A Phase 1, Three-Part, Randomized, Double-Blind, Single and Multiple Subcutaneous Dose Escalation Study to Determine the Safety, Tolerability, and Pharmacokinetics of Rezafungin in Healthy Adult Subjects
Phase: PHASE1
Conditions: Fungal Infection
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

DMID Protocol 17-0088 
Version 6.0 
Safety and Pharmacokinetics of Rezafungin 
31 MAR 2020 
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DMID eCTD Compliant Interventional Protocol Template and Instructions, Version 4.0, Dated May 18, 2018 
 
 
A Phase 1, Three-Part, Randomized, Double-Blind, Single and 
Multiple Subcutaneous Dose Escalation Study to Determine the 
Safety, Tolerability, and Pharmacokinetics of Rezafungin in Healthy 
Adult Subjects 
DMID Protocol Number: 17-0088 
DMID Funding Mechanism: HHSN272201500007I 
Pharmaceutical Support: Cidara Therapeutics, Inc. 
IND Sponsor: DMID 
Lead Principal Investigator: Dennis Ruff, MD 
DMID Clinical Project Manager: Maureen Mehigan, RN 
Version Number: 6.0 
 
31 MAR 2020 
 
 
 

DMID Protocol 17-0088 
Version 6.0 
Safety and Pharmacokinetics of Rezafungin 
31 MAR 2020 
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DMID eCTD Compliant Interventional Protocol Template and Instructions, Version 4.0, Dated May 18, 2018 
 
STATEMENT OF ASSURANCE 
Each Institution will hold a current Federal Wide Assurance (FWA) issued by the Office for 
Human Research Protections (OHRP) for federally-funded human subjects research. Each FWA 
will designate at least one Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) registered with OHRP, for which the research will be reviewed and approved by the 
IRB/IEC and will be subject to continuing review [45 Code of Federal Regulations (CFR) 
46.103(b)]. The IRB/IEC designated under an FWA may include an institution’s IRB/IEC, an 
independent IRB/IEC, or an IRB/IEC of another institution after establishing a written agreement 
with that other institution. 

DMID Protocol 17-0088 
Version 6.0 
Safety and Pharmacokinetics of Rezafungin 
31 MAR 2020 
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DMID eCTD Compliant Interventional Protocol Template and Instructions, Version 4.0, Dated May 18, 2018 
 
STATEMENT OF COMPLIANCE 
This trial will be carried out in accordance with Good Clinical Practice (GCP) and as required by 
the following: 
United States (US) CFR 45 CFR Part 46: Protection of Human Subjects 
Food and Drug Administration (FDA) Regulations, as applicable: 21 CFR Part 50 (Protection of 
Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical Investigators), 21 CFR Part 
56 (IRBs), 21 CFR Part 11(Electronic Records and Electronic Signatures), and 21 CFR Part 312 
(Investigational New Drug Application) 
International Conference on Harmonization: GCP (ICH E6); 62 Federal Register 25691 (1997); 
and revisions 
Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of 
Research, Report of the National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research 
National Institutes of Health (NIH) Office of Extramural Research, Research Involving Human 
Subjects, as applicable 
National Institute of Allergy and Infectious Diseases (NIAID) Clinical Terms of Award, as 
applicable 
Applicable Federal, State, and Local Regulations and Guidance 

DMID Protocol 17-0088 
Version 6.0 
Safety and Pharmacokinetics of Rezafungin 
31 MAR 2020 
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DMID eCTD Compliant Interventional Protocol Template and Instructions, Version 4.0, Dated May 18, 2018 
 
TABLE OF CONTENTS 
STATEMENT OF ASSURANCE ...................................................................................................2 
STATEMENT OF COMPLIANCE .................................................................................................3 
SIGNATURE PAGE .......................................................................................................................4 
TABLE OF CONTENTS .................................................................................................................5 
LIST OF TABLES .........................................................................................................................12 
LIST OF FIGURES .......................................................................................................................13 
LIST OF ABBREVIATIONS ........................................................................................................14 
PROTOCOL SUMMARY .............................................................................................................18 
 
KEY ROLES.........................................................................................................................26 
 
BACKGROUND AND SCIENTIFIC RATIONALE ..........................................................27 
 
Background .................................................................................................................27 
 
Scientific Rationale .....................................................................................................29 
2.2.1 Purpose of Study ............................................................................................29 
2.2.2 Study Population ............................................................................................30 
 
Potential Risks and Benefits .......................................................................................30 
2.3.1 Potential Risks ...............................................................................................30 
2.3.2 Potential Benefits ...........................................................................................33 
 
STUDY DESIGN, OBJECTIVES AND ENDPOINTS OR OUTCOME MEASURES .....34 
 
Study Design Description ...........................................................................................34 
3.1.1 Dosing Scheme and Duration of Study ..........................................................34 
3.1.1.1 
Part 1 (SAD) .....................................................................................34 
3.1.1.2 
Part 2 (MAD) ....................................................................................35 
3.1.1.3 
Part 3 (BA) ........................................................................................36 
3.1.2 Rationale for Starting Dose ............................................................................37 
3.1.3 Dose Escalations ............................................................................................38 

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Safety and Pharmacokinetics of Rezafungin 
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Study Objectives .........................................................................................................39 
3.2.1 Primary ...........................................................................................................39 
3.2.2 Secondary .......................................................................................................40 
 
Study Endpoints or Outcome Measures .....................................................................40 
3.3.1 Primary ...........................................................................................................40 
3.3.2 Secondary .......................................................................................................40 
 
STUDY INTERVENTION/INVESTIGATIONAL PRODUCT .........................................41 
 
Study Product Description ..........................................................................................41 
4.1.1 Formulation, Packaging, and Labeling ..........................................................41 
4.1.2 Product Storage and Stability .........................................................................43 
 
Acquisition/Distribution .............................................................................................43 
 
Dosage/Regimen, Preparation, Dispensing and Administration of Study 
Intervention/Investigational Product.........................................................................44 
 
Accountability Procedures for the Study Intervention/Investigational Product(s) .....45 
 
SELECTION OF SUBJECTS AND STUDY ENROLLMENT AND WITHDRAWAL ....46 
 
Eligibility Criteria .......................................................................................................46 
5.1.1 Subject Inclusion Criteria...............................................................................46 
5.1.2 Subject Exclusion Criteria .............................................................................48 
 
Withdrawal from the Study, Discontinuation of Study Product, or Study Termination
 ..................................................................................................................................50 
5.2.1 Withdrawal from the Study or Discontinuation of the Study Product ...........50 
5.2.2 Handling of Withdrawals and Discontinuation of Administration ................51 
5.2.3 Lost to Follow-Up ..........................................................................................51 
5.2.4 Subject Replacement ......................................................................................51 
5.2.5 Study Termination .........................................................................................52 
 
STUDY PROCEDURES ......................................................................................................53 
 
Recruitment .................................................................................................................53 

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Screening (Day -28 to Day -2) Parts 1-3 (All Cohorts) ..............................................53 
 
Admission to the CRU (Day -1) Parts 1 and 2 (All Cohorts) and Part 3 (Cohort 11) 
Days -1 and 21 ..........................................................................................................55 
 
Part 1 (Cohorts 1 through 6) .......................................................................................56 
6.4.1 Day 1 – Inpatient CRU ..................................................................................56 
6.4.2 Day 2 – Inpatient CRU ..................................................................................57 
6.4.3 Day 3 – Inpatient CRU ..................................................................................58 
6.4.4 Day 4 – Inpatient CRU ..................................................................................58 
6.4.5 Day 5 – Inpatient CRU ..................................................................................58 
6.4.6 Day 6 – Inpatient CRU ..................................................................................59 
6.4.7 Day 7 – Inpatient CRU ..................................................................................59 
6.4.8 Day 14 (±1 Day) – Follow-Up - Outpatient ...................................................60 
6.4.9 Day 21 (±1 Day) – Telephone Follow-Up .....................................................60 
6.4.10 Day 30 (±1 Day) – Follow-Up – Final Study Visit........................................61 
 
Part 2 (Cohorts 7 through 10) .....................................................................................61 
6.5.1 Days 1, 8, and 15 – Inpatient CRU ................................................................61 
6.5.2 Days 2, 9, and 16 – Inpatient CRU ................................................................63 
6.5.3 Days 3, 10, and 17 – Inpatient CRU ..............................................................63 
6.5.4 Days 4, 11, and 18 – Inpatient CRU ..............................................................63 
6.5.5 Days 5, 12, and 19 – Inpatient CRU ..............................................................64 
6.5.6 Days 6, 13, and 20 – Inpatient CRU ..............................................................64 
6.5.7 Days 7, 14, and 21 – Inpatient CRU ..............................................................64 
6.5.8 Day 30 (±1 Day) – Follow-Up - Outpatient ...................................................65 
6.5.9 Day 45 (±1 Day) – Follow-Up – Final Study Visit........................................66 
 
Part 3 (Cohort 11) .......................................................................................................66 
6.6.1 Days 1 and 22 – Inpatient CRU .....................................................................66 
6.6.2 Days 2 and 23 – Inpatient CRU .....................................................................68 

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Safety and Pharmacokinetics of Rezafungin 
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6.6.3 Days 3 and 24 – Inpatient CRU .....................................................................68 
6.6.4 Days 4 and 25 – Inpatient CRU .....................................................................69 
6.6.5 Days 5 and 26 – Inpatient CRU .....................................................................69 
6.6.6 Days 6 and 27 – Inpatient CRU .....................................................................69 
6.6.7 Days 7 and 28 – Inpatient CRU .....................................................................69 
6.6.8 Days 14 (±1 Day) and 35 (±1 Day) – Follow-Up - Outpatient ......................70 
6.6.9 Day 52 (±1 Day) – Follow-Up – Final Study Visit........................................71 
6.6.10 Early Termination (ET) Visit (if needed) ......................................................71 
 
Unscheduled Study Visits ...........................................................................................72 
 
Protocol Deviations ....................................................................................................73 
 
DESCRIPTION OF CLINICAL AND LABORATORY EVALUATIONS .......................74 
 
Clinical Evaluations ....................................................................................................74 
7.1.1 Medical History .............................................................................................74 
7.1.2 Height, Weight, Body Mass Index (BMI)......................................................74 
7.1.3 Physical Examinations ...................................................................................74 
7.1.4 Local Reactogenicity Symptoms ...................................................................74 
7.1.5 Vital Signs ......................................................................................................76 
7.1.6 Electrocardiograms ........................................................................................76 
7.1.7 Assessment of Concomitant Medications/Treatments Other than Study 
Product ...........................................................................................................77 
 
Laboratory Evaluations ...............................................................................................78 
7.2.1 Clinical Laboratory Evaluations ....................................................................78 
7.2.2 Research Assays .............................................................................................80 
 
ASSESSMENT OF SAFETY ...............................................................................................86 
 
Assessing and Recording Safety Parameters ..............................................................86 
8.1.1 Adverse Events ..............................................................................................86 
8.1.2 Serious Adverse Events .................................................................................89 

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Safety and Pharmacokinetics of Rezafungin 
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8.1.3 Adverse Events of Special Interest ................................................................90 
 
Specification of Safety Parameters .............................................................................91 
8.2.1 Injection Site Reactogenicity .........................................................................91 
8.2.2 New-Onset Chronic Medical Conditions .......................................................91 
8.2.3 Dose Escalation Criteria ................................................................................91 
 
Reporting Procedures ..................................................................................................92 
8.3.1 Reporting Serious Adverse Events ................................................................92 
 
Type and Duration of Follow-Up of Subjects after Adverts Events ..........................92 
8.4.1 Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND
 ........................................................................................................................93 
8.4.2 Reporting of Pregnancy .................................................................................93 
 
Type and Duration of Follow-Up of Subjects after Adverse Events ..........................94 
 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings......................................................................................94 
 
Halting Rules ..............................................................................................................95 
8.7.1 Study Halting Rules .......................................................................................95 
8.7.2 Dose Escalation Halting Rules .......................................................................95 
8.7.3 Individual Halting Rules ................................................................................96 
 
Safety Oversight (ISM and SMC) ..............................................................................97 
8.8.1 Independent Safety Monitor...........................................................................97 
8.8.2 Safety Monitoring Committee .......................................................................98 
 
HUMAN SUBJECTS PROTECTION .................................................................................99 
 
Institutional Review Board/Independent Ethics Committee ......................................99 
 
Informed Consent Process ..........................................................................................99 
 
Consent for Future Use of Stored Specimens and Data ...........................................101 
 
Exclusion of Women, Minorities, and Children (Special Populations) ....................102 
 
Subject Confidentiality .............................................................................................102 

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Certificate of Confidentiality ....................................................................................103 
 
Costs, Subject Compensation, and Research Related Injuries .................................104 
 
STATISTICAL CONSIDERATIONS ...............................................................................105 
 Study Hypotheses .....................................................................................................105 
 Sample Size Considerations .....................................................................................105 
 Treatment Assignment Procedures ...........................................................................105 
10.3.1 Randomization Procedures ..........................................................................105 
10.3.2 Masking Procedures .....................................................................................106 
10.3.2.1 Blinding ..........................................................................................106 
10.3.3 Emergency Unblinding ................................................................................107 
 Planned Interim Analyses .........................................................................................107 
10.4.1 Interim Safety Review .................................................................................107 
10.4.2 Interim Immunogenicity or Efficacy Review ..............................................108 
 Final Analysis Plan ...................................................................................................108 
10.5.1 Adverse and Serious Adverse Events ..........................................................108 
10.5.2 Clinical Safety Labs, Vital Signs, and Electrocardiograms .........................109 
10.5.3 Additional Safety Analyses ..........................................................................110 
10.5.4 PK Analysis Plan .........................................................................................110 
 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ............112 
 Compliance with Standards of Medical Research/Deviations ..................................112 
 
QUALITY CONTROL AND QUALITY ASSURANCE .................................................113 
 
DATA HANDLING AND RECORD KEEPING ..............................................................114 
 Data Management Responsibilities ..........................................................................114 
 Data Management Responsibilities ..........................................................................115 
 Data Capture Methods ..............................................................................................115 
 Types of Data ............................................................................................................116 
 Study Records Retention ..........................................................................................116 

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CLINICAL MONITORING ...............................................................................................117 
 Site Monitoring Plan .................................................................................................117 
 
PUBLICATION POLICY ..................................................................................................118 
 
LITERATURE REFERENCES ..........................................................................................119 
 
APPENDICES ....................................................................................................................121 
 
Schedules of Events ........................................................................122 
 
TOXICITY TABLE ........................................................................129 

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LIST OF TABLES 
Table 1: Design for SC Dosing in SAD (Study Part 1) .................................................................35 
Table 2: Design for SC Dosing in MAD (Study Part 2) ................................................................36 
Table 3: Design for SC Dosing in Absolute BA Cohort (Study Part 3) ........................................37 
Table 4: Proposed Starting Dose Level in the Clinic .....................................................................38 
Table 5: Blood Sampling Timepoints for Rezafungin Pharmacokinetic Analysis Cohorts 
2, 3, 4, 5 and 6 SAD (Part 1) ...........................................................................................81 
Table 6: Blood Sampling Timepoints for Rezafungin Pharmacokinetic Analysis Cohorts 
7, 8, 9, and 10 MAD (Part 2) ..........................................................................................81 
Table 7: Blood Sampling Timepoints for Rezafungin Pharmacokinetic Analysis Cohort 
11 BA (Part 3) .................................................................................................................82 
Table 8: Total Volume of Blood Drawn From Each Subject - Part 1 (SAD) Cohorts 1-6 ............83 
Table 9: Total Volume of Blood Drawn From Each Subject - Part 2 (MAD) Cohorts 7-
10.....................................................................................................................................84 
Table 10: Total Volume of Blood Drawn From Each Subject - Part 3 (BA) Cohort 11 ...............85 
Table 11: Schedule of Study Procedures and Evaluations for Cohorts 1-6 in SAD (Part 
1) ...................................................................................................................................122 
Table 12: Schedule of Study Procedures and Evaluations for Cohorts 7-10 in MAD (Part 
2) ...................................................................................................................................124 
Table 13: Schedule of Study Procedures and Evaluations for Cohort 11 in BA (Part 3) ............126 
 
 

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LIST OF FIGURES 
Figure 1: Study Schematic – SAD Study (Part 1) Cohorts 1, 2, 3, 4, 5, and 6 ..............................23 
Figure 2: Study Schematic – MAD Study (Part 2) Cohorts 7, 8, 9, and 10 ...................................24 
Figure 3: Study Schematic – Absolute BA Cross-over (Part 3) Cohort 11 ...................................25 
 
 
 

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LIST OF ABBREVIATIONS 
λz 
Apparent first-order terminal elimination rate constant 
AE 
Adverse Event/Adverse Experience 
AESI 
Adverse Event of Special Interest 
ALT 
Alanine aminotransferase 
AmB 
Amphotericin B 
AR 
Accumulation ratio 
AST 
Aspartate aminotransferase 
AUC 
Area under the plasma concentration versus time curve 
AUCinf 
Area under the plasma concentration versus time curve from time 0 
to infinite time 
AUClast 
Area under the plasma concentration versus time curve from time 0 
to the time of the last quantifiable concentration 
AV 
Atrioventricular block 
BA 
Bioavailability 
BMI 
Body Mass Index 
bpm 
Beats per minute 
BUN 
Blood Urea Nitrogen 
CFR 
Code of Federal Regulations 
CK 
Creatine Kinase 
CL 
Total clearance 
CL/F 
Apparent clearance 
Cmax 
Maximum measured plasma concentration 

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CMS 
Clinical Materials Services 
CROMS 
Clinical Research Operations and Management Support 
CRU 
Clinical Research Unit 
DCF 
Data Collection Form(s) 
DMID 
Division of Microbiology and Infectious Diseases 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
FEV 
Forced expiratory volume 
FU 
Follow-Up 
FWA 
Federal Wide Assurance 
GCP 
Good Clinical Practice 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IFIs 
Invasive Fungal Infections 
IND 
Investigational New Drug Application 
INR 
International Normalized Ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 

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IV 
Intravenous 
LC-MS/MS 
Liquid Chromatography-Mass Spectrometry/Mass Spectrometry 
MAD 
Multiple Ascending Dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MTD 
Maximum tolerated dose 
N 
Number (typically refers to subjects) 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PCP 
Pneumocystis pneumonia 
PE 
Physical Examination 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PR (interval) 
Interval measured from the beginning of the P wave to the 
beginning of the QRS complex in the heart’s electrical cycle as 
measured by electrocardiogram 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
QA 
Quality Assurance 
QC 
Quality Control 
QRS (interval) 
The interval between the Q wave and the S wave in the heart’s 
electrical cycle as measured by electrocardiogram; principal 
deflection in the electrocardiogram 

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QT (interval) 
A measure of the time between the start of the Q wave and the end 
of the T wave in the heart’s electrical cycle as measured by 
electrocardiogram 
QTc (interval) 
A measure of time between the start of the Q wave and the end of 
the T wave in the heart’s electrical cycle measured by 
electrocardiogram corrected for heart rate 
QTcB 
QT interval corrected for heart rate using Bazett’s formula 
SAD 
Single Ascending Dose 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SDCC 
Statistical and Data Coordinating Center 
SMC 
Safety Monitoring Committee 
SOC 
System Organ Classes 
SOP 
Standard Operating Procedure 
t1/2 
Terminal phase half-life 
Tmax 
Time to reach maximum measured plasma concentration 
TMP/SMX 
Trimethoprim/Sulfamethoxazole 
US 
United States 
USP 
United States Pharmacopeia 
VCT 
Verified Clinical Trials 
Vss or Vz/F 
Volume of distribution (adjusted for bioavailability) 
WBC 
White Blood Cell 
 

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PROTOCOL SUMMARY 
 
Title: 
A Phase 1, Three-Part, Randomized, Double-Blind, Single and 
Multiple Subcutaneous Dose Escalation Study to Determine the 
Safety, Tolerability, and Pharmacokinetics of Rezafungin in 
Healthy Adult Subjects 
Design of the Study: 
 
This is a Phase 1, double-blind, placebo-controlled trial in 
three parts. A single ascending dose (SAD) study in six cohorts 
receiving a single subcutaneous (SC) dose of 1, 10, 30, 60, 100, 
or 200 mg of rezafungin; a multiple ascending dose (MAD) 
study in four cohorts receiving 30 mg x 3 doses, 60 x 3 doses, 
100 mg x 3 doses, or 200 mg x 3 doses of rezafungin SC with 
dosing frequency of once every 7 days; and a two-period cross-
over bioavailability (BA) study receiving 100 mg of rezafungin. 
The two-period cross-over BA study will be assessed unblinded 
in two sequences (10 subjects, 100 mg or maximum tolerated 
dose (MTD) of rezafungin in Part 1); 5 subjects will receive an 
SC injection of rezafungin in Period 1 followed by an 
intravenous (IV) infusion of rezafungin in Period 2, and 
5 subjects will receive an IV infusion of rezafungin in Period 1 
followed by an SC injection of rezafungin in Period 2. Each 
SAD (except cohort 1) and MAD cohort will contain 8 subjects 
(6 subjects will receive a SC injection of rezafungin, and 2 
subjects will receive placebo). Each SAD (except cohort 1) and 
MAD cohort will be conducted with sentinel dosing. SAD cohort 
1 will be comprised of 4 subjects (3:1 rezafungin to placebo) 
with no sentinel dosing.  Parts 2 and 3 of the study will only be 
conducted after FDA review for safety data and PK data from all 
subjects participating in Part 1; Part 3 may be run in parallel with 
the first cohort (Cohort 7) of Part 2.  

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Study Phase: 
1 
Study Population: 
Approximately 86 healthy male and female subjects, aged 18-45 
years (inclusive) 
Number of Sites: 
1 
Description of Study 
Product or Intervention: 
Subcutaneous formulation: Rezafungin for Injection, 
Subcutaneous Use, 100 mg/mL, is a sterile liquid product 
supplied in single-dose vials containing 1.0 mL of extractable 
volume. The active pharmaceutical ingredient is rezafungin 
acetate, a water-soluble amorphous acetate salt. The inactive 
ingredient is mannitol.  
Intravenous (IV) formulation: Rezafungin for Injection, 
200 mg/vial, is a sterile product supplied as a white to pale 
yellow lyophilized powder in single-dose glass vials for 
reconstitution with Sterile Water for Injection, United States 
Pharmacopeia (USP). The reconstituted product is diluted in 
sterile, 0.9% Sodium Chloride Injection, USP for IV infusion. 
The active pharmaceutical ingredient is rezafungin acetate, a 
water-soluble amorphous acetate salt. The inactive ingredients 
include excipients of mannitol, polysorbate 80, and histidine. 
Placebo is 5% Dextrose Injection, USP, a sterile, nonpyrogenic 
solution of dextrose in water for injection. The solution has the 
osmolarity of 252 mOsmol/L, which is slightly hypotonic. 
For 1 mg subcutaneous doses, the Subcutaneous formulation will 
be diluted 1:10 in 5% Dextrose Injection, USP prior to 
administration. The diluent solution, 5% Dextrose Injection, USP 
is a sterile and nonpyrogenic parenteral solution. 
Reconstitution solution is Sterile Water for Injection, WFI, USP, 
which is a clear, colorless solution. 

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Study Objectives: 
 
Primary: 
• 
To determine the safety and tolerability of single-ascending 
SC doses (SAD) of rezafungin. 
• 
To determine the safety and tolerability of 
multiple-ascending SC doses (MAD) of rezafungin. 
• 
To determine the pharmacokinetic (PK) profile in plasma of 
rezafungin in healthy adult subjects; 
Secondary: 
To evaluate the bioavailability (BA) of rezafungin when 
administered by SC injection relative to IV infusion in 
healthy adult subjects. 

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Outcome Measures 
Primary: 
SAD 
Safety will be assessed by adverse events and serious adverse 
events (SAEs) from start of dosing to Day 30, clinical laboratory 
tests at baseline and from Day 2 to Day 30, ECGs at Screening 
and post-dose on Days 1, 7, and 30, physical exams at baseline 
and post-dose on Day 1 to Day 30, vital signs at baseline and 
from Day 1 to Day 30, and injection site evaluation from dosing 
to Day 30.  
Tolerability will be assessed by occurrence of solicited local 
reactogenicity (injection site evaluation) from dosing to Day 30. 
MAD 
Safety will be evaluated for multiple-ascending SC doses (MAD) 
of rezafungin. Safety will be assessed by adverse events and 
SAEs from start of dosing to Day 45, clinical laboratory tests at 
baseline and from Day 2 to Day 45, ECGs at Screening and post-
dose on Days 1, 8, 15, 21, 30, and 45, physical exams at baseline 
to Day 45, and vital signs at baseline to Day 45.  
Tolerability will be assessed by occurrence of solicited local 
reactogenicity (injection site evaluation) from first dose to 
Day 45.   
PK 
Pharmacokinetic (PK) profiles of rezafungin will be assessed by 
measurement of drug levels in plasma after SC administration in 
each cohort. Plasma for PK analysis will be collected at planned 
timepoints up to Day 30 in the SAD cohorts, and Day 45 in the 

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MAD cohorts. PK parameters will be estimated from the 
rezafungin plasma concentration-time data. 
 
Secondary: 
The BA of rezafungin when administered by SC injection 
relative to IV infusion will be assessed by measurement of drug 
levels in plasma after administration by SC injection or by IV 
infusion in each cross over period. Plasma samples will be 
collected at planned timepoints up to Day 52 for Part 3/BA The 
absolute BA will be calculated as the ratio of AUC for the SC 
injection and AUC for the IV infusion of administration. 
 
