 
8.2.8.3.4. The International Shopping List Test (ISLT) and The International Shopping List 
Test – Delayed Recall (ISRL; Verbal Learning)  
The ISLT is a measure of verbal learning and uses a well-validated list-learning paradigm. High 
frequencies, high imagery, concrete nouns (items from a shopping list) are read to the subject by 
the test supervisor at the rate of one word every 2 seconds. Once all 12 words have been read, the 
subject is asked to recall as many of the words as he/she can as quickly as possible. The test 
supervisor records the words recalled by the subject on the testing device. When the subject can 
recall no more words, the same list is read a second time. The test supervisor records the words 
recalled by the subject on this trial. This is then repeated a third time.  
Delayed recall and recognition conditions will also be used in this study. The delayed recall 
condition requires the subject to recall the words from the list 10-30 minutes later without having 
the list read again. During the recognition condition, the test supervisor reads a shopping list item 
that may or may not have been on the original list and the subject has to respond either 
affirmatively (if the item was on the original list) or negatively (if it was not). The software 
measures the number of correct responses as recorded by the test supervisor.  
Duration of Test: 5 minutes for ISLT ± 1 minute for ISRL. 
8.2.8.3.5. International Digit Symbol Substitution Test – Symbols (IDSSTS; Processing Speed) 
The IDSSTS is a processing speed test that is based on the well-established digit symbol coding 
paradigm. In this test, subjects are presented with a legend that defines 9 symbols, with each 
symbol corresponding to a digit from 1 to 9. The subject is then presented with a conveyer belt in 
the middle of the screen that displays a series of empty boxes labelled with a number. The 
subject must select the symbol that corresponds to the number of a given highlighted box from 
symbol options presented at the bottom of the screen. The subject must try to place as many 
correct symbols in the boxes as possible over the duration of the test. Performance is measured 
by calculating the total number of correct responses.  
Duration of Test: 3 minutes. 

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Total Estimated Time (with familiarization): approximately 19 minutes. 
8.2.8.4. 
Beacon Dreem EEG 
The Beacon Dreem 3B device is a wearable EEG headband that collects EEG signals from dry 
EEG electrodes and head movement from an accelerometer to provide deep learning-powered 
sleep staging. If a subject opts into EEG, they or their authorized caregiver will receive initial 
training by the site staff at Screening before being shipped all Beacon Dreem System 
Components and provided device final configuration training from Beacon study staff. Training 
will include instructions for device setup, companion application and mobile phone use, device 
application, system maintenance, and troubleshooting recommendations. Subjects who opt out of 
the Beacon Dreem EEG collection can continue their study participation.  
Overnight EEG recordings will occur up to 3 consecutive nights prior to Baseline (Visit 2) and 
Week 14 (Visit 7); as well as immediately following Week 4 (Visit 4) and Week 12 (Visit 6).  
Change from baseline in EEG derived sleep metrics, including sleep macro-architectural features 
will be assessed between CVN424 150 mg and placebo at Week 4 (Visit 4) and Week 12 
(Visit 6). 
Figure 2. Beacon Dreem EEG Schema 
 
8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (Section 1.3). 
8.3.1. 
Physical and Neurological Examinations 
A full physical examination will be performed by a trained physician as indicated in the SoA 
(Section 1.3). The physical examination will include: 
• Body weight (kg)  
• Height (cm) (at the Screening Visit only) 

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• General appearance 
• Head, ears, eyes, nose, throat, and mouth 
• Neck 
• Heart 
• Lungs 
• Abdomen 
• Musculoskeletal and neurological systems 
• Extremities 
• Skin 
A standard neurological examination by a trained neurologist will be performed as indicated in 
the SoA (see Section 1.3). The same physician should perform all neurological examinations for 
a given subject, if possible.  
8.3.2. 
Vital Signs 
Vital signs will include temperature, respiration rate, heart rate, and blood pressure and will be 
collected at timepoints specified in the SoA (see Section 1.3). Blood pressure will be measured 
after at least 5 minutes supine and again within 1 to 3 minutes of standing. Study personnel will 
carefully monitor subjects for signs of orthostatic hypotension, defined as a systolic blood 
pressure decrease of ≥ 20 mm Hg and/or a diastolic blood pressure decrease of ≥ 10 mm Hg 
within 3 minutes of standing up from a supine position. 
8.3.3. 
Electrocardiograms (ECGs) 
Standard 12-lead ECGs will be recorded at time points specified in the SoA (see Section 1.3). 
ECG recordings will be obtained in a supine position following an approximately 10-minute 
period of rest. ECGs will be interpreted by qualified personnel at the central ECG lab. The 
Investigator or sub-Investigator will categorize the ECG findings using one of the following 
categories: within normal limits, abnormal but not clinically significant, or abnormal and 
clinically significant. All 12-lead ECGs will be stored for manual measurement of intervals, if 
necessary. Twelve-lead ECGs will be recorded using an ECG machine that automatically 
calculates the heart rate and measures PR interval, RR interval, QRS interval, QT interval, and 
QTcF, and QTcB (Fridericia’s and Bazett’s correction method) intervals. 
8.3.4. 
Modified Hoehn and Yahr Scale  
The Modified Hoehn and Yahr scale (Hoehn and Yahr, 1967) captures typical patterns of 
progressive motor impairment, and is widely used for the staging of functional disability in PD. 
It includes stages 1 to 5, ranging from 0, absence of symptoms to 5, wheelchair-bound or 

