A Two-Part Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of PDM608 in Healthy Adult Subjects
Phase: PHASE1
Conditions: Parkinson Disease
Sponsor: Calibr, a division of Scripps Research

 
 
 
CLINICAL STUDY PROTOCOL 
A Two-Part Phase 1 Study to Assess the Safety, Tolerability, and 
Pharmacokinetics of PDM608 in Healthy Adult Subjects 
Sponsor Study Number: CBR-PDM608-3001 
IND Number: 163942 
Clinical Study Site: Quotient Sciences – Miami, Inc. 
3898 NW 7 Street 
Miami, FL 33126 
USA 
Tel: 305-644-9903 
Sponsor: Calibr 
11119 N. Torrey Pines Rd. 
Suite 100 
La Jolla, CA 92037 
Tel: (858) 242 1000 
Funder:The Michael J. Fox Foundation for Parkinson’s 
Research 
Date of Protocol:30 JANUARY 2023 
Status of Protocol: Version 1.0 
CONFIDENTIAL 
 
This clinical protocol may not be reproduced or communicated to a third party 
without the written permission of Calibr, a Division of Scripps Research. 

 
CONFIDENTIAL 
 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 2 of 64  
 
Document History 
Protocol Version 
Classification 
Date  
1.0 
Original Protocol 
30 Jan 2023 

 
CONFIDENTIAL 
 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 3 of 64  
 
1 Table of Contents 
1 
Table of Contents ............................................................................................. 3 
2 
List of Tables and Figures ................................................................................ 8 
2.1 
Table of In-Text Tables ....................................................................... 8 
2.2 
Table of In-Text Figures ...................................................................... 8 
3 
Synopsis ........................................................................................................... 9 
4 
List of Abbreviations ....................................................................................... 12 
5 
Background Information .................................................................................. 14 
5.1 
Introduction ....................................................................................... 14 
5.2 
Investigational Medicinal Product(s) ................................................. 14 
5.3 
Previous Study Findings ................................................................... 15 
5.3.1 
Nonclinical Findings .............................................................. 15 
6 
Rationale ......................................................................................................... 16 
6.1 
Study Rationale................................................................................. 16 
6.2 
Dose Rationale ................................................................................. 16 
6.3 
Population Rationale ......................................................................... 18 
6.4 
Pharmacodynamic Rationale ............................................................ 18 
6.5 
Safety Rationale................................................................................ 19 
6.6 
Risks and Benefits ............................................................................ 20 
6.6.1 
Risks Associated with PDM608 Administration .................... 20 
6.6.2 
COVID-19 Related Risks and Risk Mitigation Measures ...... 20 
6.6.3 
General Risks and Overall Risk-Benefit Assessment ........... 21 
7 
Objectives and Endpoints ............................................................................... 22 
8 
Study Design .................................................................................................. 22 
8.1 
Study Plan......................................................................................... 22 
8.1.1 
Study Plan: Part 1 Single Ascending Doses ......................... 22 
8.1.2 
Study Plan: Part 2 Multiple Ascending Doses ....................... 24 
8.2 
Criteria for In-Study Decisions .......................................................... 25 
8.2.1 
Decision Points ..................................................................... 26 

 
CONFIDENTIAL 
 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 4 of 64  
 
8.2.2 
Criteria for Dose Decision ..................................................... 26 
8.3 
Subject Withdrawal ........................................................................... 28 
8.4 
Subject Replacement ........................................................................ 29 
8.5 
Stopping Criteria ............................................................................... 29 
8.6 
Study Termination ............................................................................. 30 
8.7 
Lost to Follow-Up .............................................................................. 30 
8.8 
Subject Selection List and Randomization ........................................ 30 
8.8.1 
Subject Numbers .................................................................. 31 
8.8.2 
Blinding ................................................................................. 31 
9 
Selection of Subjects ...................................................................................... 32 
9.1 
Informed Consent ............................................................................. 32 
9.2 
Inclusion Criteria ............................................................................... 32 
9.3 
Exclusion Criteria .............................................................................. 33 
9.4 
Contraception and Restrictions ......................................................... 35 
9.4.1 
Sperm Donation .................................................................... 36 
9.4.2 
Egg Donation ........................................................................ 36 
9.5 
Pregnancy ......................................................................................... 36 
9.6 
Additional Study Restrictions ............................................................ 36 
10 
Study Procedures ........................................................................................... 36 
10.1 
Screening .......................................................................................... 37 
10.1.1 Subject Re-Screening ........................................................... 37 
10.2 
Admission and Pre-dose Procedures ............................................... 37 
10.3 
Study Day Procedures ...................................................................... 37 
10.3.1 Blood Volume ........................................................................ 37 
10.3.2 Timing of Procedures ............................................................ 38 
10.3.3 Discharge from the Clinical Unit ............................................ 38 
10.3.4 Return Visits .......................................................................... 38 
10.3.5 Medical Supervision .............................................................. 38 
10.3.6 Follow-up .............................................................................. 38 
11 
Dosing of Subjects ............................................................................ 38 
11.1 
Food and Fluid Intake ....................................................................... 38 

 
CONFIDENTIAL 
 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 5 of 64  
 
11.2 
Dosing Compliance ........................................................................... 39 
11.3 
Prior and Concomitant Medications .................................................. 39 
12 
Pharmacokinetic and Pharmacodynamic Blood Sampling ............................. 39 
13 
Assessment of Safety ..................................................................................... 40 
13.1 
Definition and Classification of Adverse Events ................................ 40 
13.2 
Assessment of Causality ................................................................... 40 
13.3 
Recording Adverse Events ............................................................... 41 
13.4 
Serious Adverse Events .................................................................... 41 
13.4.1  Definition of Serious Adverse Events .................................... 41 
13.4.2  Definition of Suspected Unexpected Serious Adverse 
Reactions .......................................................................................... 42 
13.5 
Adverse Events of Special Interest (AESI) ....................................... 42 
13.6 
Safety Laboratory Measurements ..................................................... 42 
13.6.1  Hematology and Clinical Chemistry ...................................... 43 
13.6.2  Anti-Drug Antibodies ............................................................. 43 
13.6.3  Urinalysis .............................................................................. 43 
13.6.4  Pregnancy Test ..................................................................... 43 
13.6.5  Follicle-Stimulating Hormone Test ........................................ 43 
13.6.6  Alcohol, Cotinine, and Drug Screen ...................................... 44 
13.6.7  Abnormal Laboratory Findings .............................................. 44 
13.7 
Vital Signs Measurements ................................................................ 44 
13.8 
12-Lead Electrocardiogram Measurements ...................................... 44 
13.9 
Body Weight, Height and Body Mass Index ...................................... 45 
13.10 
Physical Examination ........................................................................ 45 
13.11 
Additional Safety Procedures ............................................................ 45 
14 
Statistics and Data Analysis ........................................................................... 45 
14.1 
Sample Size Justification .................................................................. 45 
14.2 
Data Management ............................................................................ 45 
14.3 
Pharmacokinetic Data Analysis ........................................................ 46 
 

CONFIDENTIAL 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 6 of 64  
14.4 
Statistical Data Analysis .................................................................... 47 
14.5 
Interim Analysis ................................................................................. 49 
15 
Safety Reporting to Institutional Review Board and Regulatory 
Authorities ....................................................................................................... 49 
15.1 
Events Requiring Expedited Reporting ............................................. 49 
15.2 
Urgent Safety Measures ................................................................... 49 
15.3 
Reporting .......................................................................................... 50 
15.3.1  Reporting Serious Adverse Events and AESI ....................... 50 
15.3.2  Reporting of Suspected Unexpected Serious Adverse 
Reactions .......................................................................................... 50 
15.3.3  Expedited Reporting of Events ............................................. 50 
15.3.4  Reporting of Urgent Safety Issues ........................................ 50 
15.4 
Reporting Other Serious Important Medical Events .......................... 50 
16 
Protocol Amendments and Deviations ............................................................ 51 
16.1 
Amendments ..................................................................................... 51 
16.2 
Protocol Deviations ........................................................................... 51 
17 
Regulatory ...................................................................................................... 51 
17.1 
Compliance ....................................................................................... 51 
17.2 
Ethical Approval ................................................................................ 51 
17.3 
Investigator Responsibilities ............................................................. 51 
17.4 
Source Data ...................................................................................... 52 
17.5 
Declaration of the End of the Study .................................................. 52 
17.6 
Document Storage and Archiving ..................................................... 52 
17.7 
Protection of Personal Data and Confidentiality ............................... 52 
18 
Quality Control and Quality Assurance ........................................................... 53 
18.1 
Monitoring ......................................................................................... 53 
19 
Publication ...................................................................................................... 54 
20 
References ..................................................................................................... 55 

 
CONFIDENTIAL 
 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 7 of 64  
 
 
Appendix 1 
Clinical Laboratory Parameters ......................................................... 56 
Appendix 2 
Schedule of Assessments: Part 1 Single Ascending Dose ............... 57 
Appendix 3 
Schedule of Assessments: Part 2 Multiple Ascending Dose ............ 59 
 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 8 of 64  
 
2 List of Tables and Figures  
2.1 
Table of In-Text Tables 
Table 1  
Investigational Medicinal Products ................................................................... 14 
Table 2 
Description of Dosing: Part 1 Single Ascending Doses ................................... 23 
Table 3 
Description of Dosing: Part 2 Multiple Ascending Doses ................................. 24 
Table 4 
Pharmacokinetic Parameters ........................................................................... 46 
 
2.2 
Table of In-Text Figures 
Figure 1 
Study Sequence: Part 1 Single Ascending Doses ........................................... 24 
Figure 2 
Study Sequence: Part 2 Multiple Ascending Doses ......................................... 25 
 
 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 9 of 64  
 
3 Synopsis 
Sponsor:  
Calibr, a Division of Scripps 
Research 
Investigational Medicinal Product: 
PDM608 
IND No.: 
163942 
 
Title of Study: A two-part Phase 1 study to assess the safety, tolerability, pharmacokinetics 
and pharmacodynamics of PDM608 in healthy adult subjects 
Study Center: Quotient Sciences – Miami, Inc., 3898 NW 7th Street, Miami, FL 33126, USA 
Objectives and Endpoints: Please see Section 7 of the protocol 
Methodology and Study Design: 
This is a 2-part, single-center, first-in-human study of single ascending doses (SAD; 
Part 1) and multiple ascending doses (MAD; Part 2) of PDM608 in healthy adult subjects. 
Part 1 is a double-blind, randomized, placebo-controlled assessment of subcutaneous 
(SC) SAD administrations of PDM608 across 5 cohorts of subjects. All SAD cohorts will 
follow a sentinel design. Following completion of each cohort, safety and tolerability data 
will be reviewed to determine whether to progress to the next dose level and the dose level 
for the next cohort. Anticipated SAD cohort PDM608 dose levels are described in Table 2; 
see Section 8.1.1 for further details. 
Part 2 is a double-blind, randomized, placebo-controlled assessment of SC MAD 
administrations (once weekly for 4 weeks) of PDM608 across up to 4 cohorts of subjects. 
Following completion of each cohort the safety and tolerability data will be reviewed to 
determine whether to progress to the next dose level and the dose level to be 
administered. MAD cohorts will receive PDM608 regimens as described in Table 3; see 
Section 8.1.2 for further details. 
A Safety Advisory Committee (SAC) (Section 8.2) will oversee decisions to dose the next 
dose level for SAD and MAD cohorts, and the initiation of Part 2 (MAD).  MAD cohorts will 
not include a sentinel design unless requested by the SAC. 
Number of Subjects Planned: 
It is planned to enroll 40 healthy adult subjects into up to 5 cohorts of 8 subjects each in 
Part 1 (SAD) to ensure data in a minimum of 6 evaluable subjects per cohort. Up to 
2 replacement subjects per cohort may be enrolled into Part 1 of the study. 
It is planned to enroll up to 48 healthy adult subjects into up to 4 cohorts of 12 subjects 
each (MAD Cohort 4 is optional) in Part 2 (MAD) to ensure data in a minimum of 8 
evaluable subjects per cohort. Up to 3 replacement subjects per cohort may be enrolled 
into Part 2 of the study. 
See Section 8.4 for further details. 
Duration of Study: 
In Part 1 (SAD), subjects will receive a single administration on one occasion. The 
estimated time from consent until the follow-up visit is 7 weeks. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 10 of 64  
 
In Part 2 (MAD), subjects will receive multiple administrations (4 doses) across a period of 
4 weeks (once weekly dosing). The estimated time from consent until the follow-up visit is 
13 weeks. 
Main Inclusion Criteria: 
Healthy men and non-pregnant, non-lactating healthy women of non-childbearing 
potential, aged 18 to 65 years inclusive at time of signing informed consent.  See Section 
10. 
Body mass index of 18.0 to 33.0 kg/m2 as measured at screening. 
Investigational Medicinal Product, Dose and Mode of Administration: 
The following investigational medicinal products (IMPs) will be used in this clinical study: 
• 
PDM608 solution - 25 mg/mL 
• 
Placebo for PDM608 - 0 mg/mL 
See Section 5.2 and Pharmacy Manual for further IMP details. 
Pharmacokinetic Assessments: 
Blood samples will be collected throughout each study part for PK analysis. Analysis of 
PDM608 plasma concentration data will be performed using appropriate 
non-compartmental techniques to obtain estimates of the PK parameters detailed in 
Table 4, where possible and appropriate. 
Immunogenicity Assessments: 
Blood samples will be collected throughout each study part for detection and titering of 
antidrug antibodies (ADA) using a validated assay.   
Pharmacodynamic Assessments: 
Blood samples will be collected throughout each study part for pharmacodynamic (PD) 
analysis, which include the number of immunologic cell types and the concentration of 
cytokines. 
Safety Assessments:  
The safety assessments to be conducted include adverse event monitoring, clinical 
laboratory tests (clinical chemistry, hematology and urinalysis), physical examinations, 12-
lead electrocardiograms and vital signs. 
Statistical Methodology: 
No formal statistical analysis will be performed on the safety and tolerability data for this 
study. Descriptive statistics are considered adequate for a study of this type. Descriptive 
summaries for all PK and PD data by cohort will be provided. In addition, formal statistical 
analyses will be performed to assess dose proportionality (Part 1 and Part 2), 
accumulation following multiple dosing (Part 2) and changes in the numbers of Treg cells. 
See Section 14.4 for further information. 
Sample Size and Power: 
Based on experience from previous similar studies, the target numbers of subjects to be 
enrolled (N = 8 and N = 12) should be sufficient to achieve a minimum of 6 and 8 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 11 of 64  
 
evaluable subjects in each cohort in Part 1 and Part 2, respectively. Based on 
sargramostim treatment of Parkinson’s Disease patients (Gendelman 2017), the MAD 
sample size is sufficient to detect an increase of 5% in mean Treg percentages compared 
with pooled placebo subjects, which is considered a meaningful treatment effect for future 
patient studies (Section 14.1).  Similar sample sizes have detected changes in WBC, 
MNC, monocytes and eosinophils in healthy volunteers (Lane 1995; Fishmeister 1999).     
An evaluable subject for Part 1 is defined as a subject who has received the IMP dose and 
completed relevant safety and tolerability assessments (inclusive of all scheduled 
hematology assessments) through 96 hours post-dose. 
An evaluable subject for Part 2 is defined as a subject who has received all 4 doses of IMP 
and completed relevant safety and tolerability assessments (inclusive of all scheduled 
hematology assessments) through 96 hours post-final dose (Dose 4). 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 12 of 64  
 
