Open-Label Study to Evaluate the Efficacy and Safety of SCY-078 (Ibrexafungerp) in Patients With Fungal Diseases That Are Refractory to or Intolerant of Standard Antifungal Treatment (FURI)
Phase: PHASE3
Conditions: Invasive Candidiasis, Mucocutaneous Candidiasis, Coccidioidomycosis, Histoplasmosis, Blastomycosis, Chronic Pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis, Invasive Pulmonary Aspergillosis, Recurrent Vulvovaginal Candidiasis, Other Emerging Fungi
Sponsor: Scynexis, Inc.

 
 
SCYNEXIS, Inc. 
Clinical Trial Protocol 
Open-Label Study to Evaluate the Efficacy and Safety of SCY-078 
(Ibrexafungerp) in Patients with Fungal Diseases that are Refractory to, 
Resistant to or Intolerant of Standard Antifungal Treatment (FURI) 
SCYNEXIS Protocol Number SCY-078-301 
 
 
 
Original Protocol Issue Date: 
 
30 November 2016 
Protocol Amendment 1 Issue Date:  
23 March 2017 
Protocol Amendment 2 Issue Date  
13 August 2019 
Protocol Amendment 3 Issue Date:  
21 November 2022 
US IND Number 107,521  
EudraCT Number 2017-000381-29 
STATEMENT OF CONFIDENTIALITY 
The information in this document contains trade secrets and commercial information 
that are privileged or confidential and may not be disclosed unless such disclosure is 
required by federal or state law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or 
confidential and may not be further disclosed by them. These restrictions on disclosure 
will apply equally to all future information supplied to you which is indicated as 
privileged or confidential. 

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Contact Information 
 
  Contract Research Organization 
 
 
 
Study Medical Monitor 
 
 
 
Clinical Project Manager 
 
  
Safety Contact  
 
 
Sponsor 
SCYNEXIS, Inc. 
 
 
 
 

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Protocol Approvals 
 
 
 
PROTOCOL ID: SCY-078-301 
 
Open-Label Study to Evaluate the Efficacy and Safety of Ibrexafungerp in Patients with 
Fungal Diseases that are Refractory to, Resistant to or Intolerant of Standard Antifungal 
Treatment (FURI) 
SCYNEXIS, Inc. Approval: 
 
 
 
 
21 November 2022 
VP Clinical Development and Medical Affairs 
1 Evertrust Plaza, 13th Floor  
Jersey City, NJ 07302 
Phone: +201 884 2243 
Fax: +1 201 884 5490 
E-mail: nkechi.azie@scynexis.com 
 
Date 
 

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Investigator Agreement Statement 
PROTOCOL ID: SCY-078-301 
Open-Label Study to Evaluate the Efficacy and Safety of Ibrexafungerp in Patients with 
Fungal Diseases that are Refractory to, Resistant to or Intolerant of Standard Antifungal 
Treatment (FURI) 
 
I understand that all documentation provided to me by SCYNEXIS, Inc. or its designated 
representative(s) concerning this study that has not been published previously will be kept 
in the strictest confidence. This documentation includes the study protocol, Investigator’s 
Brochure, case report forms, and other scientific data. This study will not commence 
without the prior written approval of a properly constituted Institutional Review Board or 
Ethics Committee. No changes will be made to the study protocol without the prior written 
approval of SCYNEXIS, Inc. and the Institutional Review Board/Ethics Committee, except 
where necessary to eliminate an immediate hazard to the subject. All patients will provide 
a written informed consent prior to participation. If the patient is not able to provide written 
consent due to the severity of their illness and I consider the patient’s condition to be life-
threatening or highly debilitating without participation in this clinical study, I will obtain 
written consent from a legal representative (LAR) of the patient. Once the patient is able 
to provide oral or written consent, I will obtain appropriate consent. If the patient is capable 
of giving consent but does not give consent to continue, the patient will be withdrawn from 
the trial. 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I have read, understood and 
agree to abide by all the conditions and instructions contained in this protocol, and in 
compliance with International Conference on Harmonization (ICH) guidelines, Good 
Clinical Practices (GCP), Safety Reporting obligations and any applicable local 
requirements. 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
Principal Investigator’s Name (Printed) 
 
 