Duration of Individual 
Subject Participation: 
 
Part 1 SAD: Individual subjects will participate for 
approximately 58 days, including up to 28 days for screening 
and 30 days for dosing and follow-up (FU). 
Part 2 MAD: Individual subjects will participate for 
approximately 73 days, including up to 28 days for screening 
and 45 days for dosing and FU. 
Part 3 BA: Individual subjects will participate for approximately 
80 days, including up to 28 days for screening and 52 days for 
dosing and FU. 
Estimated Time to Last 
Subject/Last Study Day: 
Approximately 30 months 
 
 

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Figure 1 
 
Day 1
Vital signs (Vitals), Concomitant medications (Conmeds), Randomization,Physical exam (PE), ECG, Reactogenicity eval,
 Rezafungin administration (per cohort dose regimen),PK (pharmacokinetic) blood sampling (All Cohorts, except cohort 1)
pre-dose; 0.5 1, 2, 4, 6, 8 and 12 hours post-dose, Assess adverse events (AEs)
Cumulative Safety Data Review**
**for sentinels, through Day 30 prior to admit/dosing remainder of cohort;
for entire cohort, prior to dose escalation (next cohort)
Day 30 outpatient (+/- 1 day)
Weight/BMI, PE, Vitals, ECG, Conmeds, Clin labs, Reactogenicity eval,
PK blood sample collection (All Cohorts, except cohort 1), Assess AEs
Day 21 telephone follow-up (+/- 1 day)
Query subjects (All Cohorts) on any changes to injection site since Day 14
Day 14 outpatient (+/- 1 day)
Vitals, Conmeds, Reactogenicity eval
PK blood sample collection (All Cohorts, except cohort 1), Assess AEs
Counsel/reminders (post-discharge instructions)
Day 7
PE, Vitals, ECG, Conmeds, Clin labs
144 hour PK blood sample collection (All Cohorts, except cohort 1), Reactogenicity eval, Assess AEs
Counsel (post-discharge instructions), Discharge from CRU
Days 3-6 (confined)
Vitals on Day 4, Conmeds on Days 3 and 5,
48 (Day 3) and 96 (Day 5) hr PK blood sample collection (All Cohorts, except cohort 1), Reactogenicity eval, Assess AEs
PE on Day 4
Day 2 (confined)
Vitals, PE, Clin labs, Reactogenicity eval,
 24 hr PK blood sample collection (All Cohorts, except cohort 1), Assess AEs
Day -1
Enrollment and baseline assessments
Admitted and confined to Clinical Research Unit (CRU)*
*admit and dosing of 2 sentinel subjects.  Remainder of cohort is admitted and dosed following same schedule after cumulative safety data assessment (through Day 30,no halting criteria met).
Day -28 to Day -2
Screening
Study Schematic - SAD Study (Part 1) Cohorts 1, 2, 3, 4, 5, and 6

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Figure 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Days 1, 8 and 15
Vitals, PE, Conmeds, ECG, Rezafungin administration (per cohort dose regimen), Reactogenicity evaluation
PK blood sampling pre-dose; 0.5 1, 2, 4, 6, 8 and 12 hours post-dose (Days 1 and 15 only)
 or pre-dose, 1, and 4 hours post-dose (Day 8 only), Assess AEs
Cumulative Safety Data Review**
**for sentinels, through Day 30 prior to admit/dosing remainder of cohort;
for entire cohort, through Day 30 prior to dose escalation (next cohort)
Days 30 & 45 outpatient (+/- 1 day)
Vitals, PE, ECG, Conmeds, Clin labs (Day 45 only), Reactogenicity evaluation (Day 30 only)
PK blood sample collection, Assess AEs
 Days 7, 14 and 21
Vitals, PE, ECG on Day 21, Conmeds, Clin labs, Reactogenicity evaluation
144 hour PK blood sample collection (All Days), Assess AEs
Discharge from CRU on Day 21
Days 3-6, 10-13 and 17-20
Vitals (Days 4, 11, and 18), Conmeds (Days 3, 5, 10, 12, 17, and 19,) Reactogenicity evaluation
48 hr (Days 3 & 17) and 96 hr (Days 5, 12, & 19) PK blood sample collection
PE on Days 4, 11 and 18 (all Cohorts), Assess AEs
 Days 2, 9 and 16
Vitals, PE, Clin labs, Reactogenicity evaluation
 24 hr PK blood sample collection (Days 2 and 16 only), Assess AEs
Day -1 (All Cohorts)
Enrollment and baseline assessments
Admitted and confined to CRU*
*admit and dosing of 2 sentinel subjects.  Remainder of cohort is admitted and dosed following same schedule after cumulative safety data assessment (through Day 45,no halting criteria met).
Day -28 to Day -2 (All cohorts)
Screening
Study Schematic - MAD Study (Part 2) Cohorts 7, 8, 9, and10

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Figure 3 
Figure 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*For IV portion, PK blood draws are timed from start of infusion. 
Days 1 and 22
Conmeds, Vitals, Physical exam, ECG, Rezafungin administration (per cohort dose regimen)
Reactogenicity evaluation
PK blood sampling pre-dose; 0.5 1, 2, 4, 6, 8 and 12 hours post-dose*, Assess AEs
Day 52 (+/- 1 day)
Vitals, ECG, Clin labs, Conmeds, Physical exam
PK blood sample collection, Assess AEs
Days 14 & 35 outpatient (+/- 1 day)
PE, Vitals, Conmeds
PK blood sample collection
Reactogenicity eval, Assess AEs
Days 7 and 28
Physical exam, Vitals, Clin labs, Conmeds, Reactogenicity evaluation
144 hour PK blood sample collection (Days 7 and 28), Assess AEs
Discharge from CRU on Day 7 and Day 28
Days 3-6  and 24-27
Vitals (Days 4 and 25), Conmeds (Days 3 and 5), PE (Days 24 and 26), Reactogenicity evaluation
PK blood sampling 48 hr (Days 3 & 24,) and 96 hr (Days 5 & 26), Assess AEs
Days 2 and 23
Vitals, PE, Clin labs, Reactogenicity evaluation
 24 hr PK blood sample collection, Assess AEs
Days -1 and 21
Enrollment and baseline assessments
Admitted and confined to CRU
Day -28 to Day -2 (All cohorts)
Screening
Study Schematic - Absolute BA Cross-over (Part 3) Cohort 11

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KEY ROLES 
Lead Principal 
Investigator: 
 
 
 
DMID Clinical Project 
Manager: 
 
Dennis Ruff, MD 
ICON Early Phase Services, LLC 
8307 Gault Lane 
San Antonio, TX 78209 
Phone: 210-283-4572 
Email: Dennis.Ruff@iconplc.com  
 
Maureen Mehigan, RN 
5601 Fishers Lane, Room 7E19 
Rockville, MD 20852 
Phone: 240-627-3317 
Email: mmehigan@niaid.nih.gov  
Statistical and Data 
Coordinating Center: 
 
 
The Emmes Company 
401 North Washington Street, Suite 700 
Rockville, MD 20850 
Phone: 301-251-1161 
Email: phase1@emmes.com  
 
Contact information for additional key personnel is in the Manual of Procedures (MOP) for 
this trial. 

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BACKGROUND AND SCIENTIFIC RATIONALE 
 
Background  
Immunocompromised patients, particularly those with hematological malignancies undergoing 
chemotherapy, and those undergoing hematopoietic stem cell transplant or solid organ transplant, 
are at risk for invasive fungal infections (IFIs) caused by Pneumocystis, Candida, Aspergillus 
and other fungal pathogens. These patients have impaired immune defenses against fungi owing 
to their underlying diseases and treatments. 
Pneumocystis jirovecii causes lethal Pneumocystis pneumonia (PCP) in immunodeficient 
humans. Initially predominant among human immunodeficiency virus (HIV)+ individuals, PCP 
is now a public health concern for a broader population of immunosuppressed or otherwise 
immunodeficient patients, such as hematopoietic stem cell and solid organ transplant recipients; 
patients receiving cancer chemotherapy or biologic therapy, high-dose corticosteroids, 
immunotherapies, or anti-lymphocyte antibodies; patients with congenital immune deficiencies; 
and patients with autoimmune or chronic inflammatory disease1,2. 
PCP continues to be a problem worldwide even in the context of combined antiretroviral therapy 
in HIV+ patients3. The mortality rate of PCP remains unchanged at about 15% in HIV+ 
populations2. The rate in the developing world and certain urban areas of the US underserved by 
the healthcare establishment approaches 80%4. Recent evidence correlating P. jirovecii as a co-
morbidity agent in respiratory conditions like chronic obstructive pulmonary disease5, in 
association with anti-Tumor Necrosis Factor therapies6, or with lung cancers7 indicates a 
broadening of the PCP-susceptible population. Patients in these non-HIV+ categories fare worse 
than HIV+ patients. In a recent report, the mortality rate of non-HIV+ patients were 48% vs 17% 
in HIV+ patients8. A recent European estimate reported PCP incidence to be 1.5/100,000, with a 
fatality rate of 9.5%, lower than in past studies1. Though in support of previous evidence, lower 
mortality was observed in the HIV+ population (10-20%) compared with the non-HIV+ 
population (30-60%). Finally, productivity losses due to PCP have been calculated to be 
>$12 billion US dollars in 1999-20144. 
The current standard for PCP treatment is trimethoprim/sulfamethoxazole (TMP/SMX), which is 
also highly effective and widely recommended for PCP prophylaxis. The efficacy of TMP/SMX, 
along with limited alternative options, has likely contributed to acceptance of its safety and 
tolerability issues. However, these issues are not minor and have a significant clinical impact on 
the use of TMP/SMX for prophylaxis with adverse effects reported in more than half of cases, 

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and treatment-limiting toxicities occurring in up to one-third of cases. Potential side effects 
include myelosuppression, renal failure, liver dysfunction, and hyperkalemia; in some cases, side 
effects require permanent discontinuation of TMP/SMX. Additional agents in use include 
atovaquone, dapsone, and inhaled pentamidine, which are considered second- or third- line to 
TMP/SMX based on reduced relative efficacy and cause treatment-limiting adverse effects5. In 
addition, resistance to TMP/SMX has been reported and may impact the efficacy of this first-line 
therapy and prophylaxis9. Rezafungin was highly effective in preventing Pneumocystis infections 
through inhibition asci (cyst) forms in a 6-week immunosuppressed mouse model for PCP 
prophylaxis10. In this model, prophylaxis was equivalent to TMP/SMX at lower and/or less 
frequent doses than required for Candida. 
These safety/tolerability and resistance concerns may be a limiting factor to effective PCP 
prophylaxis. In addition to challenges to compliance, there is a lack of consensus on the 
appropriate duration of prophylaxis and longer durations, though warranted, may be difficult to 
implement with current agents. For example, in the context of transplantation, where practices 
vary by institution, transplant type, and individual immunosuppression risk, some patients may 
be recommended for lifetime prophylaxis2,5. 
Furthermore, evidence regarding the incidence and risks of late-onset PCP (> 1-year 
post-transplant) suggest a need for efficacious agents that can be tolerated in long-term 
prophylaxis6,7,11. 
The majority of IFIs in transplant and hematology are caused by Candida and Aspergillus 
species. Fluconazole, posaconazole, and micafungin are approved by the US FDA for the 
prevention of IFIs among HCT patients. Posaconazole is additionally approved for antifungal 
prophylaxis in those with hematological malignancies at least 13 years of age with prolonged 
neutropenia from chemotherapy. While the azoles are far more utilized for IFI prophylaxis and 
are better studies for this indication, these drugs are metabolized by cytochrome 
P450 isoenzymes, leading to the potential for serious drug interactions with concomitant 
administration of certain chemotherapeutic agents (including cyclophosphamide, vincristine, and 
thymidine kinase (TK) inhibitors or other immunosuppressants (including cyclosporine, 
tacrolimus and sirolimus). QT prolongation may be a limiting factor for patients on multiple 
medications. Administration of oral posaconazole in particular can be challenging in the 
presence of mucositis that prevents administration of food or nutritional supplements required for 
optimal posaconazole absorption. Discontinuations due to mucositis and colitis limit the utility of 
posaconazole prophylaxis. In a single-center, prospective study of patients with AML or after 
HCT taking posaconazole tablets, 80.5% of samples showed a concentration of at least 

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700 ng/mL at steady state, but 16% of patients stopped posaconazole prematurely owing to 
colitis, transaminase elevations and mucositis12. 
Voriconazole demonstrates wider inter-patient variability in serum concentrations that is due in 
part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultra-rapid metabolizers have 
decreased voriconazole through concentrations, whereas poor metabolizers have increased 
through concentrations and are at increased risk of adverse experiences. Up to one-third of HCT 
recipients develop biochemical hepatotoxicity while on voriconazole that often leads to 
discontinuation of voriconazole by the clinicians regardless of causality. A long-term safety 
concern is the association of prolonged exposure to voriconazole with the development of 
non-melanoma skin cancers in HCT recipients. Use of amphotericin B (AmB) and its lipid 
derivatives for prophylaxis is problematic due to infusion and renal toxicities, as well as 
insufficient evidence regarding their efficacy in prophylaxis12. 
Echinocandins are the only class of antifungal agents at present that exerts activity on the fungal 
cell wall and not the cell membrane, resulting in no cross-reactivity with mammalian cell 
functions and thus reducing toxicity. Unlikely the azoles, echinocandins have significant 
fungicidal activity against Candida species and are currently recommended as first-line therapy 
for the treatment of candidemia. The echinocandins are generally very well tolerated with few 
adverse events (AEs) or drug interactions requiring discontinuation of the drug. Compared with 
the triazoles, the echinocandins had less than half the likelihood of discontinuation of therapy 
due to AEs. All the drugs in this class, caspofungin, micafungin, and anidulafungin, have a 
similar tolerability profile. The most common AE is injection site pain or phlebitis, occurring in 
up to 25% of patients receiving caspofungin, but in < 1% with anidulafungin13. 
 
Scientific Rationale 
2.2.1 
Purpose of Study 
Rezafungin is an investigational echinocandin with many of the favorable efficacy and safety 
profiles of its echinocandin class. As with other echinocandins, rezafungin has excellent activity 
against Candida, Aspergillus, dermatophytes, and even some less common fungal infections such 
as Talaromyces (formerly Penicilliosis) marneffei, which has a substantial mortality in HIV+ 
people in Southeast Asia. Additionally, rezafungin possesses unique attributes. Its efficacy 
against PCP, pharmacokinetic (PK) behavior, and stability/solubility are of particular importance 
to the current context. In a study, rezafungin was highly effective in preventing Pneumocystis 
infections through inhibition asci (cyst) forms in a 6-week immunosuppressed mouse model for 

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PCP prophylaxis10. The prolonged half-life of rezafungin allows for once-weekly (or longer) 
dosing14, and its stability/solubility enables subcutaneous (SC) formulation15 that had moderate 
to high BA in rats and monkeys (up to ~80%). The smaller dose requirement also supports the 
possibility of SC dosing volume, as it would require smaller volumes to be administered. Safety 
advantages of rezafungin compared with TMP/SMX include lack of myelosuppression, low/no 
risk of drug-drug interactions, and no risk of sulfa allergy. Additionally, rezafungin appears to 
have safety advantages compared to second-line PCP agents, azoles and AmB, which are often 
poorly tolerated. Currently marketed echinocandins are dosed IV once-daily and are therefore 
not practical for prolonged or outpatient prophylaxis. Based on these preliminary factors, further 
trial is warranted to explore the potential of rezafungin as antifungal prophylaxis as a once-
weekly IV or SC formulation. 
2.2.2 
Study Population 
Up to 86 subjects aged 18-45 (inclusive) who are in good health and meet all eligibility criteria 
will be enrolled in the study. The demographics in the local population should ensure that male, 
female, and minorities (African American, Native American, Asian, and Hispanics) will be 
represented in the enrolled population. Subjects will be recruited using IRB-approved 
advertising/web site listing of the essential inclusion and exclusion criteria. Subjects will self-
schedule online for a screening appointment based on their desire to participate and their 
evaluation of their suitability based on inclusion/exclusion criteria. Children, pregnant or breast-
feeding women, prisoners, and other vulnerable populations will not be enrolled. See Section 9.4. 
Neither women nor minorities will be excluded from participation in this study. Women of child- 
bearing potential may be included as per the inclusion criteria (Section 5.1). Subjects will be 
recruited without regard to gender or race. It is expected that race will reflect that within the 
community. 
 
Potential Risks and Benefits 
2.3.1 
Potential Risks 
This is the first study in humans using rezafungin via the SC route. The drug has been 
administered IV in multiple clinical trials. Risks of IV rezafungin exposure include possible 
histamine release reactions, including chest discomfort and flushing, as well as nausea and 
myalgia. The majority of events were mild, and all were transient. 

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Additionally, 71 participants with candidemia or invasive candidiasis were treated with rezafungin.  
The most commonly reported side effects for rezafungin were:  
• Decreases in potassium in the blood, which may cause muscle cramps, constipation, 
weakness, and abnormal heart rhythms, especially in people with heart disease.  This can 
cause you to feel lightheaded or faint.  A very low potassium level can even cause your 
heart to stop. 
• Diarrhea 
• Nausea 
• Anemia  
One serious side effect that was possibly related to the study drug was reported in this study, the 
side effect was a delay in the timing of the way the heart normally beats and resolved without 
treatment.   
In the group of participants with candidemia or invasive candidiasis, one participant in the 
rezafungin group had a side effect of sunburn (dosing group 400 mg on Day 1 and Day 8, with 
optional dosing on Days 15 and 21) following substantial sun exposure (photosensitivity).  There 
were two side effects (reported in 2.8% of participants) that may represent tremor or nerve injury 
causing numbness or weakness: intensive care unit acquired weakness (reported as moderate 
intensity), and tremor (reported as mild intensity).  These events of tremor/neuropathy that were 
potentially related to rezafungin were followed until resolution and both resolved 
Echinocandins are typically well tolerated (Eraxis [anidulafungin] Prescribing information, 2013; 
Mycamine [micafungin sodium] Prescribing Information, 2013; Cancidas [caspofungin acetate] 
Prescribing Information, 2014). Potential drug class effects include risk of abnormal liver 
function tests, hepatitis, and hepatic failure. General and administration site events (infusion 
related reactions, peripheral edema, rigors, infusion site inflammation, and pyrexia) have been 
reported for echinocandins (Eraxis [anidulafungin] Prescribing Information, 2013; Mycamine 
[micafungin sodium] Prescribing Information, 2013; Cancidas [caspofungin acetate] Prescribing 
Information, 2014). Possible histamine-mediated symptoms have been reported in patients who 
received rapid infusions of echinocandins, including rash, urticarial, flushing, pruritus, dyspnea, 
hypotension, facial swelling, and vasodilation. Anaphylactic-like reactions have been reported 
with micafungin (Mycamine [micafungin sodium] Prescribing Information, 2013). 
Due to preliminary results from a nonclinical phototoxicity study in rats (positive response to in 
vitro UV absorption), subjects should be advised to avoid sun exposure and any other type of 

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ultraviolet radiation (including tanning beds) without adequate protection. Investigators should 
report any AE potentially related to phototoxicity to the Sponsor. 
Based on a fertility study in male rats, there is the potential risk for decreased sperm motility, 
increased incidences of abnormal sperm morphology, and testicular seminiferous tubular 
epithelial degeneration. These findings were noted at 2.5-fold the exposure expected at the 
highest dose in this study. The risk to humans is unknown, thus the male contraception 
requirements in inclusion criteria (see numbers 4 and 5 in Section 5.1.1) prohibit unprotected 
sexual intercourse and sperm donation within the study period and for 90 days thereafter (a total 
of 120 days from the last dose of study drug). This risk will be included in the ICF. 
In a 3-month study in monkeys, there were observations of tremors, intention tremors, and 
histology consistent with axonal degeneration (potentially consistent with clinical presentation of 
neuropathy) first appearing at Week 6 of dosing. Dose-related microscopic findings of Schwann 
cell phospholipidosis were observed in the ganglia (≥3 mg/kg) and peripheral nerves (≥30 
mg/kg) and dose-related Schwann cell hyperplasia was observed in the ganglia at ≥30 mg/kg; 
hyperplasia partially reversed but phospholipidosis was still present at the end of a 4-week 
recovery period. Tremoring reversed after 1 month of recovery but Schwann cell 
phospholipidosis was still present at the end of a 3-month recovery period. These observations 
occurred at 11.4-fold the maximum intended dose in this study. Given the high nonclinical 
exposure, relative to the current dose levels and expected exposure, the risk to study subjects is 
assessed as low. At the highest dose (about 20 times greater than the proposed human dose), 
severe neurobehavioral effects were observed. These effects were not seen in the levels at 11.4 
times the maximum exposure proposed for humans. 
Potential risks include temporary physical discomfort and emotional stress due to the nature of 
the evaluations and specimen collection procedures in this trial. Subcutaneous drug exposure 
may also be associated with pain and irritation at the injection site, risk of nodules, thickening 
and open sores at the injection sites; as seen in the cynomolgus monkey study. There was partial 
recovery of the sores after 4 weeks at the 120 mg/kg dosing level. The risks associated with 
insertion of the indwelling catheter and frequent blood draws are fainting, pain, bruising, and 
scarring. The catheter may pose a risk for clotting and infection. These risks are discussed with 
the subject during the consent process. 

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2.3.2 
Potential Benefits 
There are no known benefits to subjects participating in this trial. The knowledge gained in this 
trial may help society, especially those requiring treatment or prophylaxis of invasive fungal 
infections. 

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STUDY DESIGN, OBJECTIVES AND ENDPOINTS OR 
OUTCOME MEASURES 
 
Study Design Description 
This is a Phase 1, single-center, three-part, prospective, randomized, double-blind trial of 
single- and multiple-ascending doses of rezafungin administered by SC injection to healthy adult 
subjects and a two-period crossover bioavailability study with two dosing sequences of 
rezafungin administered by SC → IV or IV → SC doses to healthy adult subjects. 
 
 
3.1.1 
Dosing Scheme and Duration of Study 
3.1.1.1 
Part 1 (SAD) 
In Part 1 of this trial, 44 subjects will be split into six cohorts – one cohort of 4 subjects (3 
rezafungin, 1 placebo) and five cohorts of 8 subjects each (6 rezafungin, 2 placebo) – will be 
randomized to receive single SC doses of rezafungin or placebo with dose escalation separated 
by a minimum of 4 weeks. Single-dose levels of rezafungin to be assessed will follow an 
ascending single-dose regimen in all except Cohort 1. The 1, 10, 30, 60, and 100 mg doses will 
be administered as 0.1 – 1.0 mL SC injections (abdomen) and the 200 mg dose as 2 x 1 mL 
injections (in same abdominal quadrant). A schematic of the SAD study design is shown in 
(Table 1). Administration details are included in the protocol-specific Manual of Procedures 
(MOP) to this study. 
 
 

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Table 1: Design for SC Dosing in SAD (Study Part 1) 
Cohort 
Dose 
(mg) 
Dose 
Volume 
(mL) 
Number  
of Doses 
Number of Subjects* 
Rezafungin SC 
Injection 
Placebo 
1 
1 
0.1** 
1 
3 
1 
2 
10 
0.1 
1 
6 
2 
3 
30 
0.3 
1 
6 
2 
4 
60 
0.6 
1 
6 
2 
5 
100 
1 
1 
6 
2 
6 
200 
1 (in each of 2 
injections) *** 
1 
6 
2 
Total Number of Subjects 
33 
11 
44 
*Within each cohort two sentinel subjects will be admitted initially, and the randomization scheme will be designed 
to ensure that one subject will receive rezafungin and the other will receive placebo. All sentinel subject safety data 
through Day 30 will be reviewed by the PI prior to dosing the remainder of cohort. Safety data for each cohort 
through Day 30 will be confirmed by review of objective pre-defined criteria before continuing to the next cohort. 
**In order to administer this dose, the drug product solution from the SC drug product vial (Rezafungin Injection, 
for subcutaneous use, 100 mg/mL) will be diluted 1:10 in 5% Dextrose Injection, USP. Then 0.1 mL of the diluted 
solution will be administered. Details are included in the MOP for this study. 
***The 200 mg (2 x 1 mL) SC dose will be injected as 1 mL each in the same abdominal quadrant, separated by 
approximately 5 cm. Details are included in the MOP for this study. 
 
 
3.1.1.2 
Part 2 (MAD) 
The first cohort for Part 2 of this trial (Cohort 7) can begin after the FDA has reviewed and 
assessed the SAD safety and PK data and providing no halting criteria have been met. In Part 2, 
subjects in four cohorts of 8 subjects each (6 rezafungin, 2 placebo) will be randomized to 
receive SC doses of rezafungin or placebo on Days 1, 8, and 15 of the MAD portion of the study. 
Dose levels of rezafungin to be assessed will follow an ascending multiple-dose regimen (30 mg 
x 3 doses, 60 mg x 3 doses, 100 mg x 3 doses, and 200 mg x 3 doses). A schematic of the MAD 
study design is shown in (Table 2). 

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Table 2: Design for SC Dosing in MAD (Study Part 2) 
Cohort 
Dose 
(mg) 
Dose 
Volume 
(mL) 
Number  
of Doses 
Number of Subjects* 
Rezafungin SC 
Injection 
Placebo 
7 
30 
0.3 
3 
6 
2 
8 
60 
0.6 
3 
6 
2 
9 
100 
1 
3 
6 
2 
10 
200 
1 (in each of 2 
injections)** 
3 
6 
2 
Total Number of Subjects 
24 
8 
32 
*Within each cohort two sentinel subjects will be admitted initially, and the randomization scheme will be designed 
to ensure that one subject will receive rezafungin and the other will receive placebo. All sentinel subject safety data 
through Day 30 will be reviewed by the PI prior to dosing the remainder of cohort. Safety data for each cohort 
through Day 30 will be confirmed by review of objective pre-defined criteria before continuing to the next cohort. 
**The 200 mg (2 x 1 mL) SC dose will be injected as 1 mL each in the same abdominal quadrant, separated by 
approximately 5 cm. Each dose will be administered in a different quadrant (total 3 quadrants). Details are included 
in the MOP for this study. 
 
 
3.1.1.3 
Part 3 (BA) 
Part 3 of this study may be run in parallel with Cohort 7 of the Part 2 (MAD) portion of this 
study, upon completion of safety data review for all Cohorts 1-6 of Part 1 (SAD). In the 
unblinded Part 3 cross-over portion of this trial, 10 subjects will be randomized to one of two 
sequences of 5 subjects each to receive a SC→IV or IV→SC sequence of study drug 
administration. In sequence 1 (SC→IV), rezafungin (100 mg or MTD in Part 1) administered by 
SC injection on Day 1 followed by rezafungin (100 mg or MTD in Part 1) administered by IV 
infusion over 60 minutes on Day 22; or in Sequence 2 (IV→SC), rezafungin (100 mg or the 
maximum tolerated dose in Part 1) administered by IV infusion over 60 minutes on Day 1 
followed by rezafungin (100 mg or the maximum tolerated dose in Part 1) administered by SC 
injection on Day 22.  Maximum tolerated dose (MTD) is defined as the highest dose level with 
no withdrawals by subject or investigator due to AEs related to study product for Part 1 (SAD) 
Cohorts 1-6.  A schematic of the BA study design is shown in Table 3. 