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bedridden. The modified version of the Hoehn and Yahr scale includes midway stages to help 
describe the intermediate course of the disease. 
8.3.5. 
Montreal Cognitive Assessment (MoCA) 
The MoCA (Nasreddine et al, 2005) takes approximately 10 minutes to administer and was 
designed to detect mild cognitive impairment in elders scoring in the normal range on the 
Mini-Mental State Examination (MMSE). Thirty items assessing multiple cognitive domains are 
contained in the MoCA: short-term memory (5 points); visuospatial abilities via clock drawing 
(3 points), and a cube copy task (1 point); executive functioning via an adaptation of Trail 
Making Test Part B (1 point), phonemic fluency (1 point), and verbal abstraction (2 points); 
attention, concentration, and working memory via target detection (1 point), serial subtraction 
(3 points), digits forward (1 point), and digits backward (1 point); language via confrontation 
naming with low-familiarity animals (3 points), and repetition of complex sentences (2 points); 
and orientation to time and place (6 points). The MoCA is scored by obtaining an item total and 
the authors recommend a clinical cutoff score of 26. 
8.3.6. 
The Beck Depression Inventory-II (BDI-II) 
The BDI-II (Becket al, 1996) is a 21-item, self-rated scale that evaluates key symptoms of 
depression including mood, pessimism, sense of failure, self-dissatisfaction, guilt, punishment, 
self-dislike, self-accusation, suicidal ideas, crying, irritability, social withdrawal, indecisiveness, 
body image change, work difficulty, insomnia, fatigability, loss of appetite, weight loss, somatic 
preoccupation, loss of libido, agitation, worthlessness, concentration difficulty, and loss of 
energy. The 21 symptoms and attitudes contained in the BDI reflect the intensity of the 
depression; items receive a rating of 0 to 3 to reflect their intensity and are summed linearly to 
create a score which ranges from 0 to 63. The BDI administration is straightforward, and it can 
be given as an interview by the clinician or as a self-report instrument (requiring a fifth or sixth 
grade reading level).  
BDI-II scoring:  
• 0-13 is considered none or minimal range depression 
• 14-19 is considered mild depression 
• 20-28 is considered moderate depression 
• 29-63 is considered severe depression. 
8.3.7. 
The Columbia Suicide Severity Rating Scale (C-SSRS) 
The C-SSRS (Posner et al, 2011) is used to assess suicidal tendency. The Baseline/Screening 
version of the C-SSRS will be used at the Screening visit. This version assesses suicidality in a 
subject’s lifetime and during the past 12 months. The “Since Last Visit” version of the C-SSRS 
will be used at all other visits. This version assesses suicidality since the subject’s last visit. 
Efforts must be made to ensure that the same trained team member completes this questionnaire 
for each subject. A subject with any suicidal ideation that answers “Yes” to questions 4 or 5 in 
the C-SSRS questionnaire at Screening is excluded and should be referred to a mental health 

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professional. Sites must have institutional procedures in place that will be followed if a referral 
to a mental health professional is necessary.  
8.3.8. 
Clinical Safety Laboratory Tests 
See Section 10.2 for the list of clinical laboratory tests to be performed and the SoA (see 
Section 1.3) for the timing and frequency. 
The Investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study as an AE. The laboratory reports must 
be filed with the source documents.  
All laboratory tests with values considered clinically significant and abnormal during 
participation in the study or within two weeks after the last dose of study drug should be repeated 
until the values return to normal or baseline or are no longer considered clinically significant by 
the Investigator or medical monitor. 
If clinically significant values do not return to normal/baseline within a period of time judged 
reasonable by the Investigator, the etiology should be identified, and the Sponsor notified. 
All protocol-required laboratory tests, as defined in Section 10.2, must be conducted in 
accordance with the laboratory manual and the SoA (see Section 1.3). 
If laboratory values from non-protocol-specified laboratory tests performed at the institution’s 
local laboratory require a change in subject management or are considered clinically significant 
by the Investigator (eg, SAE or AE or dose modification), then the results must be recorded. 
The tests detailed in Table 10-1 will be performed by the central laboratory. Unscheduled tests 
may be performed at any time during the clinical trial as determined necessary by the 
Investigator or required by local requirements. 
8.3.9. 
Pregnancy Testing 
Women who are pregnant or breastfeeding will not be included in this study (see Section 5).  
Pregnancy testing will be performed at screening and after study start, as specified in the SoA 
(see Section 1.3), for all women of childbearing potential. Additional serum or urine pregnancy 
tests may be performed, as determined necessary by the Investigator, or required by local 
regulation, to establish the absence of pregnancy at any time during the subject’s participation in 
the study. The pregnancy test will be performed at the central laboratory using a beta-human 
chorionic gonadotropin (β-HCG) test for the screening visit. Urine pregnancy tests will be 
collected at subsequent visit as per the SoA (see Section 1.3). 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other 
Safety Reporting 
The definitions of AEs and SAEs can be found in Section 10.3. 
AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject’s legally authorized representative). 

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The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study drug, or that caused the subject to 
discontinue the study (see Section 7). 
The method of recording, evaluating, and assessing causality of AEs and SAEs, and the 
procedures for completing and transmitting SAE reports, are provided in Section 10.3. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All SAEs will be collected from the signing of the ICF until 30 days following the last dose or 
early termination at the timepoints specified in the SoA (see Section 1.3). 
All AEs will be collected from the signing of the ICF until 14 days following the last dose or 
early termination at the timepoints specified in the SoA (see Section 1.3). 
Medical events that begin before the Screening Visit will be recorded as medical history/current 
medical conditions, not as AEs. However, if the study subject’s condition worsens at any time 
during the study, it will be recorded as an AE. 
All AEs will be captured in the appropriate eCRF. Information to be collected includes event 
description, time of onset, clinician’s assessment of severity, relationship to study product 
(assessed only by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. All AEs occurring while on study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution.  
All SAEs will be recorded and reported to the Sponsor or designee immediately within 24 hours, 
as indicated in Section 10.3. The Investigator will submit any updated SAE data to the Sponsor 
within 24 hours of it being available. 
If the Investigator has been made aware of any SAE, including a death, at any time after a 
subject has completed the study, and he/she considers the event to be reasonably related to the 
study drug or study participation, the Investigator must promptly notify the Sponsor. 
8.4.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the subject is the preferred method to inquire about AE 
occurrences. 
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs and AEs of special interest (as defined in Section 8.4.6) will 
be followed until resolution, stabilization, the event is otherwise explained, or the subject is lost 
to follow-up (as defined in Section 7.3). Other supporting documentation of the event may be 
requested by Pharmacovigilance and/or study Sponsor and should be provided as soon as 
possible. Further information on follow-up procedures is provided in Section 10.3. 