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Table of Contents 
1.0 
Contact Information ................................................................................................ 2 
2.0 
Protocol Approvals ................................................................................................. 3 
3.0 
Table of Contents .................................................................................................... 5 
4.0 
Abbreviations ........................................................................................................ 11 
5.0 
Protocol Synopsis.................................................................................................. 14 
6.0 
Schematic of Study Design ................................................................................... 22 
7.0 
Background Information and Scientific Rationale ............................................... 23 
7.1 
Background Information ............................................................................... 23 
7.2 
Rationale for the Study ................................................................................. 30 
8.0 
Study Objectives ................................................................................................... 31 
8.1 
Primary Objectives........................................................................................ 31 
8.2 
Secondary Objectives.................................................................................... 31 
8.2.1 
Overall Secondary Objectives................................................................... 31 
8.2.2 
Disease-Specific Secondary Objectives .................................................... 31 
9.0 
Study Endpoints .................................................................................................... 31 
9.1 
Primary Endpoints ........................................................................................ 31 
9.2 
Secondary Endpoints .................................................................................... 32 
9.2.1 
Overall Secondary Endpoints ................................................................... 32 
9.2.2 
Disease-Specific Secondary Endpoints ..................................................... 32 
10.0 
Study Design ......................................................................................................... 34 
10.1 
Overall Description of the Study .................................................................. 34 
10.2 
Blinding, Randomization and Stratification ................................................. 37 
10.3 
Study Duration .............................................................................................. 37 
10.4 
Number of Centers ........................................................................................ 37 
11.0 
Study Population ................................................................................................... 37 
11.1 
Inclusion Criteria .......................................................................................... 37 
11.2 
Exclusion Criteria ......................................................................................... 47 

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11.3 
Discontinuation Criteria ................................................................................ 48 
11.4 
Replacement of Discontinued Subjects ........................................................ 48 
12.0 
Study Treatments .................................................................................................. 48 
12.1 
Study Treatment Groups ............................................................................... 48 
12.1.1 
Ibrexafungerp Monotherapy for All Fungal Diseases, Excluding VVC ... 49 
12.1.2 
Ibrexafungerp Monotherapy for VVC ...................................................... 49 
12.1.3 
Ibrexafungerp Combination Therapy ........................................................ 50 
12.1.4 
Dietary Requirements ............................................................................... 51 
12.2 
Study Drugs .................................................................................................. 51 
12.2.1 
Ibrexafungerp Description ........................................................................ 51 
12.2.2 
Formulation, Packaging and Labelling ..................................................... 52 
12.2.3 
Storage and Stability ................................................................................. 52 
12.3 
Drug Accountability...................................................................................... 52 
12.4 
Subject Compliance with Study Drug Dosing .............................................. 53 
13.0 
Non-Study Treatments .......................................................................................... 53 
13.1 
Prior and Concomitant Medications ............................................................. 53 
13.2 
Prohibited Medications ................................................................................. 54 
13.3 
Medications to be Administered with Caution and Monitored as Appropriate
 
54 
13.4 
Study Restrictions ......................................................................................... 55 
14.0 
Study Procedures .................................................................................................. 55 
14.1 
General Procedures ....................................................................................... 55 
14.1.1 
Informed Consent...................................................................................... 55 
14.1.2 
Enrollment and ID Assignment ................................................................ 55 
14.1.3 
Medical History and Demographics ......................................................... 56 
14.1.4 
Inclusion and Exclusion Criteria ............................................................... 56 
14.1.5 
Pregnancy Test .......................................................................................... 56 
14.1.6 
Prior and Concomitant Medications ......................................................... 56 
14.1.7 
Study Drug Dispensing, Collection and Accountability Review.............. 57 
14.1.8 
Study Drug Dosing ................................................................................... 57 