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Table 3: Design for SC Dosing in Absolute BA Cohort (Study Part 3) 
Sequence 
 
Day 1 (Period 1) 
Dose/Volume/Route 
Day 22 (Period 2) 
Dose/Volume/Route 
Number of 
Subjects* 
1 (SC → IV) 
 
100 mg x 1 mL 
SC injection 
100 mg 250 mL 
IV infusion 
5 
2 (IV → SC) 
 
100 mg 250 mL 
IV infusion 
100 mg 1 mL 
SC injection 
5 
 
Total Number of Subjects 
10 
*Part 3 may be run following the cohort dosed at the same dose level (100 mg or MTD) in Part 1 (SAD).  
 
The BA of the SC dose compared to the IV dose will be determined as the ratio of the rezafungin 
area under the plasma concentration versus time curve (AUC) values from each administration.  
3.1.2 
Rationale for Starting Dose 
In the single-dose cynomolgus monkey trial (NC101), SC rezafungin 30 mg/kg (1 mL per 
injection of 100 mg/mL solution) was well tolerated with minor non-adverse skin findings 
ranging from very slight to slight erythema, and very slight to moderate edema. A multiple dose 
cynomolgus monkey trial (NC107), at doses of 30, 60, and 120 mg/kg (given as 1 mL per 
injection of 100 mg/mL solution in 1, 2, or 4 injections/animal every 3 days, respectively) was 
not tolerated, with all dose groups having adverse toxicity at the injection sites. Inflammation 
ranged from minimal to severe, with moderate severity and higher grades resulting in clinical 
and macroscopic observations of nodules, thickening, and in the most severe cases, open sores at 
the injection sites. At the low adverse effect level of 30 mg/kg, adverse observable skin lesions 
were first observed from Day 11 to 14 and were generally associated with the 4th (Day 9) 
injection (4-6 animals). One lesion was observed on Day 12 at the site of the 2nd (Day 3) 
injection, and one animal had no lesions. These findings reversed following 4 weeks of recovery 
at the low- and mid-dose levels and in all but one animal at the high-dose level.   A suitable 
starting dose was selected per Estimating the Maximum Safe Starting Dose in Initial Clinical 
Trials for Therapeutics in Adult Healthy Volunteers16. This guidance recommends that if local 
toxicities are dose limiting the “therapeutics should be normalized to concentration (e.g., mg/area 
of application) or amount of drug (mg) at the application sites”. 
In the NHP study, cynomolgus monkeys weighing approximately 3 kg were dosed multiple times 
with 30 mg/kg, or 90 mg of rezafungin.  

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As shown in Table 4, the SAD escalation will begin with a lower starting dose and propose an 
initial single-dose cohort of 1 mg/injection, which would represent roughly an hundred-fold 
safety margin (by total absolute dose)  from the 30 mg/kg dose cohort used in both the single 
dose subcutaneous toxicology study (NC-101) and the lowest dose tested from the repeat dose 
toxicology study (NC-107).  
Table 4: Proposed Starting Dose Level in the Clinic 
mg 
mg/kg dose 
Volume 
mL/kg 
Cynomolgus Monkey (~3 kg) 
100 
30 
1 mL 
0.33 
200 
60 
2 mL* 
0.67 
400 
120 
4 mL* 
1 
Human (~70 kg) 
1 
0.0143 
0.10 mL 
0.0014 
*Given as multiple 1-mL injections 
3.1.3 
Dose Escalations 
In Part 1/SAD, the initial cohort of 4 subjects will be administered 1 mg of rezafungin 
(3 subjects) or placebo (1 subject) as a single SC injection. 
Dose escalation to each successive cohort during Part 1 will occur if none of the predefined dose 
escalation halting criteria are met through Day 30 (final visit).  The FDA will review all safety 
and PK data from the SAD (Part 1) and determine if the study may proceed to the MAD (Part 2) 
and BA (Part 3) portions. Rezafungin doses for the MAD and BA portions will be determined 
after FDA review of the SAD data. Dose escalation during Part 2 will occur if none of the 
predefined dose escalation halting criteria are met through Day 30 after the first dose. This will 
be communicated through the following process: 
1. An email from the site to the SDCC attesting that all data entry has been completed after 
the last subject has had their Day 30 visit, then data cleaning, as applicable, prior to the 
SDCC being able to generate the report. 
2. A halting criteria report will be provided by the SDCC to DMID.  
3. If based on the entered data in EDC, none of the escalation criterion is met, then the 
SDCC will open the database for the following cohort after confirmation from DMID 
that the study may proceed to the next cohort.    
4. 
If any of the criterion is met, the SDCC will provide the dose escalation report and an 
ad-hoc SMC meeting will be convened to seek recommendation from the SMC.  

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Part 2 (MAD) and Part 3 (BA) may not begin until after FDA has reviewed all safety and 
PK data from Part 1 (SAD) and given agreement that it is safe to proceed. The doses for 
Parts 2 and 3 may be updated after FDA review of the SAD data. There will be a scheduled 
SMC data review meeting prior to start of Part 2 (MAD) Cohort 7.  
In order to efficiently identify the optimal therapeutic doses for use in future clinical trials, a 
flexible scheme of dose escalation, (based on ongoing study data) will be used that allows 
intermediate doses higher or lower than the planned doses (30, 60, 100, and 200 mg), upon 
protocol amendment and with IRB approval. However, no cohort will be dosed higher than the 
200 mg free base equivalent. 
Cohorts 2-6 in the SAD and all MAD cohorts will be conducted with sentinel dosing of 
rezafungin (i.e., dosing in 2 subjects followed by remaining six subjects). The randomization 
scheme will be designed to ensure that 1 subject will receive rezafungin and the other will 
receive placebo in sentinel dosing. The dosing of the remaining six subjects in the same cohort 
will not be initiated until a minimum of 4 weeks after the second sentinel dosing, and no serious 
adverse events (SAEs)/adverse events (AEs) have occurred that meet the predefined objective 
halting criteria for sentinels. The blinded safety and clinical laboratory data from all subjects in 
the cohort will be reviewed and confirm that none of the dose-escalation halting rules have been 
met before moving to the next higher dose cohort. If any of the predefined halting criteria is met, 
the study enrollment and dosing will be stopped until the SMC provides recommendations 
regarding continuation of the study (See Section 8.2.3). 
 
Study Objectives 
3.2.1 
Primary  
• To determine the safety and tolerability of single-ascending SC doses (SAD) of rezafungin. 
• To determine the safety and tolerability of multiple-ascending SC doses (MAD) of 
rezafungin. 
• To determine the pharmacokinetic (PK) profile in plasma of rezafungin in healthy adult 
subjects; 

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3.2.2 
Secondary 
To evaluate the bioavailability (BA) of rezafungin when administered by SC injection relative to 
IV infusion in healthy adult subjects. 
 
Study Endpoints or Outcome Measures 
3.3.1 
Primary  
• Safety and tolerability will be evaluated for single-ascending SC doses (SAD) of rezafungin.  
Safety will be assessed by adverse events and SAEs from start of dosing to Day 30, clinical 
laboratory tests at baseline and from Day 2 to Day 30, ECGs at Screening and post-dose on 
Days 1, 7, and 30, physical exams at baseline and post-dose on Day 1 to Day 30, vital signs 
at baseline and from Day 1 to Day 30, and injection site evaluation from dosing to Day 30. 
Tolerability will be assessed by occurrence of solicited local reactogenicity (injection site 
evaluation) from dosing to Day 30. 
• Safety will be evaluated for multiple-ascending SC doses (MAD) of rezafungin. Safety will 
be assessed by adverse events and SAEs from start of dosing to Day 45, clinical laboratory 
tests at baseline and from Day 2 to Day 45, ECGs at Screening and post-dose on Days 1, 8, 
15, 21, 30, and 45, physical exams at baseline to Day 45, and vital signs at baseline to Day 
45. Tolerability will be assessed by occurrence of solicited local reactogenicity (injection site 
evaluation) from first dose to Day 45.  
• Pharmacokinetic (PK) profiles of rezafungin will be assessed by measurement of drug levels 
in plasma after SC administration in each cohort (except for SAD Cohort 1). Plasma for PK 
analysis will be collected at planned timepoints up to Day 30 in the SAD cohorts, and Day 45 
in the MAD cohorts. PK parameters will be estimated from the rezafungin plasma 
concentration-time data. 
3.3.2 
Secondary 
The BA of rezafungin when administered by SC injection relative to IV infusion will be assessed 
by measurement of drug levels in plasma after administration by SC injection or by IV infusion 
in each cross over period. Plasma samples will be collected at planned timepoints up to Day 52 
for Part 3/BA The absolute BA will be calculated as the ratio of AUC for the SC injection and 
AUC for the IV infusion of administration. 

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STUDY INTERVENTION/INVESTIGATIONAL 
PRODUCT 
 
Study Product Description 
The active ingredient, rezafungin acetate, a cyclic hexapeptide, is a semi-synthetic echinocandin 
synthesized from a fermentation product of Aspergillus nidulans. Two formulations will be used 
for the study, one for SC administration and one for IV administration.   
Subcutaneous (SC) formulation: Rezafungin Injection, for Subcutaneous Use, 100 mg/mL, is a 
sterile liquid product supplied as a colorless to pale yellow liquid in single-dose vials containing 
1.0 mL of extractable volume. The active pharmaceutical ingredient is rezafungin acetate, a 
water-soluble amorphous acetate salt. The inactive ingredient is mannitol.  
Intravenous (IV) formulation: Rezafungin for Injection, 200 mg/vial, is a sterile product supplied 
as a white to pale yellow lyophilized powder in single-dose glass vials for reconstitution with 
Sterile Water for Injection, United States Pharmacopeia (USP). The reconstituted product is 
diluted in 0.9% Sodium Chloride Injection, USP for IV infusion. The active pharmaceutical 
ingredient is rezafungin acetate, a water-soluble amorphous acetate salt. The inactive ingredients 
include excipients of mannitol, polysorbate 80, and histidine. 
Placebo is 5% Dextrose Injection, USP, a sterile, nonpyrogenic solution of dextrose in water for 
injection. The solution has the osmolarity of 252 mOsmol/L, which is slightly hypotonic. This 
solution contains no bacteriostat, antimicrobial agent or added buffer. 
Reconstitution solution is Sterile Water for Injection, (WFI), USP, which is a clear, colorless 
solution. 
4.1.1 
Formulation, Packaging, and Labeling 
Subcutaneous Formulation: Rezafungin Injection, for Subcutaneous Use, 100 mg/mL 
Rezafungin Injection is a sterile liquid product supplied in single-dose 2 mL vials containing 
100 mg of rezafungin in 1.0 mL of extractable volume. The active pharmaceutical ingredient is 
rezafungin acetate, a water-soluble acetate salt. The inactive ingredient is mannitol.  
For SC administration for Parts 1, 2, and 3 of the study, the appropriate volume of solution is 
withdrawn via syringe for administration to the subject for doses of 10 mg and up. To administer 

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a 1 mg dose, the solution from the product vial (Rezafungin Injection, for Subcutaneous use, 100 
mg/mL) is diluted 1:10 in 5% Dextrose Injection, USP, then 0.1 mL of the diluted solution is 
injected. Further details are provided in the protocol-specific MOP.  
Rezafungin Injection, for Subcutaneous Use, 100 mg/mL, will be labelled according to 
manufacturer or regulatory specifications and will include the statement “Caution: New Drug – 
Limited by Federal Law to Investigational Use”. 
IV Formulation: Rezafungin for Injection, 200 mg/vial 
The IV formulation will be used for Part 3 of the study.  
Rezafungin for Injection, 200 mg/vial, is supplied as a white-to-pale-yellow lyophilized powder 
(200 mg/vial) in single-dose 20 mL glass vials for reconstitution with Sterile Water for Injection, 
USP. The reconstituted product is a clear, colorless to pale yellow solution free of visible 
particulate. The reconstituted product is diluted in 250 mL of normal saline and administered by 
IV infusion. Further details are provided in the protocol-specific Manual of MOP. 
The active pharmaceutical ingredient is rezafungin acetate, a water-soluble acetate salt. The 
inactive ingredients include excipients of mannitol, polysorbate 80, and histidine. 
Rezafungin for Injection, 200 mg/vial, will be labelled according to manufacturer or regulatory 
specifications and will include the statement “Caution: New Drug – Limited by Federal Law to 
Investigational Use”. 
Placebo (5% Dextrose Injection, USP) 
 
5% Dextrose Injection, USP solution is sterile and nonpyrogenic. It is a parenteral solution 
containing dextrose in water for injection intended for intravenous administration. Each 100 mL 
of 5% Dextrose Injection, USP, contains dextrose monohydrate, 5 g in water for injection. The 
caloric value is 170 kcal/L. The osmolarity is 252 mOsmol/L (calc.), which is slightly hypotonic. 
The solution pH is 4.3 (3.2 to 6.5). 
WFI (Reconstitution Solution)  
WFI is USP grade sterile water for injection that is nonpyrogenic and contains no bacteriostatic 
agent or added buffer. 
 
 

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4.1.2 
Product Storage and Stability 
Rezafungin Injection, for Subcutaneous Use, 100 mg/mL 
Store at 2-8°C (36-46°F). 
Rezafungin for Injection, 200 mg/vial 
Store at 20-25°C (68-77°F) (See USP Controlled Room Temperature; excursions between 15°C 
and 30°C [59-86°F] are permitted).  
Placebo (5% Dextrose Injection, USP) 
Store at 20-25°C (68-77°F) (See USP Controlled Room Temperature). Protect from freezing. 
WFI (Reconstitution Solution) 
Store at 20-25°C (68-77°F) (See USP Controlled Room Temperature; excursions between 15°C 
and 30°C [59-86°F] are permitted). Protect from freezing. 
 
Acquisition/Distribution 
Rezafungin Injection, for Subcutaneous Use, 100 mg/mL and Rezafungin for Injection, 
200 mg/vial 
Rezafungin will be provided by Cidara Therapeutics, Inc. Upon request by Division of 
Microbiology and Infectious Diseases (DMID), it will be shipped to the following address: 
DMID-Clinical Materials Services (CMS) 
Fisher BioServices 
20439 Seneca Meadows Parkway 
Germantown, MD 20876 
Tel: 240-477-1350 
Email: DMID.CMS@thermofisher.com 
Rezafungin will be shipped from DMID-CMS to the ICON Early Phase Services upon request 
and approval by DMID. 
Placebo (5% Dextrose Injection, USP) 
5% Dextrose Injection, USP will be supplied by ICON. 
WFI (Reconstitution Solution) 
WFI will be supplied by ICON. 

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Dosage/Regimen, Preparation, Dispensing and Administration of 
Study Intervention/Investigational Product 
See the protocol-specific MOP for detailed information on the preparation, labeling, storage, and 
administration of Rezafungin for Injection – SC (100 mg/mL) and Rezafungin for Injection-IV 
(200 mg). Study product preparation will be performed by the site’s unblinded research 
pharmacist on the same day of study drug administration. 
Visually inspect all study products/diluent upon receipt and prior to use. If the study 
products/diluent appear to have been damaged, contaminated, or discolored, contain visible 
particulate matter, or if there are any concerns regarding its integrity, do NOT use the affected 
study products/diluent. The affected study products/diluent must be quarantined at the 
appropriate temperature and labeled ‘Do Not Use’ (until further notice). The Site Principal 
Investigator (PI) or responsible person should immediately contact the DMID Product Support 
Team (see MOP for contact information) and DMID Clinical Project Manager for further 
instructions before any additional study product administrations are administered. Based on the 
information collected, DMID and/or the manufacturer will determine whether the affected study 
products/diluent can be used. If it cannot be used, the site will receive specific instructions on 
how to return the affected study products/diluent to the DMID CMS or destroy it on site. If the 
study products/diluent are unusable, study personnel will use another vial from the study supply. 
Replacement vials may be requested by contacting DMID. Additional instructions for quarantine 
and DMID contact information are provided in the protocol-specific MOP. 
Two formulations will be used for the study. 
Subcutaneous Formulation: Rezafungin Injection, for Subcutaneous Use, 100 mg/mL  
An appropriate volume of solution is withdrawn from the vial via syringe and administered for 
doses of 10 mg and up. To administer a 1 mg dose, the solution from the product vial 
(Rezafungin Injection, for Subcutaneous use, 100 mg/mL) is diluted 1:10 in 5% Dextrose 
Injection, USP, then 0.1 mL of the diluted solution is injected. Refer to the MOP for further 
details.  
IV Formulation: Rezafungin for Injection, 200 mg/vial  
The lyophilized powder is first reconstituted with Sterile Water for Injection, USP, and then 
diluted with Normal Saline, 0.9% Sodium Chloride Injection, USP, 250 mL, for infusion. For 
detailed instructions on reconstitution and/or dilution, refer to the MOP for this study. 

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Placebo (5% Dextrose Injection, USP) 
For placebo SC injection, the appropriate volume to match the volume to be administered in the 
active arm of the trial is withdrawn using a syringe. 
 
Accountability Procedures for the Study Intervention/Investigational 
Product(s) 
The Site PI is responsible for the distribution and disposition of study drug and has ultimate 
responsibility for its accountability. As this is a blinded trial, the Site PI will delegate this 
responsibility to the unblinded Site Pharmacist. The Site Pharmacist will be responsible for 
maintaining complete records and documentation of study drug receipt, accountability, 
dispensation, temperature monitoring, storage conditions, and final disposition. 
Study drugs, whether administered or not, will be documented on the appropriate study drug 
accountability record or dispensing log. Used and unused Rezafungin vials will be retained at 
temperature specified on the label until monitored and released for disposition as per DMID 
Requirements in the MOP. Any unused solution left in the IV infusion bag or IV tubing after 
administration to the subject will be discarded as biohazardous waste in accordance with local 
institutional policies. The infusion bag may be discarded prior to monitoring. 
Upon completion of this trial and after the final monitoring visit, any remaining unused study 
drug will either be returned or destroyed appropriately at the clinical site as per sponsor 
requirements and instructions, or in accordance with disposition plans. 

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SELECTION OF SUBJECTS AND STUDY 
ENROLLMENT AND WITHDRAWAL 
The inclusion/exclusion criteria for participation in this trial are listed below. All screening 
procedures must be completed during the screening period but may be performed on different 
days. Abnormal laboratory values may be confirmed at the PIs’ discretion and one repeat value 
can be used to determine eligibility. Subjects cannot be re-screened if they do not meet eligibility 
criteria. Subjects who meet criteria but fall outside the screening window (i.e. subjects screened 
as alternative subjects and not selected on dosing day) may be rescreened a maximum of one 
time. Subjects may only be enrolled once into this trial. 
No exemptions are granted on subject inclusion/exclusion criteria in DMID-sponsored studies. 
Questions about eligibility will be directed to the DMID Medical Officer. 
 
Eligibility Criteria 
5.1.1 
Subject Inclusion Criteria 
Subjects are eligible to enroll in this trial if they meet all the following criteria: 
1) Males and females aged 18 to 45 years, inclusive. 
2) Willing and able to provide written informed consent and authorization for use of protected 
health information; 
3) Willing and able to comply with protocol requirements, instructions, and protocol-stated 
restrictions (including confinement to the CRU) and is likely to complete the study as 
planned; 
4) Males must be vasectomized or agree to use barrier contraception (condom with spermicide) 
from first dose of study drug until at least 18 weeks following the last dose of study drug. 
5) Males must agree to refrain from sperm donation from first dose of IP through at least 18 
weeks after last dose of investigational product (IP). 

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6) Females are eligible if they are of non-childbearing potential3 or if they use a highly 
effective4 method of contraception for 30 days prior to dosing and for a minimum of 30 days 
after dosing; 
3Non-childbearing potential is defined as: Pre-menopausal with documentation of irreversible surgical 
sterilization (i.e., hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (but not tubal ligation 
alone); or, Post-menopausal defined as amenorrhea for at least 12 months following cessation of all exogenous 
hormonal treatments and with FSH levels ≥40 mIU/mL at Screening. 
4A highly effective contraceptive method is, defined by <1% failure rate that is not affected by user adherence, 
include surgical sterilization and long-acting reversible contraception (LARC).  LARC comes in three forms: 
progestin-releasing subdermal implants (Nexplanon and Implanon [Merck]); copper intrauterine devices (IUD) 
(ParaGard [Teva]); and levonorgestrel-releasing IUDs (Mirena [Bayer], Skyla [Bayer], and Liletta 
[Allergan/Medicines360]. Subjects must use one of these three methods.  
7) Subject is in good health as deemed by the Investigator.1-2 
1Good health is defined by the absence of any medical condition described in the exclusion criteria in a subject 
who undergoes a medical history, with a normal complete physical examination including resting vital signs 
(heart rate of 51-60 bpm allowed, per PI discretion), and screening safety laboratory testing.   
2If the subject has an active, ongoing medical condition, the condition cannot meet any of the following criteria:  
1.) first diagnosed within 3 months of enrollment; 2.) is worsening in terms of clinical outcome in last 6 months; 
or 3.) involves need for medication that may pose a risk to subject’s safety or significantly impede assessment 
of adverse events if they participate in the study.   
8) Subjects with a body mass index (BMI) (weight in kg divided by height in m, squared) 
between 18.5 and/or 35.0 kg/m2, inclusive, and a minimum weight of 50 kg; 
9) Subjects must refrain from strenuous physical activity that could cause muscle aches or 
injury, including contact sports, at any time from screening until completion of the trial. 
10) Subjects must refrain from over-the-counter and prescription medications1 and nutritional 
supplements within 14 days before first study drug administration, and until after the final 
study visit.  
1except for hormonal contraceptives, acetaminophen or ibuprofen. 
11) Subject has adequate venous access for blood collection. 

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5.1.2 
Subject Exclusion Criteria 
Subjects must NOT meet any of the following exclusion criteria: 
1) History of any hypersensitivity or allergic reaction to echinocandins or excipients (mannitol, 
polysorbate 80, histidine) of the rezafungin for injection and rezafungin for infusion 
formulations. 
2) Subjects presenting with a clinically significant condition;5  
5Subjects with any of the following must not be included into the study: clinically significant oncologic, 
infectious, cardiovascular, pulmonary, hepatic, gastrointestinal, hematologic, metabolic, endocrine, neurologic, 
immunologic, renal, psychiatric, or other condition that in the opinion of the Investigator would preclude the 
safe participation of the subject in the study or would prevent the subject from meeting the study requirements. 
3) Any condition that in the opinion of the Investigator could significantly impact drug 
absorption, distribution, or elimination; 
4) Symptoms of acute illness or chronic disease within 14 days of initial dosing; 
5) Positive screen for hepatitis B virus surface antigen, hepatitis C virus antibody, or HIV 
antibody; 
6) Subjects with clinical laboratory values outside the site reference ranges1 prior to initial 
dosing; 
1Clinical laboratory values outside the site reference ranges, if considered by the site investigator to be clinically 
insignificant, are acceptable if not exceeding Grade 1 severity. One repeat of lab testing is allowed to make this 
determination during screening. 
7) Abnormal ECGs. See Section 7.1 Clinical Evaluations for exceptions; 
8) Female subject of childbearing potential who is pregnant,6 lactating, or planning to become 
pregnant during the study period or at least 30 days after the final dose of study product; 
6Having a positive serum pregnancy test at the Screening Visit or any other specified time point prior to the 
dose of study product. 
9) Received any prescription medications (except for hormonal contraceptives) within 14 days 
before first study drug administration; 

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10) Received any non-prescription medications, vitamins, herbal or dietary supplements7 within 
14 days of initial dosing, unless prior approval is granted by both the Investigator and the 
Sponsor; 
7Excluded from this list is intermittent use of acetaminophen at doses of ≤2 g/day or ibuprofen ≤1200 mg/day. 
However, acetaminophen only is accepted to treat AEs for pain (i.e. headaches) during in-clinic stay.  
11) Current smoker or tobacco8 use within 90 days prior to screening or while a subject is 
enrolled in the study;  
8Tobacco use includes vaping, smoking tobacco, the use of snuff and chewing tobacco, and other nicotine or 
nicotine- containing products 
12) History of illicit/illegal drug use prior to dosing or while a subject is enrolled in the study9 or 
reports an alcohol or substance abuse problem* within 6 months of dosing;  
9A urine drug test will be performed at screening and upon admission to the CRU.  Drug screen includes 
amphetamines, barbiturates, cocaine, opiates, cannabinoids, phencyclidine, and benzodiazepines. 
*Inclusive of vaping of non-nicotine products 
13) Consumed foods or beverages containing alcohol or xanthines/caffeine a,b: 
a. Alcohol: ≤ 48 hours before the first study drug administration, until discharge; 
b. Xanthines/caffeine: ≤ 24 hours before the first study drug administration, until discharge; 
14) Received any live or killed vaccines or immunoglobulins within 14 days of dosing; 
15) Donated blood or blood products or experienced significant blood loss within 60 days of 
dosing; 
16) Received a blood transfusion within 14 days of dosing; 
17) Previous participation in this trial, any other rezafungin trial, or any trial10 within 28 days of 
dosing. Plans to enroll in another clinical trial11;  
10 Includes trials that have a study intervention such as a drug, biologic, or device. 
11 Includes trials that could interfere with safety assessment of the investigational product at any time during the 
study period 
18) The PI considers that the subject should not participate in the trial. 