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8.4.4. 
Regulatory Reporting Requirements for SAEs 
The Investigator will immediately report to the Sponsor any SAE, whether or not considered 
study drug related, including those listed in the protocol or IB and must include an assessment of 
whether there is a reasonable possibility that the study drug caused the event. Study endpoints 
that are SAEs (eg, all-cause mortality) must be reported in accordance with the protocol, unless 
there is evidence suggesting a causal relationship between the study drug and the event (eg, death 
from anaphylaxis). In that case, the Investigator must immediately report the event to the 
Sponsor. 
All SAEs will be followed until satisfactory resolution or until the site investigator deems the 
event to be chronic or the subject is stable. Other supporting documentation of the event may be 
requested by Pharmacovigilance and/or study Sponsor and should be provided as soon as 
possible. 
The Sponsor will be responsible for notifying the FDA or other applicable Regulatory Authority 
of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible, but in 
no case later than 7 calendar days after the Sponsor's initial receipt of the information. In 
addition, the Sponsor must notify FDA or other applicable Regulatory Authority and all 
participating Investigators in an Investigational New Drug (IND) safety report of potential 
serious risks, from clinical trials or any other source, as soon as possible, but in no case later than 
15 calendar days after the Sponsor determines that the information qualifies for reporting.  
8.4.5. 
Pregnancy 
Women who are pregnant or breastfeeding will not be included in this study.  
If any subject is found to be pregnant during the study, they should be withdrawn, and any 
Sponsor-supplied drug should be immediately discontinued. In addition, any pregnancies in the 
partner of a male subject during the study or for 15 weeks after the last dose should also be 
recorded following authorization from the subject’s partner.  
If the pregnancy occurs during administration of active study drug, eg, after Day 0 or within 
12 weeks of the last dose of active study drug, the pregnancy should be reported immediately, 
using a pregnancy notification form, to the medical monitor and Sponsor.  
If the female subject and/or female partner of a male subject agrees to the primary care physician 
being informed, the Investigator should notify the primary care physician that the subject/female 
partner of the subject was participating in a clinical study at the time they became pregnant and 
provide details of treatment the subject received (blinded or unblinded, as applicable). 
All reported pregnancies will be followed up to the final outcome using the pregnancy form. All 
outcomes, including any premature termination, may be asked to be reported to the Sponsor. An 
evaluation after the birth of the child will also be conducted.  

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8.4.6. 
Adverse Events of Special Interest 
Abuse Potential Adverse Events 
The assessment of abuse potential is a regular part of the safety evaluation for any investigational 
compound that has central nervous system (CNS) activity. While preclinical or preliminary 
clinical data to date do not suggest a role of CVN424 for potential abuse or misuse, the 
Investigators will pay particular attention to any AE that emerges during the study treatment or 
after study drug discontinuation that may be suggestive of a signal of abuse potential. 
The following categories of terms will be monitored per FDA recommendation: 
• Euphoria-related terms 
o Euphoric mood; Elevated mood; Feeling abnormal; Feeling drunk; Feeling of relaxation; 
Dizziness; Thinking abnormal; Hallucinations; Inappropriate affect 
• Terms indicative of impaired attention, cognition, and mood 
o Somnolence; Mood disorders and disturbances 
• Dissociative/psychotic terms 
o Psychosis; Aggression; Confusion and disorientation 
• Related terms not captured elsewhere 
o Drug tolerance; Habituation; Drug withdrawal syndrome; Substance-related disorders 
The study team will ensure adequate review, coding and follow-up of AEs recommended by the 
FDA for emerging patterns suggestive of misuse or abuse. For each abuse-related AE, the 
dedicated study team will write a detailed narrative based on a study-specific narrative template. 
Narratives will include time of onset and duration of the event, dose of drug taken, severity and 
outcome. When available, PK values will be provided for each subject who experiences 
abuse-related AEs.  
To investigate the potential for abuse, misuse and diversion, an accurate check of study drug 
accountability will be performed at each study visit. Investigators must report any significant 
discrepancies that, in the opinion of the Investigator, raise the suspicion of abuse, misuse, or 
diversion:  
• Failure to return unused study drug without explanation 
• Running out of drug early  
• Drug-seeking behaviors 
• Returned drug is damaged or there is evidence of tampering. 
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8.5. 
Pharmacokinetics, Metabolite, and 
 
8.5.1. 
Pharmacokinetic, Metabolite, and 
 Sample Collection 
Blood samples (one sample per scheduled time) for analysis of CVN424 plasma concentrations 
will be collected into chilled vacutainers containing dipotassium ethylenediaminetetraacetic acid 
(K2EDTA) according to the schedule in Table 8-1. Instructions for sample processing and 
shipment are provided in a separate laboratory manual.  
Table 8-1. Collection of Blood Samples for PK Analysis 
Week/Visit 
Time Post-dose (hours) 
Baseline/Visit 2 Pre-dose (0 h) and at 4 h post-dose (± 30 mins) 
Week 4/Visit 4 
Post-dose (time not specified but actual time to be recorded based on time 
last dose was administered)a 
Week 8/Visit 5 
Post-dose (time not specified but actual time to be recorded based on time 
last dose was administered)a 
Week 12/Visit 6 Post-dose (time not specified but actual time to be recorded based on time 
last dose was administered)a 
PK = pharmacokinetics. 
a 
Time of last administered dose to be accurately recorded by subject. Time of last administered dose could be the 
day before visit or on the day of visit. 
 
PK samples will be collected at the nominal timepoint within the allowable windows. The actual 
time of sample collection will be recorded. 
Placebo samples will not be analyzed by the bioanalytical laboratory, except 2 samples per 
subject receiving placebo, one following the first dose (4 hours post-dose) and one at 
Week 8/Visit 5 to ensure from a safety perspective that no additional subjects could have been on 
active treatment. 
An additional blood sample will be collected to analyze metabolite and 
 in a 
patient population that is PD drug naïve. The sample will be collected at each time PK is 
collected. 
8.5.2. 
Bioanalytical Methods 
Plasma concentrations of CVN424 will be measured using a validated high-performance liquid 
chromatography - tandem mass spectrometry (HPLC-MS/MS) method. Plasma samples will be 
archived to support potential post hoc laboratory testing. 
8.5.3. 
Pharmacokinetic Parameters 
Where possible, the PK parameters of CVN424 will be derived using the concentration-time data 
for all evaluable subjects and a population PK model. Actual sampling times will be used in all 
computations using sampling times.  