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14.1.9 
Subject Diaries .......................................................................................... 57 
14.2 
Efficacy Procedures ...................................................................................... 57 
14.2.1 
Targeted Physical Examination, Including Clinical Evaluation of Signs and 
Symptoms ................................................................................................................. 57 
14.2.2 
Mycological Testing ................................................................................. 59 
14.2.3 
Imaging ..................................................................................................... 63 
14.2.4 
Serological Testing ................................................................................... 64 
14.2.5 
Esophagoscopy ......................................................................................... 66 
14.2.6 
Spirometry................................................................................................. 66 
14.2.7 
St. George’s Respiratory Questionnaire (SGRQ) ..................................... 66 
14.2.8 
Six-Minute Walk Test and Medical Research Council (MRC) Dyspnea 
Scale 
67 
14.2.9 
Recurrence ................................................................................................ 67 
14.2.10 Survival ..................................................................................................... 67 
14.2.11 Assessment of Efficacy ............................................................................. 67 
14.3 
Safety Procedures.......................................................................................... 68 
14.3.1 
Vital Signs ................................................................................................. 68 
14.3.2 
General Physical Examination .................................................................. 68 
14.3.3 
Clinical Laboratory Safety Assessments .................................................. 68 
14.3.4 
Adverse Events ......................................................................................... 70 
14.4 
Pharmacokinetic Procedures ......................................................................... 70 
15.0 
Study Schedules .................................................................................................... 72 
16.0 
Safety Assessments and Monitoring ..................................................................... 76 
16.1 
Definition of an Adverse Event .................................................................... 76 
16.2 
Definition of a Serious Adverse Event ......................................................... 77 
16.3 
Events of Clinical Interest ............................................................................. 77 
16.4 
Overdose ....................................................................................................... 78 
16.5 
Pregnancy ...................................................................................................... 78 
16.6 
Unexpected Adverse Event ........................................................................... 78 
16.7 
Grading of Adverse Events ........................................................................... 79 

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16.8 
Causality Assessment.................................................................................... 79 
16.9 
Adverse Event Collection Timeframe .......................................................... 80 
16.10 
Serious Adverse Event Reporting Requirements .......................................... 80 
16.11 
Adverse Event and Serious Adverse Event Follow-up ................................. 80 
16.12 
Serious Adverse Event Reporting – Procedures for Investigators ................ 80 
16.13 
Procedures for Emergency Unblinding ......................................................... 81 
17.0 
Data Collection, Study Monitoring and Record Management.............................. 81 
17.1 
Data Collection and Reporting...................................................................... 81 
17.2 
Study Monitoring .......................................................................................... 82 
17.3 
Investigator Study Files ................................................................................ 82 
17.4 
Retention of Records..................................................................................... 82 
18.0 
Analytical Plan ...................................................................................................... 83 
18.1 
Sample Size Determination........................................................................... 83 
18.2 
Analysis Populations ..................................................................................... 83 
18.3 
Interim Analyses and Supplemental Analysis .............................................. 84 
18.4 
Efficacy ......................................................................................................... 84 
18.4.1 
Enrollment Categories .............................................................................. 84 
18.4.2 
Efficacy Assessments................................................................................ 84 
18.4.3 
Efficacy Analyses ..................................................................................... 91 
18.4.4 
Data Review Committee ........................................................................... 92 
18.4.5 
Investigator’s Assessment of Overall Response ....................................... 92 
18.5 
Pharmacokinetics .......................................................................................... 93 
18.5.1 
Pharmacokinetic Assessments .................................................................. 93 
18.5.2 
Pharmacokinetic Analyses ........................................................................ 94 
18.6 
Safety ............................................................................................................ 94 
18.6.1 
Safety Assessments ................................................................................... 94 
18.6.2 
Safety Analyses ......................................................................................... 94 
19.0 
Ethics and Protection of Human Patients.............................................................. 95 
19.1 
Ethical Conduct of the Study ........................................................................ 95 

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19.2 
Institutional Review Board/Ethics Committee Review ................................ 95 
19.3 
Informed Consent.......................................................................................... 95 
19.4 
Future Use of Samples .................................................................................. 96 
19.5 
Subject Privacy and Subject Confidentiality ................................................ 96 
19.6 
Study Termination ........................................................................................ 96 
19.7 
Financial Disclosure...................................................................................... 96 
20.0 
References ............................................................................................................. 97 
21.0 
Appendices ............................................................................................................ 99 
21.1 
Appendix A: Protocol Revision History ....................................................... 99 
21.1.1 
Protocol Amendment 3 ............................................................................. 99 
21.1.2 
Protocol Amendment 2 ........................................................................... 104 
21.1.3 
Protocol Amendment 1 ........................................................................... 113 
21.2 
Appendix B: Prohibited Medications and Medications to be Administered 
with Caution ................................................................................................................ 122 
21.2.1 
Prohibited Medications ........................................................................... 122 
21.2.2 
Medications to be administered with Caution and Monitored as Appropriate
 