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Withdrawal from the Study, Discontinuation of Study Product, or 
Study Termination  
5.2.1 
Withdrawal from the Study or Discontinuation of the Study Product  
Subjects may withdraw their consent at any time without penalty or loss of benefits to which 
they are otherwise entitled. 
A Site PI may also withdraw a subject from the study or from receiving the study drug for any 
reason. Follow-Up safety evaluations will be conducted, if the subject agrees. If a subject 
withdraws or is withdrawn before completion of this trial, the reason(s) will be recorded in the 
electronic case report form (eCRF). In either case, the reason for withdrawal will be clearly 
documented and specifically if the reason for withdrawal was related to study drug intolerance or 
other adverse event. 
The reason(s) for withdrawal from the study might include, but are not limited to, the following: 
• Subject no longer meets eligibility criteria; 
• subject meets individual halting criteria (listed in Section 8.7.3); 
• subject becomes noncompliant; 
• medical disease or condition or new clinical finding(s) for which continued participation, in 
the opinion of the Site PI, might compromise the subject’s safety, interfere with the subject's 
successful completion of this trial, or interfere with the evaluation of responses; 
• subject is lost to FU; 
• determined by a physician’s discretion to require additional therapy not indicated in the 
protocol to ensure subject’s health and well-being. The reason(s) for discontinuation of the 
study drug might include, but are not limited to; 
o subject becomes pregnant; 
o determined by a physician’s discretion to require additional therapy not indicated 
in the protocol to ensure subject’s health and well-being.  

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The Site PI will be explicit regarding trial FU (e.g., safety FU) that might be carried out if the 
subject will not receive further study drug. If the subject consents, every attempt will be made to 
follow all AEs through resolution. The procedures that collect safety data for the purposes of 
research will be included in the original ICF or the Site PI may seek subsequent informed 
consent using an IRB/IEC-approved ICF with the revised procedures. 
The Site PI will inform the subject that data already collected will be retained and analyzed even 
if the subject withdraws from this trial.  
5.2.2 
Handling of Withdrawals and Discontinuation of Administration 
Subjects who sign and date the ICF but fail to be randomized will be defined as screen failures. 
Site personnel will maintain documentation for all subjects who sign an ICF. 
Subjects will be informed that they have the right to discontinue study drug and/or withdraw 
from this trial at any time for any reason without prejudice to their medical care. If the subject 
has received the study drug, data collected for withdrawn subjects will be evaluated for safety 
and PK. 
In all cases of withdrawal, the reason for withdrawal will be recorded. Subjects who receive any 
amount of study drug and who are discontinued from this trial will be asked to complete all FU 
safety assessments including FU of any AEs before termination from this trial. 
5.2.3 
Lost to Follow-Up 
If subjects fail to appear for a FU assessment, extensive effort, (i.e., three documented contact 
attempts via phone calls, email, etc., made on separate occasions and followed by a certified 
letter) will be made to locate or recall them, or at least to determine their health status. These 
efforts will be documented in the subjects’ records. 
5.2.4 
Subject Replacement 
Subjects who have not received any amount of study drug and discontinue their participation 
may be replaced.  
Additionally, the first subject in each cohort to discontinue from participation due to loss to 
follow up, after receiving any amount of study product, is not replaced; if more than one subject 
in any cohort discontinues participation, these subjects will be replaced. Replacement of any 
subject is at the discretion of the PI in consultation with the Sponsor. Replacement subjects 

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should be allocated to the same treatment as the subject they replaced. The SDCC must be 
contacted prior to enrolling a replacement subject. 
5.2.5 
Study Termination  
Although DMID has every intention of completing this trial, it reserves the right to terminate this 
trial at any time for clinical or administrative reasons. 
If this trial is prematurely terminated by the Sponsor, any regulatory authority, or the Site PI for 
any reason, the Site PI will promptly inform the subjects and assure appropriate therapy or FU 
for the subjects, as necessary. The Site PI will provide a detailed written explanation of the 
termination to the IRB/IEC. 

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STUDY PROCEDURES 
 
Recruitment 
Up to 86 subjects aged 18-45 years (inclusive) who are in good health and meet all eligibility 
criteria will be enrolled in this trial. The demographics in the local population should ensure that 
male, females, and minorities (African American, Native American, Asian and Hispanics) will 
be represented in the enrolled population. Subjects will be recruited using IRB-approved 
advertising/web site listings of the essential inclusion and exclusion criteria. Subjects will self-
schedule online for a screening appointment based on their desire to participate and their 
evaluation of their suitability based on inclusion/exclusion criteria. Children, pregnant or breast-
feeding women, prisoners, and other vulnerable populations will not be enrolled. 
Upon arrival to the Clinical Research Unit (CRU), individuals will be checked for eligibility 
through the Verified Clinical Trials (VCT) process (after signing the IRB-approved VCT ICF) 
and then given the IRB-approved ICF and HIPAA form, and be assigned to Part 1, 2 or 3 of the 
study for enrollment.  After presentation of the ICF and individuals indicate their desire to 
proceed, they will be brought to a private room and given an opportunity to ask questions of the 
licensed nurse or doctor delegated to perform consenting. After the subject signs the ICF, 
protocol procedures will be initiated. 
Trial retention strategies will include education and explanation of the trial schedule and 
procedures during Screening and Enrollment visits. In addition, reimbursements will be 
disbursed at specific timepoints during this trial with the amount contingent on completing trial 
procedures. Subjects will be reminded of visits ahead of time, and trial staff will contact subjects 
who miss appointments to encourage them to return for completion of safety evaluations. 
 
Screening (Day -28 to Day -2) Parts 1-3 (All Cohorts) 
After providing written informed consent, each subject will be assigned a subject identification 
number and undergo an eligibility assessment. The following will be done during the screening 
period (within 28 days before study drug administration). Results of screening tests and 
procedures will be evaluated by the Site PI to determine eligibility before enrollment and 
randomization. 

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• Record demographics including age, gender, race, and ethnicity. Obtain contact 
information. 
• Obtain medical history that includes: 
a) 
current medical diagnoses, 
b) 
past medical diagnoses, 
c) 
hospitalizations, 
d) 
major surgical procedure, 
e) 
blood transfusions or immunoglobulin administrations within 14 days of dosing, 
f) 
live vaccines within14 days of dosing, 
g) 
killed vaccines within 14 days of dosing, 
h) 
blood or blood product donation, or significant blood loss within 60 days of 
dosing, 
i) 
allergic reactions, 
j) 
drug and/or alcohol use or dependence, 
k) 
receipt of an investigational drug within 28 days of dosing. 
• Review concomitant medication history, including all medications taken within 14 days 
of dosing. 
• Review recent menstrual history (female subjects only) and current use of contraceptive 
method. 
• Perform complete PE by licensed clinician listed on Form FDA 1572. 
• Obtain height and weight and calculate BMI. 
• Take resting vital signs after being at rest for at least 5 minutes. 

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• Obtain fasting (at least 8 hours) blood samples for clinical chemistry, hematology, 
coagulation tests, serum pregnancy test [if female of childbearing potential], FSH [if 
female and post-menopausal], and serology screen (serum HIV, HBsAg, and HCV 
antibodies). 
• Obtain urine sample for urinalysis, urine drug screen and urine alcohol. 
• Obtain urine sample for cotinine test. 
• Obtain a 12-lead ECG, after at least 5 minutes in the supine position (triplicate readings, at 
least 1 minute apart within a 15-minute period) to assess heart rate, rhythm, and interval 
information such as PR, QRS, QT, and QTc, after being supine for at least 5 minutes. 
• Counsel on the avoidance of pregnancy for women of child-bearing potential and use of 
barrier contraception for men. 
• Counsel on the avoidance of vaccines, blood/blood product/sperm donation and drugs and 
dietary restrictions listed in Section 5.1. 
 
Admission to the CRU (Day -1) Parts 1 and 2 (All Cohorts) and Part 
3 (Cohort 11) Days -1 and 21  
Subjects will be admitted to the CRU on the day before injection (or infusion for Part 3) and the 
following procedures will be performed: 
• On admission to the CRU on Day-1, review inclusion/exclusion criteria to ensure the 
subject is eligible for enrollment.   For Part 3, Day 21, review inclusion criteria numbers 
2-7 and 10-11, and exclusion criteria numbers 2-4 and 8-18 (from Section 5.1.2) to ensure 
the subject remains eligible for dosing.  
• Update medical history. 
• Review and update concomitant medications. 
• Perform targeted PE. 

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• Obtain resting vital signs after being at rest for at least 5 minutes. 
• Obtain weight, calculate BMI. 
• Obtain blood samples for baseline fasting (at least 8 hours) clinical chemistry, 
hematology, coagulation tests, serum pregnancy test [if female of childbearing potential]); 
for the Day -1 visit, if clinical chemistry, hematology or coagulation test result(s) are 
outside of the reference range(s), they may not be repeated; if a result is not considered by 
the site investigator to be clinically insignificant, the subject is removed from the study. 
• For women of child-bearing potential, perform a serum pregnancy test (results must be 
confirmed negative before dosing). 
• Obtain blood and urine samples for safety clinical labs. 
• Obtain urine sample for drug screen and urine alcohol. 
• Obtain urine sample for cotinine test. 
• Part 3 (Cohort 11) only, Day 21 – review Memory Aid. 
 
Part 1 (Cohorts 1 through 6) 
6.4.1 
Day 1 – Inpatient CRU 
• On the morning of Day 1, study drug or placebo will be administered via SC injection in 
the abdomen at a slow steady pace. Subjects will be inpatients in the CRU and will 
undergo the following procedures, which are listed in the Schedule of Study Procedures 
and Evaluations (Appendix A) and detailed in Clinical Evaluations (Section 7).  
• Randomize the subject. 
• Obtain vital signs before study drug dosing (within 60 minutes of study drug dosing) after 
resting in a supine or semi-supine position for at least 5 minutes. This is to be documented 
as the Baseline prior to dosing. 
• Perform targeted PE. 

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• Obtain a 12-lead ECG after at least 5 minutes in the supine position (triplicate readings, at 
least 1 minute apart within a 15-minute period) and within 60 minutes before study drug 
dosing. 
• Baseline skin assessment at SC injection site area prior to study drug dosing (see Section 
7.1.3 and MOP for this study). 
• Administer study drug. 
• Obtain vital signs at 15 minutes (±5 min), 1 hour (±10 min), and 2 hours (±10 min) after 
dosing, after resting in a supine or semi-supine position for at least 5 minutes. 
• Collect PK blood samples for pre-dose, (collected within 60 minutes before study drug 
dosing) and at 0.5 h (±5 min), 1 h (±10 min), 2 h (±10 min), 4 h (±10 min), 6 h (±10 min), 
8 h (±10 min), and 12 h (±10 min). No PK blood samples collected in Cohort 1. 
• Assess reactogenicity at SC injection site(s) at 1 h (±10 min) and 4 h (±10 min) post-dose 
(see Section 7.1.3 and MOP for this study). 
• 12-lead ECG at 4 hours (±10 minutes) after injection after at least 5 minutes in the supine 
position (triplicate readings, at least 1 minute apart within a 15-minute period). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
• Issue Memory Aid. Details regarding the subject Memory Aid are included in the MOP 
for this study. 
6.4.2 
Day 2 – Inpatient CRU 
• Obtain vital signs 24 hours (±30 min) after resting in a supine or semi-supine position for 
at least 5 minutes. 
• Perform targeted PE. 

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• Obtain blood for hematology/coagulation/chemistry and urine for urinalysis. 
• Obtain PK blood sample 24 hours (±30 min) after dosing. No PK blood samples collected 
in Cohort 1. 
• Assess reactogenicity at SC injection site at 24 h (±30 min) post-dose (see Section 7.1.3 
and MOP for this study). 
• Assess AEs. 
6.4.3 
Day 3 – Inpatient CRU 
• Obtain PK blood sample 48 hours (±30 min) after dosing. No PK blood samples collected 
in Cohort 1. 
• Assess reactogenicity at SC injection site(s) at 48 h (±30 min) post-dose (see Section 7.1.3 
and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
6.4.4 
Day 4 – Inpatient CRU 
• Obtain resting vital signs 72 h (±30 min) after being at rest for at least 5 minutes. 
• Perform targeted PE. 
• Assess reactogenicity at SC injection site(s) at 72 h (±30 min) post-dose (see Section 7.1.3 
and MOP for this study). 
• Assess AEs. 
6.4.5 
Day 5 – Inpatient CRU 
• Obtain PK blood sample 96 hours (±30 min) after dosing. No PK blood samples collected 
in Cohort 1. 

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• Assess reactogenicity at SC injection site(s) at 96 h (±30 min) post-dose (see Section 7.1.3 
and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
6.4.6 
Day 6 – Inpatient CRU 
• Assess reactogenicity at SC injection site(s) at 120 h (±30 min) post-dose (see Section 
7.1.3 and MOP for this study). 
• Assess AEs. 
6.4.7 
Day 7 – Inpatient CRU 
• Obtain resting vital signs 144 hours (±30 min) after being at rest for at least 5 minutes. 
• 12-lead ECG after at least 5 minutes in the supine position (triplicate readings, at least 1 
minute apart within a 15-minute period). 
• Perform targeted PE. 
• Obtain blood for hematology/coagulation/chemistries and urine for urinalysis. 
• Obtain PK blood sample 144 hours (±30 min) after dosing. No PK blood samples 
collected in Cohort 1. 
• Assess reactogenicity at SC injection site(s) at 144 h (±30 min) post-dose (see Section 
7.1.3 and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 

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• Counsel on contraceptive use and provide post-discharge instructions (dietary and 
medication/nonmedication, vaccine and blood/blood product/sperm donation restrictions). 
• Train on proper completion of Memory Aid. 
• Subject discharge from CRU after all procedures are completed. 
6.4.8 
Day 14 (±1 Day) – Follow-Up - Outpatient 
• Obtain resting vital signs after being at rest for at least 5 minutes. 
• Obtain PK blood sample. No PK blood samples collected in Cohort 1. 
• Assess reactogenicity at SC injection site(s) (see Section 7.1.4 and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
• Review Memory Aid. 
• Reminder of contraceptive use and post-discharge instructions (dietary and 
medication/nonmedication, vaccine and blood/blood product/sperm donation restrictions). 
 
6.4.9 
Day 21 (±1 Day) – Telephone Follow-Up 
• Interview subjects for changes at SC injection site(s); refer subjects for unscheduled visit 
if changes at SC injection site(s) reported. 
• Review Memory Aid. 
• Remind subjects to report changes at SC injection site(s) immediately. 
 

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6.4.10 
Day 30 (±1 Day) – Follow-Up – Final Study Visit 
• Obtain resting vital signs after being at rest for at least 5 minutes. 
• 12-lead ECG after at least 5 minutes in the supine position (triplicate readings, at least 1 
minute apart within a 15-minute period). 
• Perform targeted PE. 
• Obtain weight, calculate BMI. 
• Obtain blood for hematology/coagulation/chemistry and urine for urinalysis. 
• Perform serum pregnancy test (females of childbearing potential only). 
• Obtain PK blood sample. No PK blood samples collected in Cohort 1. 
• Assess reactogenicity at SC injection site(s) (see Section 7.1.3 and MOP for this study). 
• Assess AEs. 
• Review Memory Aid. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
• Review post-study instructions (contraceptive use, pregnancy reporting). 
 
 
Part 2 (Cohorts 7 through 10) 
6.5.1 
Days 1, 8, and 15 – Inpatient CRU 
Study drug or placebo will be administered via SC injection in the morning on Days 1, 8, and 15. 
Subjects will be inpatients in the CRU and will undergo the following procedures, which are 
listed in the Schedule of Study Procedures and Evaluations (Appendix A) and detailed in Clinical 
Evaluations (Section 7): 

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• Randomize the subject (Day 1 only). 
• Review inclusion criteria numbers 2-7 and 10-11, and exclusion criteria numbers 2-4 and 
8-18 (from Section 5.1.2) to ensure the subject remains eligible for dosing (Days 8 and 15 
only). 
• Obtain resting vital signs before study drug dosing (within 60 minutes of study drug 
dosing for Day 1). This is to be documented as the Baseline prior to dosing on Day 1. 
• Perform targeted PE. 
• Obtain a 12-lead ECG before study drug dosing (Day 1 only) after at least 5 minutes in the 
supine position (triplicate readings, at least 1 minute apart within a 15-minute period) and 
within 60 minutes before study drug dosing. 
• Baseline (Day 1) and pre-dose (Days 8 and 15) skin assessment at SC injection site area(s) 
prior to study drug dosing (see Section 7.1.3 and MOP for this study). 
• Administer study drug via SC injection in the abdomen at a slow, steady pace. 
• Obtain vital signs at 15 minutes (±5 min), 1 hour (±10 min), and 2 hours (±10 min) after 
dosing, after resting in a supine or semi-supine position for at least 5 minutes. 
• 12-lead ECG at 4 hours (±10 minutes) after injection after at least 5 minutes in the supine 
position (triplicate readings, at least 1 minute apart within a 15-minute period). 
• Obtain PK blood samples within 60 minutes prior to study drug dosing (for Day 1) and at 
0.5 h (±5 min), 1 h (±10 min), 2 h (±10 min), 4 h (±10 min), 6 h (±10 min), 8 h (±10 min), 
and 12 h (±10 min) after dosing (Days 1 and 15); or within 15 minutes prior to dosing and 
at 1 h (±10 min), and 4 h (±10 min) after dosing (Day 8 only). 
• Assess reactogenicity at SC injection site(s) at 1 h (±10 min) and 4 h (±10 min) post-dose 
(see Section 7.1.3 and MOP for this study). 
• Assess AEs. 

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• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since administration to the CRU, 
• Issue Memory Aid. Details regarding the subject Memory Aid are included in the MOP 
for this study. 
6.5.2 
Days 2, 9, and 16 – Inpatient CRU 
• Obtain resting vital signs 24 hours (±30 min) after being at rest for at least 5 minutes. 
• Perform targeted PE. 
• Assess reactogenicity at SC injection site(s) at 24 h (±30 min) post dose (see Section 7.1.3 
and MOP for this study). 
• Obtain blood for hematology/coagulation/chemistry and urine for urinalysis. 
• Obtain PK blood sample 24 hours (±30 min) after dosing (Days 2 and 16 only). 
• Assess AEs. 
6.5.3 
Days 3, 10, and 17 – Inpatient CRU 
• Obtain PK blood sample 48 hours (±30 min) after dosing (Days 3 and 17 only). 
• Assess reactogenicity at SC injection site(s) at 48 h (±30 min) post dose (see Section 7.1.3 
and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
6.5.4 
Days 4, 11, and 18 – Inpatient CRU 
• Obtain resting vital signs 72 hours (±30 min) after being at rest for at least 5 minutes. 
• Perform targeted PE. 

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• Assess reactogenicity at SC injection site(s) at 72 h (±30 min) post dose (see Section 7.1.3 
and MOP for this study). 
• Assess AEs. 
6.5.5 
Days 5, 12, and 19 – Inpatient CRU 
• Obtain PK blood sample 96 hours (±30 min) after dosing. 
• Assess reactogenicity at SC injection site(s) at 96 h (±30 min) post dose (see Section 7.1.3 
and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
6.5.6 
Days 6, 13, and 20 – Inpatient CRU 
• Assess reactogenicity at SC injection site(s) at 120 h (±30 min) post dose (see Section 
7.1.3 and MOP for this study). 
• Assess AEs. 
6.5.7 
Days 7, 14, and 21 – Inpatient CRU 
• Obtain resting vital signs 144 hours (±30 min) after being at rest for at least 5 minutes. 
• 12-lead ECG after at least 5 minutes in the supine position (triplicate readings, at least 1 
minute apart within a 15-minute period). (Day 21 only) 
• Perform targeted PE. 
• Obtain blood for hematology/coagulation/chemistry and urine for urinalysis. 
• Obtain PK blood sample 144 hours (±30 min) after dosing. 
• Assess reactogenicity at SC injection site(s) at 144 h (±30 min) post dose (see Section 
7.1.3 and MOP for this study). 

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• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU.  
• Counsel on contraceptive use and provide post-discharge instructions (dietary and 
medication/nonmedication, vaccine and blood/blood product/sperm donation restrictions). 
• Train on proper completion of Memory Aid (Day 21 only). 
• Subject discharge from CRU after all procedures completed (Day 21 only). 
6.5.8 
Day 30 (±1 Day) – Follow-Up - Outpatient 
• Obtain resting vital signs after being at rest for at least 5 minutes. 
• 12-lead ECG after at least 5 minutes in the supine position (triplicate readings, at least 1 
minute apart within a 15-minute period). 
• Perform targeted PE. 
• Obtain PK blood sample. 
• Assess reactogenicity at SC injection site(s) (see Section 7.1.3 and MOP for this study). 
• Assess AEs. 
• Review Memory Aid. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since discharge from the CRU. 
• Reminder of contraceptive use and post-discharge instructions (dietary and 
medication/nonmedication, vaccine and blood/blood product/sperm donation restrictions). 
 

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6.5.9 
Day 45 (±1 Day) – Follow-Up – Final Study Visit 
• Obtain resting vital signs after being at rest for at least 5 minutes. 
• 12-lead ECG after at least 5 minutes in the supine position (triplicate readings, at least 1 
minute apart within a 15-minute period). 
• Perform targeted PE. 
• Obtain weight, calculate BMI. 
• Obtain blood for hematology/coagulation/chemistry and urine for urinalysis. 
• Perform serum pregnancy test (females only). 
• Obtain PK blood sample. 
• Assess reactogenicity at SC injection site(s) (see Section 7.1.4 and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since Day 30. 
• Review Memory Aid. 
• Review post-study instructions (contraceptive use, pregnancy reporting).  
 
 
Part 3 (Cohort 11) 
6.6.1 
Days 1 and 22 – Inpatient CRU 
For Cohort 11, the subject will be randomized to sequence and either the study drug will be 
administered via SC injection in the morning on Day 1 and as an IV infusion over 60 (±5) 
minutes in the morning on Day 22; or the study drug will be administered via IV infusion over 
60 (±5) minutes in the morning on Day 1 and via SC injection in the morning on Day 22. 
Subjects will be inpatients in the CRU and will undergo the following procedures, which are 

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listed in the Schedule of Study Procedures and Evaluations (Appendix A) and detailed in Clinical 
Evaluations (Section 7): 
• Randomize the subject (Day 1 only). 
• Review inclusion criteria numbers 2-7 and 10-11, and exclusion criteria numbers 2-4 and 
8-18 (from Section 5.1.2) to ensure the subject remains eligible for dosing (Day 22 only). 
• Obtain resting vital signs before study drug dosing (within 60 minutes of study drug 
dosing. This is to be documented as the Baseline prior to dosing on Day 1. 
• Perform targeted PE. 
• Obtain a 12-lead ECG within 60 minutes of study drug dosing, (Day 1 only), after at least 
5 minutes in the supine position (triplicate readings, at least 1 minute apart within a 15-
minute period). 
• Baseline skin assessment at SC injection site area prior to study drug dosing: assess 
reactogenicity at SC injection site before study drug dosing on Day 22 (see Section 7.1.3 
and MOP for this study). 
• Administer study drug. 
• Obtain vital signs (SC): at 15 minutes (±5 min), 1 hour (±10 min), and 2 hours (±10 min) 
after dosing, after resting in a supine or semi-supine position for at least 5 minutes. 
• Obtain vital signs (IV): at 15 minutes (±5 min), 1 hour (±10 min), and 2 hours (±10 min) 
after start of infusion, and after resting in a supine or semi-supine position for at least 5 
minutes. 
• Obtain PK blood samples within 60minutes before study drug dosing and at 0.5 h 
(±5 min), 1 h (±10 min), 2 h (±10 min), 4 h (±10 min), 6 h (±10 min), 8 h (±10 min), and 
12 h (±10 min) after the start of infusion or injection. 
• Post dose ECG (SC) at 4 hours (±10 minutes) after SC injection, 12-lead ECG after at 
least 5 minutes in the supine position (triplicate readings, at least 1 minute apart within a 
15-minute period). 

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• Post dose ECG (IV) at 1 hour (±10 minutes) from beginning of IV infusion, 12-lead ECG 
after at least 5 minutes in the supine position (triplicate readings, at least 1 minute apart 
within a 15-minute period). 
• Assess reactogenicity at SC injection site at 1 h (±10 min) and 4 h (±10 min) post dose 
(see Section 7.1.3 and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
• Issue Memory Aid (Day 1 only). Details regarding the subject Memory Aid are included 
in the MOP for this study. 
6.6.2 
Days 2 and 23 – Inpatient CRU 
• Obtain resting vital signs 24 hours (±30 min) after being at rest for at least 5 minutes. 
• Perform targeted PE. 
• Assess reactogenicity at SC injection site at 24 h (±30 min) post dose (see Section 7.1.4 
and MOP for this study). 
• Obtain blood for hematology/coagulation/chemistry and urine for urinalysis. 
• Obtain PK blood sample 24 hours (±30 min) after dosing. 
• Assess AEs. 
6.6.3 
Days 3 and 24 – Inpatient CRU 
• Obtain PK blood sample 48 hours (±30 min) after dosing. 
• Assess reactogenicity at SC injection site at 48 h (±30 min) post dose (see Section 7.1.4 
and MOP for this study). 
• Assess AEs. 

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• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
6.6.4 
Days 4 and 25 – Inpatient CRU 
• Obtain resting vital signs 72 hours (±30 min) after being at rest for at least 5 minutes. 
• Perform targeted PE. 
• Assess reactogenicity at SC injection site at 72 h (±30 min) post dose (see Section 7.1.4 
and MOP for this study). 
• Assess AEs. 
6.6.5 
Days 5 and 26 – Inpatient CRU 
• Obtain PK blood sample 96 hours (±30 min) after dosing. 
• Assess reactogenicity at SC injection site at 96 h (±30 min) post dose (see Section 7.1.4 
and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
 
6.6.6 
Days 6 and 27 – Inpatient CRU 
• Assess reactogenicity at SC injection site at 120 h (±30 min) post dose (see Section 7.1.4 
and MOP for this study). 
• Assess AEs. 
6.6.7 
Days 7 and 28 – Inpatient CRU 
• Obtain resting vital signs 144 hours (±30 min) after being at rest for at least 5 minutes. 
• Perform targeted PE. 