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9. 
Statistical Considerations 
The statistical analysis plan (SAP) will be finalized prior to database lock and unblinding of the 
study data and it will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses of the most 
important endpoints including primary endpoints. 
9.1. 
Sample Size Determination 
A sample size of approximately 62 subjects with a 1:1 randomization to CVN424 150 mg or 
placebo will provide 75% power to detect a difference of 5 or more points for the sum of 
MDS-UPDRS Parts II and III, assuming a standard deviation (SD) of 8, two-sided alpha of 0.10, 
and a 10% dropout rate. 
The effect size of 5 points for Part II + Part III is felt to reflect a meaningful threshold that, if 
achieved, would be comparable to other effective PD medications at 12 weeks (pramipexole, 
levodopa). 
Figure 3. Parameters for Sample Size and Power Calculations 
 
9.2. 
Populations For Analyses 
All data analyses will be performed using at least one of the following analysis sets: 
• Safety Analysis Set:  
Includes all subjects who have received at least 1 dose of study drug. All safety population 

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analyses will be based on the treatment the subject received. Subjects in this analysis set will 
be used for demographic, baseline characteristics, and safety analyses. 
• Modified Intention To Treat (mITT):  
Includes all subjects who are randomized, and administered study drug, classified according 
to the treatment received, and have at least one post-baseline evaluation of efficacy 
endpoints.  
• Intention-to-Treat (ITT) Set:  
Includes all randomized subjects.  
• Completer Set:  
Includes all subjects who completed all study treatment for 12 weeks.  
• Pharmacokinetic Analysis Set:  
Includes all subjects who received at least 1 dose of study drug and have at least 1 
measurable plasma concentration. 
• Per Protocol Analysis Set:  
Includes all subjects who completed the study and who received all study treatment and have 
no significant protocol deviations. All significant protocol deviations will be assessed, and a 
decision will be made on a case-by-case basis whether to exclude subjects from the Per 
Protocol analysis set prior to breaking the blind. All per protocol analyses will be based on 
the treatment the subject received. This set will be used as a sensitivity analysis for primary 
and secondary efficacy outcomes. 
9.3. 
Statistical Analyses 
9.3.1. 
Efficacy Endpoint Analysis  
Hierarchy of Efficacy Endpoints: 
Each efficacy endpoint (primary and secondary) includes a comparison of CVN424 versus 
placebo. The overall Type I error rate within the family of efficacy endpoints will be maintained 
by using Hochberg’s step-up method to maintain alpha while comparing CVN424 to placebo. 
Efficacy endpoints will be evaluated in a hierarchical manner. Significance of successive 
endpoints cannot be claimed unless prior endpoints in the hierarchy are significant. Nominal 
p-values will be reported for descriptive purposes and interpreted in an exploratory manner.  
Analytic Methods  
The primary estimand will be defined as follows:  
• Population: Subjects with PD as defined by inclusion/exclusion criteria and are in the mITT 
population 
• Variable: The primary endpoint is the change from Baseline to Week 12 in the MDS-UPDRS 
Part II + Part III score (Motor Aspects of Experiences of Daily Living + Motor Examination)  
• Intercurrent Events and Proposed Strategy: Treatment Discontinuation: Hypothetical 
Strategy. Initiation of Parkinsonian medication for treatment of motor features: Hypothetical 
Strategy 

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• Population Level Summary: Treatment difference of the least-squares mean change from 
Baseline to Week 12 in the MDS-UPDRS Part II + Part III score (Motor Aspects of 
Experiences of Daily Living + Motor Examination) between placebo and CVN424 groups. 
Efficacy endpoints will be analyzed in the mITT population using a MMRM with no imputation. 
This will include response data from each post-baseline visit based on the mITT population 
(defined as subjects that are randomized, receive treatment, and have post-baseline data with 
respect to the primary endpoint). The baseline score will be included as a covariate as well as the 
treatment group (150 mg CVN424 or placebo), visits, interaction between treatment group and 
visit, as fixed factors in the MMRM. The difference between CVN424 versus placebo at the final 
visit will be estimated from the MMRM. An unstructured covariance matrix will be used 
initially, and if it fails to converge, a Compound Symmetry (CS) or an AR (1) matrix shall be 
employed, in that order. 
Sensitivity analyses for efficacy endpoints will be conducted on the ITT set with the multiple 
imputation method, both assuming that data are missing at random (MAR) and missing not at 
random (MNAR). MNAR analyses will include tipping point and jump-to-reference (placebo) 
assumptions. Further sensitivity analysis will be conducted in the completer and per-protocol set 
with MMRM. Sensitivity analyses will also be conducted by including retrieved dropout data 
(data captured from subjects who are free of study treatment and may have started 
anti-parkinsonian medication).  
Categorical secondary efficacy endpoints (proportion of subjects improving based on CGI-S or 
PGI-S) will be analyzed in the mITT population using the Cochran–Mantel–Haenszel (CMH) 
test. This test will include the frequency and percentage of proportions for each group, along 
with their respective 95% confidence interval (CI). Additionally, the difference in proportions 
between the treatment groups, along with its CI, will be calculated. As a sensitivity analysis, a 
GLIMMIX model that can incorporate all response data from each post-baseline visit into the 
analysis will be employed. The model will include the treatment group, visit, interaction between 
treatment groups and visit. An unstructured covariance structure will be used for the repeated 
measures. The odds ratio for the treatment difference, 95% CI for the odds ratio and p-value will 
be provided. 
9.3.2. 
Tolerability and Safety Analysis  
Tolerability will be assessed by comparing percentages of premature drug and study 
discontinuations in the treatment groups (CVN424 vs placebo).  
The safety analysis, including suicidality, will be conducted on the Safety Analysis Set that 
includes all randomized subjects. TEAEs will be coded according to the Medical Dictionary for 
Regulatory Activities (MedDRA) and summarized by treatment group, organ class and preferred 
term, and duration. Further summaries will be done by seriousness, severity, relationship to study 
treatment and dose at the time of onset. Safety endpoints will be summarized with descriptive 
statistics. 

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9.3.3. 
Data Monitoring Committee 
No data monitoring committee will be appointed for this study. 