123 
21.3 
Appendix C: Sample Eligibility Form ........................................................ 124 
21.4 
Appendix D: Vulvovaginal Signs and Symptoms Scale............................. 126 
 
LIST OF FIGURES 
Figure 1 
Schematic of Study Design ........................................................................... 22 
Figure 1 
Chemical Structure of Ibrexafungerp Citrate ................................................ 51 
 
LIST OF TABLES 
Table 1 In Vitro Activity of Ibrexafungerp and Caspofungin Against Aspergillus spp. 25 
Table 2 Disease -Specific Secondary Endpoints ............................................................ 33 
Table 3 
Summary of Overall Treatment and Follow-Up Schedule for All Subjects 
Except VVC Subjects ....................................................................................................... 35 
Table 4 Summary of Overall Treatment and Follow-Up Schedule for VVC Subjects.. 35 

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Table 5 Eligible Fungal Diseases ................................................................................... 38 
Table 6 Ibrexafungerp Monotherapy Dosing Regimen (Excluding VVC) .................... 49 
Table 7 Ibrexafungerp Monotherapy Dosing Regimen for VVC .................................. 50 
Table 8 Ibrexafungerp Combination Therapy Dosing Regimen .................................... 50 
Table 9 
Schedule of Visits for Targeted Physical Examinations by Fungal Disease 
(Excluding VVC) .............................................................................................................. 58 
Table 10 
Schedule of Visits for Mycological Assessments by Fungal Disease 
(Excluding VVC) .............................................................................................................. 60 
Table 11: 
Fungal Isolates to be Collect for the Study. .................................................. 62 
Table 12  
Schedule of Visits for Recommended Imaging Assessments by Fungal 
Disease, if obtained for Routine Care (Excluding VVC) ................................................. 64 
Table 13 
Schedule of Visits for Recommended Serological Assessments by Fungal 
Disease (Excluding VVC)................................................................................................. 65 
Table 14 
Schedule of Treatment Visits and Procedures (All Fungal Diseases Except 
VVC) 
....................................................................................................................... 72 
Table 15 
Schedule of Treatment Visits and Study Procedures for VVC ..................... 75 
Table 16  
Efficacy Time Points and Outcome Definitions for Primary and Secondary 
Endpoints ....................................................................................................................... 86 
Table 17 
EORTC-MSG General Criteria for Global Responses to Antifungal Therapy  
 
....................................................................................................................... 90 
 
 
 
 

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Abbreviations 
ABBREVIATION 
DEFINITION 
ABPA 
allergic bronchopulmonary aspergillosis 
ACM 
all-cause mortality 
AE 
adverse event 
ALT 
alanine aminotransferase 
AMB 
amphotericin B 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUC0-24 
area under the concentration-time curve from 0 to 24 
hours 
AUClast 
area under the concentration-time curve up to the last 
measurable concentration 
Azole-R 
azole-resistant 
BAL 
bronchoalveolar lavage 
BDG 
β-D-glucan 
BID 
twice daily 
BL 
baseline 
BUN 
blood urea nitrogen 
Cavg 
average concentration 
CD 
compact disk 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CL/F 
clearance/fraction absorbed 
CLSI 
Clinical and Laboratory Standards Institute 
Cmax 
maximum concentration 
CMC 
chronic mucocutaneous candidiasis 
CPA 
chronic pulmonary aspergillosis 
CPK 
creatine phosphokinase 
CRO 
contract research organization 
CRP 
c-reactive protein 
CT 
computerized tomography 
CYP 
cytochrome  
D 
day 
D/I 
disseminated/invasive 
DF 
dimorphic fungi 
DRC 
Data Review Committee 
DVD 
digital versatile disk 