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• Obtain blood for hematology/coagulation/chemistry and urine for urinalysis. 
• Obtain PK blood sample 144 hours (±30 min) after dosing. 
• Assess reactogenicity at SC injection site at 144 h (±30 min) post dose (see Section 7.1.4 
and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU. 
• Counsel on contraceptive use and provide post-discharge instructions (dietary and 
medication/nonmedication, vaccine and blood/blood product/sperm donation restrictions), 
• Train on proper completion of Memory Aid (Day 7), refresher (Day 28). 
• Subject discharge from CRU after all procedures completed. 
6.6.8 
Days 14 (±1 Day) and 35 (±1 Day) – Follow-Up - Outpatient 
• Obtain vital signs after resting in a supine or semi-supine position for at least 5 minutes. 
• Perform targeted PE. 
• Obtain PK blood sample. 
• Assess reactogenicity at SC injection site (see Section 7.1.4 and MOP for this study). 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since discharge from the CRU.  
• Review Memory Aid. 
• Reminder of contraceptive use and post-discharge instructions (dietary and 
medication/nonmedication, vaccine and blood/blood product/sperm donation restrictions). 

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6.6.9 
Day 52 (±1 Day) – Follow-Up – Final Study Visit 
• Obtain vital signs after resting in a supine or semi-supine position for at least 5 minutes. 
• 12-lead ECG after at least 5 minutes in the supine position (triplicate readings, at least 1 
minute apart within a 15-minute period). 
• Perform targeted PE. 
• Obtain weight, calculate BMI. 
• Obtain blood for hematology/coagulation/chemistry and urine for urinalysis. 
• Perform serum pregnancy test (females only). 
• Obtain PK blood sample. 
• Assess AEs. 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since Day 35. 
• Review Memory Aid. 
• Review post-study instructions (contraceptive use, pregnancy reporting). 
 
6.6.10 
Early Termination (ET) Visit (if needed) 
The CRU will make every effort to perform all assessments listed for the last scheduled FU visit 
if a subject is terminated prematurely from this trial. All information collected will be 
documented in eCRFs or study records. 

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Unscheduled Study Visits  
Subjects will return to the CRU at the direction of the Site PI for FU and data from unscheduled 
visits or procedures (if any) and will be captured and presented in data listings. These data will 
be clearly identified as unscheduled observations. Safety assessments, including updated history, 
AEs, PE, and any other trial procedures deemed necessary by the PI, will be obtained. 
Subjects returning to the CRU for unscheduled visit(s) may undergo procedures, including but 
not limited to, the following, which are listed in the Schedule of Study Procedures and 
Evaluations (Appendix A) and detailed in Clinical Evaluations (Section 7): 
• Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since last visit, 
• Obtain a 12-lead ECG after at least 5 minutes in the supine position (triplicate readings, at 
least 1 minute apart within a 15-minute period), 
• Obtain blood for hematology/coagulation/chemistry and urine for urinalysis, 
• Perform targeted PE including resting vital signs (heart rate, blood pressure, oral 
temperature, and respiration rate, taken after resting for at least 5 minutes). If abnormal, 
these measurements may be repeated once, 
• Review Memory Aid, 
• Assess AEs. 
 
 

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Protocol Deviations 
A protocol deviation is any noncompliance with this protocol, GCP, or protocol-specific MOP 
requirements. The noncompliance may be either on the part of the subject, the Site PI, or the site 
personnel. As a result of deviations, corrective actions will be developed by the site and 
implemented promptly. 
These practices are consistent with ICH E6: 
4.5 
Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3 
5.1 
Quality Assurance (QA) and Quality Control (QC), Section 5.1.1 
5.20 
Noncompliance, Sections 5.20.1, and 5.20.2. 
It is the responsibility of the Site PI and personnel to use continuous vigilance to identify and 
report deviations within 5 working days of identification of the protocol deviation, or within 
5 working days of the scheduled protocol-required activity. All deviations must be promptly 
reported to DMID per the Statistical and Data Coordinating Center (SDCC) protocol deviation 
reporting procedures. 
All protocol deviations, as defined above, must be addressed in subject data collection forms 
(DCFs). Protocol deviations must be sent to the local IRB/IEC per their guidelines. The Site PI 
and personnel are responsible for knowing and adhering to their IRB requirements. 

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DESCRIPTION OF CLINICAL AND LABORATORY 
EVALUATIONS 
 
Clinical Evaluations 
7.1.1 
Medical History 
Medical history will be obtained by direct interview. Subjects will be queried regarding a history 
of significant medical disorders of the head, eyes, ears, nose, throat, mouth, cardiovascular 
system, lungs, gastrointestinal tract, liver, pancreas, kidney, urologic, nervous system, blood, 
lymph glands, endocrine system, musculoskeletal system, skin, and genital/reproductive tract. A 
history of any allergies, cancer, immunodeficiency, psychiatric illness, substance abuse, and 
autoimmune disease will be solicited. The medical history will include current and past medical 
diagnoses, hospitalizations and major surgical procedures. Demographic information (date of 
birth, gender, race, ethnicity) will be obtained as part of the medical history assessment. The 
medical history will be obtained at screening and updated upon admission to the CRU on Day -1. 
7.1.2 
Height, Weight, Body Mass Index (BMI) 
All subjects will have height measured (at Screening only) and be weighed following the CRU’s 
standard operating procedures at Screening, Day -1 and at the final study visit.  BMI is calculated 
as: (weight in kg divided by height in m, squared). Subjects who no longer meet inclusion 
criteria due to changes in weight or BMI after dosing remain eligible and will not be removed 
from the study.   
7.1.3 
Physical Examinations 
A complete PE at Screening will evaluate vital signs (taken after resting for at least 5 minutes); 
general appearance; head, eyes, ears, nose, and throat; neck; chest and lungs; cardiovascular 
system, abdomen, musculoskeletal system, lymph nodes, extremities/skin, and neurological 
system. 
A targeted PE will evaluate resting vital signs, skin, and suspected organ systems described in 
any solicited or unsolicited AEs, at times specified in Appendix A. 
7.1.4 
Local Reactogenicity Symptoms 
Reactogenicity assessments will include an assessment of AEs occurring after dose 
administration on Day 1 through Day 30 of Part 1 (SAD), Day 30 of Part 2 (MAD) or Day 35 of 

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Part 3 (BA), which includes an assessment of SC injection site reactions (see Additional 
Characterization of Reactogenicity at Injection Sites, below). Pre-administration (baseline) 
injection site skin assessments will be performed prior to each study injection to establish 
baseline, then the study injection will be given. 
The study SC injection site(s) will be examined pre-dose and at 1 and 4 h (±10 minutes), 24, 48, 
72, 96, 120, 144 h (±30 minutes) post-administration in all cohorts (SAD/MAD/BA). Additional 
injection site examinations will occur on Day 14 of Part 1 (SAD), Day 30 of Part 2 (MAD), and 
Days 14 and 35 of Part 3 (BA), and any AE/SAEs will be recorded on the appropriate data 
collection form. 
Additional Characterization of Reactogenicity at Injection Sites 
Lesions at the injection site will be characterized by the study site staff as follows:  
1. Ecchymosis: non-raised skin discoloration caused by the escape of blood into the tissues from 
ruptured blood vessels  
2. Erythema: localized redness  
3. Induration: (hardness)/swelling 
4. Nodule: solid or cystic raised bump in the skin  
5. Ulcer: an open lesion on the surface of the skin caused by superficial loss of tissue.  NOTE:  
Ulcers at the injection site, regardless of size or severity, are of special interest and must be 
measured as well as photographed*, according to the MOP for this study.  Please see Section 
8.1.3 for reporting details and Section 8.7 for halting rules. 
6. Healed**: previously observed lesion that has dried up without any persistent induration or 
ulcer.   
7. Scar**: replacement of normal skin with fibrous tissue 
*All SC site reactions will be photographed at each visit, scheduled and unscheduled until 
resolution. 
**Recorded, but not graded. 
 
 

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7.1.5 
Vital Signs 
Vital signs (body temperature, heart rate, respiration rate, and blood pressure) will be obtained at 
times specified in Appendix A. Vital signs will be measured after resting at least 5 minutes. The 
pre-dose vital signs on days of dosing will be measured within 60 minutes of study drug dosing; 
Day 1 post-dose vital signs measurements should be taken within ± 5 minutes of the 15-minute 
post-dose timepoint and within ± 10 minutes for additional post-dose timepoints. Other vital 
signs during the inpatient stay will be taken within ±30 minutes of the nominal timepoint. For 
outpatient visits, vital signs will be measured within the visit window. 
Day 1 post-dose timepoints for vital sign measurements for the IV portion of Part 3 will be based 
on the start of infusion.    
7.1.6 
Electrocardiograms 
Standard 12-lead ECGs to assess heart rate, rhythm, and PR, QRS, QT, and QTc interval 
durations will be obtained at times specified in Appendix A. 
ECGs (triplicate readings, at least 1 minute apart within a 15-minute period), will be taken after 
at least 5 minutes in the supine position. The pre-dose ECGs on days of dosing will be taken 
within 60 minutes of study drug dosing. Post dose ECGs on days of dosing will be taken at 4 
hours (±10 minutes) after SC dosing. Post dose ECGs on days of dosing will be taken at 1 hour 
(±10 minutes) from start of infusion for IV administration in Part 3. 
ECGs will also be taken at the following timepoints: 
• Day 7, Day 30, and Unscheduled visits for SAD 
• Day 21, Day 30, Day 45, and Unscheduled visits for MAD 
• Day 52 and Unscheduled visits for BA 
The screening ECG will be used by the PI to determine a subject’s eligibility for enrolment. The 
Day 1 pre-dose ECG will be reviewed to determine if subjects can be dosed. 
All ECGs will be reviewed by the PI or designee. ECGs with the following readings will be 
considered acceptable for trial participation and will not be considered abnormal for trial 
purposes unless the PI or physician designee believes they represent a new medical condition 
when compared to baseline ECGs. In such cases an AE will be documented, and the subject will 
be followed for safety evaluations as appropriate. The following pre-existing conditions 
identified at enrolment will not be considered AEs: 

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• Sinus bradycardia, 
• Sinus arrhythmia, 
• Subjects without a history of prolonged QTc and an abnormal QTc interval at Screening 
will undergo repeat ECG assessment within the screening period before randomization to 
confirm prolongation. If the repeat ECG QTcF is within normal limits (see Appendix B) 
the subject may be considered for enrolment. 
The Sponsor may review all or individual screening ECGs or may delegate to determine if meets 
intention of entry criteria goal of enrolling healthy normal subjects. 
If a subject has possible cardiac-related symptoms, repeat ECGs will be obtained every 
30 minutes (±3 minutes) until the waveform reverts to its baseline appearance, or symptoms 
resolve, or are determined not to be cardiac-related. Subjects with cardiac-related symptoms that 
are associated with ECG changes will be transferred to appropriate emergency department for 
further evaluation and treatment at the discretion of the PI. 
7.1.7 
Assessment of Concomitant Medications/Treatments Other than Study Product 
Subjects are required to abide by the following rules regarding intake of medications and other 
substances before and during the study: 
1) Refrain from the use of any prescription medications (with the exception of hormonal 
contraceptives), within 14 days before the first study drug administration and until after the 
final study visit. 
2) Refrain from the use of over-the-counter medications including vitamins, supplements, and 
herbal supplements (except for acetaminophen or ibuprofen) within 14 days before the first 
study drug administration, 
3) The use of tobacco product, including smoking and the use of snuff and chewing tobacco, 
and other nicotine or nicotine-containing products (including patches), is not permitted by a 
subject within 90 days of Screening for the study or while a subject is enrolled in the study. 
A urine test for cotinine will be performed at Screening and upon admission to the CRU. 
4) Refrain from consuming foods or beverages containing the following substances for the 
duration of the study: 
5) Alcohol: ≤48 hours before the first study drug administration until discharge. A urine alcohol 
test will be performed at Screening and upon admission to the CRU. 

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6) Xanthines/caffeine: ≤24 hours before the first study drug administration and until discharge.  
7) Refrain from receiving a live or killed vaccine, or immunoglobin, within 14 days prior to 
dosing. 
8) The use of illegal drugs is not permitted while a subject is enrolled in this study. A urine drug 
test will be performed at Screening and upon admission to the CRU. 
9) Previous participation in this trial, any other rezafungin trial, or any trial involving 
administration of drug product within 28 days of study drug dosing. Plans to enroll in another 
clinical trial that could interfere with safety assessment of the investigational product at any 
time during the study period; 
If a subject is unable to comply with the restrictions described above, the subject’s continued 
participation in the study will be re-evaluated by the Investigator, in consultation with the 
Medical Monitor. 
 
Laboratory Evaluations 
7.2.1 
Clinical Laboratory Evaluations 
All laboratory assessments will be done by the clinical site’s certified laboratory. Laboratory 
toxicity grading will be determined by use of the FDA Guidance for Industry: Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Trials September 2007 and the Division of Microbiology and Infectious Diseases (DMID) Adult 
Toxicity Table November 2007, as modified for this study and appropriate for the administration 
of rezafungin (Appendix B. Toxicity Grading Criteria for Normal Human Subjects). 
At Screening, laboratory test values that fall outside the reference range on the laboratory reports 
and deemed not clinically significant by the Investigator may be repeated at the discretion of the 
Investigator (to assess for transitional conditions). Laboratory values that fall outside of the 
reference range on Day -1 (baseline), may not be repeated, and subject will be withdrawn from 
the study. (See Note below for exceptions). 
If a single repeat Screening evaluation is within the reference range, the subject may be further 
considered for study eligibility.   
Note: Hematuria during active menses causing urinalysis results outside the reference range will 
not be considered clinically significant (not an AE). 
 
 

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Viral Serology Testing 
Subjects will be screened for HIV antibody, hepatitis B surface antigen, and hepatitis C virus 
antibody. These tests must be negative for eligibility into this trial. In cases where a false positive 
result is suspected, confirmatory testing may be performed (e.g., Polymerase Chain Reaction). 
Drug, Alcohol, and Cotinine Testing 
The urine toxicology screen will be performed to detect the presence of amphetamines, 
barbiturates, cocaine, opiates, cannabinoids, phencyclidine, and benzodiazepines. The results 
must be negative for eligibility into this trial. A urine alcohol test will also be performed to detect 
alcohol use and must be negative prior to randomization. A urine cotinine test will also be 
performed to detect nicotine use and must be negative prior to randomization. 
Follicle Stimulating Hormone (FSH) and Pregnancy Testing 
For women of child-bearing potential, a serum pregnancy test will be done at screening and must 
be negative for eligibility into this trial. A serum pregnancy test will be done on Day -1, which 
must be reported as negative before dosing. A serum pregnancy test will be repeated at the final 
trial visit. Perform FSH test in postmenopausal females only, prior to randomization. 
Safety Laboratory Tests 
The following laboratory tests will be performed as specified in Appendix A. Subjects will be 
fasting. This means no food or drink (other than water) for at least 8 hours before sampling. 
• Hematology: complete blood count (CBC) with differential (red blood cell count, total and 
differential white blood cell counts, hemoglobin, hematocrit, and platelet count), 
• Coagulation; (activated partial thromboplastin time [APTT], prothrombin time [PT}, and 
international normalized ratio [INR]), 
 
 

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• All subjects must undergo clinical chemistry testing (albumin, glucose, blood urea 
nitrogen or urea, potassium, calcium, sodium, chloride, total protein, creatinine, total 
carbon dioxide (CO2), creatine phosphokinase (CK), phosphorus, alkaline phosphatase, 
aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct 
bilirubin at Screening and Baseline to assess protocol eligibility. Clinical chemistry tests 
will be performed thereafter as specified in the Schedule of Assessments and Procedures 
Appendix A. Subjects must fast a minimum of 8 hours before blood collection for a 
clinical chemistry panel. 
• Dipstick urinalysis: protein, blood, and glucose must be negative or trace (complete 
urinalysis to be performed if dipstick urinalysis is positive for blood). Menstruating 
females failing inclusion criteria due to a positive result may be retested following 
cessation of menses. Do not exclude subjects with >5 red blood cells/high power field if 
menstruating. 
Laboratory values will be entered in the Clinical Labs eCRF. 
7.2.2 
Research Assays  
Bioanalytical Assay 
Plasma concentrations of rezafungin in EDTA will be determined by a validated LC-MS/MS 
method. Details are provided in the MOP for sample collection time in each cohort for SAD 
(except cohort 1), MAD, and BA. 
For Part 1/SAD blood samples will be collected at the following scheduled timepoints for 
Cohorts 2, 3, 4, 5, and 6 (see Table 5). For Part 2/MAD, blood samples will be collected at the 
following scheduled timepoints for Cohorts 7, 8, 9, and 10 (see Table 6). For Part 3/BA, blood 
samples will be collected at the following scheduled timepoints for Cohort 11 (see Table 7). 
 
 

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Table 5: Blood Sampling Timepoints for Rezafungin Pharmacokinetic Analysis Cohorts 2, 
3, 4, 5 and 6 SAD (Part 1) 
Dosing Day 
Timepoint 
Day 1 (pre-dose) 
Taken within 60 minutes before study drug dosing 
Day 1 (hours post-dose) 
0.5 
1 
2 
4 
6 
8 
12 
Day 2 (hours post-dose) 
24 
 
Day 3 (hours post-dose) 
48 
 
Day 5 (hours post-dose) 
96 
 
Day 7 (hours post-dose) 
144 
 
Day 14 
±1 Day 
 
Day 30  
±1 Day 
 
 
 
Table 6: Blood Sampling Timepoints for Rezafungin Pharmacokinetic Analysis Cohorts 7, 
8, 9, and 10 MAD (Part 2) 
Dosing Day 
Timepoint 
Day 1, 8, and 15 (pre-dose) 
For Day 1 taken within 60 minutes before study drug 
dosing and for Days 8 and 15, taken within 15 minutes 
before study drug dosing 
Day 1 and 15 (hours post-dose) 
0.5 
1 
2 
4 
6 
8 
12 
Day 2 and 16 (hours post-dose) 
24 
 
Day 3 and 17 (hours post-dose) 
48 
 
Day 5, 12, and 19 (hours post-dose) 
96 
 
Day 7, 14, and 21 (hours post-dose) 
144 
 
Day 8 (hours post dose) 
1 and 4 
1 
 
4 
 
Day 30 
±1 Day 
 
Day 45 
±1 Day 
 
 
 
 
 
 

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Table 7: Blood Sampling Timepoints for Rezafungin Pharmacokinetic Analysis Cohort 11 
BA (Part 3) 
Dosing Day 
Timepoint 
Day 1 and 22 (pre-dose) 
Taken within 60 minutes before study drug dosing 
Day 1 and 22 (hours post-dose*) 
0.5 
1 
2 
4 
6 
8 
12 
Day 2 and 23 (hours post-dose*) 
24 
 
Day 3 and 24 (hours post-dose*) 
48 
 
Day 5 and 26 (hours post-dose*) 
96 
 
Day 7 and 2 (hours post-dose*) 
144 
 
Day 14 and 35 
±1 Day 
 
Day 52 
±1 Day 
 
*Post-dose timepoints for PK blood sampling for the IV portion of Part 3 will be based on the 
start of infusion 
 
Laboratory Specimen Preparation, Handling, and Storage 
Detailed instructions for plasma and urine for drug testing and urinalyses specimen preparation, 
handling and storage are outlined in the MOP for this study. 
 
 

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Total Blood Volume Drawn                 
The total volume of blood that will be drawn from each subject is described in Table 8: 
Table 8: Total Volume of Blood Drawn From Each Subject - Part 1 (SAD) Cohorts 1-6 
Laboratory Test 
Sample Volume (mL) Number of Samples Total Volume (mL) 
Safety: 
Clinical chemistry 
4 
5 
20 
 
Hematology 
2 
5 
10 
 
Coagulation 
2.7 
5 
13.5 
 
Serology 
4 
1 
4 
 
Pharmacokinetic:* 
3 
14 
42 
 
When using an indwelling catheter 1.0 mL of blood will be removed prior to sample collection
Total 
15.7 
30 
89.5 
 
Cohort 1 Total* 
12.7 
16 
47.5 
 
*No PK blood samples collected in Cohort 1. 
 
 

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Table 9: Total Volume of Blood Drawn From Each Subject - Part 2 (MAD) Cohorts 7-10 
Laboratory Test 
Sample Volume (mL) 
Number of Samples 
Total Volume (mL) 
Safety: 
Clinical chemistry 
4 
9 
36 
 
Hematology 
2 
9 
18 
 
Coagulation 
2.7 
9 
24.3 
 
Serology 
4 
1 
4 
 
Pharmacokinetic: 
3 
27 
81 
 
When using an indwelling catheter 1.0 mL of blood will be removed prior to sample collection
Total 
15.7 
55 
163.3 
 
 
 
 

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Table 10: Total Volume of Blood Drawn From Each Subject - Part 3 (BA) Cohort 11 
Laboratory Test 
Sample Volume (mL) 
Number of Samples 
Total Volume (mL) 
Safety: 
Clinical chemistry 
4 
7 
28 
Hematology 
2 
7 
14 
Coagulation 
2.7 
7 
18.9 
Serology 
4 
1 
4 
Pharmacokinetic: 
3 
27 
81 
When using an indwelling catheter 1.0 mL of blood will be removed prior to sample collection
Total 
15.7 
43 
145.9 
 
Laboratory PK Specimen Shipping 
All PK specimens will be shipped to the Fisher Biorepository for storage and/or transfer to the 
ICON ABL. Detailed instructions for shipping plasma are outlined in the MOP for this study.   
 

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ASSESSMENT OF SAFETY 
 
Assessing and Recording Safety Parameters 
Regulatory requirements including FDA regulations, ICH Guidelines for GCP, and European 
Union Clinical Trials Directive set forth safety monitoring and reporting responsibilities of the 
Sponsors and Site PI to ensure the safety and protection of human subjects participating in 
clinical trials. 
Responsibilities 
Site PIs participating in this trial are responsible for and will: 
• Evaluate subject safety including assessment of AEs for seriousness, severity, and 
causality; 
• notify the Sponsor of SAEs immediately; 
• provide detailed written reports, including necessary documentation requested by the 
Sponsor or IRB/IEC, promptly following immediate initial reports; 
• inform the IRB/IEC of AEs as requested by applicable regulatory requirements. 
8.1.1 
Adverse Events 
ICH E6 defines an AE as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product regardless of its causal relationship to the study 
treatment. FDA defines an AE as any untoward medical occurrence associated with the use of a 
drug in humans, whether or not considered drug-related. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of medicinal (investigational) 
product. The occurrence of an AE may come to the attention of study personnel during study 
visits and interviews of a study recipient presenting for medical care, or upon review by a study 
monitor.  
All AEs, including solicited local (injection site), starting from administration of the first dose of 
study drug until the final study visit will be captured on the appropriate data DCF and eCRF. 
Information to be collected for AEs includes event description, date of onset, assessment of 

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severity, relationship to study product, and alternate etiology (assessed only by those with the 
training and authority to make a diagnosis and listed on Form FDA 1572 as a PI), date of 
resolution, seriousness and outcome. AEs occurring during the trial collection and reporting 
period will be documented appropriately regardless of relationship. AEs will be followed 
through resolution or until assessed to be stable by the PI. 
Any medical condition that is present at the time that the subject is screened will be considered 
as baseline and not reported as an AE. However, if the severity of any pre-existing medical 
condition increases, it should be recorded as an AE. 
Adverse Events Grading 
All AEs (laboratory and clinical symptoms) will be graded for severity and assessed for 
relationship to study product (see definitions). Abnormalities present at baseline will not be 
reported as AEs unless worsening in severity post-dosing. AEs characterized as intermittent 
require documentation of onset and duration of each episode. The start and stop date of each 
reported AE will be recorded on the appropriate DCF and eCRF. For vital sign AEs, when 
multiple readings are taken within the same day the AE of highest severity will be documented to 
allow an assessment of the duration of the AE from the highest level of intensity. If a subject was 
enrolled in the trial with a laboratory value that is outside the reference range, but within the 
acceptable ranges, an AE will be recorded if it otherwise meets the definition of AE in Section 
8.1.1 and the on-study value is higher (if initially high) or lower (if initially low) than the 
screening value. 
Severity of Event:   
AEs will be assessed by the Site PI using a protocol-defined grading system (Appendix B). For 
events not included in the protocol-defined grading system, the following guidelines will be used 
to quantify severity: 
Mild (Grade 1): Events that are usually transient and may require only minimal or no treatment 
or therapeutic intervention and generally do not interfere with the subject’s usual activities of 
daily living, 
Moderate (Grade 2): Events that are usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing discomfort but 
poses no significant or permanent risk of harm to the subject, 

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Severe (Grade 3): Events interrupt usual activities of daily living, or significantly affects clinical 
status, or may require intensive therapeutic intervention. Severe events are usually 
incapacitating. 
 
 

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Relationship to Study Product: The assessment of the AE’s relationship to study product will 
be done by the licensed study physician indicated on Form FDA 1572 and the assessment will be 
part of the documentation process. Whether the AE is related or not, is not a factor in 
determining what is or is not reported in this trial. If there is any doubt as to whether a clinical 
observation is an AE, the event should be reported. 
In a clinical trial, the study product must always be suspect. The relationship to study product 
will be assessed for AEs using the terms related or not related: 
Related – There is a reasonable possibility that the study product caused the AE. Reasonable 
possibility means that there is evidence to suggest a causal relationship between the study 
product and the AE, 
Not Related – There is not a reasonable possibility that the administration of the study product 
caused the AE. 
8.1.2 
Serious Adverse Events 
An AE or suspected adverse reaction is considered a SAE if, in the view of either the Site PI or 
Sponsor, it results in any of the following outcomes: 
Death, 
a life-threatening adverse AE1, 
inpatient hospitalization or prolongation of existing hospitalization,  
a persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions, or 
a congenital anomaly/birth defect, 
Important medical events that may not result in death, be life-threatening, or require 
hospitalizations may be considered serious when, based upon appropriate medical judgment they 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, skin ulcers (open 
sores) at the injection site, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 

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1 An AE is considered “life-threatening” if, in the view of either the Site PI or Sponsor, its 
occurrence places the patient or subject at immediate risk of death. It does not include an AE 
that, had it occurred in a more severe form, might have caused death. 
SAEs will be: 
Assessed for severity and relationship to study product and alternate etiology (if not related to 
study product) by a licensed study physician listed on Form FDA 1572 or by the Site PI or Sub-
Investigator. 
Recorded on the appropriate SAE DCF and eCRF. 
Followed through resolution by a licensed study physician (for Investigation New Drug (IND) 
studies, a physician listed on Form FDA 1572 as the Site PI or Sub-Investigator). 
Reviewed and evaluated by DMID, an Independent Safety Monitor (ISM) (as deemed 
necessary), the SMC (periodic review unless related), and the IRB/IEC. 
8.1.3 
Adverse Events of Special Interest 
In addition to SAEs, the following adverse events of special interest (AESIs) should be promptly 
reported to the Sponsor even if the nature of the adverse event is deemed non-serious according 
to the usual regulatory criteria. 
Intravenous Infusion Intolerability 
Events that, in the opinion of the Investigator, may represent intolerance of the IV infusion of the 
study drug must be recorded as AEs on the eCRF. In general, these events would be temporally 
associated with the IV infusion of the Sponsor’s study drug. 
Phototoxicity 
Due to preliminary results from a nonclinical phototoxicity study in rats, subjects should be 
advised to avoid sun exposure without adequate protection. Site PIs should report any AE 
potentially related to phototoxicity to the Sponsor. 
Neuropathy and Tremors 
In a rezafungin 3-month toxicity study in monkeys, there were observations of tremors, and 
histology consistent with axonal degeneration (potentially consistent with clinical presentation of 
neuropathy) first appearing at Week 6 of dosing and at 11-fold the exposure for the rezafungin 
for Injection dose in this study. Ataxia, axonal neuropathy, hypoesthesia, paresthesia, peripheral 

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motor neuropathy, peripheral neuropathy, peripheral sensory neuropathies, peripheral 
sensorimotor neuropathy, polyneuropathy, toxic neuropathy, and tremors should be considered 
AESIs. Site PIs should report any AE potentially related to neuropathy to the Sponsor. 
 