4 List of Abbreviations 
Abbreviation Definition 
ADA anti-drug antibodies 
ADR adverse drug reaction 
AE adverse event 
AESI adverse event of special interest 
ALP alkaline phosphatase 
ALT alanine aminotransferase 
AR accumulation ratio 
AST aspartate aminotransferase 
AUC area under the curve 
BMI body mass index 
CBC complete blood count 
CDER Center for Drug Evaluation and Research 
CFR Code of Federal Regulations 
CHMP Committee for Medicinal Products for Human Use 
CI confidence interval 
CK creatine kinase 
CLcr creatinine clearance 
COVID-19 Coronavirus Disease 2019 
CRF case report form 
CSF colony-stimulating factor 
CSPM Clinical Sample Processing Manual 
CV% coefficient of variation 
CYP cytochrome P450 
DC discontinuation 
DMP Data Management Plan 
ECG electrocardiogram 
eCRF electronic case report form 
F absolute bioavailability 
FDA US Food and Drug Administration 
FIH first in human 
FSH follicle stimulating hormone 
GCP good clinical practice 
GI gastrointestinal 
GM-CSF granulocyte-macrophage colony stimulating factor 
HBsAg hepatitis B surface antigen 
HCV Ab hepatitis C virus antibody 
HED human equivalent dose 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 13 of 64  
 
Abbreviation Definition 
HIV human immunodeficiency virus 
HRT hormone replacement therapy 
IB Investigator’s Brochure 
IC50 50% inhibition of activity 
ICF informed consent form 
ICH International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IMP investigational medicinal product 
IRB Institutional Review Board 
ISF Investigator Site File 
IV intravenous 
MAD multiple ascending dose 
NOAEL no-observed-adverse-effect-level 
NSAOD nonsteroidal anti-inflammatory 
PAD pharmacologically active dose 
PD pharmacodynamic 
PK pharmacokinetic(s) 
QA quality assurance 
QTcF Corrected QT interval by Fridericia’s formula 
RAP Reporting and Analysis Plan 
SAC safety advisory committee 
SAD single ascending dose 
SAE serious adverse event 
SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 
SBS short bowel syndrome 
SC subcutaneous 
SOP standard operating procedure 
SUSAR suspected unexpected serious adverse reaction 
TB tuberculosis 
TMF trial master file 
Treg T-regulatory cells 
ULN upper limit of normal 
WOCBP woman of childbearing potential 
WONCBP woman of non-childbearing potential 
 
The pharmacokinetic definitions used in this study are presented in Section 14.3. 
 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 14 of 64  
 
5 Background Information 
5.1 
Introduction  
Granulocyte-macrophage colony stimulating factor (GM-CSF; also known as colony-
stimulating factor 2, CSF2) is a glycoprotein cytokine secreted by macrophages, T cells, 
mast cells, natural killer cells, endothelial cells and fibroblasts. It is an important 
hematopoietic growth factor and immune modulator that has profound effects on the 
function of circulating peripheral leukocytes. GM-CSF binds with high affinity to the GM-
CSF receptor, a heterodimeric receptor expressed by granulocyte-monocyte progenitors, 
monocyte progenitors and most innate immune cells including granulocytes, monocytes, 
macrophages, dendritic cells and microglia. 
Sargamostim (Leukine®) is a yeast-derived, recombinant GM-CSF (rGM-CSF) agonist 
used to treat neutropenia, to mobilize stem cells for hematopoietic stem cell transplant, to 
accelerate myeloid reconstitution following bone marrow transplant and to facilitate 
recovery from myelosuppression. Recent clinical studies suggest that sargramostim may 
also provide clinical benefits for patients with Alzheimer’s disease and Parkinson’s disease 
(Gendelman 2017, Olson 2021, Potter 2021). These effects may be mediated at least in 
part by selective increases in Treg numbers (Chen 2016, Gendelman 2017, Kosloski 2013, 
Olson 2020). Sargramostim treatment is generally safe and well-tolerated; however, 
sargramostim has a short half-life, and chronic treatment for these and other indications is 
possible only with daily subcutaneous (SC) injections. This dosing regimen is burdensome 
for patients. 
Calibr is developing PDM608, a novel molecule consisting of rGM-CSF fused to the 
complementarity-determining region (CDR) of the immunoglobulin heavy chain of the 
clinically approved human trastuzumab (branded Herceptin®) antibody. Protein design 
was optimized by incorporating wild-type GM-CSF peptide into an engineered, de-
immunized antibody scaffold with optimized linkers. PDM608 has a substantially longer 
half-life in animals (~200-300 hours in rat) and improved 
pharmacokinetic/pharmacodynamic (PK/PD) profile over sargramostim. PDM608 is being 
developed as a once-weekly injectable therapy for neurodegenerative, autoimmune and 
immuno-oncology applications. 
5.2 
Investigational Medicinal Product(s) 
The investigational medicinal products (IMPs) that will be used in this clinical study are 
presented in Table 1. 
Table 1  
Investigational Medicinal Products 
Investigational 
Medicinal Product 
Name:  
PDM608 solution for SC injection  
Matching placebo for PDM608 solution for 
SC injection  
Product Type:  
Test  
Placebo  
Dosage 
Formulation:  
Solution  
Solution  
Unit Dose 
Strength(s)/  
Dosage Level(s):  
25 mg/mL  
0 mg/mL  
Route of 
Administration:  
SC  
SC  

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 15 of 64  
 
Dosing 
instructions:  
Administered as a SC injection to the 
abdomen  
Administered as a SC injection to the 
abdomen  
Packaging and 
Labeling:  
Each vial is individually labelled. Each box 
contains 100 vials. 
Each vial is individually labelled. Each box 
contains 36 vials. 
Storage and 
Handling:  
-20°C, excursions permitted between -
15°C to -25°C 
-20°C, excursions permitted between -15°C 
to -25°C 
Manufacturer:  
Manufactured by Wuxi 
Manufactured by Wuxi 
SC: subcutaneous. Further information will be provided in the Pharmacy Manual.  
The PDM608 solutions for SC and matching placebo injections are un-licensed medicinal 
products for use only in the proposed clinical trial. 
Only subjects enrolled in the study may receive study treatment and only authorized site 
staff may supply or administer study treatment. All study treatments will be stored in a 
secure, environmentally-controlled and monitored (manual or automated) area in 
accordance with the labelled storage conditions with access limited to the investigator and 
authorized site staff. 
IMPs will be reconciled and destroyed in accordance with the applicable standard 
operating procedures (SOPs). 
5.3 
Previous Study Findings 
This is a first-in-human study. Full details of non-clinical study findings can be found in the 
Investigator’s Brochure (IB). A summary of the non-clinical findings is provided below. 
5.3.1 Nonclinical Findings 
5.3.1.1 Nonclinical Pharmacokinetics,Metabolism and Toxicology 
In vivo pharmacokinetics (PK), toxicokinetics and in vitro metabolism of PDM608 and 
toxicology have been evaluated and PDM608 exhibited a low clearance (< 0.1 mL/min/kg) 
and volume of distribution (< 0.2 L/kg) in mice, rats, and monkeys following IV 
administration. The half-life of PDM608 in mice, rats, and monkeys were 21.4 hr, 211 hr 
and 19.8 hr, respectively. SC bioavailability was > 44%.  
Following IV and SC administration at 5 mg/kg to cynomolgus monkeys, the number of 
lymphocyte subpopulations in cynomolgus monkey peripheral blood showed a transient 
increase in Total T cells, Helper T cells, Regulatory Helper T cells, Cytotoxic T cells, 
Regulatory Cytotoxic T cells and B cells, and then decreased close to baseline.  
The PK, PD, and safety pharmacology of PDM608 were assessed following repeat dosing 
SC administration to naïve male cynomolgus monkeys at 0.1, 0.5, or 5 mg/kg PDM608 
(once weekly for 22 days). The systemic exposure of PDM608 increased proportional to 
dose or greater than dose proportional. PDM608 induced a dose-proportional increase in 
TREG. Most PDM608-treated animals at all doses were positive for ADAs from 336 
through 672 hours.  
In a non-GLP 14-day dose range-finding toxicity study in cynomolgus monkeys, the toxicity 
profile and PK of PDM608 was accessed at doses of 0, 5, 30, or 120 mg/kg (actual doses 
were 0, 6.2, 37.3, and 149.3 mg/kg) over 14 days by SC injection on Days 1, 4, 7, 10, and 
13. The systemic exposure increased proportional to dose or greater than dose 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 16 of 64  
 
proportional. The systemic exposure was lower at the end of study than Day 1, likely due 
to the immunogenicity response.  
 In a 4-week GLP toxicity study in cynomolgus monkeys (CBR-PDM608-0106), PDM608 
was administered once every 3 days by SC injection at dose levels of 0, 2, 6, or 18 
mg/kg/dose. The systemic exposure increased dose proportionally. On Day 13 and 28, 
plasma concentrations were below the lower limit of quantification in most of the animals, 
likely due to high ADA. 
The NOAEL with PDM608 effect for this study was considered to be 18 mg/kg/dose. There 
was no NOAEL identified for the effects of ADA induced by PDM608.  
Overall, no marked sex difference was observed in systemic exposure. 
5.3.1.2 Clinical Findings 
Effects of PDM608 in humans have not yet been characterized. It is anticipated that 
PDM608 will stimulate immune cells and cytokine production in a similar fashion to the 
short-acting GM-CSF, sargramostim, which shares a similar mechanism of action.  Please 
see the Investigator’s Brochure for a brief description of the safety of GM-CSF in different 
populations.  
Because it is a protein biologic, treatment with PDM608 could be associated with the 
generation of anti-drug antibodies (ADAs). ADAs have been observed in patients treated 
with rGM-CSF produced in E. coli and with sargramostim; these antibodies were 
associated with decreased treatment efficacy but not with increased likelihood of AEs 
(Ragnhammar 1994, Leukine package insert).   
6 Rationale 
6.1 
Study Rationale 
This Phase 1 study will evaluate the safety, tolerability, PK and PD of single ascending 
doses (SAD; Part 1) and multiple ascending doses (MAD; Part 2) of PDM608. 
This study is placebo-controlled to establish the frequency and magnitude of changes in 
clinical endpoints that may occur in the absence of active treatment. Randomization will be 
used to minimize bias in the assignment of subjects to treatment groups, to increase the 
likelihood that known and unknown subject attributes (e.g., demographic and baseline 
characteristics) are evenly balanced across treatment groups and to enhance the validity 
of comparisons across dose groups. Blinded treatment will be used to reduce potential 
bias during data collection and evaluation of clinical endpoints. 
As this study will be the first time PDM608 has been administered to humans, sentinel 
dosing will be used for all SAD cohorts. The first two subjects of each cohort (i.e., one 
subject receiving active and one subject receiving placebo) will be dosed prior to the 
remaining subjects (sentinel group). After review of the safety data up to 72 hours post-
dose the Investigator will decide whether to proceed with dosing the remaining subjects in 
the cohort (main group). 
6.2 
Dose Rationale 
The recommendations of the following guidelines have been considered when setting the 
starting dose and escalation rules for this trial:  

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 17 of 64  
 
• 
Guideline on strategies to identify and mitigate risks for first-in-human and early 
clinical trials with IMPs (EMEA/Committee for Medicinal Products for Human Use 
[CHMP]/SWP/28367/07 Rev. 1), 20 July 2017 
Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials 
for Therapeutics in Adult Healthy Volunteers. U.S. Department of Health and Human 
Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). 
July 2005 
PDM608 will be administered by SC injection to healthy participants beginning in Part 1 
with a single starting dose of 350 µg (flat dose) with subsequent single dose escalation to 
anticipated doses of 1050, 3150, 6300, up to 12600 µg. The safety of PDM608 by this 
route has been assessed in non-GLP and GLP nonclinical toxicology studies in monkeys, 
and PD studies have been conducted in monkeys and was considered safe and well 
tolerated. A broad dose range was selected for adult healthy volunteers to ensure a safe 
starting dose, to assess the safety of PDM608 across the anticipated clinical range of drug 
exposures, and to provide PK and PD data for further clinical development.   
The FIH starting dose for PDM608 was calculated using toxicology data together with a 
pharmacologically active dose (PAD)-based approach. The proposed starting dose of 350 
µg in humans is adequately supported by data from the toxicology study in cynomolgus 
monkeys (CBR-PDM608-0106). Using the NOAEL of 18 mg/kg in monkeys, the HED-
based safety factor is approximately 1161. With the predicted human PK at 350 µg, the 
dose-based, concentration (Cmax)-based, and exposure (AUC)-based safety factors are 
estimated to be 3600, 8333, and 857, respectively. This proposed starting dose is also 
expected to be lower than the PAD in humans based on the PD response in cynomolgus 
monkeys (a single dose of 0.5 mg/kg (IV/SC) achieved an increase in TReg Cells of ~1% 
(CBR- PDM608-0110)). Of note, as PDM608 is not cross-reactive in rats or mice but is 
fully cross-reactive in cynomolgus monkeys, monkeys are considered the 
pharmacologically relevant species. It should also be noted that PDM608 may be 
eliminated faster than projected at low doses, including the starting dose, due to the 
impact of target on PK (i.e., target-mediated drug disposition), which provides an additional 
safety margin for this FIH dose. 
GM-CSF has demonstrated clinical activity in patients with PD at 6 µg/kg/day Leukine (1). 
The HED of PDM608 was calculated by matching the molar exposure of Leukine (6 
µg/kg/day) and the lowest efficacious dose is 1.21 µg/kg (Q1W, based on Cmax). 
Considering that PDM608 is about 22-fold less potent than recombinant human GM-CSF, 
the lowest HED of PDM608 is projected to be 27 µg/kg for every week [1.21 µg/kg (lowest 
HED of PDM608) x 22 = 27 µg/kg].  
The proposed starting dose level of PDM608 at 350 µg (5 µg/kg for a 70 kg subject) is 
expected to be lower than the dose likely to have efficacy in humans. Escalation between 
cohorts will be limited to a maximum of 3-fold between SAD cohorts and a maximum of 3-
fold between MAD cohorts. This is considered appropriate in the context of 
dose/exposure-toxicity and dose/exposure-effect relationship defined in non-clinical 
studies. Emerging clinical data relating to the safety and PK/PD and profile of PDM608 
may also be considered, as appropriate and available, when dose decisions are made 
throughout the study. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 18 of 64  
 