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EC 
Ethics Committee 
esophageal candidiasis 
ECI 
event of clinical interest 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
EOT 
End of Treatment 
EUCAST 
European Committee on Antimicrobial Susceptibility 
Testing 
FDA 
Food and Drug Administration 
FEV1 
Forced expiratory volume during the first second 
FU 
follow up 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyl transferase 
GMI 
galactomannan index 
GSI 
glucan synthesis inhibitors 
HIPAA 
Health Information Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HRCT 
high resolution computerized tomography 
IC 
invasive candidiasis 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
ID 
identification 
IDSA 
Infectious Disease Society of America 
IgE 
immunoglobulin E 
IPA 
invasive pulmonary aspergillosis 
IRB 
Institutional Review Board 
ITT 
intent to treat 
IV 
intravenous 
KOH 
potassium hydroxide 
LAM 
lactation amenorrhea method 
LDH 
lactate dehydrogenase 
MALDI-TOF 
matrix-assisted laser desorption/ionization 
MEC 
minimum effective concentration 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
minimum inhibitory concentration 
MRC 
Medical Research Council 
MRI 
magnetic resonance imaging 

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MSG-EORTC 
Mycosis Study Group and European Organization for 
Research and Treatment of Cancer Consensus Criteria 
NG 
nasogastric  
NOAEL 
no-observed-adverse-effect-level 
OATP1B3 
organic anion transporting polypeptide 1B3 
OPC 
oropharyngeal candidiasis 
PCR 
polymerase chain reaction 
PE 
physical exam 
PEG 
percutaneous endoscopic gastrostomy 
PI 
principal investigator 
PK 
pharmacokinetics 
Pop PK 
population pharmacokinetics 
PP 
per protocol 
QD 
once daily 
RBC 
red blood cell 
SAE 
serious adverse event 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SGRQ 
St. George’s Respiratory Questionnaire 
SOC 
standard of care 
spp 
species 
TOC 
test of cure 
Tx 
treatment 
ULN 
upper limit of normal 
US 
United States 
VSS 
vulvovaginal signs and symptoms 
VVC 
vulvovaginal candidiasis 
WBC 
white blood cell 
WHO 
World Health Organization 
WK 
week 
β-hCG 
β-human chorionic gonadotropin 
 
 
 
 

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Protocol Synopsis 
Title: Open-Label Study to Evaluate the Efficacy and Safety of SCY-078 (Ibrexafungerp) in Patients with 
Fungal Diseases that are Refractory to, Resistant to or Intolerant of Standard Antifungal Treatment (FURI) 
Primary Objectives:  
The primary objectives listed below apply to all eligible fungal diseases: 
• 
To evaluate the efficacy of ibrexafungerp in the treatment of severe fungal diseases as determined 
by a Data Review Committee (DRC) at the primary time point for the fungal disease 
• 
To evaluate the safety of ibrexafungerp 
 
Overall Secondary Objectives: 
The overall secondary objectives listed below apply to all eligible fungal diseases: 
• 
To evaluate the efficacy of ibrexafungerp as determined by the DRC at other time points 
• 
To evaluate the efficacy of ibrexafungerp as determined by the Investigator 
• 
To determine the efficacy of ibrexafungerp by pathogen 
• 
To determine the efficacy of ibrexafungerp by fungal disease and disease category 
• 
To evaluate the efficacy of ibrexafungerp by recurrence of the baseline fungal disease  
• 
To evaluate the efficacy of ibrexafungerp by reason for enrollment (refractory, resistance, relapse, 
intolerance, toxicity, need for oral therapy) 
• 
To determine All-Cause Mortality (ACM)  
• 
To evaluate the pharmacokinetics (PK) of ibrexafungerp by population PK analysis 
 
Disease-Specific Secondary Objectives: 
• 
To evaluate the efficacy of ibrexafungerp as determined by other disease-specific endpoints (see 
below).  
Primary Endpoints:  
The primary endpoints listed below apply to all eligible fungal diseases: 
• 
Efficacy as measured by the percentage of subjects with Global Response at: 
TOC for Vulvovaginal Candidiasis (VVC, Day 17), Chronic Mucocutaneous Candidiasis (CMC, 
EOT or Day 84), Chronic Pulmonary Aspergillosis (CPA, EOT or Day 90), Allergic 
Bronchopulmonary Aspergillosis (ABPA, EOT or Day 90) (whichever comes first) and at  
EOT for all other diseases as determined by a DRC  
• 
Safety as measured by: physical examination, vital signs, AEs, and laboratory tests  
Overall Secondary Endpoints:  
The overall secondary endpoints listed below apply to all eligible fungal diseases: 
• 
The percentage of subjects who achieve Global Response at additional time points as applicable for 
each disease, disease category and reason for enrollment (Table 16 in the full protocol), as 
determined by the DRC and by the Investigator 
• 
The percentage of subjects who achieve Clinical Response by pathogen at time points applicable for 
each disease, disease category and reason for enrollment (Table 16 in the full protocol), as 
determined by the DRC and the Investigator  
• 
The percentage of subjects who achieve Mycological Response by pathogen at time points applicable 
for each disease, disease category and reason for enrollment (Table 16 in the full protocol), as 
determined by the DRC and the Investigator 