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10. 
Supporting Documentation and Operational Considerations 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) international ethical guidelines 
o Applicable International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines 
o Applicable laws and regulations 
The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the Investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study subjects. 
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation, except for changes necessary to eliminate an immediate hazard to 
study subjects. 
The Investigator will be responsible for the following: 
o Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
o Providing oversight of the conduct of the study at the site and adherence to requirements 
of Title 21 of the Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, and 
all other applicable local regulations 
10.1.2. Financial Disclosure 
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 

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certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.1.3. Informed Consent Process 
Informed consent forms describing in detail the study drug, study procedures, and risks are given 
to the subject and written documentation of informed consent is required prior to the subject 
entering the study and before any protocol-related procedures are performed. 
The Investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the subject or their legally authorized representative and answer all questions 
regarding the study. 
Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representatives will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and data protection 
requirements, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained before 
the subject was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Subjects must be reconsented to the most current version of the ICF(s) during their participation 
in the study. 
A copy of the ICF(s) must be provided to the subject or their legally authorized representative. 
Subjects who are rescreened are required to sign a new ICF. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples 
for optional exploratory research. The Investigator or authorized designee will explain to each 
subject the objectives of the exploratory research. Subjects will be told that they are free to 
refuse to participate and may withdraw their consent at any time and for any reason during the 
storage period. A separate signature will be required to document a subject’s agreement to allow 
any remaining specimens to be used for exploratory research. Subjects who decline to participate 
in this optional research will not provide this separate signature. 
10.1.4. Data Protection 
Subjects will be assigned a unique identifier by the Sponsor. Any subject records or datasets that 
are transferred to the Sponsor will contain the identifier only; subject names or any information 
which would make the subject identifiable will not be transferred. 
The subject must be informed that their personal study-related data will be used by the Sponsor 
in accordance with local data protection law. The level of disclosure must also be explained to 

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the subject who will be required to give consent for their data to be used as described in the 
informed consent. 
The subject must be informed that their medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the Sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.5. Committees Structure 
An EAC will review subject eligibility and suitability for participation prior to enrollment into 
the study. EAC approval will occur after laboratory and ECG results have been received and 
screening data has been entered into the electronic data capture system. 
10.1.6. Dissemination of Clinical Study Data 
The Sponsor will register and/or disclose the existence of and the results of clinical studies as 
required by local laws and regulations. 
10.1.7. Data Quality Assurance 
All subject data relating to the study will be recorded in eCRFs unless transmitted to the Sponsor 
or designee electronically (eg, laboratory data). The Investigator is responsible for verifying that 
data entries are accurate and correct by physically or electronically signing the eCRF. 
Guidance on completion of eCRFs will be provided in eCRF Completion Guidelines. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents for the purpose of 
monitoring and auditing by the Sponsor, and inspection by local and regulatory authorities. 
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan. The monitors will verify that 
the clinical trial is conducted, data are generated and biological specimens are collected, 
documented (recorded), and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements (eg, Good Laboratory Practices, Good Manufacturing Practices). 
The Sponsor or designee is responsible for the data management of this study, including quality 
checking of the data. Quality control (QC) procedures will be implemented beginning with the 
data entry system and data QC checks that will be run on the database will be generated. Any 
missing data or data anomalies will be communicated to the site(s) for clarification/resolution. 
The Sponsor assumes accountability for actions delegated to other individuals (eg, contract 
research organizations). 

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Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for a time period that complies with local regulations or institutional 
policies. No records may be destroyed during the retention period without the written approval of 
the Sponsor. No records may be transferred to another location or party without written 
notification to the Sponsor. 
10.1.8. Source Documents 
Source documents provide evidence for the existence of the subject and substantiate the integrity 
of the data collected. Source documents are filed at the Investigator’s site. 
Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. The Investigator may need to request 
previous medical records or transfer records, depending on the study. Also, current medical 
records must be available. 
Definition of what constitutes source data and its origin can be found in the monitoring 
guidelines. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of subjects are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. 
10.1.9. Study Termination 
The Sponsor or designee reserves the right to terminate the study at any time for any reason at 
the sole discretion of the Sponsor.  
Reasons for the early closure of the study by the Sponsor or Investigator may include but are not 
limited to: 
Discontinuation of further study drug development 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by the 
applicable regulatory requirements. The Investigator shall promptly inform the subject and 
should assure appropriate subject therapy and/or follow-up. 

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10.1.10. Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
10.1.11. Sample Storage and Destruction 
Any blood PK sample collected according to the SoA (see Section 1.3) can be analyzed for any 
of the tests outlined in the protocol and for any tests necessary to minimize risks to study 
subjects. This includes testing to ensure analytical methods produce reliable and valid data 
throughout the course of the study. This can also include, but is not limited to, investigation of 
unexpected results, incurred sample reanalysis, and analyses for method transfer and 
comparability. 
All samples and associated results will be coded prior to being shipped from the site for analysis 
or storage. Samples will be tracked using a unique identifier that is assigned to the samples for 
the study. Results are stored in a secure database to ensure confidentiality.  
If informed consent is provided by the subject, Cerevance Beta, Inc. can do additional testing on 
remaining samples (ie, residual and back-up) to investigate and better understand the therapeutic 
area, the dose response and/or prediction of response to CVN424, and characterize aspects of the 
molecule (eg, mechanism of action/target, metabolites). Results from this analysis are to be 
documented and maintained but are not necessarily reported as part of this study. Samples can be 
retained for up to 10 years. 
Since the evaluations are not expected to benefit the subject directly or to alter the treatment 
course, the results of pharmacogenetic, or other exploratory studies are not placed in the 
subject’s medical record and are not to be made available to the subject, members of the family, 
the personal physician, or other third parties, except as specified in the informed consent. 
The subject retains the right to request that the sample material be destroyed by contacting the 
Investigator. Following the request from the subject, the Investigator is to provide the Sponsor 
with the required study and subject number so that any remaining blood samples and any other 
components from the cells can be located and destroyed. Samples will be destroyed once all 
protocol-defined procedures are completed. However, information collected from samples prior 
to the request for destruction, will be retained by Cerevance Beta, Inc. 