Based on the maximum allowed escalations and anticipated PD activity, the highest 
anticipated dose will be 12600 µg. Using the NOAEL of 18 mg/kg in monkeys, the HED-
based safety factor is approximately 32, With the predicted human PK at 12600 µg 
(assuming 70kg patients and 90% SC bioavailability), the dose-based, concentration 
(Cmax)-based, and exposure (AUC)-based safety factors are estimated to be 100, 231, 
and 24, respectively. 
Doses administered will be predicted not to exceed a mean Cmax of 103,950 ng/mL and a 
mean AUC(0-24h) of 1,775,000 ng.h/mL, which is the sex-averaged mean NOAEL exposure 
limits after the first dose of 18 mg/kg in the cynomolgus NOAEL 28-day good laboratory 
practice (GLP) toxicology study, in any individual subject. 
The non-clinical program, containing pharmacology, PK, PD, and toxicology data of 
PDM608, supports the initiation of a human clinical study for the treatment of 
neurodegenerative diseases. 
6.3 
Population Rationale 
As this is a Phase I study assessing the PK, PD, tolerability and safety of PDM608, the 
most relevant population is healthy volunteers. Subjects who are non-smokers without a 
history of alcohol, drug abuse or regular co-medication are proposed to avoid interaction 
on drug metabolism and noncompliance. 
It is not known whether PDM608 can cause fetal harm when administered to pregnant 
women, affect male or female fertility, or whether it is secreted in human milk. Therefore, 
women of childbearing potential will not be enrolled in this study, men will be allowed to 
participate as long as they comply with the contraception requirements as detailed in 
Section 9.4, and men with pregnant partners will be excluded from the study (see 
Section 9.3). 
Based on the above considerations and target population, healthy non-pregnant and 
non-lactating women of non-childbearing potential (WONCBP) and healthy men aged 18 
to 65 years are considered suitable subjects for this study.  GM-CSF preparations have 
previously been studied in healthy volunteers (Lane 1995; Fishmeister 1999).   
6.4 
Pharmacodynamic Rationale 
GM-CSF is approved for peripheral blood mobilization of CD34+ stem cells for 
transplantation.  The approved dose of sargramostim for autologous mobilization is 250 
mcg/m2/day SC (6-7 mcg/kg) which greatly increases precursor cell frequencies.  For 
allogeneic transplant, donors are often prepared with four daily doses of GM-CSF followed 
by apheresis.   
One goal of the PDM608 early development program is to identify a safe, tolerated dose of 
PDM608 that increases peripheral blood Tregs, which can be profiled in 
neurodegenerative diseases, such as Parkinson’s disease.  Short-acting GM-CSF appears 
to increase various cell lineages with roughly similar kinetics, with the degree of change 
dependent on the cell type.  We will take advantage of the known pharmacodynamic 
effects of GM-CSF to inform dose escalation decisions.    
GM-CSF at a dose of 5-10 mcg/kg/day for 4-5 days increased numerous cell lineages in 
peripheral blood of healthy volunteers, with increases in WBC, MNC, PMN, monocytes, 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 19 of 64  
 
and eosinophils (Lane 1995; Fishmeister 1999): WBC increased greater than 3-fold, MNC 
and monocytes increased greater than 2-fold and eosinophils increased greater than 7-
fold. The time course of Treg elevation in humans is not well-known, but was increased 
two-fold after 2 weeks daily exposure to GM-CSF in persons with Parkinson’s disease 
(Gendelman 2017). A preclinical PKPD study with PDM608 demonstrated dose-dependent 
elevation of Regulatory Helper T cells and Regulatory Cytotoxic T Cells in cynomolgus 
monkey 10 days after weekly dosing (CBR-PDM608-110). 
An increase of 5% in mean Treg percentages compared with pooled placebo subjects may 
be considered a meaningful treatment effect for future patient studies (Section 14.1), thus 
dose escalation will be optimized through analysis of Tregs as a pharmacodynamic 
parameter.  
Pharmacodynamic analysis may include immunophenotyping by flow cytometry to 
determine numbers/percentages of certain immune cells, and cytokine analysis (section 
12), as well as analysis of a subset of the safety hematology labs (WBC, monocyte, and 
eosinophil values) as an indicator of pharmacodynamic activity.  
The maximum PDM608 dose administered in either part of this trial will not exceed a dose 
that is more than two-fold above the dose at which any two of the following three 
pharmacodynamic activities are observed in a sample that includes a minimum 5 of 6 
PDM608-treated subjects in SAD or 7 of 9 PDM608-treated subjects in MAD, treated 
within the same cohort, and observed at any laboratory timepoint up to and including 96 
hours post-dose (SAD) and post-final dose (MAD): 
• 
An increase in mean WBC from pre-dose baseline by ≥ 3-fold  
• 
An increase in mean monocytes from pre-dose baseline by ≥ 2-fold 
• 
An increase in mean eosinophils from pre-dose baseline by ≥ 7-fold 
 
The above three hematologic parameters will be described and made available for review 
by the SAC when making dose level decisions. 
 Intra-subject changes are considered because of the wide-variability of hematological 
parameters between subjects, and because smaller numbers of subjects are allocated to 
placebo treatment. Multiple pharmacodynamic endpoints are selected to minimize the 
impact of outliers on mean values.  A statistical test is not applied to these 
pharmacodynamic effects. Dose escalation beyond this point (as described above) is 
permitted in order to obtain pharmacokinetic and pharmacodynamic margin for subsequent 
patient studies.  This pharmacodynamic limit assumes that PDM608 remains safe as 
defined by the other stopping rules in Section 8.5. 
6.5 
Safety Rationale 
The major risks of PDM608 administration to humans are excessive pharmacology of 
stimulation of GM-CSF activity and the consequences of development of ADA against the 
product.  The pharmacology of GM-CSF is outlined in the Investigator’s Brochure.  
Common AE in clinical studies with sargramostim include injection site reactions, 
headache, bone pain, flu-like symptoms and increased blood leukocyte levels (Leukine 
USPI).  This protocol specifies white count as an adverse event of special interest (Section 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 20 of 64  
 
13.5).  This protocol allows the use of acetaminophen if the Investigator believes it is 
appropriate to manage AE (Section 11.3).  Sargramostim, a yeast derived GM-CSF, has 
been associated with the development of ADA, but there is little evidence that these 
antibodies result in AE, and the evidence that they reduce pharmacological activity of 
sargramostim is mixed (see the Investigator’s Brochure).  PDM608 is designed to have low 
immunogenicity in humans.  This protocol will measure ADA with a validated assay.   
Serum sickness-like reactions, which may be a consequence of ADA, will be monitored 
through vital signs, laboratory safety testing and AE. This protocol instructs the 
Investigator to contact the Sponsor if a rash develops that may be part of a serum 
sickness-like reactions (Section 13.5). 
6.6 
Risks and Benefits 
6.6.1 Risks Associated with PDM608 Administration 
Human data have yet to be generated for PDM608. However, over 30 years of clinical data 
for sargramostim suggests that GM-CSF is safe and well-tolerated. Please see the IB for 
details of risks and benefits of PDM608 administration. 
6.6.2 COVID-19 Related Risks and Risk Mitigation Measures 
The following risks and risk mitigating measures apply to the time in which the study is 
conducted during the Coronavirus Disease 2019 (COVID-19) pandemic.  
6.6.2.1 IMP Related Risk 
Against the background of the COVID-19 pandemic, the potential risk of a subject 
developing COVID-19 has been considered in terms of the risk-benefit evaluation. The 
mode of action of the IMP – as a GM-CSF agonist – has been considered alongside 
available nonclinical and clinical data (including class effects) and it is considered that a 
subject would not be at increased risk of either becoming infected with severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2; the virus that causes COVID-19) or 
experiencing a more severe illness. That is, the IMP has no known immunomodulatory 
effect that would confer an increased risk to healthy subjects enrolled in the study. 
6.6.2.2 General COVID-19 Related Risks and Risk Mitigation Measures 
General risk mitigation against COVID-19 will be implemented in accordance with 
Quotient’s monitoring and prevention control measures. 
The risk mitigation measures, where applicable, will be amended based on emerging 
government guidance.  
6.6.2.3 COVID-19 Vaccine-Related Risk 
Approved (including health authority conditional marketing authorization) COVID-19 
vaccines (e.g., killed, inactivated, peptide, DNA and RNA vaccines) may be permitted 
according to the investigator’s discretion and as per local guidance.  
Based on the mechanism of action of the IMP, as a GM-CSF agonist, there is no 
perceived impact on the safety of the study subjects or on the study objectives for subjects 
who may receive these vaccines. It is also anticipated to be very unlikely that 
administration of the IMP would interfere with COVID19 vaccination response; however, 
no specific preclinical or clinical investigations have been conducted at this point with 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 21 of 64  
 
PDM608. Therefore, no COVID-19 vaccines will be permitted within 14 days prior to first 
dose until a subject’s final visit on this trial, and COVID19 vaccinations are not acceptable 
concomitant medications. 
6.6.3 General Risks and Overall Risk-Benefit Assessment 
PDM608 shares its mechanism of action with GM-CSF, sargramostim.  The safety of 
sargramostim in various populations including healthy volunteers is outlined in the 
Investigator’s Brochure.  Flu-like symptoms and injection site rash were reported with a 
dose of  5-10 mcg/kg/day in these studies, while GM-CSF at 15 mcg/kg/day was not 
tolerated by donors, with 2 of 21 donors experiencing fever, chills and capillary leak 
syndrome (Devine  2005). This protocol allows the Investigator to manage headache, bone 
pain and flu-like symptoms as described in Section 11.3. 
Therapeutic proteins may cause the development of ADA, which might cause AE(s).  
Antibodies to GM-CSF have been associated with loss of pharmacodynamic activity in 
humans, but not with an increase in adverse events.  ADA to GM-CSF have been shown 
to clear with time (Ragnhammar 1994, Leukine package insert).    
Collecting a blood sample from a vein may cause pain, swelling, bruising, 
lightheadedness, fainting and, very rarely, clot formation, nerve damage and/or infection at 
the site of the needle stick. 
Electrocardiogram (ECGs) stickers on the subjects' chests and limbs may cause some 
local irritation and may be uncomfortable to remove but subjects will be closely monitored 
to ensure any local irritation does not persist. 
There is no anticipated clinical benefit to the subjects taking part in this study. The 
development of a product to treat neurodegenerative, autoimmune and oncological 
diseases may be of benefit to future patients. 
The overall risk benefit balance is considered to be acceptable. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 22 of 64  
 
7 Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To assess the safety, tolerability and PK 
of single (Part 1) and multiple (Part 2) SC 
doses of PDM608  
• Incidence of AEs, change from baseline for 
physical examinations and vital signs, 
electrocardiograms (ECGs) and laboratory 
safety tests including ADA in blood 
• PK parameters for PDM608 
Secondary 
To assess immunogenicity following 
single and multiple doses of PDM608 
Incidence of ADA in blood 
Exploratorya 
To assess PD following administration of 
single (Part 1) and multiple (Part 2) 
ascending SC doses of PDM608 
• Individual baseline corrected leukocyte, 
Treg 
and 
other 
immune 
cell 
numbers/percentages  
• Individual baseline corrected cytokine 
levels  
a Exploratory PD biomarker objectives may be reported separately to the Clinical Study Report. 
8 Study Design 
8.1 
Study Plan 
This is a 2-part, single-center, first-in-human study of SAD (Part 1) and MAD (Part 2) 
doses of PDM608 in healthy adult subjects. The 2 parts are not required to be conducted 
entirely sequentially provided that this is justified by safety data obtained from completed 
cohorts. The first MAD cohort will not be dosed until a minimum 3 SAD cohorts have 
undergone review by the SAC, and dosing for each MAD cohort will be at a dose level 2-3 
fold lower than the highest SAD cohort dose deemed safe by the SAC at the time of each 
MAD cohort initiation. 
8.1.1 Study Plan: Part 1 Single Ascending Doses 
Part 1 is a double-blind, randomized, placebo-controlled assessment of SC PDM608 SAD 
administrations. Subjects will be enrolled sequentially into 1 of up to 5 cohorts, each 
containing 8 subjects. Within each cohort, 6 subjects will be randomly assigned to receive 
PDM608 and 2 subjects will be randomly assigned to receive matching placebo. An 
evaluable subject for Part 1 is defined as a subject who has received the IMP dose and 
undergone all safety and tolerability assessments (inclusive of all scheduled hematology 
assessments) out to 96 hours post. 
All SAD Cohorts will follow a sentinel design. On the first day of dosing only 2 (sentinel) 
subjects will be dosed. The randomization schedule will be constructed such that 1 of the 
subjects dosed on the first day will receive PDM608 and 1 will receive placebo. After 
review of the safety data from the 72 hours post-dose period the Investigator will decide 
whether to proceed with dosing the remaining subjects in the cohort (main group; 5 
subjects randomized to receive PDM608 and 1 subject randomized to receive placebo).  

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 23 of 64  
 
Following completion of each cohort the safety and tolerability assessments through 
96 hours post-dose (Day 5) will be reviewed by the SAC to determine whether to progress 
to the next dose level and the dose level for the next cohort, with a maximum 3-fold 
increase in dose level between SAD cohorts.  
Following dosing of at least 3 SAD cohorts, the SAC will also decide whether to progress 
to MAD Part 2 of the study and, if so, on the starting dose for the first MAD cohort. Part 2 
may be dosed in parallel with Part 1, but the decision to proceed to Part 2 can only be 
made following interim review of safety and tolerability data from doses through SAD 
Cohort 3. Full details of the interim data reviews are provided in Section 8.2. 
Table 2 
Description of Dosing: Part 1 Single Ascending Doses 
SAD Cohort   
Investigational Medicinal Product   
Dosea, b   
1   
PDM608 or matching placebo   
350 µg   
2   
PDM608 or matching placebo   
1050 µg   
3   
PDM608 or matching placebo   
3150 µg   
4   
PDM608 or matching placebo   
6300 µg   
5   
PDM608 or matching placebo   
12600 µg   
Details of the IMP are provided in Section 5.2. 
a Anticipated doses. The actual doses to be administered in this study will be determined following interim review 
by the SAC. 
b Administration detailed in the Pharmacy Manual. 
Each cohort will follow the same study design (Figure 1), detailed in the Schedule of 
Assessments (Appendix 2). 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 24 of 64  
 
Figure 1 
Study Sequence: Part 1 Single Ascending Doses 
Screening: Day -28 to Day -2 
 
Admission: Day -1 
 
Dose: Day 1 
 
Clinic Discharge: Day 8 
 
Return Visit: Day 11 
 
Return Visit: Day 15 
 
Return Visit: Day 22 
8.1.2 Study Plan: Part 2 Multiple Ascending Doses 
Part 2 is a double-blind, randomized, placebo-controlled assessment of SC PDM608 MAD 
administrations. Subjects will be enrolled sequentially into 1 of up to 4 cohorts, each 
containing 12 subjects. Within each cohort, 9 subjects will be randomly assigned to receive 
PDM608 and 3 subjects will be randomly assigned to receive matching placebo. MAD 
Cohort 4 is optional; the decision on whether to dose this cohort will be based on interim 
review of preceding MAD Cohorts 1 to 3.  
Part 2 may be dosed in parallel with Part 1, but can only proceed following interim review 
of safety and tolerability data from at least the first 3 SAD cohorts in Part 1. Dosing for 
each MAD cohort will be at a dose level 2-3 fold lower than the highest SAD cohort dose 
deemed safe by the SAC at the time of each MAD cohort initiation.  
An evaluable subject for Part 2 is defined as a subject who has received all 4 doses of IMP 
and undergone all safety and tolerability assessments out to 96 hours post-final dose 
(dose 4). Sentinel dosing is not planned for MAD cohorts, but the SAC may implement a 
sentinel design if deemed appropriate. 
Following completion of each cohort, the safety and tolerability assessments out to 
96 hours post-final dose (Day 26) will be reviewed to determine whether to progress to the 
next dose level and the dose to be administered. Full details of the interim data reviews 
are provided in Section 8.2. 
Table 3 
Description of Dosing: Part 2 Multiple Ascending Doses 
MAD Cohort   Investigational Medicinal Product   Dosea, b   
Dosing Schedule   
1   
PDM608 or matching placebo   
XX µg   Once weekly for 4 weeks   
2   
PDM608 or matching placebo   
XX µg   Once weekly for 4 weeks   
3   
PDM608 or matching placebo   
XX µg   Once weekly for 4 weeks   

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 25 of 64  
 
4   
(optional)c   
PDM608 or matching placebo   
XX µg   Once weekly for 4 weeks   
Details of the IMPs are provided in Section 5.2. 
a MAD cohort dose levels will be determined following interim review by the SAC. 
b Administration detailed in the Pharmacy Manual. 
c The decision on whether to dose MAD Cohort 4 will be based on interim review of preceding MAD Cohorts 1 
to 3. 
Each cohort will follow the same study design (Figure 2), detailed in the Schedule of 
Assessments (Appendix 3). 
Figure 2 
Study Sequence: Part 2 Multiple Ascending Doses 
Screening 
Day -28 to Day -2 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Admission 
Day -1 
 
 
Clinic Admission 
Day 14 
 
 
Clinic Admission 
Day 21 
 
 
 
 
 
 
 
Dose 1 
Day 1 
 
 
Dose 3 
Day 15 
 
 
Dose 4 
Day 22 
 
 
 
 
 
 
 
Dose 2 
Day 8 
 
 
Clinic Discharge 
Day 16 
 
 
Clinic Discharge 
Day 29 
 
 
 
 
 
 
 
Clinic Discharge 
Day 9 
 
 
 
 
 
Return Visit 
Day 32 
 
 
 
 
 
 
 
 
 
 
 
 
 
Return Visit 
Day 36 
 
 
 
 
 
 
 
 
 
 
 
 
 
Return Visit 
Day 43 
 
 
 
 
 
 
 
 
 
 
 
 
 
Return Visit 
Day 50 
 
 
 
 
 
 
 
 
 
 
 
 
 
Return Visit 
Day 60 
8.2 
Criteria for In-Study Decisions 
In-study decisions will be made by the safety advisory committee (SAC) which will always 
comprise the Sponsor, investigator (or delegate), the Sponsor’s representative medical 
monitor (or delegate) and a PK expert, where PK expertise is required.  