Skin Ulcers 
Skin ulcerations of any grade at study drug injection sites will be of special interest. Site PIs 
should report any skin ulcerations at injection sites to the Sponsor within 24 hours of site 
awareness. Sponsor will report skin ulcerations at injection sites to the FDA as per Expedited 
Reporting guidelines. Any skin ulcerations at site(s) of injection will be assessed daily while 
inpatient; following discharge from the unit, the Site PI will determine the frequency of 
monitoring until resolution or stabilization. The status of skin ulcerations will be followed until 
resolution.   
 
Specification of Safety Parameters 
Safety will be assessed by the frequency and severity of AEs following administration of 
rezafungin. 
8.2.1 
Injection Site Reactogenicity 
The local injection site(s) will be assessed for reactogenicity with respect to symptoms.  All Skin 
reactions at the injection site will also be measured and photographed, according to the MOP for 
this study. See Appendix B and Section 7.1.4 for additional information. 
8.2.2 
New-Onset Chronic Medical Conditions 
New-Onset Chronic Medical Conditions are defined as any new International Class of Diseases, 
Tenth Revision diagnosis that is applied to the subject during this trial, after receipt of the study 
agent, that is expected to continue for at least 3 months and requires continued health care 
intervention. 
8.2.3 
Dose Escalation Criteria 
Dose escalation to each successive cohort of subjects will occur if none of the predefined dose 
escalation halting criterion is met (for all subjects through Day 30 [SAD] or Day 30 [MAD]). 
The SDCC will provide notification to the PI upon analysis of data for the cohort (for all subjects 
through Day 30 [SAD] or Day 30 [MAD]) for halting criteria as described in Section 8.7 Study 

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Design, Objectives and Endpoints or Outcome Measures, Dose Escalation. If any of the criterion 
for dose escalation is met, or, at the discretion of the PI or DMID Medical Monitor, the study 
enrollment and dosing will be stopped until the SMC reviews the data and provides its 
recommendations. There will be a scheduled SMC data review meeting prior to start of Part 2 
(MAD).  
 
Reporting Procedures 
8.3.1 
Reporting Serious Adverse Events 
Any AE that meets a protocol-defined serious criterion must be submitted immediately (within 
24 hours of site awareness) on an SAE form to the DMID Pharmacovigilance Group, at the 
following address:  
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US) 
SAE FAX Number: 1-800-275-7619 (US) or 1-301-897-1710 (outside US) 
SAE Email Address: PVG@dmidcroms.com 
In addition to the SAE form, select SAE data fields must also be entered into Advantage EDC. 
Please see the protocol-specific MOP for details regarding this procedure.  
Other supporting documentation of the event may be requested by the DMID Pharmacovigilance 
Group and should be provided as soon as possible.  
 
Type and Duration of Follow-Up of Subjects after Adverts Events 
The site will send a copy of the SAE report(s) to the ISM (as deemed necessary) when they are 
provided to the DMID Pharmacovigilance Group. The DMID Medical Monitor and DMID 
Clinical Project Manager will be notified of the SAE by the DMID Pharmacovigilance Group. 
The DMID Medical Monitor will review and assess the SAE for regulatory reporting and 
potential impact on study subject safety and protocol conduct. 

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At any time after completion of the study, if the site principal investigator or appropriate sub-
investigator becomes aware of an SAE that is suspected to be related to study product, the site PI 
or appropriate sub-investigator will report the event to the DMID Pharmacovigilance Group. 
8.4.1 
Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND 
Following notification from the Site PI, DMID, the IND sponsor, will report any suspected 
adverse reaction that is both serious and unexpected. DMID will report an AE as a suspected 
adverse reaction only if there is evidence to suggest a causal relationship between the study drug 
and the AE. DMID will notify FDA and all participating PI’s (i.e., all PI’s to whom the Sponsor 
is providing drug under its IND or under the PI’s IND[s]) in an IND safety report of potential 
serious risks from clinical trials or any other source, as soon as possible, but in no case later than 
15 calendar days after the Sponsor determines that the information qualifies for reporting as 
specified in 21 CFR Part 312.32. DMID will also notify FDA of any unexpected fatal or 
life-threatening suspected adverse reaction as soon as possible, but in no case later than 
7 calendar days after the Sponsor’s initial receipt of the information. Relevant FU information to 
an IND safety report will be submitted as soon as the information is available. Upon request 
from FDA, DMID will submit to FDA any additional data or information that the agency deems 
necessary, as soon as possible, but in no case later than 15 calendar days after receiving the 
request. 
All serious events designated as “not related” to study drug will be reported to the FDA at least 
annually in a summary format. 
8.4.2 
Reporting of Pregnancy 
A Notification of Pregnancy form will be completed for any female study subject or for any 
female partner of a male study subject who becomes pregnant following their exposure to study 
product (Day 1) through 4 months (120 days) after the last dose of study product is administered. 
The site will discuss pregnancy reporting with subjects at the Final Study visit with instructions 
and provide contact information in case pregnancy occurs. The pregnant subject will be followed 
by monthly telephone calls until 2 months after the birth of the baby or until the end of the 
pregnancy (in case pregnancy is terminated) at which time the Pregnancy Outcome form will be 
completed. Infants born to these study subjects will also be monitored for SAEs for up to 
2 months after birth (information regarding SAEs will be captured on the Pregnancy Outcome 
form and the SAE form). If an SAE occurs during the pregnancy, the SAE will be reported on 
the appropriate SAE form and provided to DMID pharmacovigilance. Pregnancy Outcome forms 
will be used to collect, but not be limited to, data on the following information, should it be 

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identified during the monthly telephone calls, at the end of the pregnancy, or at the follow-up 
telephone call at 2 months after birth of the baby: 
1. 
Prior maternal history including congenital abnormalities or pregnancy complications; 
2. 
Estimated date of conception; 
3. 
Estimated and actual date of delivery or pregnancy termination; 
4. 
Mode of delivery; 
5. 
Maternal complications; 
6. 
Neonatal complications (i.e. lethal or nonlethal congenital abnormality). 
 
Type and Duration of Follow-Up of Subjects after Adverse Events 
SAEs will be followed until resolution even if this extends beyond the trial-reporting period. 
Resolution of an AE/SAE is defined as the return to pretreatment status or stabilization of the 
condition with the expectation that it will remain chronic. 
 
Procedures to be Followed in the Event of Abnormal Laboratory 
Test Values or Abnormal Clinical Findings 
Laboratory values will be graded according to Appendix B. Abnormal laboratory values, 
performed as part of hematology, chemistry panel, or urinalysis but not listed in Appendix B, 
will be evaluated by the study clinicians, recorded in the source document and, if clinically 
significant, considered AEs and graded according to the criteria details described in Section 8.1.  
The site principal investigator or appropriate sub-investigator is responsible for recording all AE 
and SAEs that are observed or reported during this study, regardless of the relationship to study 
product. AE and SAEs or abnormal clinical findings will be collected, assessed, documented, 
reported, and followed appropriately. 

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Halting Rules 
8.7.1 
Study Halting Rules 
Trial dosing can be halted at any time if medically indicated. Trial dosing will be stopped, and all 
available safety data will be reviewed by the SMC if any of the following occur: 
• Any SAE (regardless of the relationship to the study drug) throughout duration of study. 
• 5 or more subjects in study (cumulative among all cohorts) experience a same grade 2 (or 
higher) related AE (laboratory or systemic) which is coded in the same high-level group term                         
(HLGT) per MedDRA coding, throughout duration of study. Exception to this includes 
scenarios where there are obvious and acceptable physiological explanations for a Grade 2 or 
higher abnormality (e.g., Grade 3 hematuria in a menstruating female). 
• Any subject experiences skin ulceration of any grade at an injection site.  
8.7.2 
Dose Escalation Halting Rules 
Sentinel Subject Halting Rules  
If any of the criterion below are met, the cohort will be suspended (enrollment and dosing), and 
the SMC ad hoc meeting will convene:  
• Any SAE (regardless of the relationship to the study drug) through 48 hours post study drug 
administration. 
• Any Grade 2 (or higher) adverse event deemed to be related to the study medication by the 
PI, having an initial onset within the first 72 hours post study drug administration that does 
not resolve within 72 hours from onset. 
• Any subject experiences skin ulceration of any grade at an injection site.  
Cohort Dose Escalation Halting Rules  
If any of the criterion below are met, the escalation to the next cohort will be suspended 
(enrollment and dosing), and the SMC ad hoc meeting will convene.  
• 2 or more subjects in a cohort experience the same grade 2 (or higher) related AE (laboratory 
or systemic) which is coded in the same HLGT per MedDRA coding, through Day 30 (SAD) 
or Day 30 (MAD) of the study. 

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• Two or more subjects within a cohort with post-dose QTcF > 500 or change from baseline 
>60 ms.  
• Any subject experiences skin ulceration of any grade at an injection site.  
 
8.7.3 
Individual Halting Rules 
If any of the criterion below are met, the subject will be discontinued from further dosing:  
• Any SAE regardless of the relationship to the study drug, throughout the duration of the 
study. 
• Any other condition that the Site PI judges to unduly increase the risk to the subject. 
• Any subject experiences skin ulceration of any grade at an injection site. (Does not apply to 
infusion site). 
8.7.4 
Infusion Halting Rules (Part 3 for IV Dosing Only) 
Infusion of study drug will be halted if any of the following manifestations of anaphylaxis 
develop and will not be restarted: 
• Skin or mucous membrane manifestations: hives, moderate or severe pruritus, flushing, 
swollen joints, swollen lips, tongue or uvula. 
• Respiratory compromise: dyspnea, wheezing, stridor. 
• A decrease in systolic blood pressure to <90 mmHg or >30% decrease from baseline blood 
pressure or a decrease in diastolic blood pressure of >30% from baseline. 
• Tachycardia with an increase in resting heart rate to ≥130 beats per minute (bpm); or 
development of a ventricular dysrhythmia; or bradycardia <45 bpm (or <40 bpm in subjects 
with a baseline of <60 bpm) that is associated with complaints of dizziness, nausea, or 
feeling faint. 
• Syncope. 
• Confusion. 

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Safety Oversight (ISM and SMC) 
8.8.1 
Independent Safety Monitor 
An ISM is a physician with relevant expertise whose primary responsibility is to provide to 
DMID an independent safety assessment in a timely fashion. This ISM is identified by the 
investigator site and approved by DMID. Participation is for the duration of the DMID study and 
is a voluntary position that does not receive payment. The ISM must meet the requirements of 
the NIAID conflict of interest policy.   
The ISM: 
• Is near the site and has the authority and ability to readily access subject records in real time. 
• May be a member of the participating institution’s staff but preferably be from a different 
organizational group within the institution. 
• Should not be in a direct supervisory relationship with the PI. 
• Should have no direct involvement in the conduct of this trial. 
The ISM will: 
• Sign a Conflict of Interest certification at the time they are asked to participate and provide 
updates to this information as needed. 
• Receive reports of SAEs from the Site PI and will be notified by email when DMID is 
notified of the SAE. 
• Evaluate the SAE and report their clinical assessment to DMID, through DMID-CROMS 
system organ classes (SOCS) in a timely manner using the attached report form and email the 
report to DMID-CROMS SOCS. 
• Communicate with the Site PI as needed. 
• Review additional safety related events at the request of DMID. 
• Provide additional information to DMID by teleconference as requested. 

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8.8.2 
Safety Monitoring Committee 
This trial will utilize an SMC, an independent group of experts that advises DMID. The primary 
responsibility of the SMC is to monitor subject safety. The SMC is external to DMID and 
comprises at least 3 voting members. The SMC will consist of members with appropriate Phase 1 
trial expertise to contribute to the interpretation of data from this trial. Its activities will be 
delineated in a SMC charter that will describe the membership, responsibilities, and the scope 
and frequency of data reviews. The SMC will operate on a conflict-free basis independently of 
the trial team. DMID or the SMC may convene ad hoc meetings of the SMC according to 
protocol criteria or if there are concerns that arise during this trial. 
The SMC will review the safety data at the following timepoints: 
• Organizational meeting (before starting this trial). 
• Data review meeting, following completion of Part 1 and prior to Part 2 (MAD). 
• Ad hoc meeting(s). 
• Final review meeting, to be conducted 6-8 months after clinical database lock to review the 
cumulative unblinded safety data for this trial. Data will be provided in a standard summary 
format. The SMC may be asked to provide recommendations in response to questions posed 
by DMID. 
All SMC reviews will be performed using unblinded data. Only blinded data will be presented 
during the open session. Study drug administration data, including dose interruptions, 
modifications, and the associated reason(s), will be reported to the SMC. 

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HUMAN SUBJECTS PROTECTION 
 
Institutional Review Board/Independent Ethics Committee 
The site principal investigator will obtain IRB approval for this protocol to be conducted at his 
research site and send supporting documentation to the DMID before initiating recruitment of 
subjects. The investigator will submit applicable information to the IRB/IEC on which it relies 
for the review, to conduct the review in accordance with 45 CFR 46, ICH E6 GCP, and as 
applicable, 21 CFR 56 (Institutional Review Boards) and 21 CFR 50 (Protection of Human 
Subjects), other federal, state, and local regulations. DMID must receive the documentation that 
verifies IRB/IEC-approval for this protocol, associated informed consent documents, and upon 
request any recruitment material and handouts or surveys intended for the subjects, prior to the 
recruitment and enrollment of subjects.     
Any amendments to the protocol or consent materials will be approved by the IRB/IEC before 
they are implemented. IRB/IEC review and approval will occur at least annually throughout the 
enrollment and follow-up of subjects and may cease if annual review is no longer required by 
applicable regulations. The investigator will notify the IRB/IEC of deviations from the protocol 
and reportable SAEs, as applicable to the IRB/IEC policy. 
 
Informed Consent Process 
Informed consent is a process that is initiated before an individual agrees to participate in a trial 
and continuing throughout a subject’s participation in a trial. Before any trial procedures are 
performed, informed consent will be obtained and documented. Subjects will receive a concise 
and focused presentation of key information about the clinical trial, verbally and with a written 
ICF. The explanation will be organized and presented in lay terminology and language that 
facilitates understanding why one might or might not want to participate. 
The Site PI or designee will describe the protocol to potential subjects face-to-face. The key 
information about the purpose of this trial, the procedures and experimental aspects of this trial, 
risks and discomforts, and any expected benefits to the subject will be presented first to the 
subject.   
Subjects will also receive an explanation that this trial involves research, and a detailed summary 
of the proposed trial procedures and trial interventions/drugs. This will include aspects of this 

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trial that are experimental, the probability for random assignment to study drug groups, any 
expected benefits, all possible risks (including a statement that particular study drugs or 
procedures may involve risks to the subject or to the embryo or fetus, if the subject is or may 
become pregnant, that are currently unforeseeable), and the expected duration of the subject’s 
participation in this trial.  
Subjects will be informed that they will be notified in a timely manner if information becomes 
available that may be relevant to their willingness to continue participation in this trial. Subjects 
will receive an explanation as to whether any compensation and any medical treatments are 
available if injury occurs, and, if so, what they consist of, or where further information may be 
obtained. Subjects will be informed that there are no financial expenses to the subject for 
participating in this trial, as well as be informed of the anticipated prorated payments to the 
subject for participating in this trial. They will be informed of whom to contact (e.g., the Site PI) 
for answers to any questions relating to this trial.  
Information will also include the foreseeable circumstances and/or reasons under which the 
subject’s participation in this trial may be terminated. The subjects will be informed that 
participation is voluntary and that they are free to withdraw from this trial for any reason at any 
time without penalty or loss of benefits to which they were otherwise entitled.   
The extent of the confidentiality of the subjects’ records will be defined, and subjects will be 
informed that applicable data protection legislation will be followed. Subjects will be informed 
that the monitor(s), auditors(s), IRB, NIAID, and regulatory authorities will be granted direct 
access to the subject’s original medical records for verification of clinical trial procedures and/or 
data without violating the confidentiality of the subject, to the extent permitted by the applicable 
laws and regulations, and that, by signing a written ICF, the subject is authorizing such access.  
Subjects will be informed that 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 
and, if the results of this trial are published, the subject’s identity will remain confidential. 
Subjects will be informed whether confidential information collected from this research and/or 
specimens will be used for additional research, even if identifiers are removed.   
Subjects will be allowed sufficient time to consider participation in this trial and to discuss this 
trial with their family, friends, or legally authorized representative, or think about it before 
agreeing to participate. 

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ICFs will be IRB-approved and subjects will be asked to read and review the ICF. Subjects will 
sign the ICF before starting any trial procedures being done specifically for this trial. 
Once signed, a copy of the ICF will be given to the subject(s) for their records. The subject(s) 
may withdraw consent at any time throughout the course of this trial. The rights and welfare of 
the subject(s) will be protected by emphasizing to them that the quality of their medical care will 
not be adversely affected if they decline to participate in this trial. 
Trial personnel may employ recruitment efforts before obtaining trial consent if a patient-specific 
screening consent is on record or if the IRB has agreed that chart review is allowed without a 
fully executed screening consent. In cases where there is not a patient-specific screening consent 
on record, site clinical staff may pre-screen via chart review and refer potential subjects to the 
research staff. Research staff would obtain written consent per the standard informed consent 
process before conducting protocol-specific screening activities. 
New information will be communicated by the Site PI or delegated staff to subjects who consent 
to participate in this trial in accordance with IRB requirements. The ICF will be updated and 
subjects will be re-consented per IRB requirements, if necessary. Subjects will be given a copy 
of all ICFs that they sign. 
 
Consent for Future Use of Stored Specimens and Data 
Residual clinical samples will be available upon the completion of the study; however, future use 
clinical samples may be requested from DMID and shipped from the DMID CMS at any time. 
These clinical samples will be shipped to and stored for up to 2 years at the Fisher Biorepository 
(DMID CMS).  
The samples will not be sold or used directly for production of any commercial product. No 
human genetic tests will be performed on the samples. Each sample will be encoded (labeled) 
only with a barcode and a unique tracking number to protect subject confidentiality. The 
recipients of specimens will be informed that these specimens have a NIH certificate of 
confidentiality. 
There are no benefits to subjects in the collection, storage and subsequent use of their specimens 
for future research. Reports about future research done with subjects’ samples will NOT be kept 
in their health records. 

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Subjects may be given the option to decide if they want their residual specimens to be used for 
future research or have these specimens destroyed at the end of this trial. The subject’s decision 
can be changed at any time by notifying the study doctors or nurses in writing. However, if the 
subject originally consents to the future use of residual specimens and subsequently changes 
his/her decision, any data from a previously collected specimen may still be used for future 
research. 
 
Exclusion of Women, Minorities, and Children (Special Populations) 
Children aged <18 years and elderly populations will be excluded from participation because 
insufficient data are available in adults to judge potential risk in children and elderly individuals, 
and as a Phase 1 trial in healthy subjects, there is no known benefit. For these same reasons, this 
trial will not include other special classes of subjects, such as fetuses, neonates, prisoners, 
institutionalized individuals, or others who may be considered vulnerable populations. 
Neither women nor minorities will be excluded from participation in this trial. Women of 
child-bearing potential may be included as per the inclusion criteria (Section 5.1.1). Subjects will 
be recruited without regard to gender or race. It is expected that race will reflect that within the 
community. 
 
Subject Confidentiality 
Subject confidentiality is strictly held in trust by the participating PI’s, their staff, and the 
Sponsor and their agents. This confidentiality includes documentation, investigation data, 
subject’s clinical information, and all other information generated during participation in this 
trial. No information concerning this trial, or the data generated from this trial will be released to 
any unauthorized third party without prior written approval of the DMID and the subject. Subject 
confidentiality will be maintained when trial results are published or discussed in conferences. 
The trial monitor or other authorized representatives of the Sponsor or governmental regulatory 
agencies may inspect all documents and records required to be maintained by the PI, including 
but not limited to, medical records (office, clinic, or hospital) and pharmacy records for the 
subjects in this trial. The CRU will permit access to such records. 
All records will be kept locked and all computer entry and networking programs will be carried 
out with coded numbers only and with password protected systems. All non-clinical specimens, 

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evaluation forms, reports, and other records that leave the site will be identified only by a coded 
number. 
 
Certificate of Confidentiality 
To protect privacy, we have received a Certificate of Confidentiality. With this Certificate, the 
researchers cannot be forced to release information that may identify the research subject, even 
by a court subpoena, in any federal, state, or local civil, criminal, administrative, legislative, or 
other proceedings. The researchers will use the Certificate to resist any demands for information 
that would identify the subject, except as explained below. 
The Certificate cannot be used to resist a demand for information from personnel of the US 
Government that is used for auditing or evaluation of federally funded projects, like this trial, or 
for information that must be released in order to meet the requirements of the FDA. 
A Certificate of Confidentiality does not prevent the subject from voluntarily releasing 
information about themselves or their involvement in this research. If any person or agency 
obtains a written consent to receive research information, then the researchers may not use the 
Certificate to withhold that information. 
The Certificate of Confidentiality does not prevent the researchers from reporting without the 
subject’s consent, information that would identify the subject as a participant in the research 
project regarding matters that must be legally reported including: child and elder abuse, sexual 
abuse, or wanting to harm themselves or others. 
The release of individual private information or specimens for other research will only occur if 
consent was obtained from the individual to whom the information, document, or biospecimen 
pertains, or for the purposes of other research that is in compliance with applicable Federal 
regulations governing the protection of human subjects in research. 
 
 

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Costs, Subject Compensation, and Research Related Injuries 
There is no cost to subjects for the research tests, procedures, and study drug while participating 
in this trial. Procedures and treatment for clinical care may be billed to the subject, subject’s 
insurance, or third party.   
Subjects may be compensated for their participation in this trial. Compensation will be in 
accordance with the local IRB’s policies and procedures, and subject to IRB approval. 
If the Site PI determines that an injury occurred to a subject as a direct result of the tests or 
treatments that are done for this trial, then referrals to appropriate health care facilities will be 
provided to the subject. Trial personnel will try to reduce, control, and treat any complications 
from this trial. Immediate medical treatment may be provided by the site. No financial 
compensation will be provided to the subject by the NIAID, NIH to the subject, or by the 
participating site for any injury suffered due to participation in this trial. 

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STATISTICAL CONSIDERATIONS 
A formal Statistical Analysis Plan (SAP) will be created prior to database lock. This document 
will provide a more technical and detailed description of the proposed data analysis methods and 
procedures. Any deviation from the analysis outlined in the protocol will be described in the 
SAP. 
For continuous variables, data will be summarized using descriptive statistics (such as sample 
size, mean, median, standard deviation, minimum, and maximum). For discrete variables, data 
will be summarized using frequencies and percentages. 
 
Study Hypotheses 
The objectives of this trial are to obtain safety, tolerability, and PK data for rezafungin. There are 
no formal hypotheses being tested in this trial. 
 
Sample Size Considerations 
No formal sample-size calculations based on testing a statistical hypothesis were constructed. 
There will be a total of 86 subjects in this three-part trial, 44 subjects in 6 cohorts will receive 
rezafungin or placebo via SC injection in Part 1/SAD, 32 subjects in 4 cohorts will receive 
rezafungin or placebo via SC injection in Part 2/MAD, and 10 subjects will receive rezafungin 
via both SC and IV injections in Part 3/BA. The number of subjects was selected to allow 
sufficient evaluation of safety, tolerability, and PK of the various dose regimens, and to be 
consistent with standards of practice for Phase 1 trials. 
 
Treatment Assignment Procedures 
10.3.1 
Randomization Procedures 
Each subject who completes the Screening assessment, meets all eligibility criteria, and is 
enrolled into this trial will randomized to rezafungin or placebo (Cohorts 1-10) or randomized to 
treatment sequence (Cohort 11),, except for replacement subjects. Replacement subjects will be 
assigned the same study drug dosing regimen as the replaced subject. 