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The Sponsor is the exclusive owner of any data, discoveries, or derivative materials from the 
sample materials and is responsible for the destruction of the sample(s) at the request of the 
subject through the Investigator, at the end of the storage period, or as appropriate (eg, the 
scientific rationale for experimentation with a certain sample type no longer justifies keeping the 
sample). If a commercial product is developed from this research project, the Sponsor owns the 
commercial product. The subject has no commercial rights to such product and has no 
commercial rights to the data, information, discoveries, or derivative materials gained or 
produced from the sample. See Section 10.1.4 for subject confidentiality. 
 
 

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10.2. 
Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 10-1 will be performed by the central laboratory. 
• Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Section 5. 
• Additional tests may be performed at any time during the study as determined necessary by 
the Investigator or required by local regulations. 
• Investigators must document their review of each laboratory safety report. 
Table 10-1. Protocol-required Laboratory Tests 
Hematology 
Clinical Chemistry 
Coagulation  
hematocrit 
hemoglobin 
platelet count 
RBC count 
RBC indices: 
 
MCH 
 
MCHC 
 
MCV 
 
%/nL reticulocytes 
WBC count with 
differential: 
 
neutrophils 
 
lymphocytes 
 
monocytes 
 
eosinophils 
 
basophils 
albumin 
alkaline phosphatase 
ALT/SGPT 
AST/SGOT 
BUN 
calcium 
bicarbonate 
chloride 
creatinine 
creatinine kinase 
GGT 
glucose [nonfasting] 
LDH 
potassium 
sodium 
total and direct bilirubin 
total protein 
INR 
PT 
PTT/aPTT 
Urinalysis 
specific gravity 
 
pH, glucose, protein, blood, ketones, 
nitrite [by dipstick] 
 
microscopic examination (if blood or 
protein is abnormal): 
RBC/high power field 
WBC/high power field 
Epithelial cells, casts, etc. 
 
Diagnostic Screening in 
Serum 
Diagnostic Screening in Urine/ Blood 
Serum hCGa 
FSHb 
Hepatitis panel including:  
• HBsAg 
• Anti-HCV 
HIV 
COVID-19 
Drug screen including amphetamines, barbiturates, benzodiazepines, 
cocaine, opiates, methadone, methylenedioxymethamphetamine 
(MDMA), phencyclidine (PCP), tetrahydrocannabinol (THC) 
 
Urine Pregnancy Testa 
ALT = alanine transaminase; anti-HCV = hepatitis C virus antibody; aPTT = activated partial thromboplastin time; 
AST = aspartate transaminase; BUN = blood urea nitrogen; COVID-19 = coronavirus disease 2019; GGT = gamma-
glutamyl transferase; FSH = follicle-stimulating hormone; HBsAg = hepatitis B surface antigen; hCG = human 
chorionic gonadotropin; HIV = Human Immunodeficiency Virus; INR = international normalized ratio; 
LDH = lactate dehydrogenase; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin 
concentration; MCV = mean corpuscular volume; PT = prothrombin time; PTT = partial thromboplastin time; 
RBC = red blood cell; SGOT = serum glutamic-oxaloacetic transaminase; SGPT = serum glutamic-pyruvic 
transaminase; WBC = white blood cell. 

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a 
Serum pregnancy test at screening and urine pregnancy test at all other indicated visits for women of 
child-bearing potential only. 
b 
For women of child-bearing potential only.  
 
 

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10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. Definition of AE 
AE Definition 
An AE is any untoward medical occurrence in a clinical study subject, temporally associated 
with the use of study intervention, whether or not considered related to the study intervention. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of study intervention. 
A TEAE is an AE that begins on or after administration of the first dose of trial medication or an 
increase in severity or frequency on or after administration of the first dose of trial medication. 
Events Meeting the AE Definition 
Any abnormal laboratory test results (hematology, clinical chemistry, coagulation, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital signs measurements), including 
those that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the Investigator (ie, not related to progression of underlying disease, or more severe 
than expected for the subject’s condition). 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
New condition detected or diagnosed after study intervention administration even though it may 
have been present before the start of the study. 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention or 
a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
Lack of efficacy or failure of expected pharmacological action per se will not be reported as an 
AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE 
if they fulfill the definition of an AE or SAE. 
Events not Meeting the AE Definition 
Any abnormal laboratory findings or other abnormal safety assessments that are associated with 
the underlying disease, unless judged by the Investigator to be more severe than expected for the 
subject’s condition. 

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The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the subject’s condition. 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected 
at the start of the study that do not worsen. 
10.3.2. Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of 
the criteria listed: 
a. Results in death 
b. Is life threatening 
The term life threatening in the definition of serious refers to an event in which the subject was 
at risk of death at the time of the event. It does not refer to an event, which hypothetically might 
have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the subject has been admitted (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting. Complications that occur during hospitalization are AEs. If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious. When in 
doubt as to whether hospitalization occurred or was necessary, the AE should be 
considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) that may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 

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f. Other situations: 
• Medical or scientific judgment should be exercised by the Investigator in deciding 
whether SAE reporting is appropriate in other situations such as important medical events 
that may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the subject or may require medical or surgical intervention to prevent one of 
the other outcomes listed in the above definition. These events should usually be 
considered serious. 
o Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias, convulsions not resulting in hospitalization, or development of 
intervention dependency or intervention abuse. 
10.3.3. Recording and Follow-up of AE and/or SAE 
AE and SAE Recording 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
The Investigator will then record all relevant AE/SAE information. 
It is not acceptable for the Investigator to send photocopies of the subject’s medical records to 
Pharmacovigilance or the Sponsor in lieu of completion of the required form. 
There may be instances when copies of medical records for certain cases are requested by 
Pharmacovigilance. In this case, all subject identifiers, with the exception of the subject number, 
will be redacted on the copies of the medical records before submission to Pharmacovigilance. 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to one of the following categories:  
• Mild: 
A type of AE that is usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily living. 
• Moderate:  
A type of AE that is usually alleviated with additional specific therapeutic intervention. The 
event interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the research subject. 