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 26 of 64  
 
8.2.1 Decision Points  
For all cohorts where a sentinel dosing strategy is utilized, the decision to proceed with 
dosing of the main group will be made by the investigator based on safety data through 72 
hours post-dose of the sentinel subjects. The investigator will inform the Sponsor of any 
safety concerns. 
The following in-study decisions will be made by the SAC during this study: 
• 
Whether to progress to the next dose level 
• 
Dose level selection for each SAD and MAD regimen 
• 
After at least SAD Cohort 3 has been dosed: whether to progress to MAD Part 2 of 
the study 
• 
When progressing to MAD Part 2 of the study, whether a loading dose is required 
and the amount of the loading dose: loading doses will be chosen based on PK/PD 
(if available) and safety data and will not exceed the highest dose given in the SAD 
study 
• 
After MAD Cohorts 1 to 3: whether optional MAD Cohort 4 is required 
• 
Changes to safety and/or PK and/or PD time points if there is reason to believe that 
the change might improve the quality of the data based on review of emerging 
data. These changes may also be implemented by the Sponsor alone. 
8.2.2 Criteria for Dose Decision 
Progression to the next dose group will be permitted after review of defined safety and 
tolerability data suggests that it is safe to do so. All SAC decisions will be documented and 
signed by the investigator and Sponsor medical monitor or delegate. Evidence of the 
decision will be retained in the Trial Master File (TMF).  
For dose escalation in the SAD phase to proceed data must be available from a minimum 
of 6 subjects who have completed the planned safety and tolerability assessments out to 
96 hours post-dose (Day 5), to ensure at least 4 subjects receive active IMP. For dose 
escalation in the MAD phase to proceed data must be available from a minimum of 8 
subjects who have completed the planned safety and tolerability assessments out to 
96 hours post-final dose (Day 26) to ensure at least 6 subjects receive active IMP. 
It is planned that the dose will be escalated for each subsequent cohort; however, the SAC 
may also agree to enroll additional subjects for an intermediate dose level if warranted or 
may agree to reduce the dose with no limit on the possible extent of reduction. Any 
decision to investigate an intermediate or reduced dose level will be fully documented. 
The decision to proceed to the next dose level will be based on safety and tolerability and 
data. The following data are required: 
• 
AEs 
• 
Vital signs 
• 
Safety laboratory, including review of PD hematology parameters outlined in 
Section 6.4 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 27 of 64  
 
• 
12-lead ECG 
• 
Physical examinations 
The SAC may also consider additional data as it becomes available and as relevant to 
decisions, including ADA, PD, and PK. 
Rules for dose decision are as follows: 
• 
Dose escalation will not be more than 3-fold between SAD cohorts. Anticipated 
SAD dose levels are described in Table 2. 
• 
Dose escalation will not be more than 3-fold between MAD cohorts.  
• 
Dosing for each MAD cohort will be at a dose level 2-3 fold lower than the highest 
SAD cohort dose deemed safe by the SAC at the time of each MAD cohort 
initiation. 
• 
Doses administered will be predicted not to exceed a mean Cmax of 103,950 ng/mL 
and a mean AUC(0-24h) of 1,775,000 ng.h/mL, which is the sex-averaged mean 
NOAEL exposure limits after the first dose of 18 mg/kg in the cynomolgus NOAEL 
28-day good laboratory practice (GLP) toxicology study, in any individual subject. 
• 
The predicted mean steady state exposures in the MAD (Cmax and AUC) factoring 
the potential for accumulation will not be anticipated to exceed mean maximal 
exposures observed in the SAD that were confirmed to be safe and well tolerated. 
• 
The maximum PDM608 dose administered in either part of this trial will not exceed 
a dose that is more than two-fold above the dose at which any two of the following 
three pharmacodynamic activities are observed in a sample that includes a 
minimum 5 of 6 PDM608-treated subjects in SAD or 7 of 9 PDM608-treated 
subjects in MAD, treated within the same cohort, and observed at any laboratory 
timepoint up to and including 96 hours post-dose (SAD) and post-final dose (MAD): 
o An increase in mean WBC from pre-dose baseline by ≥ 3-fold  
o An increase in mean monocytes from pre-dose baseline by ≥ 2-fold 
o An increase in mean eosinophils from pre-dose baseline by ≥ 7-fold 
• 
The study will be halted and further dose decisions will be paused: 
o One or more subjects experience a possibly IMP-related serious adverse 
event (SAE) 
o Two or more subjects experience a possibly IMP-related  non-serious AE of 
severe severity in one cohort in the same organ system class  
The decision to reinitiate dosing will be made by the Sponsor in consultation with the 
investigator after review of safety data and notification to the Institutional Review 
Board (IRB). 
If, following review by the SAC, it is deemed acceptable to continue dose escalation above 
a defined exposure limit, a substantial amendment with relevant data will be submitted for 
approval to the regulatory authorities and IRB. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 28 of 64  
 
8.3 
Subject Withdrawal 
A subject may withdraw his/her participation from the study at any time or may be 
discontinued for any of the reasons below. In either case, every reasonable effort will be 
made by Quotient to complete a final assessment/discharge procedures and to provide 
medical follow-up as indicated. Quotient will advise the Sponsor of the withdrawal of any 
subject from the study. 
Early withdrawal is defined as the date of the decision to withdraw the subject from the 
study. Subject completion is defined as the date of the last procedure conducted or last 
contact (e.g., phone call or unscheduled visit) for that subject. 
If a subject requests to leave the clinical unit earlier than the planned discharge time (e.g., 
due to unforeseen personal circumstances) but aims to return to the clinical unit to 
complete the study, this will be documented as a subject self-discharge and a protocol 
deviation. The subject must complete the planned assessments/discharge procedures 
before discharge from the clinical unit and will return for the next study 
period/assessments, as planned following agreement between the Sponsor and the 
investigator.  
Part 1 is a single dose assessment; therefore, after an individual subject has received a 
dose of IMP withdrawal of that subject from further dosing is not possible. Subjects will be 
monitored for the criteria detailed below which may require their withdrawal from some or 
all study procedures if continuation is not in their best interests, except when the 
withdrawal is a result of withdrawal of consent. 
Part 2 is a multiple dose assessment; therefore, subjects will be withdrawn from the study 
drug(s) for the reasons detailed below. 
• 
Experiencing a SAE, severe AE or laboratory abnormality including but not limited 
to: 
o corrected QT interval by Fridericia’s formula (QTcF) interval of >500 msec 
or increase in QTcF interval of >60 msec from baseline at a value of >450 
msec (confirmed following a repeat ECG)  
o alanine aminotransferase (ALT) concentration >3 × the upper limit of the 
reference range (confirmed following a repeat ALT blood test) 
o proteinuria, hematuria and/or hyaline casts in urine (confirmed following a 
repeat urinalysis) 
o other clinically significant laboratory abnormalities that necessitate study 
discontinuation in the opinion of the investigator and medical monitor 
• 
Pregnancy 
• 
Termination of the study by the Sponsor, regulatory agency or IRB 
• 
Upon the subject’s request (withdrawal of consent) 
• 
Significant deviation from the protocol, as determined by the Investigator and 
Sponsor 
• 
Significant concurrent illness or requirement for prohibited medication 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 29 of 64  
 
• 
Subject non-compliance  
• 
At the discretion of the investigator 
Baseline will be considered the last available assessment prior to first dose for the purpose 
of withdrawal criteria. 
Every effort will be made to ensure that subjects who discontinue IMP administration 
because of an IMP-related AE will complete all safety follow-up procedures.  
Early withdrawal for any of the above reasons should be documented and distinguished 
from withdrawal of consent by the subject to participate in any further activities. 
8.4 
Subject Replacement 
Up to 2 replacement subjects per cohort may be enrolled into Part 1 (SAD). The maximum 
number of subjects that may be dosed is 50. 
Up to 3 replacement subjects per cohort may be enrolled into Part 2 (MAD). The maximum 
number of subjects that may be dosed is 60. 
Any subject withdrawn due to an IMP-related AE will not be replaced. Subjects 
withdrawing for other reasons may be replaced as required by agreement between the 
investigator and Sponsor to ensure sufficient evaluable subjects. 
8.5 
Stopping Criteria 
The study will be halted, and the risk to other subjects evaluated, if any of the following 
criteria are met:  
• 
A serious adverse reaction (i.e., a SAE considered at least possibly related to the 
test product) in one subject 
• 
Severe adverse reactions (i.e., severe AEs considered as at least possibly related 
to the test product) in two subjects in the same cohort, within the same system 
organ class. 
• 
There is evidence of drug-induced liver injury in any subject: 
o ALT or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) 
and total bilirubin >2 × ULN or INR >1.5 with no alternative etiology OR 
o ALT or AST >3 ULN with fatigue, nausea, vomiting, right upper quadrant 
(RUQ) pain/tenderness, fever, rash and/or eosinophilia with no alternative 
etiology OR 
o ALT or AST >8 × ULN with no alternative etiology 
Relatedness to IMP will be determined by the investigator.  
The IRB will be notified if the study is halted. The study may be resumed or terminated; 
however, it will not be resumed until a further notice to resume the study is submitted and 
approved by the IRB. 
Also see the pharmacodynamic criteria to cap dose escalation in SAD or MAD in the 
Pharmacodynamic Rationale Section 6.4. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 30 of 64  
 
8.6 
Study Termination 
The study may be terminated by the Sponsor at any time. Notification of termination must 
be provided to the IRB as soon as possible, clearly explaining the reasons for termination. 
A description of follow-up measures taken for safety reasons, if applicable, should also be 
provided. 
If the study is abandoned prior to commencement of any protocol activities, the 
investigator must notify the IRB outlining the reasons for abandonment of the trial. 
The study will be completed as planned unless there is a need for temporary suspension 
or early termination of the study secondary to any of the following: 
• 
Occurrence of stopping events otherwise defined in this protocol. 
• 
New information regarding the safety of the IMP that indicates that the risk/benefit 
profile is no longer acceptable. 
• 
Significant violation of Good Clinical Practice (GCP) that compromises subject 
safety or the ability to achieve the primary study objectives. 
If any of the above occur the study will be terminated if careful review of the overall 
risk/benefit analysis described in Section 6.6 demonstrates that the assumptions have 
changed and that the overall balance is no longer acceptable. The IRB will be informed of 
study termination. 
If it becomes necessary to consider termination of the study, dosing may be suspended 
pending discussion between the investigator and Sponsor.  
The study may be terminated or suspended at the request of the IRB. 
8.7 
Lost to Follow-Up 
A subject will be considered lost to follow-up if they fail to return for scheduled visits and 
cannot be contacted by the clinical unit.  
If a subject fails to return to the clinical unit for a required study visit: 
• 
The clinical unit must attempt to contact the subject and reschedule the missed 
visit as soon as possible 
• 
The investigator or designee must make every effort to regain contact with the 
participant (e.g., three telephone calls and, if necessary, a certified letter to the 
participant’s last known mailing address or local equivalent methods). These 
contact attempts should be documented in the subjects’ electronic case report form 
(eCRF) 
• 
If the subject cannot be contacted, they will be considered lost to follow-up 
8.8 
Subject Selection List and Randomization 
This is a double-blind, randomized, placebo-controlled study; therefore, a randomization 
schedule will be produced for each study part. 
A subject selection list will be produced for each study part prior to dosing using the 
randomization schedule and will be retained in the Investigative Site File (ISF). 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 31 of 64  
 
In Part 1, for sentinel dosing, a group of 2 subjects will be dosed ahead of the remaining 
subjects in each cohort. A randomization schedule will be used such that the first 2 subject 
numbers will be allocated to active or placebo in a 1:1 ratio (i.e., 1 subject will be randomly 
assigned to receive PDM608 and 1 subject will be randomly assigned to receive matching 
placebo). The remaining 6 subject numbers will be allocated to active or placebo in a 5:1 
ratio (i.e., 5 subjects will be randomly assigned to receive PDM608 and 1 subject will be 
randomly assigned to receive matching placebo). 
For Part 2, a randomization schedule will be used to allocate subject numbers to PDM608 
or placebo in a 3:1 ratio (i.e., in each cohort, 9 subjects will be randomly assigned to 
receive PDM608 and 3 subjects will be randomly assigned to receive matching placebo). 
Subjects will be randomized prior to administration of the first dose. 
8.8.1 Subject Numbers 
Four-digit subject numbers will be allocated prior to initial dosing according to a code 
established by Quotient. Replacement subjects will be allocated subject numbers where 
the last three digits are the same as those of the original subject (e.g., if Subject 1005 
withdraws, the replacement will have Subject Number 9005 and will receive the same 
regimen as Subject 1005). 
8.8.2 Blinding 
This is a double-blind study; treatment assignment will not be known to the subjects, the 
Sponsor or the staff involved in the clinical evaluation of the subjects and the analysis of 
data. The randomization schedule and disclosure envelopes will be generated by an 
unblinded statistician at Quotient according to Quotient’s SOPs. The unblinded statistician 
will not be involved in any decisions relating to populations for analysis prior to unblinding. 
Prior to database lock and unblinding, all original randomization materials including the 
original final signed and dated randomization schedule will be held by the Quality 
Assurance (QA) department at Quotient. The Data Sciences department will not have 
access to the randomization schedule before database lock and unblinding.  
Interim PK parameter estimations will be performed using bioanalytical data applied with 
subject aliases to maintain blinding.  
There may be instances where interim data have the potential to reveal treatment (e.g., 
missed blood sampling occasions). In these cases, every effort will be made by the 
unblinded pharmacokineticist to maintain blinding by appropriate presentation of data to 
the study team. Data demonstrating extremes of exposure will always be presented 
regardless of the potential to break blinding. To permit selection of the appropriate dose, 
individual data if judged necessary will be presented to the review committee, regardless 
of the potential to reveal blinding. 
The unblinded Pharmacist or designee at the clinical site will receive a copy of the final 
randomization schedule for preparation of the study drug and preparation of the subject 
selection list. A copy of the randomization schedule will also be made available to the 
laboratory performing the bioanalysis to allow selective analysis of drug concentrations 
and to the pharmacovigilance provider for analysis of pharmacovigilance. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 32 of 64  
 
Two sets of disclosure envelopes (i.e., sealed envelopes containing individual subject 
randomization details) will be provided. One set will be held in the clinical area and the 
other retained in the ISF. These may be used in the event of an emergency by the 
investigator. Any request for information on the randomization schedule after initial issue 
must be made using a randomization disclosure form to the designee of the randomization 
except in the case of emergency unblinding, which must be recorded on the emergency 
unblinding form including details of timing, those unblinded and scope of unblinding. 
Access to study drug assignment will be immediately available if the investigator deems it 
necessary to break blinding in the interest of a subject’s medical safety, in case of a 
medical emergency or if warranted during scheduled safety reviews. The medical monitor 
must be contacted within 24 hours following disclosure of study drug assignment.  
Details of any disclosure of the randomization schedule will be documented and retained 
in the ISF. The Sponsor will be notified if blinding is broken. 
For each individual study part blinding will be broken after the study database has been 
locked and the safety and necessary populations have been defined.  
9 Selection of Subjects 
9.1 
Informed Consent 
The investigator or delegated, qualified study staff member will explain and review the IRB 
approved informed consent form (ICF) with each subject. Subjects will then be given the 
opportunity to ask questions and will be informed of their right to withdraw from the study 
without prejudice. After this explanation and before any study specific procedures are 
performed the subject will voluntarily sign and date the IRB approved ICF. 
9.2 
Inclusion Criteria 
Informed Consent and Compliance 
1. Must be able to understand a written informed consent, which must be obtained prior to 
initiation of study procedures 
2. Must be willing and able to comply with all study requirements 
Demographics and Contraception 
3. Aged 18 to 65 years inclusive at time of signing informed consent 
4. Must agree to use an adequate method of contraception (as defined in Section 9.4) 
Baseline Characteristics 
5. Healthy men or non-pregnant, non-lactating healthy women of non-childbearing potential 
6. Body mass index (BMI) of 18.0 to 33.0 kg/m2 as measured at screening  
7. Weight ≤100 kg at screening 
Inclusion criterion 5 from the list above will be re-assessed at admission/pre-dose on Day 1. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 33 of 64  
 