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The randomization schedule will be generated centrally through AdvantageEDCSM (Electronic 
Data Capture [EDC] System, Emmes) by the unblinded biostatistician, and a list will be 
transferred to the unblinded Site Pharmacist before the start of this trial as an emergency 
back-up. Part 1 Cohort 1 will have 4 subjects randomized 3:1 to receive rezafungin or placebo, 
respectively. There will be no sentinel dosing for Cohort 1. Within cohorts 2-6 in Part 1 and all 
cohorts of Part 2, 8 subjects will be randomized 3:1 to receive rezafungin or placebo, 
respectively. In each dosing cohorts 2-6 in Part 1 and all cohorts of Part 2, the first two subjects 
will be randomized 1:1 to receive rezafungin or placebo to ensure that one of the first two 
subjects receives rezafungin and the other placebo. The study drug assignment of the remaining 
subjects in each cohort will be randomly assigned in a 5:1 ratio of active drug to placebo to 
ensure the 3:1 ratio for the entire dosing cohort. In Part 3, 10 subjects will be randomized in a 
1:1 ratio of dose route order (SC → IV or IV → SC). Enrollment will occur at one CRU. 
Per ICH guideline E6: GCP, screening records that document why an individual was screened 
but not enrolled will be kept at the CRU. Reasons for screen failures will also be recorded in 
AdvantageEDCSM. 
Subjects will be enrolled online using the enrollment module of AdvantageEDCSM. The 
randomization code will be prepared by statisticians at the SDCC and included in the enrollment 
module for this trial. AdvantageEDCSM will assign each subject to a rezafungin or placebo group 
after demographic and eligibility data have been entered into the system. A designated individual 
at the CRU will be provided with a code list for emergency unblinding purposes, which will be 
kept in a secure place. 
Instructions for using the enrollment module are included in the AdvantageEDCSM User’s Guide. 
Manual back-up procedures and instructions are provided for use in case the CRU temporarily 
loses access to the Internet or the online enrollment system is unavailable. 
10.3.2 
Masking Procedures 
10.3.2.1 
Blinding 
For SAD and MAD subjects, the Site Pharmacist will be unblinded as to randomization 
assignment. Subjects, the PI, and CRU personnel other than the Site Pharmacist, the 
bioanalytical laboratory staff, and Fisher repository personnel will remain blinded to all 
randomization assignments. The PK analyst(s) will be unblinded. The DMID Medical Monitor, 
other NIAID personnel, and ICON personnel will remain blinded to all randomization 

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assignments. For subjects enrolled in Part 3 (Bioavailability), the subjects, the PI, and CRU 
personnel will be unblinded to randomization assignment. 
Selected individuals not involved in conducting this trial, including members of the SMC, may 
have access to the unblinded data as needed for safety or other data review. The Site Pharmacist 
will remain unblinded during this trial. 
10.3.3 
Emergency Unblinding 
Emergency unblinding of study drug assignment for a subject may be necessary due to a medical 
emergency, or any other significant medical event, if knowledge of the subject’s study drug 
assignment impacts the subject’s care. If an SAE or other circumstance requires the blind to be 
broken to ensure a subject’s safety, the PI will immediately notify the DMID Medical Monitor if 
possible (within 24 hours) to discuss the case and reason for unblinding (a written narrative will 
follow within 48 hours of the event). 
Procedures for emergency unblinding are detailed in the MOP for this trial. 
 
Planned Interim Analyses 
10.4.1 
Interim Safety Review 
An interim safety review will be performed upon completion of the SAD cohorts (1-6) and prior 
to starting the MAD and BA parts of the study.  
An interim safety review will also be performed by the SMC upon completion of Day 30 for all 
subjects upon completion of the SAD cohorts (1-6) and prior to starting the MAD and BA parts 
of the study. This safety review may include but is not limited to enrollment, laboratory, and 
safety data. If criteria for halting the trial (as listed in Section 8.7) are met, an ad hoc SMC 
meeting will be held to review all available safety data and to make recommendations about the 
dosing of all further subjects in the trial. The SMC will receive data presented in aggregate (by 
cohort). Analysis by treatment assignment may be provided to the SMC in the closed session 
only. 
 
 

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10.4.2 
Interim Immunogenicity or Efficacy Review 
An interim PK analysis will be conducted upon the completion of the SAD cohorts (2-6).  
All safety and PK data will be provided to the FDA for review prior to initiation of the MAD and 
BA portions of the trial.  FDA will approve continued enrollment in the MAD and BA parts of 
the study and possibly recommend dose changes.  
 
Final Analysis Plan 
The safety analysis population will include all subjects that received any amount of study 
product and will be analyzed by treatment received. All subjects who receive a dose of 
rezafungin or placebo will be included in the safety analysis population. All subjects who receive 
a dose of rezafungin and have at least 1 measurable drug concentration after dosing in plasma 
will be included in the PK analysis population. 
Placebo subjects may be pooled across multiple cohorts for analysis. The PK analysis population 
will include all subjects with at least one measurable rezafungin plasma concentration. Missing 
data will not be imputed. Details of study analyses for safety and PK data and their presentation 
will be fully described in the SAP, prepared by the SDCC and finalized prior to data lock. 
10.5.1 
Adverse and Serious Adverse Events 
AEs will be coded using Medical Dictionary for Regulatory Activities® (MedDRA). All AEs 
occurring after study drug dosing will be summarized using frequency counts and percentages. 
Summaries will be presented by dose cohort and control group. The following summaries will be 
presented for AEs and SAEs: 
• Overall (i.e., regardless of severity or relationship to study drug, 
• By severity grade (mild, moderate, or severe), 
• By relationship to study drug, 
• By MedDRA level hierarchy (system organ class, HLGT and preferred term). 
Unless otherwise specified, at each level of subject summarization in reporting the incidence of 
the AEs, a subject will be counted once if the subject reported one or more AEs. If more than one 
occurrence of an AE is reported, the AE of the worst severity or the worst-case relationship 
assessment will be summarized. For crossover data, AEs will be summarized separately for each 

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treatment and the worst severity and worst-case relationship after each treatment will be 
summarized. An AE that began after the first treatment, continued into the second period, and 
worsened in severity after the second treatment will be considered a new AE associated with the 
second treatment. 
10.5.2 
Clinical Safety Labs, Vital Signs, and Electrocardiograms 
Baseline for clinical safety labs, vital signs, and ECGs will be defined as the last result obtained 
before the dose of study product. For crossover data, there will be a separate baseline for each 
treatment. Changes from baseline for clinical safety labs, vital signs, and ECGs results will be 
summarized by dose group and time point. Clinical safety labs and vital signs will be graded 
(Appendix B) and summarized by severity, group, and visit. Rules for analyzing replicates for a 
safety time point (labs, vital signs, ECG), if obtained, will be described in the SAP. 
Treatment-emergent abnormal laboratory test results will be identified. Treatment-emergent 
abnormal laboratory tests are tests for which the result was not graded as mild or worse at 
baseline but graded as mild or worse after dosing. Laboratory tests graded as mild at baseline, 
but moderate or worse any time after dosing will also be regarded as treatment-emergent 
abnormal laboratory test results. 
ECG measurements will include heart rate, RR interval, QT interval, QTcF interval, PR interval, 
and QRS duration. Baseline for ECG measurements is defined per protocol as the value 
pre-dosing on Day 1 (or pre-dosing on Day 21 for period 2 of Part 3). Change from baseline will 
be summarized descriptively by regimen at each scheduled evaluation. QTc results will be 
summarized categorically according to the ICH Guideline E14 “Clinical Evaluation of QT/QTc 
Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs” (October 
2005): 
• 
QTcF >450 ms, males only 
• 
QTcF >470 ms, females only 
• 
QTcF >480 ms  
• 
QTcF >500 ms 
• 
QTcF increases from baseline by at least 30 ms but less than 60 ms 
• 
QTcF increases from baseline by at least 60 ms 

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10.5.3 
Additional Safety Analyses 
Local reactogenicity at SC injection administration sites (Appendix B) will be summarized by 
type, toxicity grading, dose group, and time point. Skin ulcers at injection sites will be 
additionally summarized by size measurements and resolution. If there are multiple injection 
sites, the maximum severity across all injection sites will be summarized by day after injection at 
the respective sites. 
10.5.4 
PK Analysis Plan 
PK profiles for rezafungin in plasma samples from all subjects who received at least one dose of 
rezafungin will be analysed for concentration of rezafungin (except Cohort 1) by a validated LC-
MS/MS method. The following PK parameters will be estimated, by noncompartmental analysis 
methods using version 7.0 or higher of Phoenix WinNonlin®, for rezafungin concentrations in 
plasma. 
Cmax: The maximum concentration occurring at Tmax, 
Tmax: The time of maximum observed concentration sampled during a dosing interval, 
AUClast: The area under the curve (AUC) from the time of dosing to the last measurable 
concentration, 
AUC extrapolated to infinity from the observed value of the last non-zero [or last quantifiable] 
concentration, , 
AUC0-168: The AUC over the interval from time of first dose to 168 h after first dose (for Part 2 
MAD only), 
t1/2: Terminal half-life, 
λz: The first order rate constant associated with the terminal (log-linear) portion of the curve, 
CL: The total body clearance for intravenous administration,  
CL/F: The total body clearance for SC administration divided by the fraction of dose absorbed,  
Vz: The volume of distribution associated with the terminal slope following IV administration  
Vz/F: The volume of distribution associated with the terminal slope following SC administration 
divided by the fraction of dose absorbed,  

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F: The absolute BA will be calculated as the ratio of AUCinf for the SC injection and the IV 
infusion of rezafungin administration (Part 3), 
Dose proportionality for SAD and MAD in terms of Cmax and AUC will be assessed using a 
power model, 
AR: Drug observed accumulation ratio (Part 2) 
Other PK parameters may be estimated as appropriate. Additional details for analysis of PK 
endpoints will be provided in the SAP. 

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SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
The site will maintain appropriate medical and research records in compliance with ICH E6, 
Section 4.9 and regulatory and institutional requirements for the protection of confidentiality of 
subjects. The site will permit authorized representatives of the DMID, its designees, and 
appropriate regulatory agencies to examine (and when required by applicable law, to copy) 
clinical records for the purposes of QA reviews, audits, and evaluation of the trial safety and 
progress. These representatives will be permitted access to all source data and source documents, 
which include, but are not limited to, hospital records, clinical and office charts, laboratory notes, 
memoranda, subjects’ memory aid or evaluation checklists, pharmacy dispensing records, 
recorded data from automated instruments, copies or transcriptions certified after verification as 
being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, 
x-rays, and subject files and records kept at the pharmacies, laboratories, and medico-technical 
departments involved in the clinical trial. 
 
Compliance with Standards of Medical Research/Deviations 
This protocol will be conducted in accordance with applicable ICH guidelines and GCP. Any 
instance of noncompliance with the protocol will result in a documented deviation. If a change is 
deemed necessary to protect the safety, rights or welfare of a subject, the Sponsor and IRB/IEC 
will be notified as soon as possible and preferably before introducing the deviation. 

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QUALITY CONTROL AND QUALITY ASSURANCE 
Following a written DMID-accepted Program Quality Management Plan (cQMP), the 
participating site and its subcontractors are responsible for conducting routine quality assurance 
(QA) and quality control (QC) activities to internally monitor study progress and protocol 
compliance. The site principal investigator will provide direct access to all study-related sites, 
source data/data collection forms, and reports for the purpose of monitoring and auditing by the 
sponsor, and inspection by local and regulatory authorities. The site principal investigator will 
ensure all study personnel are appropriately trained and applicable documentations are 
maintained on site. 
The SDCC will implement quality control procedures beginning with the data entry system and 
generate data quality control checks that will be run on the database. Any missing data or data 
anomalies will be communicated to the participating site(s) for clarification and resolution. 
DMID-designated clinical monitors will verify that the clinical trial is conducted, and data are 
generated, documented (recorded), and reported in compliance with the protocol, ICH/GCP 
guidelines, and the applicable regulatory requirements. Clinical monitoring reports will be 
submitted to DMID. 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor may 
conduct a quality assurance assessment and/or audit of the site records, and the regulatory 
agencies may conduct a regulatory inspection at any time during or after the completion of the 
study. In the event of an assessment, audit or inspection, the Investigator (and institution) must 
agree to grant the advisor(s), auditor(s), and inspector(s) direct access to all relevant documents 
and to allocate their time and the time of their staff to discuss the conduct of the study, any 
findings/relevant issues, and to implement any corrective and/or preventative actions to address 
any findings/issues identified. 

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DATA HANDLING AND RECORD KEEPING 
 
Data Management Responsibilities 
The investigator is responsible to ensure the accuracy, completeness, legibility, and timeliness of 
the data reported. All source documents should be completed in a neat, legible manner to ensure 
accurate interpretation of data. Black or blue permanent ink is required to ensure clarity of 
reproduced copies. When making changes or corrections, cross out the original entry with a 
single line, and initial and date the change. DO NOT ERASE, OVERWRITE, OR USE 
CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
Copies of the eCRF will be provided for use as source data collection forms and maintained for 
recording data for each subject enrolled in the study. Data reported in the eCRF derived from 
source data collection forms should be consistent or the discrepancies should be explained. 
The sponsor and/or its designee will provide guidance to the site principal investigators and other 
study personnel on making corrections to the data collection forms and eCRF. 
Training will be provided for the Electronic Data Capture (EDC) system. All personnel using 
the EDC system must have the appropriate education, training, and experience, or any 
combination thereof. The Investigator will be provided with standard operating procedures 
(SOPs) (contained in the SPM or a vendor-specific SOP) on the use of the EDC system. 
Documentation for employee education, training, and previous experience that pertains to the 
EDC system must be present in the Investigator files. 
If electronic data systems other than those provided and maintained by the Sponsor are used for 
documentation and data capture, the Investigator must ensure that the systems are validated and 
ensure regular data back-up. 
The eCRF will be signed by the Investigator or a Sub-Investigator listed on the FDA 1572 
form. It is the responsibility of the Investigator to ensure the eCRFs are completed and 
submitted to the Sponsor (or designee) in an accurate and timely manner. The processing of 
eCRFs will include an audit trail (to include changes made, reason for change, date of change, 
and person making change). At the completion of the study, the Sponsor will be provided with a 
final copy of each eCRF. 
 
 

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Management of clinical data will be performed in accordance with applicable Sponsor 
standards and data cleaning procedures to ensure the integrity of the data (e.g., removing errors 
and inconsistencies in the data). Adverse events and concomitant medications will be coded 
using the MedDRA® and World Health Organization Drug (WHO DD) dictionaries 
respectively. Medical Electronic CRFs will be retained by the Sponsor and copies will be sent to 
the Investigator to maintain as the Investigator copy. 
 
Data Management Responsibilities 
Any source documents and laboratory reports must be reviewed by the clinical team and data 
entry staff, who will ensure their accuracy and completeness. AEs must be recorded on the 
appropriate data collection form, assessed for severity and relationship, and reviewed by the site 
principal investigator or appropriate sub-investigator. AEs must be graded based on the FDA 
Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials September 2007, as modified for this study and as 
appropriate for the administration of rezafungin; see Appendix B. 
Electronic data capture is the responsibility of the clinical trial staff at the site under the 
supervision of the site PI. During the study, the PI must maintain complete and accurate 
documentation for the study. 
Data collection is the responsibility of the study personnel at the participating clinical study site 
under the supervision of the site principal investigator. During the study, the site principal 
investigator must maintain complete and accurate documentation for the study. 
The data coordinating center for this study, Emmes, will be responsible for data management, 
quality review, analysis, and reporting of the study data. 
 
Data Capture Methods 
Clinical data (including, but not limited to, AEs, physical assessments, clinical laboratory values, 
and concomitant medications) will be entered into AdvantageEDCSM, a 21 CFR Part 
11-compliant EDC system managed by Emmes. AdvantageEDCSM access is password protected. 
Access is granted to specific individuals based on the roles identified for this trial. The site enters 
the data into AdvantageEDCSM from the DCFs completed by the study personnel. Data are 
validated through a query resolution process, comprising both automated and manual queries. 

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Types of Data 
Data for this trial will include but are not limited to all data for safety and PK deemed necessary 
for the analysis per protocol, demographic data, ECG data, clinical laboratory values, 
concomitant medications, AEs, photographs, and medical history. 
 
Study Records Retention 
Trial documents will be retained for at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of 
clinical development of the study drug. These documents will be retained for a longer period, 
however, if required by local regulations. No records will be destroyed without the written 
consent of the Sponsor. It is the responsibility of the Sponsor to inform the Site PI when these 
documents no longer need to be retained. 

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CLINICAL MONITORING 
 
Site Monitoring Plan 
Site monitoring is conducted to ensure that the human subject protections, trial and laboratory 
procedures, trial intervention administration, and data collection processes are of high quality 
and meet Sponsor, ICH/GCP guidelines, and applicable regulations, and that this trial is 
conducted in accordance with the protocol, protocol-specific MOP, and applicable Sponsor 
SOPs. DMID, the Sponsor, or its designee will conduct site-monitoring visits as detailed in the 
clinical monitoring plan. 
Site visits will be made at standard intervals as defined by DMID and may be made more 
frequently as directed by DMID. Monitoring visits will include, but are not limited to, review of 
regulatory files, accountability records, eCRFs, ICFs, medical and laboratory reports, and 
protocol and GCP compliance. Site monitors will have access to each site, trial personnel, and all 
trial documentation according to the DMID-approved site monitoring plan. Trial monitors will 
meet with Site PI to discuss any problems and actions to be taken and will document site visit 
findings and discussions. 

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PUBLICATION POLICY 
All investigators funded by the NIH must submit or have submitted for them to the National 
Library of Medicine’s PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/) an electronic 
version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made 
publicly available no later than 12 months after the official date of publication. The NIH Public 
Access Policy ensures the public has access to the published results of NIH funded research. It 
requires investigators to submit final peer-reviewed journal manuscripts that arise from NIH 
funds to the digital archive PubMed Central upon acceptance for publication. Further, the policy 
stipulates that these papers must be accessible to the public on PubMed Central no later than 
12 months after publication. 
Refer to: 
• 
NIH Public Access Policy, http://publicaccess.nih.gov/ 
• 
NIH Office of Extramural Research (OER) Grants and Funding, 
http://grants.nih.gov/grants/oer.htm 
As of January 2018, all clinical trials supported by the NIH must be registered on 
ClinicalTrials.gov, no later than 21 days after the enrollment of the first subject. Results of all 
clinical trials supported by the NIH, generally, need to be submitted no later than 12 months 
following the primary completion date. A delay of up to 2 years is available for trials that meet 
certain criteria and have applied for certification of delayed posting. 
As part of the result posting a copy of this protocol (and its amendments) and a copy of the 
Statistical Analysis Plan will be posted on ClincialTrials.gov. 
For this trial the responsible party is DMID, which will register the trial and post results.   
The responsible party does not plan to request certification of delayed posting. 
Refer to: 
• 
Public Law 110-85, Section 801, Clinical Trial Databases 
• 
42CFR11 
• 
NIH NOT-OD-16-149 

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LITERATURE REFERENCES 
1Schmiedel Y, Zimmerli S. Common invasive fungal diseases: an overview of invasive 
candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia. Swiss Med Wkly. 
2016;146: w14281 
2Wang S, Adrianto I, Wiley GB, Lessard CJ, Kelly JA, et al. A functional haplotype of UBE2L3 
confers risk for systemic lupus erythematosus. Genes Immun. 2012 Jul;13(5):380-7. doi: 
10.1038/gene.2012.6. Epub 2012 Apr 5. 
3Monnet X, Vidal-Petiot E, Osman D, Hamzaoui O, Durrbach A, et al. Critical care management 
and outcome of severe Pneumocystis pneumonia in patients with and without HIV infection 
Crit Care. 2008;12(1): R28. doi: 10.1186/cc6806. Epub 2008 Jan 25. 
  
4Wickramasekaran RN, Jewell MP, Sorvillo F, Kuo T The changing trends and profile of 
pneumocystosis mortality in the United States, 1999-2014. Mycoses. 2017 Sep;60(9):607-615. 
doi: 10.1111/myc.12636. Epub 2017 May 31.  
 
5Martin SI, Fishman JA; AST Infectious Diseases Community of Practice. Pneumocystis 
pneumonia in solid organ transplantation. Am 2013 Mar;13 Suppl 4:272-9. doi: 
10.1111/ajt.12119. 
6Choi YI, Hwang GC, Park JM, Namgoong DH, Jung GW, et al. Clinical Outcomes of 
Pneumocystis carinii Pneumonia in Adult Liver Transplant Recipients. Transplant Proc. 2013 
Oct;45(8):3057-60. doi: 10.1016/j.transproceed.2013.08.074. 
7Iriart X, Challan Belval T, Fillaux J, Esposito L, Lavergne RA, et al. Risk Factors of 
Pneumocystis Pneumonia in Solid Organ Recipients in the Era of the Common Use of Post 
transplantation Prophylaxis. Am J Transplant. 2015 Jan;15(1):190-9. doi: 10.1111/ajt.12947. 
Epub 2014 Dec 12. 
 
8Ainoda Y, Hirai Y, Fujita T, Isoda N, Totsuka K. Analysis of clinical features of non-HIV 
Pneumocystis jirovecii Pneumonia. J Infect Chemother. 2012 Oct;18(5):722-8. doi: 
10.1007/s10156-012-0408-5. Epub 2012 Mar 30. 
 
9Ponce CA, Chabé M, George C, Cárdenas A, Durán L, et al. High prevalence of Pneumocystis 
jirovecii dihydropteroate synthase gene mutations in patients with a first episode of 
Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim 

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sulfamethoxazole therapy. Antimicrob Agents Chemother. 2017 Jan 24;61(2). pii: e01290-16. 
doi: 10.1128/AAC.01290-16. Print 2017 Feb.  
10Cushion, MT, Ashbaugh, A, Lynch K, Linke MJ, Bartizal K Efficacy of CD101, a Novel 
Echinocandin, in Prevention of Pneumocystis Pneumonia (PCP): Thwarting the Biphasic Life 
Cycle of Pneumocystis, ASH 2016. 
 
11Zmarlicka M, Martin ST, Cardwell SM, Nailor MD. Tolerability of low-dose 
sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis in kidney 
transplant recipients. Prog Transplant. 2015 Sep;25(3):210-6. doi: 10.7182/pit2015153. 
 
12Epstein DJ, Seo SK, Huang YT, Park JH, Klimek VM, et al. Micafungin versus posaconazole 
prophylaxis in acute leukemia or myelodysplastic syndrome: A randomized study. J Infect. 2018 
Sep;77(3):227-234. doi: 10.1016/j.jinf.2018.03.015. Epub 2018 May 7. 
13Mourad A, Perfect JR. Tolerability profile of the current antifungal armoury. J Antimicrob 
Chemother 2018; 73 Suppl 1: i26–i32, doi:10.1093/jac/dkx446. 
 
14Sandison T, Ong V, Lee J, Thye D. Safety and pharmacokinetics of CD101 IV, a novel 
echinocandin, in healthy adults. Antimicrob Agents Chemother. 2017 Jan 24;61(2). pii: e01627-
16. doi: 10.1128/AAC.01627-16. Print 2017 Feb. 
 
15Ong V, Hough G, Schlosser M, Bartizal K, Balkovec JM, et al. 
Preclinical evaluation of the stability, safety, and efficacy of CD101, a novel echinocandin. 
Antimicrob Agents Chemother. 2016 Oct 21;60(11):6872-6879. doi: 10.1128/AAC.00701-16. 
Print 2016.  
 
16Alert, Oprs. “Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial 
Clinical Trials for Therapeutics in Adult Healthy Volunteers.” (2005) 
 
 

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APPENDICES 
 
 

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  Schedules of Events 
 
Table 11: Schedule of Study Procedures and Evaluations for Cohorts 1-6 in SAD (Part 1) 
Procedures/Day 
Screening 
Baseline 
Check-in 
Inpatient – Confined to CRU 
FU 
Phone  
FU 
FU/ 
ET 
Unscheduled 
-28 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
14 
(±1) 
 
21 
(±1) 
30 
(±1) 
Informed Consent 
Forma 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of 
Eligibility Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Heightb, Weight, BMI 
X 
X 
 
 
 
 
 
 
 
 
 
X 
 
Review of Medical 
History 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis and HIV 
testsc 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Follicle-stimulating 
hormone(FSH) testd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy teste 
X 
X 
 
 
 
 
 
 
 
 
 
X 
 
Review of 
Concomitant 
Medications 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
X 
X 
Study drug 
randomization just 
prior to dosingf 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Administration of 
study drugg 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Vital signsh 
X 
X 
X 
X 
 
X 
 
 
X 
X 
 
X 
X 
Physical examinationi 
X 
X 
X 
X 
 
X 
 
 
X 
 
 
X 
X 
12-lead ECGsj 
X 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
Blood for hematology 
& coagulationk 
X 
X 
 
X 
 
 
 
 
X 
 
 
X 
X 
Blood for chemistry 
panelk 
X 
X 
 
X 
 
 
 
 
X 
 
 
X 
X 
Urine for urinalysis, 
drug screen, alcoholl 
X 
X 
 
X 
 
 
 
 
X 
 
 
X 
X 
Urine cotinine 
X 
X 
 
 
 
 
 
 
 
 
 
 
 

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Procedures/Day 
Screening 
Baseline 
Check-in 
Inpatient – Confined to CRU 
FU 
Phone  
FU 
FU/ 
ET 
Unscheduled 
-28 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
14 
(±1) 
 
21 
(±1) 
30 
(±1) 
Blood for PK 
analysism 
 
 
X 
X 
X 
 
X 
 
X 
X 
 
X 
 
Reactogenicity 
evaluationn 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment for AEso 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Counsel/remindersp 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
 
Memory Aidq 
 
 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
Abbreviations: AE: adverse event; BMI: body mass index; CRU: clinical research unit; ECG: electrocardiogram; 
FU: follow-up; HIV: human immunodeficiency virus; PK: pharmacokinetic. 
a. 
Informed consent will be obtained before initiating any trial-related assessments and procedures, 
b. Height at Screening only, 
c. 
Screen (serum) for hepatitis B surface antigen, hepatitis C virus antibody, and HIV antibody, 
d. Perform FSH (serum) test in postmenopausal females only, 
e. 
Perform serum pregnancy tests at Screening, Day -1, and Day 30 females only, 
f. 
Randomize subjects on Day 1 just before dosing, 
g. A single dose of study drug will be administered via SC injection on Day 1, 
h. Vital signs will be obtained at Screening; on Day -1, on Day 1 prior to study drug administration 
(within 60 minutes prior to study drug) and at 15 minutes (±5 min), 1 hour (±10 min) and 2 
hours(±10 min)  post-dose;  at 24, 72, 144 hours (±30 min), post-dose( Days 2, 4, and 7), and 
Days 14 (±1 day), and 30 (±1 day), 
i. 
A complete PE will be performed at Screening and targeted PEs will be performed on Days -1, 1, 
2, 4, 7, and 30 (±1 day), 
j. 
ECGs will be obtained at Screening and on Day 1 within 60 minutes prior to study drug 
administration, and 4 hours (± 10 minutes) post-dose, Day 7, Day 30, and Unscheduled visits 
k. Fasting (at least 8 hours) blood samples will be collected for hematology, coagulation and 
chemistries at Screening and on Days -1, 2, 7, and 30 (±1 day), Hematology tests consist of CBC 
with differential; coagulation tests consist of PT/PTT/INR; Chemistries panel includes albumin, 
glucose, blood urea nitrogen or urea, potassium, calcium, sodium, chloride, total protein, 
creatinine, CO2, CK, phosphorus, alkaline phosphatase, AST, ALT, total bilirubin, direct 
bilirubin, 
l. 
Urine will be collected for urinalysis, urine drug screen and urine alcohol at Screening and on 
Day -1. Urine will be collected for urinalysis on Days 2, 7, and 30 (±1 day),   
m. Collect PK blood samples within 60 minutes before study drug dosing and at 0.5 (±5 min), 1, 2, 
4, 6, 8, and 12 hours (±10 min),on (Day 1; 24 hours (±30 min) on Day 2; 48 hours (±30 min) on  
Day 3; 96 hours (±30 min) onDay 5; and 144 hours (±30 min) onDay 7 after dosing; and on Days 
14 (±1 day) and 30 (±1 day), (No PK blood sample collection for Cohort 1) 

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n. Injection site assessment pre-dose and at 1 and 4 (± 10 min), 24, 48, 72, 96, 120, and 144 h (± 30 
min) post dose, Day 14 (±1 day), Day 21 (±1 day), and Day 30 (±1 day). Unscheduled visits are 
not timed.  
o. Subjects are to be assessed for AEs occurring from the time of the first dose of study drug 
through Day 30 (±1 day), 
 
p. Counsel/reminder on contraceptive use and post-discharge instructions (dietary and 
medication/nonmedication vaccine and blood/blood product/sperm donation restrictions);as 
described in Section 5.1. 
q. Memory Aid issued on Day 1, training on Day 7, and review on Days 14, 21, and 30 and at 
Unscheduled visits. 
 