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• 
The percentage of subjects who achieve Clinical Response by fungal disease, disease category and 
reason for enrollment at time points applicable for each disease (Table 16 in the full protocol), as 
determined by the DRC and the Investigator 
• 
The percentage of subjects who achieve Mycological Response by fungal disease, disease category 
and reason for enrollment at time points applicable for each disease (Table 16 in the full protocol), 
as determined by the DRC and the Investigator 
• 
The percentage of subjects with a recurrence of the baseline fungal disease at the 25-Day FU for 
VVC and at the 6-Week FU for all other diseases as determined by the DRC 
• 
ACM at Day 30 for Invasive Candidiasis (IC) and candidemia and at Day 42 for all diseases 
• 
Time to death from any cause 
• 
Describe ibrexafungerp plasma concentrations  
 
Disease-Specific Secondary Endpoints: 
Disease-specific secondary endpoints, as assessed by the DRC  
Acute IC / Candidemia disease-specific endpoints 
• 
Completion of study drug antifungal treatment (i.e. no recurrence, no use of other antifungal 
treatment, no discontinuation for any reason) 
Acute or Chronic Severe Mucocutaneous Candidiasis 
• 
Percentage subjects with mycological cure by Day 84 
• 
Percentage subjects with clinical response by Day 30 and Day 84 
• 
Percentage of subjects with continued symptom relief at 6-week FU 
Chronic Pulmonary Aspergillosis (CPA) disease-specific endpoints 
• 
Six-Minute Walk test and MRC Dyspnea Score at Day 90 and Day 180 
• 
Weight change at Day 90 and Day 180 
• 
Improvement in inflammatory markers (CRP, plasma viscosity, albumin, platelet count, disease-
specific immunoglobulin levels) at Day 90 and Day 180 
• 
Change in total IgG and Aspergillus IgG at Day 90 and Day 180, if elevated at Baseline 
• 
All-cause mortality at Day 90, Day 120 and Day 180 
• 
Recurrence at Day 180 
Allergic Bronchopulmonary Aspergillosis (ABPA) disease-specific endpoints:  
• 
Percentage of subjects who exhibit a Global Response at Day 42  
• 
Percentage of subjects with Clinical Improvement (as measured on a 4-point scale) at TOC, Day 90, 
Day 180, then every 3 months while on therapy, and 6-month follow-up (FU) 
• 
Percent decline in total IgE (baseline IgE minus time point IgE/baseline IgE) at Day 42 and Day 90 
• 
Number of subjects who experience an ABPA exacerbation at the 3-month and 6-month FUs  
• 
Time to first ABPA exacerbation 
• 
Change in lung function (FEV1 and FVC) at Day 42 
• 
Number of Asthma exacerbations and ABPA exacerbations at the 3-month and 6-month FUs 
• 
All-cause mortality at Day 90, Day 120 and Day 180 
Invasive Pulmonary Aspergillosis (IPA) disease-specific endpoint 
• 
The percentage of subjects who attain a galactomannan index (GMI) decrease including absolute 
and percent reduction from Baseline to Weeks 1, 2, 4 and 6, when feasible 
• 
Time to achieve a clinically meaningful GMI absolute and percent decrease 