9.3 
Exclusion Criteria 
Medical/Surgical History and Mental Health 
1. Serious adverse reaction or serious hypersensitivity to any drug or the formulation 
excipients 
2. Presence or history of clinically significant allergy requiring treatment as judged by the 
investigator. Hay fever is allowed unless it is active 
3. Significant serious skin disease, including rash, food allergy, eczema, psoriasis or 
urticaria 
4. History of clinically significant autoimmune, cardiovascular, renal, hepatic, chronic 
respiratory or GI disease (except cholecystectomy), neurological or psychiatric disorder, 
illness/infection/hospitalization or surgical procedure within 30 days prior to first dose of 
study drug or any uncontrolled medical illness as judged by the investigator 
Physical Examination 
5. Have poor venous access that limits phlebotomy 
Diagnostic Assessments 
6. Evidence of current SARS-CoV-2 infection or exposure to confirmed infection within 
10 days prior to the first dose of study drug 
7. Clinically significant abnormal clinical chemistry, hematology or urinalysis as judged by 
the investigator (laboratory parameters are listed in Appendix 1). Subjects with Gilbert’s 
Syndrome are allowed 
8. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), 
human immunodeficiency virus (HIV) antibody results or positive tuberculosis (TB) 
screening test 
9. Evidence of renal impairment at screening, as indicated by an estimated creatinine 
clearance (CLcr) of <90 mL/min using the Cockcroft-Gault equation 
10. Subjects with a QTcF interval of >450 msec at screening or first admission. At screening, 
QTcF will be based on a single 12-lead ECG; this single ECG can be repeated once if 
parameters are outside the limits for confirmation. At admission, this value will be from 
the mean of triplicate values 
11. Positive highly sensitive serum pregnancy test at screening or highly sensitive urine 
pregnancy test at first admission. Those who are pregnant or lactating will be excluded 
Prior Study Participation 
12. Subjects who have received any IMP in a clinical research study within 5 half-lives or 
within 30 days prior to first dose (whichever is longer) 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 34 of 64  
 
13. Subjects who have previously been administered IMP in this study. Subjects who have 
taken part in Part 1 are not permitted to take part in Part 2 
Prior and Concomitant Medication 
14. Subjects who are known to have received an antibody (as a treatment or as a participant 
in another study) may be eligible to participate after review by Investigator and/or 
Sponsor, to limit subjects who may have baseline anti-human antibodies 
15. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or 
herbal remedies (other than up to 4 g per day acetaminophen and HRT) in the 14 days  
or 5 half-lives (whichever is longer) before IMP administration (see Section 11.3). 
Exceptions may apply on a case-by-case basis if considered not to interfere with the 
objectives of the study as determined by the investigator 
16. Subjects who have had a COVID-19 vaccine within 14 days prior to first dose or have a 
COVID-19 vaccine scheduled between their first dose of IMP and anticipated final study 
visit 
Lifestyle Characteristics 
17. History of any drug or alcohol abuse in the past 2 years, as determined by the 
Investigator according to the definitions of alcohol use disorder and substance abuse 
disorder in the Diagnostic and Statistical Manual (DSM)-5 
18. Regular alcohol consumption in men >21 units per week and women >14 units per week 
(1 unit = 12 oz 1 bottle/can of beer, 1 oz 40% spirit or 5 oz glass of wine) 
19. A confirmed positive alcohol urine test at screening or first admission 
20. Current smokers and those who have smoked within the last 12 months or a confirmed 
positive urine cotinine test at screening or first admission 
21. Current users of e-cigarettes and nicotine replacement products and those who have 
used these products within the last 12 months 
22. Positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1) 
Other 
23. Men with pregnant or lactating partners 
24. Donation of blood for transfusion within 2 months or donation of plasma within 7 days 
prior to first dose of study medication 
25. Subjects who are, or are immediate family members of, a study site or Sponsor 
employee 
26. Failure to satisfy the investigator of fitness to participate for any other reason 
Exclusion criteria  6, 7, 10, 11, 12, 14, 16, 19, 20, 21, 22, 23, 24 and 26 from the list above 
will be re-assessed at admission/pre-dose on Day 1. 
Healthy subjects who do not meet the inclusion/exclusion criteria for the study will not be 
enrolled. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 35 of 64  
 
9.4 
Contraception and Restrictions 
Men with Partners of Childbearing Potential 
Men who are sexually active with a partner of childbearing potential must use, with their 
partner, a condom plus an approved method of highly effective contraception from the time 
of informed consent until 175 days after last IMP administration. 
The following methods are acceptable: 
• 
Partner’s use of combined (estrogen and progestogen-containing) hormonal 
contraception associated with inhibition of ovulation:  
o oral  
o intravaginal  
o transdermal  
• 
Partner’s use of progestogen-only hormonal contraception associated with 
inhibition of ovulation:  
o oral  
o injectable/implantable 
o intrauterine hormone-releasing system  
• 
Partner’s use of intrauterine device  
• 
Vasectomized 
• 
Partner’s bilateral tubal occlusion 
Men with Partners of Non-childbearing Potential 
There is an unknown risk of drug exposure through ejaculate (which also applies to 
vasectomized men) that might be harmful to sexual partners. Therefore, even if a man is 
sexually active with a partner of non-childbearing potential they will be required to use a 
condom from the time of informed consent until 175 days after last IMP administration 
(approximately 2.5 sperm turnover rate). 
All Men 
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 
treatments. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the subject. 
Women of Non-Childbearing Potential  
Women who are not of childbearing potential do not need to use any methods of 
contraception. A woman is considered of childbearing potential (WOCBP) unless 
post-menopausal or permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal 
state is defined as no menses for 12 months without an alternative medical cause and 
confirmed by a follicle stimulating hormone (FSH) result of ≥40 IU/L. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 36 of 64  
 
9.4.1 Sperm Donation 
Men should not donate sperm from the time of informed consent until 175 days after last 
IMP administration (approximately 2.5 sperm turnover rate). 
9.4.2 Egg Donation 
Women should not participate in egg donation from dosing, from the time of informed 
consent until 115 days after last IMP administration. 
9.5 
Pregnancy 
Subjects will be instructed that if they/their partner becomes pregnant during the study this 
should be reported to the investigator. The investigator should also be notified of 
pregnancy occurring during the study but confirmed after completion of the study. In the 
event that a subject/subject’s partner is subsequently found to be pregnant after the 
subject is included in the study, then consent will be sought from the subject/partner and, if 
granted, any pregnancy will be followed and the status of mother and/or child(ren) will be 
reported to the Sponsor after delivery. Any subject reporting a pregnancy during the study 
will be discontinued from study treatment and every reasonable effort will be made by 
Quotient to follow up the pregnancy until delivery. 
A pregnancy notification form and follow-up will be completed. 
9.6 
Additional Study Restrictions 
The following additional restrictions will be in place for the duration of the study: 
• 
Subjects must abstain from alcohol during the 24 hours prior to screening and the 
24 hours prior to admission until 48 hours post-final IMP dose 
• 
Subjects should refrain from eating food containing poppy seeds for 48 hours prior 
to screening and for 48 hours prior to admission until 48 hours post-final IMP dose 
• 
Subjects must not take part in any unaccustomed strenuous exercise from the 
72 hours before the screening visit and then from 72 hours prior to admission until 
discharge from the study 
• 
Subjects must not donate blood or plasma (outside of this study) from clinical unit 
admission, throughout the study duration, and for at least 30 days following last 
dose of study medication 
The additional restrictions above are not exclusion criteria; if non-compliance occurs, the 
Sponsor will be contacted and each deviation will be assessed on a case by case basis.  
10 Study Procedures 
Study procedures will be performed as detailed in the study schedule of assessments 
Appendix 2 (Part 1) and Appendix 3 (Part 2), and in accordance with Quotient’s SOPs 
unless otherwise stated in this protocol. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 37 of 64  
 
10.1 Screening 
Within the 28 days preceding first dose all subjects will be required to undergo screening 
procedures. Screening procedures will be carried out in accordance with the schedule of 
assessments in Appendix 2 (Part 1) and Appendix 3 (Part 2). 
If the start of the study is delayed for any reason so that the interval between screening 
and first dose exceeds 28 days all or part of the screening procedures will be repeated at 
the discretion of the investigator. 
Screening safety procedures such as safety bloods, ECGs, vital signs, urine alcohol, urine 
cotinine, urine drug screen and urinalysis can be repeated as clinically indicated under the 
discretion of the investigator or sub-investigator if there is a concern regarding a subject’s 
safety or eligibility to participate in the trial. 
10.1.1 Subject Re-Screening 
This study permits the re-screening of a subject who has discontinued the study as a 
pre-treatment failure (i.e., subject has not been randomized); the reason for failure must be 
temporary and expected to resolve. If re-screened, the subject must be re-consented. 
10.2 Admission and Pre-dose Procedures 
The identity of the subjects will be confirmed at admission and pre-dose.  
In addition, the ongoing eligibility of subjects will be re-assessed at admission/pre-dose, as 
described in Sections 9.2 and 9.3. 
Admission/pre-dose safety procedures such as safety blood tests, ECGs, vital signs, 
urinalysis and drugs of abuse tests can be repeated as clinically indicated under the 
discretion of investigator or sub-investigator if there is a concern regarding a subject’s 
safety or eligibility to participate in the clinical trial.  
Alternative subjects for the first dose occasion, in any cohort, will not require admission 
procedures to be repeated if dosing is within 2 days of their prior admission.  
If dosing is delayed, subjects who have completed admission procedures do not need 
admission procedures to be repeated if dosing is within 2 days and the subjects have 
remained resident in the clinical unit. 
The admission and pre-dose procedures are presented in Appendix 2 (Part 1) and 
Appendix 3 (Part 2).  
10.3 Study Day Procedures 
10.3.1 Blood Volume 
The total blood volume for each subject will not exceed 550 mL in an 8-week period 
(based on a representative healthy subject weighing at least 110 pounds). See the study 
Lab Manual for further details on sample volumes and collection and processing 
requirements. The number and timing of samples may be amended following review by the 
Sponsor and/or SAC. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 38 of 64  
 
10.3.2 Timing of Procedures 
There are times where the protocol requires more than one procedure to be completed at 
the same time point. In these instances, the following will apply to post-dose time points: 
• 
ECGs should be taken prior to vital signs when both measurements are scheduled 
at the same time point.  
• 
PK/PD samples should take priority (i.e., taken at the nominal time point) over 
other procedures scheduled at the same time point. 
• 
Other assessments (e.g., physical examinations) will be performed within the 
required time windows. 
As guidance, the preferred order of assessments is: 
ECGs 
 
Vitals 
 
PK/PD/ADA 
blood sampling 
(nominal time) 
 
Other assessments 
(e.g., physical 
examinations) 
All safety assessments will be timed and performed relative to the start of dosing.  
10.3.3 Discharge from the Clinical Unit 
Subjects will be discharged from the clinical unit following completion of study-specific 
procedures as detailed in Appendix 2 (Part 1) and Appendix 3 (Part 2). However, the 
investigator may ask a subject to remain domiciled for additional safety observation and 
monitoring (e.g., as indicated for an AE). 
10.3.4 Return Visits 
Subjects in Part 1 and Part 2 will be required to return to the clinical unit at specified time 
points for the assessments described in Appendix 2 (Part 1) and Appendix 3 (Part 2); the 
acceptable deviations for the return visit are also described in these appendices. 
10.3.5 Medical Supervision 
A physician will be responsible for the clinical aspects of the study and will be available at 
all times during the study. 
10.3.6 Follow-up 
If a subject reports any AEs that can present a cause for concern, they will be required to 
attend the clinical unit for a further follow-up assessment (as an unscheduled visit) and will 
be followed up until the AE has resolved. Completion of the last scheduled return visit or 
unscheduled follow-up call/visit will be considered the end of the study.  
11 Dosing of Subjects 
11.1 Food and Fluid Intake 
Subjects will be allowed water up to 1 hour before each scheduled dosing time and will be 
provided with 240 mL of water at 1 h post-dose (to ensure adequate hydration). 
Thereafter, water will be allowed ad libitum after 1 h post-dose. Decaffeinated fluids will be 
allowed ad libitum from lunch time on the day of dosing. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 39 of 64  
 
The calorie/fat content of meals are not required to be controlled. Subjects will be provided 
with a standardized menu. See also the food and liquid restrictions detailed in Section 9.6. 
Meals will be provided at appropriate times. 
11.2 Dosing Compliance 
Subjects will be observed by study staff during all clinical phases of the study to assure 
compliance to all study procedures including dose administration.  
Doses will be administered by trained staff to ensure dosing compliance. 
The date and time that each subject is dosed will be recorded in the subject’s eCRF. Any 
violation of compliance will require evaluation by the investigator and Sponsor to 
determine if the subject can continue in the study. 
11.3 Prior and Concomitant Medications 
No prescribed medications, over-the-counter medications or herbal remedies will be 
permitted from 14 days or 5 half-lives (whichever is longer) before IMP administration until 
a subject’s final visit except HRT, up to 4 g per day of acetaminophen, and those deemed 
necessary by the investigator to treat AEs (see also Section 9.3). Any medications used 
will be recorded in the eCRF. 
No COVID-19 vaccines will be permitted within 14 days prior to first dose until a subject’s 
final visit on this trial. COVID-19 vaccinations are not acceptable concomitant medications. 
Emergency equipment and drugs will be available within the clinical unit as per current 
standard procedures. In the unlikely event that they are required, their use will be 
documented. 
12 Pharmacokinetic and Pharmacodynamic Blood Sampling 
Venous blood samples for analysis by a bioanalytical lab for PK and PD analysis will be 
collected from the subjects by a trained member of the clinical team.  
Samples will be sent for laboratory testing in linked anonymized form (subject number 
only). This information can be linked directly to the subject by the Quotient research team 
and study monitor but not by the laboratory staff or Sponsor. 
Venous blood samples will be withdrawn via venipuncture according to the Schedule of 
Assessments presented in Appendix 2 (Part 1) and Appendix 3 (Part 2). The acceptable 
deviations from the nominal blood sampling times are detailed in the schedules. 
The timing and number of the samples may be amended by the Sponsor and/or SAC, 
including collection over a longer duration. Any changes to blood sampling time points will 
be documented and retained in the TMF. 
Samples will be collected into appropriate tubes as specified by the bioanalytical 
laboratory. Details of sample tubes and processing will be contained in the Clinical Sample 
Processing Manual (CSPM). 
Pharmacodynamic parameters analyzed by the bioanalytical lab may include the following: 
• 
Immunophenotyping by flow cytometry to determine numbers/percentages of the 
following immune cells: 
o Total T cells (CD45+CD3+) 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 40 of 64  
 
o Helper T cells (CD45+CD3+CD4+CD8-) 
o Cytotoxic T cells (CD45+CD3+CD4-CD8+) 
o Regulatory Helper T cells (CD45+CD3+CD4+CD8-CD25+Foxp3+) 
o Regulatory Cytotoxic T cells (CD45+CD3+CD4-CD8+CD25+Foxp3+) 
o Macrophages (CD45+CD14+CD11b+) 
o Dendritic cells (CD45+CD123+HLA-DR+CD11c+) 
• 
Cytokine analysis: 
o Panel 1: IL-1α, IL-1B, IL-1RA, IL-12/IL-23p40, IFN-α2a, MCP-1 
o Panel 2: IL-1β, IL-6, IL-10, IL-12p70, IFN-Ɣ, GM-CSF, TNF-α 
As described in Section 6.4 Pharmacodynamic Rationale, a subset of the safety 
hematology labs (WBC, monocyte, and eosinophil values) will be analyzed as an indicator 
of pharmacodynamic activity to aid in defining the maximum dose level to be administered 
to subjects in this trial. 
13 Assessment of Safety 
13.1 Definition and Classification of Adverse Events 
An AE is any untoward medical occurrence in a subject that occurs either before dosing 
(referred to as a pre-dose AE) or once a medicinal product has been administered, 
including occurrences that are not necessarily caused by or related to that product.  
An adverse drug reaction (ADR) is any AE where a causal relationship with the IMP is at 
least a reasonable possibility (possibly related or related). 
AEs will be monitored from the time the subject signs the ICF until 30 days after the final 
dose of study drug. The severity of AEs should be assessed as follows: 
Mild 
An AE that is easily tolerated by the subject, causes minimal discomfort and 
does not interfere with everyday activities 
Moderate An AE that is sufficiently discomforting to interfere with normal everyday 
activities; intervention may be needed 
Severe 
An AE that prevents normal everyday activities; treatment or other intervention 
usually needed 
13.2 Assessment of Causality 
Every effort should be made by the investigator to try to explain each AE and assess its 
relationship, if any, to the IMP. The temporal relationship of the event to IMP 
administration should be considered in the causality assessment (i.e., if the event starts 
soon after IMP administration and resolves when the IMP is stopped). 
Causality should be assessed using the following categories:  