Table 12: Schedule of Study Procedures and Evaluations for Cohorts 7-10 in MAD (Part 2) 
Procedures/Day 
Screening 
Baseline 
Check-in 
Inpatient – Confined to CRU 
FU 
FU/ 
ET 
Unscheduled 
-28 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
30 
(±1) 
45 
(±1) 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
Informed Consent 
Forma 
X 
 
 
 
 
 
 
 
 
 
 
 
Assessment of 
Eligibility Criteria 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Heightb, Weight, BMI 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
Review of Medical 
History 
X 
X 
 
 
 
 
 
 
 
 
 
 
Hepatitis and HIV 
testsc 
X 
 
 
 
 
 
 
 
 
 
 
 
Follicle-stimulating 
hormone (FSH) testd 
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy teste 
X 
X 
 
 
 
 
 
 
 
 
X 
 
Review of 
Concomitant 
Medications 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Study drug 
randomization just 
prior to dosingf 
 
 
X 
 
 
 
 
 
 
 
 
 
Administration of 
study drugg 
 
 
X 
 
 
 
 
 
 
 
 
 
Vital signsh 
X 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 
Physical examinationi 
X 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 

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Procedures/Day 
Screening 
Baseline 
Check-in 
Inpatient – Confined to CRU 
FU 
FU/ 
ET 
Unscheduled 
-28 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
30 
(±1) 
45 
(±1) 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
12-lead ECGsj 
X 
 
X 
 
 
 
 
 
X 
X 
X 
X 
Blood for hematology 
& coagulationk 
X 
X 
 
X 
 
 
 
 
X 
 
X 
X 
Blood for chemistry 
panelk 
X 
X 
 
X 
 
 
 
 
X 
 
X 
X 
Urine for urinalysis, 
drug screen, alcoholl 
X 
X 
 
X 
 
 
 
 
X 
 
X 
X 
Urine cotinine 
X 
X 
 
 
 
 
 
 
 
 
 
 
Blood for PK 
analysism 
 
 
X 
X 
X 
 
X 
 
X 
X 
X 
 
Reactogenicity 
evaluationn 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess for AEso 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Counsel/remindersp 
X 
 
 
 
 
 
 
 
X 
X 
X 
 
Memory Aidq 
 
 
X 
 
 
 
 
 
X 
X 
X 
X 
Abbreviations: AE: adverse event; BMI: body mass index; CRU: clinical research unit; ECG: electrocardiogram; 
FU: follow-up; HIV: human immunodeficiency virus; PK: pharmacokinetic. 
a. 
Informed consent will be obtained before initiating any trial-related assessments and procedures, 
b. Height at Screening only, 
c. 
Screen (serum) for hepatitis B surface antigen, hepatitis C virus antibody, and HIV antibody, 
d. Perform FSH (serum) test in postmenopausal females only, 
e. 
Perform serum pregnancy tests at Screening, Day -1, and Day 45 females only, 
f. 
Randomize subjects on Day 1 only, 
g. A single dose of study drug will be administered via SC injection on Days 1, 8, and 15, 
h. Vital signs will be obtained at Screening; on Day -1; on Day 1 within 60 minutes prior to study 
drug administration and at 15 minutes (±5 min), 1 hour (±10 min) and 2 hours (± 10 min) post-
dose; and at 24, 72 and 144 hours (±30 min) post-dose on Days 2, 4, 7, 8, 9, 11, 14, 15, 16, 18, 
and 21; and on Days 30 (±1 day), and 45 (±1 day), 
i. 
A complete PE will be performed at Screening and targeted PEs will be performed on Days -1, 1, 
2, 4, 7, 8, 9, 11, 14, 15, 16, 18, 21, 30 (± 1 day), and 45 (±1 day), 
j. 
ECGs will be obtained at Screening and on Day 1 within 30 minutes prior to study drug 
administration, and 4 hours (± 10 minutes) post-dose (Days 1, 8, and 15), Day 21, Day 30, Day 
45, and Unscheduled visits 
k. Fasting (at least 8 hours) blood samples will be collected for hematology, coagulation and 
chemistries at Screening and on Days -1, 2, 9, 16, 7, 14, 21 and 45 (±1 day). Hematology tests 
consist of CBC with differential; coagulation tests consist of PT/PTT/INR; Chemistries panel 
includes albumin, glucose, blood urea nitrogen or urea, potassium, calcium, sodium, chloride, 

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total protein, creatinine, CO2, CK, phosphorus, alkaline phosphatase, AST, ALT, total bilirubin, 
direct bilirubin, 
l. 
Urine will be collected for urinalysis, urine drug screen and urine alcohol at Screening, and on 
Day -1.  Urine will be collected for urinalysis on Days 2, 7, 9, 14, 16, 21, and 45 (±1 day), 
m. Blood for PK analysis (plasma) will be drawn pre-dose within 60 minutes before study drug 
dosing and at at 0.5 h (±5 min), 1 h (±10 min), 2 h (±10 min), 4 h (±10 min), 6 h (±10 min), 8 h 
(±10 min), and 12 h (±10 min),(Days 1 and 15); pre-dose within 15 minutes before study drug 
dosing and at 1 (±10 min), and 4 hours (±10 min), on Day 8; 24 hours (±30 min), on Days 2 and 
16; 48 hours (±30 min) on Days 3 and 17; 96 hours (±30 min, on Days 5, 12, and 19; and 144 
hours (±30 min) onDays 7, 14, and 21 after dosing; and on Days 30 (±1 day) and 45 (±1 day), 
n. Injection site assessment pre-dose and at 1 and 4 (± 10 min), 24, 48, 72, 96, 120, and 144 h (± 30 
min) post-dose, Day 30 (±1 day), and Day 45 (±1 day). Unscheduled visits are not timed. 
o. Subjects are to be assessed for AEs occurring from the time of the first dose of study drug 
through Day 45 (±1 day), 
p. Counsel/reminder on contraceptive use and post-discharge instructions (dietary and 
medication/nonmedication, vaccine and blood/blood product/sperm donation restrictions); as 
described in Section 5.1. 
q. Memory Aid issued on Day 1, training on Day 7, and review on Days 30, 45 and at Unscheduled 
visits. 
 
 
 
Table 13: Schedule of Study Procedures and Evaluations for Cohort 11 in BA (Part 3) 
Procedures/Day 
Screening 
Baseline 
Check-in 
Inpatient – Confined to CRU 
FU 
FU/ 
ET 
Unscheduled 
-28 to -2 
-1 and 21 
1 
2 
3 
4 
5 
6 
7 
14 
and 
35 
(±1) 
52 
(±1) 
22 
23 
24 
25 
26 
27 
28 
Informed Consent 
Forma 
X 
 
 
 
 
 
 
 
 
 
 
 
Assessment of 
Eligibility Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Heightb, Weight, BMI 
X 
X 
 
 
 
 
 
 
 
 
X 
 
Review of Medical 
History 
X 
X 
 
 
 
 
 
 
 
 
 
 
Hepatitis and HIV 
testsc 
X 
 
 
 
 
 
 
 
 
 
 
 
Follicle-stimulating 
hormone (FSH) testd 
X 
 
 
 
 
 
 
 
 
 
 
 

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Procedures/Day 
Screening 
Baseline 
Check-in 
Inpatient – Confined to CRU 
FU 
FU/ 
ET 
Unscheduled 
-28 to -2 
-1 and 21 
1 
2 
3 
4 
5 
6 
7 
14 
and 
35 
(±1) 
52 
(±1) 
22 
23 
24 
25 
26 
27 
28 
Pregnancy teste 
X 
X 
 
 
 
 
 
 
 
 
X 
 
Review of 
Concomitant 
Medications 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Study drug 
randomization just 
prior to dosingf 
 
 
X 
 
 
 
 
 
 
 
 
 
Administration of 
study drugg 
 
 
X 
 
 
 
 
 
 
 
 
 
Vital signsh 
X 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 
Physical examinationi 
X 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 
12-lead ECGsj 
X 
 
X 
 
 
 
 
 
 
 
X 
X 
Blood for hematology 
& coagulationk 
X 
X 
 
X 
 
 
 
 
X 
 
X 
X 
Blood for chemistry 
panelk 
X 
X 
 
X 
 
 
 
 
X 
 
X 
X 
Urine for urinalysis, 
drug screen, alcoholl 
X 
X 
 
X 
 
 
 
 
X 
 
X 
X 
Urine cotinine 
X 
X 
 
 
 
 
 
 
 
 
 
 
Blood for PK 
analysism 
 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Reactogenicity 
evaluationn 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Assess for AEso 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Counsel/remindersp 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
Memory Aidq 
 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
Abbreviations: AE: adverse event; BMI: body mass index; CRU: clinical research unit; ECG: electrocardiogram; 
FU: follow-up; HIV: human immunodeficiency virus; PK: pharmacokinetic. 
a. 
Informed consent will be obtained before initiating any trial-related assessments and procedures, 
b. Height at Screening only, 
c. 
Screen (serum) for hepatitis B surface antigen, hepatitis C virus antibody, and HIV antibody, 
d. Perform FSH (serum) test for postmenopausal (females only), 
e. 
Perform serum pregnancy tests at Screening Day -1 and Day 52 females only, 
f. 
Randomize subjects on Day 1 only, 
g. A single dose of study drug will be administered via SC injection/IV infusion on Days 1 and 22, 

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h. Vital signs will be obtained at Screening; on Day -1; on Days 1 and 22 within 60 minutes to 
study drug administration and at 15 minutes (±5 min), 1 and 2 hours (±10 min), post-dose; and on 
Days 2, 4, 7, 23, 25, 28 (±30 min) and 14 (±1 day), 35 (±1 day), and 52 (±1 day), 
i. 
A complete PE will be performed at Screening and targeted PEs will be performed on Days -1, 1, 
2, 4, 7, 14, 22, 23, 25, 28, 35, and 52. Days 14, 35, and 52 have (±1 day) window. 
j. 
ECGs will be obtained at Screening and on Day 1 within 60 minutes prior to study drug 
administration, and 4 hours (± 10 minutes) post-dose (SC) and 1 hour (± 10 minutes) post-dose 
(IV) from start of infusion for IV admin, Day 52, and Unscheduled visits 
k. Fasting (at least 8 hours) blood samples will be collected for hematology, coagulation and 
chemistries at Screening and on Days -1,2, 7, 23, 28, and 52 (±1 day), Hematology tests consist 
of CBC with differential; coagulation tests consist of PT/PTT/INR; Chemistries panel includes 
albumin, glucose, blood urea nitrogen or urea, potassium, calcium, sodium, chloride, total 
protein, creatinine, CO2, CK, phosphorus, alkaline phosphatase, AST, ALT, total bilirubin, direct 
bilirubin, 
l. 
Urine will be collected for urinalysis, urine drug screen and urine alcohol at Screening, and on 
Day -1. Urine will be collected for urinalysis on Days 2, 7, 23, 28, and 52 (±1 day), 
m. Blood for PK analysis (plasma) will be drawn pre-dose within 60 minutes before study drug 
dosing and at 0.5(±5 min), 1, 2, 4, 6, 8, and 12 hours (±10 min) on Days 1 and 22; 24 hours (±30 
min), on Days 2 and 23; 48 hours(±30 min) on Days 3 and 24; 96 hours (±30 min),  on Days 5 
and 26; and 144 hours (±30 min) on Days 7 and 28 after dosing; and on Days 14 and 35 (±1 day) 
and 52 (±1 day), 
n. Injection site assessment pre-dose and at 1 and 4 (± 10 min), 24, 48, 72, 96, 120, and 144 h (± 30 
min) post-dose, Day 14 (±1 day), and Day 35 (±1 day). Unscheduled visits are not timed. 
o. Subjects are to be assessed for AEs occurring from the time of the first dose of study drug 
through Day 52 (±1 day), 
p. Counsel/reminder on contraceptive use and post-discharge instructions (dietary and 
medication/nonmedication, vaccine and blood/blood product/sperm donation restrictions);as 
described in Section 5.1. 
q. Memory Aid issued on Day 1, training on Day 7 (refresher on Day 28), reviewed on Days 21, 14, 
35, 52 and at Unscheduled visits. 
 
 
 

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 TOXICITY TABLE 
Clinical Adverse Events 
VITAL SIGNS 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
Grade 3 
Fever - °C 
  
 
38.0-38.4 
  
 
38.5-38.9 
  
 
>38.9 
  
 
Tachycardia - bpm 
101-115 
116-130 
>130 or ventricular 
dysrhythmias 
Bradycardia – bpm 
• 
Baseline ≥60 
OR, if 
                Baseline <60 
•   50-54  
OR, if Baseline 
<60,  
•   45-50 
•    45-49  
OR, if baseline <60,  
•         40-44 
•   <45  
OR, if baseline <60 
•     <40 
Hypertension (systolic) - mmHg 
141-150 
151-160 
>160 
Hypertension (diastolic) - mmHg 
91-95 
96-100 
>100 
Hypotension (systolic) - mmHg 
85-89 
80-84 
<80 
Tachypnea – breaths per min 
23-25 
26-30 
>30 
CARDIOVASCULAR 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Arrhythmia 
   
Asymptomatic; transient signs; 
no medical intervention required  
Recurrent/persistent; 
symptomatic medical 
intervention required  
Hemorrhage, Blood Loss  
Estimated blood 
loss ≤100 mL  
Estimated blood loss >100 mL; 
no transfusion required 
Transfusion required 

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QTc (Fridericia’s correction)1 
 
 
Asymptomatic, 
QTc interval 
450-479 msec  
Asymptomatic; QTc interval 480 
to 499 msec OR Increase in 
interval 30-59 msec above 
baseline 
Asymptomatic; QTc 
interval ≥ 500 msec OR 
Increase in interval ≥ 60 
msec above baseline 
PR Interval (prolonged)1 
PR interval 
0.21-0.25 sec 
PR interval >0.25 
Type II 2nd degree AV 
block OR Ventricular 
pause >3.0 sec 
RESPIRATORY    
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Cough 
Transient; no 
treatment  
Persistent cough  
Interferes with daily 
activities 
Bronchospasm, Acute 
Transient; no 
treatment; 
FEV1 71-80% 
of predicted 
peak flow  
Requires medical intervention; 
normalizes with bronchodilator; 
FEV1 60-70% of predicted peak 
flow  
No normalization with 
bronchodilator; FEV1 
<60% of predicted peak 
flow 
Dyspnea   
Does not 
interfere with 
usual and social 
activities 
Interferes with usual and social 
activities; no treatment 
Prevents daily and 
usual social activity OR 
requires treatment 
GASTROINTESTINAL   
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Nausea  
No interference 
with activity 
Some interference with activity 
Prevents daily activities 
Vomiting  
No interference 
with activity 
OR 1-2 
episodes/24 
hours 
Some interference with activity 
OR >2 episodes/24 hours 
Prevents daily activity 
OR requires IV 
hydration OR requires 
medical intervention 
 
 
1Inclusion dependent upon protocol requirements. 

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Diarrhea  
2-3 loose or 
watery stools or 
<400 g/24 hours 
4-5 loose or watery stools or 
400-800 g/24 hours 
≥6 loose or watery 
stools or >800g/24 
hours OR requires IV 
hydration OR requires 
medical intervention 
REACTOGENICITY 
 
 
 
LOCAL REACTIONS 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Pain – experienced without 
touching the injection site 
(spontaneous discomfort) 
Does not 
interfere with 
activity 
Repeated use of non-narcotic 
pain reliever >24 hours OR 
interferes with activity 
Any use of narcotic 
pain reliever OR 
prevents daily activity 
Tenderness – hurts only when 
injection site is touched, or the 
arm is moved 
Discomfort only 
to touch 
Discomfort with movement 
Significant discomfort 
at rest 
Pruritus (Itching) 
Does not 
interfere with 
daily activity 
Interferes with daily activity 
Prevents daily activity 
Ecchymosis (Bruising)* 
Does not 
interfere with 
daily activity 
Interferes with daily activity 
Prevents daily activity 
Erythema (Redness)* 
Does not 
interfere with 
daily activity 
Interferes with daily activity  
Prevents daily activity 
Induration (Hardness)/Swelling* 
Does not 
interfere with 
daily activity 
Interferes with daily activity  
Prevents daily activity 
Nodule 
Does not 
interfere with 
daily activity 
Interferes with daily activity  
Prevents daily activity 
Ulcer 
Does not 
interfere with 
daily activity 
Interferes with daily activity  
Prevents daily activity 
Ecchymosis (Bruising)* 
25 mm – 
50 mm 
51 mm – 100 mm 
>100 mm 

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Erythema (Redness)* 
25 mm – 
50 mm 
51 mm – 100 mm 
>100 mm 
Induration 
(Hardness)/Swelling* 
25 mm – 
50 mm 
51 mm – 100 mm 
>100 mm 
Nodule 
25 mm – 
50 mm 
51 mm – 100 mm 
>100 mm 
Ulcer 
1 mm – 50 mm 
51 mm – 100 mm 
>100 mm 
SYSTEMIC REACTIONS 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Allergic Reaction  
Pruritus without 
rash  
Localized urticaria OR requires 
oral therapy 
Generalized urticaria; 
angioedema OR 
anaphylaxis OR 
requires epinephrine 
Headache  
No interference 
with activity 
Repeated use of non-narcotic 
pain reliever >24 hours OR some 
interference with activity 
Significant; any use of 
narcotic pain reliever 
OR prevents daily 
activity OR requires 
triptans  
Fatigue  
No interference 
with activity 
Some interference with activity 
Significant; prevents 
daily activity 
Myalgia 
No interference 
with activity 
Some interference with activity 
Significant; prevents 
daily activity 
All Other conditions 
Mild  
(Grade 1) 
Moderate  
(Grade 2) 
Severe  
(Grade 3)  
Illness or clinical AE (as 
defined according to applicable 
regulations) 
No interference 
with activity 
Some interference with activity 
not requiring medical 
intervention 
Prevents daily activity 
and requires medical 
intervention 
 
*Will not be used as halting criteria. 
 

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Laboratory and Vital Signs Reference Ranges, Eligibility Ranges, and Toxicity Grading 
Laboratory Adverse Events* 
Mild 
Moderate  
Severe 
(Grade 1) 
(Grade 2) 
(Grade 3) 
Blood, Serum, or Plasma 
Sodium (hyponatremia) – mEq/L 
131-132 
129-130 
<129 
Sodium (hypernatremia) – 
mEq/L 
144 – 145 
146 – 147 
>147 
Potassium (hyperkalemia) – 
mEq/L 
5.2 – 5.4 
5.5 – 5.6 
>5.6 
Potassium (hypokalemia) – 
mEq/L 
3.2-3.4 
3.0 – 3.1 
<3.0 
Glucose (hypoglycemia) – 
mg/dL 
65 – 69 
55 – 64 
<55 
Glucose (hyperglycemia) – 
mg/dL Fasting 
106 – 125 
126 – 200 
>200 
Blood Urea Nitrogen – mg/dL 
21-26 
27 – 31 
> 31 
Creatinine (Male) – mg/dL 
1.3 – 2.0 
2.1-2.3 
>2.3 
Creatinine (Female) – mg/dL 
1.0 – 1.7 
1.8 – 2.0 
>2.0 
Calcium (hypocalcemia) – 
mg/dL 
8 - <LLN 
7.5 – 7.9 
<7.5 
Calcium (hypercalcemia) – 
mg/dL 
ULN - 10.8  
10.9 – 11.4 
>11.4 
CK-U/L  
309-1000 
1001-1500 
>1500 
Albumin (hypoalbuminemia) – 
g/dL 
2.8 – 3.4 
2.5 – 2.7 
< 2.5 
AST – U/L (Male) 
40-97 
98-195 
>195 
AST – U/L (Female) 
32-77 
78-155 
>155 
ALT – U/L (Male) 
41-100 
101-200 
>200 
ALT – U/L (Female) 
33-80 
81-160 
>160 

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Laboratory Adverse Events* 
Mild 
Moderate  
Severe 
(Grade 1) 
(Grade 2) 
(Grade 3) 
Alkaline phosphatase – IU/L 
(Male) 
131-260 
261-390 
>390 
Alkaline phosphatase – IU/L 
(Female) 
106-210 
211-315 
>315 
Total Bilirubin (serum) – mg/dL 
1.3-1.5 
1.6-1.9 
>1.9 
Direct Bilirubin – mg/dL 
NA 
NA 
NA 
Chloride –mEq/L 
(hypochloremia) 
NA 
NA 
NA 
Chloride –mEq/L 
(hyperchloremia) 
NA 
NA 
NA 
CO2 –mEq/L  (hypo) 
NA 
NA 
NA 
CO2 –mEq/L (hyper) 
NA 
NA 
NA 
Total Protein – g/dL 
5.5 - 5.9 
5.0 - 5.4 
<5.0 
Phosphorus- mg/dl  (hypo) 
2.3-2.4 
2.1-2.2 
<2.0 
Phosphorus-mg/dl  (hyper) 
NA 
NA 
NA 
Hemoglobin (Male) – g/dL 
11.2 - 12.2 
10.0 – 11.1 
<10.0 
Hemoglobin (Female) – g/dL 
9.8 - 10.8 
8.5 - 9.7 
<8.5 
WBC Increase – cell/mm3 
10,001– 15,000 
15,001 – 20,000 
> 20,000 
WBC Increase – cell/mm3 
(African America Males) 
9,001 – 14, 000 
14,001 – 19, 000 
>19,000 
WBC Increase – cell/mm3 
(African American Females) 
11,001 – 15,000 
15,001 – 20,000 
>20,000 
WBC Decrease – cell/mm3 
2,500– 3,999 
1,500 – 2,499 
< 1,500 
WBC Decrease – cell/mm3 
(African American Males) 
2,200 – 2,499 
1,200 – 2,199 
<1,200 
WBC Decrease – cell/mm3 
(African American Females) 
2,200 – 2,499 
1,500 – 2,199 
<1,500 

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Laboratory Adverse Events* 
Mild 
Moderate  
Severe 
(Grade 1) 
(Grade 2) 
(Grade 3) 
Neutrophils Decrease – cell/mm3 
1,300 – 1,699 
1,000 – 1,299 
< 1,000 
Neutrophils Decrease – cell/mm3 
(African American Males) 
1,000 – 1,299 
800 - 999 
<800 
Neutrophils Decrease – cell/mm3 
(African American Females) 
1,100 – 1,299 
1,000 – 1,099 
<1,000 
Platelets Decreased – 10^3/mm3 
120 – 149 
100 – 119 
<100 
Hematocrit (Male) - % 
33.0 -36.1 
29.8 - 32.9 
< 29.8 
Hematocrit (Female) - %  
29.5 - 32.6 
26.0 – 29.4 
< 26.0 
RBC (Male) – x 106/uL   
3.9 - 4.1 
3.4 - 3.8 
< 3.4 
RBC (Female) – x 106/uL   
3.5 - 3.7 
3.0 - 3.4 
< 3.0 
Lymphocytes - cell/mm3 
decrease 
600- 799 
500 – 599 
< 500 
Monocytes – cell/mm3     
increase 
1001-2000 
2001-3000 
>3000 
Eosinophils - cell/mm3     
increase 
871 - 950 
951 - 1700 
>1700 
Basophils - cell/mm3       increase 
101 - 300 
301 - 800 
> 800 
PT (prothrombin time) – seconds 
11.6-12.6 
12.7-13.7 
>13.7 
PT INR (Prothrombin INR) 
1.2-1.4 
1.5-1.9 
2.0 or higher 
PTT (partial thromboplastin 
time) –seconds 
30.1-36.8 
36.9-43.6 
>43.6 
Urine 
Protein 
1+ 
2+ 
>2+ 
Glucose 
1+ 
2+ 
>2+ 
Blood (microscopic) - red blood 
cells per high power field 
(rbc/hpf)** 
3-10* 
11-50* 
>50 and/or 
gross blood** 

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Laboratory Adverse Events* 
Mild 
Moderate  
Severe 
(Grade 1) 
(Grade 2) 
(Grade 3) 
*Abnormal laboratory values, performed as part of hematology, chemistry panel, or urinalysis 
but not listed in Appendix B, will be evaluated by the study clinicians, recorded in the source 
document and, if clinically significant, considered AEs and graded according to the criterion 
described in Section 8.1.