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• Severe:  
A type of AE that interrupts usual activities of daily living, or significantly affects clinical 
status, or may require intensive therapeutic intervention. 
Assessment of Causality 
• The Investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. The Investigator will use clinical judgment to determine the 
relationship. 
• A reasonable possibility of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study intervention administration, will be 
considered and investigated. 
• For causality assessment, the Investigator will also consult the IB and/or product information, 
for marketed products. 
• The Investigator must review and provide an assessment of causality for each AE/SAE and 
document this in the medical notes. There may be situations in which an SAE has occurred 
and the Investigator has minimal information to include in the initial report to 
Pharmacovigilance. However, it is very important that the Investigator always make an 
assessment of causality for every event before the initial transmission of the SAE data to 
Pharmacovigilance. 
• The Investigator may change their opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
The relationship of each AE to study drug(s) will be assessed using the following categories: 
• Related:  
An AE that follows a reasonable temporal sequence from administration of a drug (including 
the course after withdrawal of the drug), or for which possible involvement of the drug can 
be argued, although factors other than the drug, such as underlying diseases, complications, 
concomitant drugs, and concurrent treatments, may also be responsible. 
• Not Related: 
An AE that does not follow a reasonable temporal sequence from administration of a drug 
and/or that can reasonably be explained by other factors, such as underlying diseases, 
complications, concomitant drugs, and concurrent treatments. 
Expectedness 
Pharmacovigilance and the medical monitor, in consultation with the Sponsor, will be 
responsible for determining whether an AE is expected or unexpected. An AE will be considered 
unexpected if the nature, severity, or frequency of the event is not consistent with the risk 
information previously described for the study intervention. 

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Follow-up of AEs and SAEs 
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Pharmacovigilance 
or the Sponsor to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
If a subject dies during participation in the study or during a recognized follow-up period, the 
Investigator will provide Pharmacovigilance with a copy of any postmortem findings including 
histopathology. 
New or updated information will be recorded in the originally submitted documents. 
The Investigator will submit any updated SAE data to Pharmacovigilance within 24 hours of 
receipt of the information. 
Outcome 
The Investigator will be asked to record the outcome by choosing one of the following 
alternatives: 
• Recovered/Resolved:  
Subject returned to first assessment status with respect to the AE. 
• Recovering/Resolving:  
The intensity is lowered by one or more stages: the diagnosis or signs/symptoms has almost 
disappeared; the abnormal laboratory value improved but has not returned to the normal 
range or baseline; the subject died from a cause other than the particular AE with the 
condition remaining “recovering/resolving”. 
• Not Recovered/Not Resolved:  
There is no change in the diagnosis, signs, or symptoms; the intensity of the diagnosis, 
signs/symptoms, or laboratory value on the last day of the observed study period had got 
worse than when it started; is an irreversible congenital anomaly; the subject died from 
another cause with the particular AE state remaining “Not recovered/not resolved”. 
• Resolved with Sequelae:  
The subject recovered from an acute AE but was left with permanent/significant impairment 
(eg, recovered from a cardiovascular accident but with some persisting paresis). 
• Fatal: 
The AEs which are considered the cause of death. 
• Unknown:  
The course of the AE cannot be followed up due to hospital change or residence change at 
the end of the subject’s participation in the study. 
 
 

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10.3.4. Reporting of SAEs 
SAE Reporting to Pharmacovigilance via an Electronic Data Collection Tool 
The primary mechanism for reporting an SAE to Pharmacovigilance will be the electronic data 
collection tool. 
If the electronic system is unavailable, then the site will use the paper SAE data collection tool 
(see next section) to report the event within 24 hours. 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
After the study is completed at a given site, the electronic data collection tool will be taken 
offline to prevent the entry of new data or changes to existing data. 
If a site receives a report of a new SAE from a study subject or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken offline, then the 
site can report this information on a paper SAE form (see next section) or to the medical 
monitor/SAE coordinator by telephone. 
Contacts for SAE reporting can be found in the safety reporting plan. 
SAE Reporting to Pharmacovigilance via Paper Data Collection Tool 
Facsimile transmission of the SAE paper data collection tool is the preferred method to transmit 
this information to the medical monitor or the SAE coordinator. 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE data collection tool sent by overnight mail or courier service. 
Initial notification via telephone does not replace the need for the Investigator to complete and 
sign the SAE data collection tool within the designated reporting timeframes. 
Contacts for SAE reporting can be found in the safety reporting plan. 
 
 

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10.4. 
Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. Definitions 
Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
Following menarche 
• From the time of menarche until becoming postmenopausal unless permanently sterile (see 
below) 
• A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. 
o A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be 
used to confirm a postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy (HRT). However, in the absence of 12 months of 
amenorrhea, confirmation with more than one FSH measurement is required.  
o Females on HRT and whose menopausal status is in doubt will be required to use one of 
the nonestrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
• Permanent sterilization methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
o For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), Investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the subject’s medical 
records, medical examination, or medical history interview. 
• If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before first dose of study intervention, additional evaluation should be 
considered. 
 
 

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Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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10.4.2. Contraception Guidance 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of < 1% per 
year when used consistently and correctly. 
• Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS)c 
• Bilateral tubal occlusion 
• Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole 
sexual partner of the WOCBP, and the absence of sperm has been confirmed. If not, an 
additional highly effective method of contraception should be used. Spermatogenesis cycle 
is approximately 90 days. 
Note: documentation of azoospermia for a male subject can come from the site personnel’s 
review of the subject’s medical records, medical examination, or medical history interview. 
Highly Effective Methodsb That are User Dependent Failure rate of < 1% per year when 
used consistently and correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc  
- 
oral 
- 
intravaginal 
- 
transdermal 
- 
injectable 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
- 
oral  
- 
injectable 
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study 
intervention. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the study and the preferred and usual lifestyle of the subject. 
Effective Methodsd That are not Considered Highly Effective Failure rate of ≥ 1% per 
year when used consistently and correctly. 
• Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action 
• Male or female condom with or without spermicide 
• Cervical cap, diaphragm, or sponge with spermicide 

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Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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• A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods)c 
a Contraceptive use by men or women should be consistent with local regulations regarding 
the use of contraceptive methods for those participating in clinical studies. 
b Failure rate of < 1% per year when used consistently and correctly. Typical use failure 
rates differ from those when used consistently and correctly. 
c Male condoms can be used in addition to hormonal contraception.  
d Considered effective, but not highly effective - failure rate of ≥ 1% per year. 
Note: Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal 
(coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not 
acceptable methods of contraception. Male condom and female condom should not be used 
together (due to risk of failure from friction). 
 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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10.5. 
Appendix 5: Country-specific Requirements  
Not applicable. 
 