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 41 of 64  
 
Unrelated: 
Clinical event with an incompatible time relationship to IMP 
administration and that could be explained by underlying disease 
or other drugs or chemicals or is incontrovertibly not related to the 
IMP 
Possibly related: 
Clinical event with a reasonable time relationship to IMP 
administration that is unlikely to be attributed to concurrent disease 
or other drugs or chemicals 
Related: 
Clinical event with plausible time relationship to IMP administration 
that cannot be explained by concurrent disease or other drugs or 
chemicals 
The degree of certainty with which an AE is attributed to IMP administration (or alternative 
causes such as natural history of the underlying disease or concomitant therapy) will be 
determined by how well the experience can be understood in terms of one or more of the 
following: 
• 
Known pharmacology of the IMP 
• 
Reactions of a similar nature have been previously observed with the IMP or this 
class of drug 
• 
The experience being related by time to IMP administration, terminating with IMP 
withdrawal or recurring on rechallenge 
• 
Alternative cause 
13.3 Recording Adverse Events 
AEs will be recorded from the time of providing written informed consent until 30 days after 
the last dose of study drug. During each study visit the subject will be questioned directly 
regarding the occurrence of any adverse medical event according to the schedule in 
eCRF. All AEs, whether ascribed to study procedures or not, will be documented 
immediately in the subject’s eCRF. This will include the date and time of onset, a 
description of the AE, severity, seriousness, duration, actions taken, outcome and an 
investigator’s current opinion on the relationship between the study drug and the event. A 
diagnosis and final opinion on the relationship between the study drug and the event will 
be provided at the end of the study by the investigator.  
Any subject who withdraws from the study due to an AE will be followed until the outcome 
is determined and written reports are provided by the investigator. 
13.4 Serious Adverse Events 
13.4.1 Definition of Serious Adverse Events 
A SAE is defined as any untoward medical occurrence that at any dose:  
• 
Results in death 
• 
Is life-threatening 
• 
Requires hospitalization or prolongation of existing hospitalization 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 42 of 64  
 
• 
Results in persistent or significant disability or incapacity 
• 
Consists of a congenital anomaly or birth defect 
• 
Is an important medical event as recognized by the investigator 
SAEs must be reported to the Sponsor and IRB within 24 hours of site awareness. 
13.4.2 Definition of Suspected Unexpected Serious Adverse Reactions 
Suspected unexpected serious adverse reactions (SUSARs) are AEs that are believed to 
be related to a test product and are both unexpected (i.e., the nature or severity is not 
expected from the information provided in the IB) and serious. SUSARs are subject to 
expedited reporting to the IRB (see Section 15.3.2 for details on reporting SUSARs). 
13.5 Adverse Events of Special Interest (AESI) 
The following AESI must be reported to the Sponsor within 24 hours of site awareness 
irrespective of seriousness, severity or causality: 
• 
Serum sickness-like reaction – a type III hypersensitivity reaction presenting with a 
constellation of symptoms including fever, pruritic rash, joint 
pain/tenderness/edema/erythema, muscle pain, edema of the lips and/or eyelids, 
GI symptoms (nausea, vomiting, abdominal cramps, diarrhea), headache and 
dyspnea 
• 
A new vasculitic rash, a fixed, erythematous, non-blanching rash. Vasculitic rashes 
may be accompanied by fever, fatigue and diffuse aches or pain 
• 
Urticarial reaction 
• 
Leucocytosis with WBC > 50,000/uL 
In the event of a suspected serum sickness-like reaction blood samples will be collected 
within 1 hour of the event to assess CBC, ESR, urinalysis, serum chemistries, C3, C4 and 
fibrinogen. 
The subsequent course of therapy may include NSAIDs, antihistamines and/or 
corticosteroids depending on institutional guidelines and the severity of the event. 
The investigator is encouraged to discuss with the Sponsor medical monitor all AESI as 
defined above. 
13.6 Safety Laboratory Measurements 
Venous blood and urine samples will be collected from subjects by a trained member of 
the clinical team. 
Safety laboratory tests and virology will be carried out on blood samples, and drugs of 
abuse tests and urinalysis will be carried out on urine samples. The research will not 
involve analysis or use of human DNA. 
Blood samples will be sent for laboratory testing in linked anonymized form (subject 
number only). This information can be linked directly to the subject by the Quotient 
research team and study monitor but not by the laboratory staff or Sponsor. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 43 of 64  
 
Blood and urine sample results will be reviewed by a physician and acted upon before the 
subject is dosed, receives their next dose or is released from the study, as appropriate. A 
list of the laboratory parameters measured is presented in Appendix 1. 
13.6.1 Hematology and Clinical Chemistry 
Laboratory tests will be performed by Quotient Sciences Labs according to the Schedule 
of Assessments presented in Appendix 2 (Part 1) and Appendix 3 (Part 2). Blood samples 
will be collected and processed as detailed in the CSPM. Scheduled blood samples will be 
taken following an overnight fast of a minimum of 8 hours. Samples taken due to early 
withdrawal do not need to be fasted. The acceptable deviations from the nominal blood 
sampling times are detailed in the schedules. 
CLcr will be calculated at screening by Quotient Sciences Labs using the Cockcroft-Gault 
equation and body weight for eligibility purposes: 
CLcr (mL/min) = (140-age [years]) × body weight [kg] (x 0.85, if female) 
 72 x serum creatinine (mg/dL) 
13.6.2 Anti-Drug Antibodies 
Venous blood samples will be withdrawn via venipuncture according to the Schedule of 
Assessments presented in Appendix 2 (Part 1) and Appendix 3 (Part 2). The acceptable 
deviations from the nominal blood sampling times are detailed in the schedules. 
The timing and number of the samples may be amended by the Sponsor, including 
collection over a longer duration. Any changes to blood sampling time points would be 
documented and retained in the TMF. 
Samples will be collected into appropriate tubes as specified by the bioanalytical 
laboratory. Details of sample tubes and processing will be contained in the CSPM. 
13.6.3 Urinalysis 
Urinalysis will be performed by Quotient Sciences Labs according to the Schedule of 
Assessments presented in Appendix 2 (Part 1) and Appendix 3 (Part 2). Urine samples will 
be collected and processed as detailed in the CSPM. Microscopic analysis of sediment for 
bacteria, casts, crystals, epithelial cells, red blood cells and white blood cells will be 
performed, as required. The acceptable deviations from the nominal urine sampling times 
are detailed in the schedules. 
13.6.4 Pregnancy Test 
Serum and urine pregnancy tests will be performed as detailed in Appendix 2 (Part 1) and 
Appendix 3 (Part 2). The samples will be collected and processed as detailed in the 
CSPM. 
13.6.5 Follicle-Stimulating Hormone Test 
Serum FSH tests will be performed as detailed in Appendix 2 (Part 1) and Appendix 3 
(Part 2). The samples will be collected and processed according to the CSPM. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 44 of 64  
 
13.6.6 Alcohol, Cotinine, and Drug Screen 
A urine alcohol, cotinine and drug screen will be performed by Quotient Sciences Labs 
according to the Schedule of Assessments presented in Appendix 2 (Part 1) and 
Appendix 3 (Part 2). The sample will be collected and processed according to the CSPM.  
Subjects will be screened for the drugs of abuse listed in Appendix 1. A positive result will 
exclude the subject from dosing for the remainder of the study. 
13.6.7 Abnormal Laboratory Findings 
In cases where laboratory findings are outside the normal range and the investigator 
believes that the results may be of clinical significance, repeat sampling may be requested 
as clinically indicated. If the abnormal finding is clinically significant, the Sponsor and 
Medical Monitor may be consulted and appropriate actions will be taken (e.g., the subject 
will not be entered into or may be withdrawn from the study). The subject will be referred to 
their primary care provider or other appropriate provider for further care if necessary. The 
same will apply if the results of the HBsAg, HCV Ab or HIV test are positive and in addition 
the investigator will ensure that adequate counselling is available if requested. 
Abnormal results at follow-up assessments will also require repeat testing if the 
investigator believes the results may be of clinical significance. 
Any clinically significant laboratory finding, including changes from baseline, must be 
reported as an AE. 
Additional blood and/or urine samples may be taken for safety tests. Furthermore, 
additional assays outside those specified in the protocol may be performed for safety 
reasons as requested by the investigator. 
13.7 Vital Signs Measurements 
Blood pressure and heart rate will be measured by an automated recorder after the subject 
has been in a supine position for a minimum of 5 minutes and body temperature and 
respiratory rate will be measured according to the Schedule of Assessments presented in 
Appendix 2 (Part 1) and Appendix 3 (Part 2). The acceptable deviations from the nominal 
vital signs assessment times are detailed in the schedules. 
If a subject shows an abnormal assessment at any stage, repeat measurements may be 
made and the abnormality followed to resolution if required. Additional measurements may 
be taken as deemed necessary by the investigator or sub-investigator. 
Any clinically significant abnormality, including changes from baseline, must be reported 
as an AE. 
13.8 12-Lead Electrocardiogram Measurements 
Single 12-lead ECGs will be measured after the subject has been in the supine position for 
a minimum of 5 minutes, and triplicate 12-lead ECG measurements will be performed 
approximately 2 min apart after the subject has been in the supine position for a minimum 
of 5 min, according to the Schedule of Assessments presented in Appendix 2 (Part 1) and 
Appendix 3 (Part 2). The acceptable deviations from the nominal ECG assessment times 
are detailed in the schedules. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 45 of 64  
 
If a subject shows an abnormal assessment at any stage repeat measurements may be 
made and the abnormality followed to resolution if required. Additional measurements may 
be taken as deemed necessary by the investigator or sub-investigator. 
Any clinically significant abnormality, including changes from baseline, will be reported as 
an AE. 
13.9 
Body Weight, Height and Body Mass Index 
The subject’s body weight and height will be measured and their BMI calculated according 
to the Schedule of Assessments presented in Appendix 2 (Part 1) and Appendix 3 (Part 2). 
13.10 Physical Examination 
Subjects will undergo a physical examination according to the Schedule of Assessments 
presented in Appendix 2 (Part 1) and Appendix 3 (Part 2). 
13.11 Additional Safety Procedures 
Additional non-invasive procedures that are already specified in the protocol may be 
performed if it is believed that an important effect of the IMP is occurring, may occur at a 
time when no measurements are scheduled or if extra procedures are needed in the 
interests of safety. 
Additional blood samples, urine samples or other diagnostic tests for safety assessments 
may be taken if required by the investigator or sub-investigator at any point. 
14 Statistics and Data Analysis 
14.1 Sample Size Justification 
Based on experience from previous similar studies, the target numbers of subjects to be 
enrolled (N = 8 and N = 12) should be sufficient to achieve a minimum of 6 and 8 
evaluable subjects in each cohort in Part 1 and Part 2, respectively. Six evaluable subjects 
in SAD is customarily sufficient to assess cohorts for dose escalation. The sample size of 
12 in MAD is supported by results of daily sargramostim (6 mcg/kg/day) for 8 weeks 
administered to 20 persons with Parkinson’s Disease in a randomized (1:1), placebo-
controlled trial (Gendelman 2017). A significant transient increase of 5% CD4+Treg counts 
(Mann-Whitney U test p=0.05-0.01) and Treg activity was identified at 2-4 weeks with data 
from 5-9 sargramostim treated patients). GM-CSF at a dose of 5-10 mcg/kg/day for 4-5 
days significantly increased numerous cell lineages in peripheral blood  of 5-8 healthy 
volunteers, with increases in CD34+ mononuclear cells, WBC, MNC, PMN, monocytes, 
and eosinophils (Lane 1995; Fishmeister 1999).  PD patients also have increases in PMN 
and eosinophils in response to sargramostim (Gendelman 2017). These results suggest 
the MAD sample size is sufficient to detect an increase of 5% in mean Treg percentages 
compared with pooled placebo subjects. The sample size is also adequate to identify 
expected pharmacodynamic changes in hematology laboratory tests.   
14.2 Data Management 
Data management will be performed by Quotient. 
Study data will be managed using a validated eCRF database system and subjected to 
data consistency and validation checks. Data queries will be raised within the study eCRF 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 46 of 64  
 
database by data management staff and resolved with the assistance of clinical staff. The 
database is compliant with 21 Code of Federal Regulations (CFR) Part 11 guidelines.  
AEs, medical histories and medications will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA) (version to be specified in the Data Management Plan 
[DMP]) and the World Health Organization (WHO) Drug Dictionary Global Drug Reference 
(version to be specified in the DMP), respectively. An independent coding review will also 
be performed within the Data Sciences department. 
Clinical chemistry and hematology data (and other safety laboratory data) will be collected 
by Quotient Labs and Quest Diagnostics Clinical Laboratories Inc and stored electronically 
in their laboratory information system. The data will be transferred electronically to 
Quotient and all demographic details and sample dates will be cross-referenced with the 
corresponding data on the study database. All queries will be resolved with the assistance 
of laboratory staff, or if necessary, clinical staff.  
The database will be closed after all queries have been resolved. The database will be 
locked when all criteria listed in the DMP are met.  
Further details are addressed in the DMP. 
14.3 Pharmacokinetic Data Analysis 
The PK data for PDM608 will be analyzed by Quotient, using Phoenix WinNonlin v8.0 or a 
more recent version (Certara USA, Inc., USA). 
PK analysis of the concentration time data obtained will be performed using appropriate 
non-compartmental techniques to obtain estimates of the PK parameters presented in 
Table 4, where possible and appropriate. 
Table 4 
Pharmacokinetic Parameters 
Parameter 
Definition 
Part 1 SAD 
tmax 
Time of maximum observed concentration 
Cmax 
Maximum observed concentration 
Cmax/Dose 
Maximum observed concentration divided by dose 
AUC(0-24) 
Area under the curve from time 0 to 24 hr 
AUC(0-last) 
Area under the curve from time 0 to the time of last measurable concentration 
AUC(0-last)/Dose 
Area under the curve from time 0 to the time of last measurable concentration 
divided by dose 
AUC(0-inf) 
Area under the curve from time 0 extrapolated to infinity 
AUC(0-inf)/Dose 
Area under the curve from time 0 extrapolated to infinity divided by dose 
AUCextrap 
Area under the curve from time of the last measurable concentration to infinity 
as a percentage of the area under the curve extrapolated to infinity 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 47 of 64  
 
Parameter 
Definition 
T1/2  
Terminal elimination half-life 
Lambda-z 
First order rate constant associated with the terminal (log-linear) portion of the 
curve 
CL/F 
Total body clearance calculated after extravascular administration where F 
(fraction of dose bioavailable) is unknown 
Vz/F 
Apparent volume of distribution based on the terminal phase calculated using 
AUC(0-inf) after a single extravascular administration where F (fraction of dose 
bioavailable) is unknown 
Part 2 MAD – Dose 1, Dose 2, and Dose 3 
Tmax 
Time of maximum observed concentration 
Cmax 
Maximum observed concentration 
AUC(0-24) 
Area under the curve from time 0 to 24 hr 
AUC(tau) 
Area under the curve for the defined interval between doses (tau) 
Part 2 MAD – Dose 4 
tmax 
Time of maximum observed concentration 
Cmax 
Maximum observed concentration 
AUC(0-24) 
Area under the curve from time 0 to 24 hr 
AUC(tau) 
Area under the curve for the defined interval between doses (tau) 
T1/2  
Terminal elimination half-life 
Lambda-z 
First order rate constant associated with the terminal (log-linear) portion of the 
curve 
AR Cmax* 
Accumulation Ratio based on Cmax last dose / Cmax first dose 
AR AUC* 
Accumulation Ratio based on AUC(0-tau) last dose / AUC(0-tau) first dose 
Vz/F 
Apparent volume of distribution based on the terminal phase after extravascular 
administration where F (fraction of dose bioavailable) is unknown 
*These parameters will not be calculated if Dose 1 is a loading dose. 
Further details of the PK data analysis will be included in the Reporting and Analysis Plan 
(RAP). 
14.4 Statistical Data Analysis  
Statistical analysis and production of summary tables, figures and listings for this study will 
be performed by Quotient using the statistical package SAS (v9.4 or more recent version).  