 
 

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Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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10.6. 
Appendix 6: Protocol Amendment History 
SUMMARY OF CHANGES 
Version 2.0 (17 January 2024) replaces Version 1.0 (22 June 2023) 
Amendment 1: (17 January 2024) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: Clarification and consistency of sections listed below. 
Section # and Name 
Description of Change 
Title page 
NCT number added 
Overall 
Spotlite Overnight has been replaced with Optional 
Beacon Dreem electroencephalogram recordings 
Overall 
Formatting and style 
Synopsis, Section 3 Objectives, 
Endpoints, and Estimands 
Endpoints were updated (primary, secondary and 
exploratory endpoints) 
Synopsis, Section 4.1 Overall 
Design 
Baseline assessments added. 
Statements added to indicate subjects can continue 
participation even when unable to complete exploratory 
endpoint assessments. 
Modality assessment duration and further instruction 
added. 
Synopsis, Section 4.1.2, Section 6.1 
Number of Subjects 
Updated number of subjects to be enrolled. 
Synopsis, Section 5.2 Exclusion 
Criteria 
Exclusion criteria updated around cannabidiol use, 
autoimmune likelihood to interfere with subject safety 
or assessments, monoamine oxidase B (MAOB) 
treatment prior to Screening and duration of 
antipsychotic, metoclopramide or reserpine prior to 
Screening, PCR testing for COVID-19 removed.  
Synopsis, Section 9.1 Sample Size 
Determination 
Subject numbers updated and additional information 
provided. 
Synopsis, Section 9.3.1 Efficacy 
Endpoint Analysis 
Primary efficacy analysis language was updated. 
Secondary efficacy language was updated. 
Section 1.2 Schema 
Schema was updated. 
Section 1.3 Schedule of 
Assessments (SoA) 
To facilitate enrollment and reduce study burden on 
participants/care givers; Emerald RF Continuous 
Monitoring is removed and change Beacon EEG 
procedure to be optional 

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Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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Footnotes updated to give better clarification on blood 
pressure measurements, modality assessments, 
coagulation test timing, and Cogstate cognitive 
computerized battery assessments.  
Section 5.3 Prohibited Medications 
and Lifestyle Considerations 
Use of cannabidiol use after Screening added. 
Table 5-1 was updated with additional prohibited 
medications and dietary products. 
Section 5.3.1 Study Drug and Meals 
Considerations 
The amount of meal to eat before taking the study drug 
was updated. 
5.3.2 Study Drug Interruption or 
Suspension 
New information about study drug interruption or 
suspension was added. 
5.3.3 Alcohol 
Duration about when to stop consuming alcohol prior to 
screening was deleted. 
5.3.4 Activity 
Type of activities recommended was cancelled. 
6.2.1 Investigational Product 
Storage 
Storage temperature was updated. 
Section 8.2.1 Movement Disorders 
Society – Unified Parkinson's 
Disease Rating Scale 
(MDS-UPDRS) 
Additional information added to ensure same rater, 
where possible, performs assessments. 
Section 8.2.3 Patient Global 
Impression of Severity Scale (PGI-
S) 
Severity scale grading updated 
Section 8.2.4 Epworth Sleepiness 
Scale (ESS) 
Scale criteria updated 
Section 8.2.8.1 The Modality 
System 
Additional instructions added and estimated time 
updated for assessment completion. 
Section 8.2.8.4 Emerald RF 
Continuous Monitoring 
Emerald deleted. 
Section 8.2.8.5 EEG 
Additional instructions added about training. Figure 2 
updated. Change from baseline assessments updated 
including changing the EEG assessment to Optional 
Section 8.3.7 The Columbia Suicide 
Severity Rating Scale (C-SSRS) 
Assessment period updated to “during the past 12 
months” 
Section 8.5.1 Pharmacokinetic, 
Metabolite, and 
Sample 
Collection 
Addition of metabolite and
 sample collection 
with PK sample collections 
Appendix 2 Clinical Laboratory 
Tests 
Drug screen tests were updated; COVID-19 was added 
as a diagnostic screening in serum. 
 
 

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Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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Version 3.0 (10 July 2024) replaces Version 2.0 (17 January 2024) 
Amendment 2: (10 July 2024) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: Clarification and consistency of sections listed below. 
Section # and Name 
Description of Change 
Synopsis, Section 4.1 Overall 
Design  
4.1 Overall Design 
4.3 Justification of Dose 
5.3.1 Study Drug and Meals 
Considerations 
6.1. Investigational Product 
Dispensation, Dosing and Regimen 
Instructions for study drug administration were changed 
from, “Subjects will be dispensed study drug to be 
administered at home with the largest meal of the day at 
the same time every day, as best as possible”, to “the 
study drug will be self-administered once daily at a 
consistent time in the morning and taken with food. The 
food taken with study drug may be a snack or typical 
morning meal and should include fat in its content (e.g., 
buttered toast, peanut butter on crackers, an egg, cream 
cheese on a bagel, full fat yogurt or milk).” 
Synopsis, Section 4.1 Overall 
Design  
5.2 Exclusion Criteria 
Clarification of Exclusion Criteria #13 to include 
“ECG, prior documented history, or” clinical evidence 
of potentially unstable heart disease.   
Clinical evidence of disease listed were revised to: 
 “c. Myocardial infarction within 1 year prior to 
screening, unstable angina within 6 months, or a current 
concern for symptomatic ischemic heart disease in the 
opinion of the investigator” 
“f. NYHA Class II or higher congestive heart failure.”.   
Synopsis, Section 4.1 Overall 
Design  
5.2 Exclusion Criteria 
Clarification of Exclusion Criteria #22 to remove the 
statement, “Confirmatory test will be allowed at the 
discretion of the Investigator to rule out false 
positives.”  
 

Compound: CVN424 
Cerevance Beta, Inc. 
Protocol CVN424-203 
Protocol Date and Version: 10 July 2024; v3.0 
 
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