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 48 of 64  
 
In general terms, categorical data (including treatment-emergent AEs) will be presented 
using counts and percentages, while continuous variables will be presented using the 
mean, median, standard deviation, minimum and maximum. Additional statistics will be 
provided for PK-related data including coefficient of variation (CV%), geometric mean and 
geometric CV%.  
Descriptive summaries for all safety data (AEs, vital signs, ECGs and safety laboratory 
assessments) by treatment will be provided (including changes from baseline as required). 
Descriptive summaries for all PK and PD data by treatment will be provided, including 
changes from baseline in PD variables. The number and percentage of subjects with 
confirmed ADA response will be presented, both prevalence and incidence.  
All safety, PK and PD data will be listed. 
The following formal statistical analysis may be performed: 
Dose proportionality for SC doses - assessed using a power model using log-transformed 
AUC(0-last), AUC(0-inf) (Part 1), and AUC(0-tau) (Part 2) and Cmax values (e.g., a linear model 
with log dose as a covariate). The resulting estimated slope (b) is a measure of dose 
proportionality (e.g., the relationship is dose proportional when b=1). Dose proportionality 
will be assessed on each of Day 1/Dose 1 (SAD and MAD) and Dose 4 (MAD only). 
Accumulation - assessed in Part 2 on log-transformed parameters AUC(0-tau) and Cmax 
values using a mixed effects model with terms for treatment (e.g., dose level) and day as 
fixed effects, a day by treatment interaction term and subject as a random effect. Ratios of 
geometric means and 90% CI will be provided for Dose 2/3/4 versus Dose 1. Accumulation 
ratios will not be calculated if Dose 1 is a loading dose. 
Pharmacodynamics – Leukocyte numbers/percentages and Treg numbers/percentages 
will be compared between the active treatment and placebo groups using t-tests.  Non-
parametric statistics may be used for comparison if the data distribution suggest they are 
more appropriate. Changes from baseline in both groups will be summarized 
descriptively. Specific PK/PD modelling (e.g., Emax model fit) may be performed.  
Populations and analysis sets will be determined for safety, PK , ADA and PD (if 
applicable) after database lock using the criteria defined in the RAP; the RAP will be 
signed off prior to database lock. 
The safety and PD populations and analysis sets will be defined after database lock but 
prior to study unblinding; all other populations will be defined after database lock when the 
relevant data are available. 
Further details relating to the statistical analysis will be included in the RAP including the 
following: 
• 
Criteria to be used to define each of the population and analysis sets 
• 
Additional detail covering the analyses and/or description of primary and secondary 
analyses and safety data 
• 
Handling of missing data, unused or spurious data 
• 
Handling of data from withdrawn subjects 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 49 of 64  
 
14.5 Interim Analysis 
No formal interim analyses are planned for this study. Interim Data Reviews will be 
performed as detailed in Section 8.2. 
15 Safety Reporting to Institutional Review Board and Regulatory 
Authorities 
15.1 Events Requiring Expedited Reporting 
SUSARs (Section 13.4.2) are subject to expedited reporting to the IRB and regulatory 
authorities. 
In addition to SUSARs, other safety issues may qualify for expedited reporting where they 
might materially alter the current benefit-risk assessment of an IMP or that would be 
sufficient to consider changes in the IMPs’ administration or in the overall conduct of the 
study, for instance: 
• 
An increase in the rate of occurrence or a qualitative change of an expected 
serious adverse reaction which is judged to be clinically important 
• 
SAEs that occur after the subject has completed the clinical study where the 
Sponsor considers them to be a SUSAR 
• 
New events related to the conduct of the study or the development of the IMPs and 
likely to affect the safety of the subjects 
An SAE that could be associated with study procedures and could modify study conduct 
A major safety finding from a newly completed animal study (e.g., carcinogenicity) 
Any anticipated end or temporary halt of a study for safety reasons and conducted with the 
same IMPs in another country by the same Sponsor 
15.2 Urgent Safety Measures 
If Quotient or any of its staff or contractors becomes aware of an actual or potential urgent 
safety issue the Sponsor must be contacted immediately so that appropriate urgent safety 
measures can be agreed. An urgent safety issue is defined as:  
• 
An immediate hazard to the health or safety of subjects participating in a clinical 
study 
• 
A serious or potentially serious risk to human health 
An urgent safety issue may include issues with an investigational drug or comparators, 
study procedures, inter-current illness (including pandemic infections), concomitant 
medications, concurrent medical conditions or any other issues related to the safe conduct 
of the study or that pose a risk to study subjects. 
In exceptional circumstances of imminent hazard and to safeguard the health or safety of 
individuals, Quotient may take urgent safety measures before informing the Sponsor. The 
Sponsor must be informed immediately after the hazard has resolved.  
The Sponsor will take responsibility for informing the FDA of any urgent safety issue. 
Investigators will be responsible for notifying their IRB of any urgent safety matter.  

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 50 of 64  
 
15.3 Reporting 
15.3.1 Reporting Serious Adverse Events and AESI 
The investigator is required to notify the study Sponsor and pharmacovigilance provider if 
appropriate within 24 hours of becoming aware of the occurrence of a SAE or AESI. A 
copy of the written report of the event should promptly be sent to the study Sponsor for 
information purposes in accordance with International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines for GCP.  
15.3.2 Reporting of Suspected Unexpected Serious Adverse Reactions 
It is the responsibility of the Sponsor to determine whether a reported SAE fits the 
classification of a SUSAR and to notify the investigator of their decision as soon as 
possible. 
15.3.3 Expedited Reporting of Events 
It is the responsibility of the Sponsor to determine whether an event requires expedited 
reporting and to notify the investigator of their decision as soon as possible. 
Where expedited reporting is required, the following procedures should be followed. 
Fatal or life-threatening SUSARs 
It is the responsibility of the investigator and Sponsor to report fatal or life-threatening 
SUSARs to the IRB and relevant regulatory authorities, respectively, as soon as possible 
but no later than 7 calendar days after they first became aware of the reaction. Any 
additional relevant information should be sent within 8 days of the report. The task of 
reporting fatal or life-threatening SUSARs may be delegated to the pharmacovigilance 
provider. 
Other SUSARs 
It is the responsibility of the investigator and Sponsor to report other SUSARs to the IRB 
and relevant regulatory authorities, respectively, as soon as possible but no later than 
15 calendar days after they first became aware of the reaction. The task of reporting other 
SUSARs may be delegated to the pharmacovigilance provider. 
15.3.4 Reporting of Urgent Safety Issues 
The Sponsor is required to inform the appropriate regulatory authorities and investigators 
and the investigator is responsible for informing the IRB, within 3 calendar days of the 
urgent safety issue. 
15.4 Reporting Other Serious Important Medical Events 
Events should be reported when they do not fit other outcomes but may jeopardize the 
subject and/or may require medical or surgical intervention (treatment) to prevent one of 
the other outcomes. Examples include allergic bronchospasm (a serious problem with 
breathing) requiring treatment in an emergency room, serious blood dyscrasias (blood 
disorders) or seizures/convulsions that do not result in hospitalization. The development of 
drug dependence or drug abuse would also be examples of reportable medical events.  

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 51 of 64  
 
16 Protocol Amendments and Deviations 
16.1 Amendments 
Protocol amendments will be submitted to the FDA and IRB as required by current 
regulations. 
If the ICF is updated as a result of the substantial amendment the new approved version 
will be used to re-consent currently enrolled subjects (as required by the IRB) and must be 
provided to newly enrolled subjects prior to their entry into the study. 
16.2 Protocol Deviations 
The study must be conducted in accordance with the clinical protocol. Should a protocol 
deviation occur it must be promptly assessed to decide whether any non-compliance 
should be reported to the IRB. 
Protocol waivers are not acceptable. 
Important protocol deviations will be promptly reported to and discussed with the Sponsor 
to assess the impact on the study. 
17 Regulatory 
17.1 Compliance 
This study will be conducted in accordance with the protocol and with the following 
legislation: 
• 
ICH GCP Guidelines approved by the Committee for Medicinal Products for Human 
Use (CHMP) on 17 Jul 1996, which came into force on 17 Jan 1997, updated Jul 
2002, Integrated Addendum E6 (R2) dated 09 Nov 2016 
• 
US CFR Title 21 
• 
The ethical principles outlined in the World Medical Association Declaration of 
Helsinki and its amendments 
17.2 Ethical Approval 
Prior to the initiation of the study, the protocol and associated documentation must be 
approved by an IRB. A copy of this written approval and any correspondence with the IRB 
will be provided to the Sponsor. 
17.3 Investigator Responsibilities 
The investigator will be responsible for the following: 
• 
Providing written summaries of the study status to the IRB annually or more 
frequently in accordance with the requirements, policies and procedures 
established by the IRB 
• 
Notifying the IRB of SAEs or other significant safety findings as required by IRB 
procedures 
• 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB and all other applicable local 
regulations 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 52 of 64  
 
• 
Notifying the Sponsor of any requests for inspections by a regulatory authority 
17.4 Source Data 
A study-specific source document identification list will be finalized with the Sponsor prior 
to the start of the clinical phase of the study. The document will identify what data should 
be considered source data for this study. 
For this study, electronic data capture will be used where possible and data will be 
automatically recorded into an eCRF. In instances where paper source documents are 
used data to be transcribed into the eCRF will be identified using a Source Document 
Identification List as governed by Quotient’s SOPs. 
17.5 Declaration of the End of the Study 
The end of the study is defined as the point at which the Sponsor determines that any 
remaining optional groups are not required to meet the objectives of the trial (i.e., signed 
dose decision document or the completion of the last follow-up visit or unscheduled 
follow-up assessment for the final cohort/subject dosed, whichever occurs later). The 
Sponsor can also declare an end of the study if business reasons indicate that the 
development of PDM-608 cannot proceed, with orderly collection of follow-up data at 
safety visits from enrolled subjects. If all optional groups are utilized, completion of the last 
follow-up visit or unscheduled follow-up call/visit will be considered the end of the study. 
Any changes to this definition will be notified as a substantial amendment. 
17.6 Document Storage and Archiving 
All documentation and correspondence pertaining to the study (eCRF, raw data, letters, 
etc.) will be kept in accordance with 21 CFR and the ICH guidelines for GCP 1996, 
updated 2002, Integrated Addendum E6 (R2) dated 09 Nov 2016 (ICH GCP Section 4.9.5)  
All study related documents will be retained for a period of at least 2 years following the 
date a marketing application is approved for the indication for which it is being 
investigated; or, if no application is to be filed or if the application is not approved for such 
indication, until 2 years after the investigation is discontinued and regulatory authorities 
have been notified; or 8 years after completion of the study, whichever is longer. After this 
time, the Sponsor will be contacted to ascertain whether continued storage or destruction 
is required in accordance with current regulations. 
17.7 
Protection of Personal Data and Confidentiality 
Personal data are securely stored to prevent unauthorized access, disclosure, 
dissemination, alteration or loss of information and unauthorized personal data processing.  
Access to personal information is restricted so that only personnel who are required to 
access personal data as part of their job role can do so. All personnel who access 
personal information are bound by a duty of confidentiality. 
Technical arrangements surrounding the electronic storage and use of data are as follows: 
• 
Computers storing electronic personal data are protected by antivirus software and 
the network on which computers are linked are protected by industry grade 
firewalls 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 53 of 64  
 
• 
Off-site personnel can only access networked computers through a virtual private 
network 
• 
Electronic access of data is limited according to user roles 
• 
All data are stored on password protected computers 
Organizational arrangements are as follows: 
• 
All buildings are secured by key-card access 
• 
Manual files of personal data are stored within restricted areas of the clinical unit 
that can only be accessed by authorized personnel 
• 
Data security and/or confidentiality provisions are utilized in agreements with third 
parties 
• 
Documented back-up and disaster recovery procedures are in place 
• 
Internal audit and compliance functions provide regulatory oversight 
The Sponsor shall be the data controller of study subject personal data collected in 
connection with the study and shall act in accordance with the relevant data protection 
laws in relation to the collection and processing of those personal data. Records identifying 
the subject will be kept confidential and, to the extent permitted by the applicable laws 
and/or regulations, will not be made publicly available. Anonymized personal data shall be 
collected and processed for the purposes of the study and may also be added to research 
databases and used in the future by the Sponsor and its affiliates for certain additional 
clinical research, product regulation, safety reporting purposes and for ensuring 
compliance with legal requirements. The study subjects’ anonymized personal data may 
be processed for such purposes by other parties including the Sponsor’s affiliates and 
licensing partners, its business partners, regulatory agencies, other health authorities and 
the IRB. The study subjects’ authorization for such use and disclosure shall be obtained by 
the study subjects signing the ICF for the study. 
Additionally, Quotient personnel are contractually bound by a duty of confidentiality and 
receive training on this matter. 
18 Quality Control and Quality Assurance 
Quality control of all data collected from this study will be performed in accordance with 
Quotient’s SOPs. This study (or elements thereof) may be subject to Quotient QA audit in 
line with current internal auditing procedures. Similarly, the study (or elements thereof) 
may be subject to Sponsor QA audit. 
18.1 Monitoring 
GCP requires that studies are adequately monitored. The Sponsor should determine the 
appropriate extent and nature of monitoring. A study monitor, independent of Quotient, will 
be appointed to verify that the study is conducted in accordance with current GCP, 
regulatory requirements, the protocol and that the data are authentic, accurate and 
complete.  
The investigator agrees to receive visits from a study monitor and provide assistance to 
verify protocol implementation, eCRF completion, document storage and AE reporting. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 54 of 64  
 
Quotient will extend the professional privilege of access to the subjects’ clinical source 
documents to the study monitor, IRB, regulatory bodies or other authorized personnel 
(e.g., auditor) for the purposes of source data verification. 
Following completion of the study all study related documents and subject data, unless 
mandated by law and federal agencies, will be stored by Quotient, either on site or in long 
term storage site under Quotient’s responsibility. In the interests of confidentiality subjects 
will not be identified on any such documents or data, and specific subject consent for such 
a disposition will be obtained as required by law. 
19 Publication 
Please refer to the Master Services Agreement for information on publication.  
Quotient shall have the right to publish the results of the research, subject to the Sponsor’s 
prior written consent, which shall not be unreasonably withheld or delayed. Following the 
receipt of such consent Quotient shall submit a copy of the proposed publication to the 
Sponsor who shall have 30 days in which to request amendments thereto which, to the 
extent that such proposed amendments are reasonable, Quotient shall be obliged to 
incorporate prior to such publication. 
The Sponsor undertakes that, prior to publication of any information, article, paper, report 
or other material concerning the research, it will submit a copy of such publication to 
Quotient who shall have 30 days in which to request amendments thereto which, to the 
extent that such proposed amendments are reasonable, the Sponsor shall be obliged to 
incorporate prior to such publication. 
 
 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 55 of 64  
 
20 References 
Chen UY, Qi B, XU W, Ma B, Li L, Chen Q, Qian W, Liu Z, Qu H. Clinical correlation of 
peripheral CD4+-cell subsets, their imbalance and Parkinson’s disease. Mol Med Rep 2015, 
12, 6105-6111. 
Gendelman, H. E.;  Zhang, Y.;  Santamaria, P.;  Olson, K. E.;  Schutt, C. R.;  Bhatti, D.;  
Shetty, B. L. D.;  Lu, Y.;  Estes, K. A.;  Standaert, D. G.;  Heinrichs-Graham, E.;  Larson, L.;  
Meza, J. L.;  Follett, M.;  Forsberg, E.;  Siuzdak, G.;  Wilson, T. W.;  Peterson, C.; Mosley, 
R. L. Evaluation of the safety and immunomodulatory effects of sargramostim in a 
randomized, double-blind phase 1 clinical Parkinson's disease trial. NPJ Parkinsons Dis 
2017, 3, 10. 
Kosloski, L. M.; Kosmacek, E. A.; Olson, K. E.; Mosley, R. L.; Gendelman, H. E. GM-CSF 
induces neuroprotective and anti-inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine intoxicated mice. J Neuroimmunol 2013, 265 (1-2), 1-10. 
Olson, K. E.;  Namminga, K. L.;  Schwab, A. D.;  Thurston, M. J.;  Lu, Y.;  Woods, A.;  Lei, 
L.;  Shen, W.;  Wang, F.;  Joseph, S. B.;  Gendelman, H. E.; Mosley, R. L. Neuroprotective 
Activities of Long-Acting Granulocyte-Macrophage Colony-Stimulating Factor (mPDM608) 
in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Intoxicated Mice. Neurotherapeutics 2020, 
17 (4), 1861-1877. 
Olson, K. E.;  Namminga, K. L.;  Lu, Y.;  Schwab, A. D.;  Thurston, M. J.;  Abdelmoaty, M. 
M.;  Kumar, V.;  Wojtkiewicz, M.;  Obaro, H.;  Santamaria, P.;  Mosley, R. L.; Gendelman, 
H. E. Safety, tolerability, and immune-biomarker profiling for year-long sargramostim 
treatment of Parkinson's disease. EBioMedicine 2021, 67, 103380. 
Potter, H.;  Woodcock, J. H.;  Boyd, T. D.;  Coughlan, C. M.;  O'Shaughnessy, J. R.;  Borges, 
M. T.;  Thaker, A. A.;  Raj, B. A.;  Adamszuk, K.;  Scott, D.;  Adame, V.;  Anton, P.;  Chial, 
H. J.;  Gray, H.;  Daniels, J.;  Stocker, M. E.; Sillau, S. H. Safety and efficacy of sargramostim 
(GM-CSF) in the treatment of Alzheimer's disease. Alzheimers Dement (N Y) 2021, 7 (1), 
e12158. 
Ragnhammar P; Friesen H-J; Frodin J-E, Lefert A-K; Hassan M; Oterborg A; Mellstedt H. 
Induction of anti-recombinant human granulocyte-macrophage colony-stimulating factor 
(Escherichia coli-derived) antibodies and clinical effects in nonimmunocompromised 
patients. Blood 1994, 84, 4078-4087. 
Investigator’s Brochure: PDM608. Calibr. V1.0 / 03 Mar 2018. 
Leukine (sargramostim) for injection, for subcutaneous use or intravenous use. Highlights 
of Prescribing Information. Initial U.S. approval: 1991; revised: May 2019. 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 56 of 64  
 
Appendix 1 
Clinical Laboratory Parameters 
Hematology 
Clinical Chemistry 
Virology 
Urinalysis 
Drugs of Abuse 
Basophils 
Eosinophils 
Hematocrit  
Hemoglobin 
Lymphocytes 
Mean Cell Hemoglobin (MCH) 
Mean Cell Hemoglobin 
Concentration (MCHC) 
Mean Cell Volume (MCV) 
Monocytes 
Neutrophils 
Platelet Count 
Red Blood Cell (RBC) Count  
White Blood Cell (WBC) Count 
Alanine Aminotransferase (ALT) 
Albumin 
Alkaline Phosphatase (ALP) 
Aspartate Aminotransferase (AST) 
Bilirubin (Total) 
Bilirubin (Direct)  
Blood urea nitrogen (BUN) 
Calcium 
Carbon Dioxide (CO2) 
Chloride 
Creatine Kinase (CK) 
Creatinine 
CLcr will be calculated at screening 
only using the Cockcroft-Gault 
equation for eligibility purposes 
Follicle Stimulating Hormone (FSH; 
post-menopausal female subjects 
only at screening) 
Gamma Glutamyl Transferase 
(GGT) 
Glucose (unscheduled time points)a 
Glucose (Fasting) 
Human Chorionic 
Gonadotropin (hCG) (female 
subjects when indicated) 
Potassium 
Phosphate (Inorganic) 
Protein (Total) 
Sodium 
Triglycerides (fasted) 
Hepatitis B Surface 
Antigen 
Hepatitis C Virus 
Antibody 
HIV Antibody 
QuantiFERON®-TB 
Gold test 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocytes 
Nitrites 
pH 
Protein 
Specific gravity 
Urobilinogen 
 
Based on urinalysis 
results 
Microbiology  
Urine Microscopy (analysis 
of sediment for: bacteria, 
casts, crystals, epithelial 
cells, red blood cells and 
white blood cells) 
 
Urine Pregnancy 
Human Chorionic 
Gonadotropin (hCG) (female 
subjects when indicated) 
Amphetaminesb 
Antidepressants 
Barbiturates 
Benzodiazepines 
Cocaine 
Cotininec 
Ethanol 
Marijuana/Cannabis 
Methadone 
Morphine/Opiates 
Phencyclidine 
Tricyclic s 
Samples taken due to early withdrawal do not need to be fasted.  
a Fasting is not a requirement for unscheduled samples.  
b Refers to a group of drugs that includes methamphetamine/MDMA (commonly known as Ecstasy)  
c Urine cotinine at screening and admission only (for Part 2, this is the Day -1 admission) 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 57 of 64  
 
Appendix 2 
Schedule of Assessments: Part 1 Single Ascending Dose 
Study Day → 
SCRN 
D -1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D11 
D15 
D22 
Premature 
DC
Time Relative to 
IMP Admin→ 
Admit 
Pre- 
Dose 
0H 
1H 
3H 
12H 
24H 
48H 
72H 
96H 
120H 
144H 
168H 
240H 
336H 
504H 
Window → 
D-28 
to -2 
Day of 
1Hj 
n/a 
±10M 
±10M 
±1H 
±2H 
±2H 
±2H 
±2H 
±2H 
±2H 
±2H 
±24H 
±24H 
±24H 
Assessments ↓ 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Informed 
Consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
Xa 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Weight, Height, 
BMI 
X 
Xb 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vein Assessment 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Alcohol, 
Cotinine, Drug 
Screen 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Serum 
Pregnancy 
Xc 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Pregnancy 
  
Xd 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Randomization 
  
  
Xe 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
IMP 
Administrationf 
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical Exam 
X 
  
  
  
  
  
  
X 
  
  
X 
  
  
X 
  
  
  
X 
Hem & Chemm 
X 
X 
  
  
  
  
X 
X 
X 
  
X 
  
  
X 
  
X 
  
X 
Virology & TB 
Test 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
FSHg 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
CLcr 
X 
  
  
  
  
  
X 
X 
X 
  
X 
  
  
X 
  
X 
  
X 
Urinalysis 
X 
  
Xk 
  
  
  
  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
Single ECG 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
X 
X 
X 
X 
Triplicate ECG 
  
  
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
  

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 58 of 64  
 
Study Day → 
SCRN 
D -1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D11 
D15 
D22 
Premature 
DC
Time Relative to 
IMP Admin→ 
Admit 
Pre- 
Dose 
0H 
1H 
3H 
12H 
24H 
48H 
72H 
96H 
120H 
144H 
168H 
240H 
336H 
504H 
Window → 
D-28 
to -2 
Day of 
1Hj 
n/a 
±10M 
±10M 
±1H 
±2H 
±2H 
±2H 
±2H 
±2H 
±2H 
±2H 
±24H 
±24H 
±24H 
Assessments ↓ 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vital Signsh 
X 
X 
X 
  
  
  
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
X 
PK 
  
  
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD 
  
  
X 
  
  
  
  
X 
  
  
X 
  
  
X 
X 
X 
X 
X 
ADA 
  
  
X 
  
  
  
  
  
  
  
  
  
  
X 
  
X 
X 
X 
Adverse Events 
X 
Concomitant 
Medications 
X 
Clinical 
Residency 
  
Clinical Residency admit Day -1, discharge Day 8 
 
 RV 
 RV 
 RV 
  
RV = Return Visit 
Appendix 2 Footnotes 
a 
Update of medical history 
b 
Weight only 
c 
All female subjects 
d 
All female subjects, except those confirmed menopausal/post-menopausal by FSH ≥ 40 IU/L at screening 
e 
Subjects will be randomized on Day 1 prior to dosing (1 hour window not applicable) 
f 
See Pharmacy Manual for details on SC IMP administration 
g 
Menopausal/post-menopausal female subjects only, to confirm childbearing potential status 
h 
Vital signs to include blood pressure, heart rate, body temperature, and respiratory rate 
j 
Within 1 hour prior to IMP administration 
k 
Urinalysis within 2 hours prior to IMP administration 
m 
Scheduled blood samples will be taken following an overnight fast of a minimum of 8 hours 
 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 59 of 64  
 
Appendix 3 
Schedule of Assessments: Part 2 Multiple Ascending Dose 
Screening through Day 16 
Study Day → 
SCRN 
D -1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D9 
D14 
D15 
D16 
Time Relative to D1 
→ 
Admit 
Pre-Dose 
0H 
1H 
3H 
12
H 
24
H 
48
H 
72
H 
96
H 
120
H 
144
H 
168
H 
192
H 
Admit 
336H 
360H 
Time Relative to Prior 
Dose → 
0H 
24H 
0H 
24H 
Window Relative to 
Prior Dose → 
D-28 
to -2 
Day 
of 
≤1Hi 
n/a 
±10M 
±10M 
±1
H 
±2
H 
±2
H 
±2
H 
±2
H 
±2H 
±2H 
≤1Hi 
Day 
of 
Day 
of 
≤1Hi 
Day 
of 
Assessments ↓ 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Informed Consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
Xa 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Weight, Height, 
BMI 
X 
Xb 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vein Assessment 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Alcohol, 
Cotinine, Drug 
Screen 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
  
Serum Pregnancy 
Xc 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Pregnancy 
  
Xd 
  
  
  
  
  
  
  
  
  
  
Xd 
  
  
Xd 
  
  
Randomization 
  
  
Xe 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
IMP 
Administrationf 
  
  
  
X 
  
  
  
  
  
  
  
  
  
X 
  
  
X 
  
Physical Exam 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hem & Chemk 
X 
X 
  
  
  
  
X 
  
  
X 
  
  
X 
X 
  
X 
  
  
Urinalysis 
X 
X 
  
  
  
  
X 
X 
  
X 
  
  
X 
X 
  
X 
  
  
Virology and TB 
Test 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
FSH 
Xg 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 60 of 64  
 
Study Day → 
SCRN 
D -1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D9 
D14 
D15 
D16 
Time Relative to D1 
→ 
Admit 
Pre-Dose 
0H 
1H 
3H 
12
H 
24
H 
48
H 
72
H 
96
H 
120
H 
144
H 
168
H 
192
H 
Admit 
336H 
360H 
Time Relative to Prior 
Dose → 
0H 
24H 
0H 
24H 
Window Relative to 
Prior Dose → 
D-28 
to -2 
Day 
of 
≤1Hi 
n/a 
±10M 
±10M 
±1
H 
±2
H 
±2
H 
±2
H 
±2
H 
±2H 
±2H 
≤1Hi 
Day 
of 
Day 
of 
≤1Hi 
Day 
of 
Assessments ↓ 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
CLcr 
X 
  
  
  
  
  
X 
  
  
  
  
  
X 
X 
  
  
  
  
Single ECG 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
 
Triplicate ECG 
  
X 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
  
X 
  
Vital Signsh 
X 
X 
X 
  
  
  
X 
X 
X 
X 
X 
X 
X 
X 
X  
X 
X 
 X 
PK 
  
  
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
  
X 
  
PD 
  
  
X 
  
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
ADA 
  
  
X 
  
  
  
  
  
  
  
  
  
  
 X 
  
  
X 
  
Adverse Events 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Concomitant 
Medications 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Clinical Residency 
  
Admit Day -1, Discharge D9  
Admit D14, D/C D16 
 
 
 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 61 of 64  
 
Day 21 through 60 and Premature Discontinuation 
Study Day → 
D21 
D22 
D23 D24 D25 D26 D27 D28 D29 
D32 
D36 
D43 
D50 
D60 
Premature DC 
Time Relative to 
D1 → 
Admit 
n/a 
528H 
552H 
576H 
600H 
624H 
648H 
672H 
744H 
840H 
1008H 
1176H 
1416H 
Time Relative to 
Prior Dose → 
0H 
1H 
3H 
12H 
24H 
48H 
72H 
96H 
120H 
144H 
168H 
240H 
336H 
504H 
672H 
912H 
Window Relative 
to Prior Dose → 
Day of 
≤1Hi 
±10M 
±10M 
±1H 
±2H 
±2H 
±2H 
±2H 
±2H 
±2H 
±2H 
±24H 
±24H 
±24H 
±24H 
±24H 
Assessments ↓ 
  
  
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Alcohol, 
Cotinine, Drug 
Screen 
X 
  
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Pregnancy 
Xd 
  
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
IMP 
Administrationf 
  
X 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical Exam 
  
  
 
 
  
  
  
X 
  
  
  
  
  
  
  
  
  
X 
Hem & Chemk 
X 
  
 
 
  
  
  
X 
  
  
  
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
  
 
 
X 
X 
  
X 
  
  
X 
X 
  
  
  
  
  
  
Single ECG 
  
  
 
 
  
  
  
  
  
  
  
  
  
X 
  
  
X 
  
Triplicate ECG 
X 
X 
 
 
 X 
 X 
  
X  
  
X  
  
 X 
  
  
  
  
  
X 
Vitals Signsh 
X 
X 
 
 
X 
  
  
  
  
  
X 
X 
  
  
  
  
  
  
PK 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD 
  
X 
 
 
  
  
X 
  
  
X 
  
X 
X 
X 
X 
  
  
X 
ADA 
  
  
 
 
  
  
  
  
  
  
X 
  
  
  
X 
  
X 
X 
Adverse Events 
X 
X 
Concomitant 
Medications 
X 
X 
Clinical 
Residency 
Admit D21, Discharge 29 
RV 
RV 
RV 
RV 
RV 
 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 62 of 64  
 
 
RV = Return Visit 
Appendix 3 Footnotes 
a Update of medical history 
b Weight only 
c All female subjects 
d All female subjects, except those confirmed menopausal/post-menopausal by FSH ≥ 40 IU/L at screening 
e Subjects will be randomized on Day 1 prior to dosing (1 hr window not applicable) 
f See Pharmacy Manualfor details on IMP administration 
g Menopausal/post-menopausal female subjects only, to confirm childbearing potential status 
h Vital signs to include blood pressure, heart rate, temperature, and respiratory rate 
i Within 1 hour prior to IMP administration 
k Scheduled blood samples will be taken following an overnight fast of a minimum of 8 hours 
 

Calibr Confidential 
 
Protocol CBR-PDM608-3001 Version 1.0 30Jan2023 
Page 63 of 64  
 
Signatures for Quotient Sciences 
CONFIDENTIALITY AND GCP COMPLIANCE STATEMENT 
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, 
and any other product information provided by the Sponsor. I agree to conduct this study in 
accordance with the requirements of this protocol and also protect the rights, safety, privacy, 
and well-being of study subjects in accordance with the following: 
• 
The ethical principles that have their origin in the Declaration of Helsinki. 
• 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use E6 Good Clinical Practice: Consolidated Guideline. 
• 
All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations. 
• 
Regulatory requirements for reporting serious adverse events defined in Section 15.3.1 
of this protocol. 
Information taken from the study protocol may not be disseminated or discussed with a third 
party without the express consent of the Sponsor.  
 
 
 
Principal Investigator Print Name 
 
Signature 
 
 
 
 
 
 
Date of Signature 
 






	

		


	





	






		
	
		