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• 
All-cause mortality at Day 84  
Disseminated/invasive dimorphic fungal disease-specific endpoint 
• 
All-cause mortality at Day 84  
Other emerging fungi including yeasts and molds disease-specific endpoint 
• 
All-cause mortality at Day 84 
Study Phase: 3 
Study Design: This is a multicenter, open-label, non-comparator, single-arm study to evaluate the 
efficacy, safety and PK of ibrexafungerp in male and female subjects ≥18 years of age with documented 
severe fungal diseases for whom standard of care (SOC) antifungal treatment is not appropriate due to 
refractoriness, resistance, relapse, intolerance, toxicities, need for oral therapy or other reasons.  
Subjects must have a documented eligible fungal disease that has been refractory to, has relapsed after, or 
subject has intolerance to or demonstrated toxicities resulting from an approved SOC antifungal treatment 
as listed in the full protocol, or isolate is resistant to, or has a high MIC and is unlikely to respond to 
antifungal SOC. Subjects are also eligible if, in the judgement of the Investigator, continued IV antifungal 
therapy is not feasible or desirable due to clinical or logistical circumstances or if other oral antifungal 
alternatives are not appropriate. Subjects should meet these and other study criteria to be considered for 
enrollment. Inclusion of each subject in the study must be approved by the Sponsor (or Sponsor designee) 
prior to initiation of study drug.  
The study will be conducted at approximately 40 sites globally and is planned to enroll and treat 
approximately 220 (+10%) subjects. 
For all subjects except VVC subjects, there will be a Screening visit, a Baseline visit (also considered Day 
1), several scheduled visits depending on the subject’s fungal disease, an EOT visit and a follow-up visit 
6 weeks after EOT.  FOR ABPA subjects there will be additional follow-up visits 3 months and 6 months 
after EOT. For CMC, CPA and ABPA subjects, there will be a TOC visit on EOT or Day 84 for CMC or 
Day 90 for CPA and ABPA subjects, whichever comes first.  Following Screening, eligible subjects will 
receive the study drug loading dose on Days 1 and 2 and the study drug maintenance dose from Day 3 up 
to EOT.  
Subjects with VVC will have a Screening visit, a Baseline/Day 1 visit, and scheduled visits on Day 4, Day 
7 (EOT), Day 17 (TOC), 25-day FU (Day 32) and 35-day FU (Day 42). VVC subjects will receive 
treatment every three days for a total of three dosing days (i.e., on Days 1, 4 and 7). The EOT and 35-Day 
FU visits may be a phone contact for asymptomatic subjects 
All eligible subjects will receive ibrexafungerp monotherapy for up to 180 days at a dosing regimen that 
will depend on fungal disease. Ibrexafungerp will be available as combination therapy for selected 
subjects. The treatment duration may be extended beyond 180 days, if needed, for certain fungal diseases. 
Sponsor approval must be obtained for any extension of treatment beyond 180 days. Subjects with VVC 
will receive oral doses of 375 mg BID every three days for a total of three dosing days (Day 1, Day 4 and 
Day 7). Subjects who have a recurrence after TOC (VVC subjects) or EOT (other subjects), may be 
considered for re enrollment upon discussion with the sponsor.  
Efficacy evaluations will consist of clinical evaluations of the signs and symptoms of infection, 
mycological testing, imaging and serological testing as applicable for each fungal disease. Additional 
procedures will be conducted for selected fungal diseases. 
PK: The PK data obtained from this study will be part of the Population PK analyses that will be 
performed. For subjects who are willing to participate in the PK sampling, blood samples will be collected 

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on Day 2 (one sample collected anytime post dosing), Days 3 to 5 (one sample collected predose on any 
of these days) and Days 7 to 10 (one sample collected predose on any of these days). Additional blood PK 
samples will be collected when clinically indicated. Tissue samples collected as part of SOC procedures 
(e.g., biopsies) may be sent for drug concentration analysis, when available.  
Subjects will be evaluated for safety throughout the study, including parameters such as physical exam, 
vital signs, adverse events (AEs) and concomitant medications, and safety laboratory tests (hematology, 
blood chemistry and urinalysis).  
Results from the study will be analyzed against historical and concurrent SOC-treated subjects, who will 
be selected from literature reviews and other data resources. 
Target Population: Male and female subjects ≥18 years of age with documented eligible severe fungal 
diseases for whom SOC antifungal treatment is not appropriate due to refractoriness, resistance, 
intolerance, relapse, toxicities, need for oral therapy or other reasons. 
KEY Inclusion Criteria:  
Subject must fulfill all of the following KEY criteria at Screening and/or Baseline to be eligible for study 
admission: 
1. Subject is a male or female adult ≥18 years of age on the day the study informed consent form (ICF) 
is signed. 
2. Subject has a documented eligible fungal disease that has been refractory or resistant to SOC, has 
relapsed after, or the subject has intolerance to or demonstrated toxicities resulting from an approved 
SOC antifungal treatment. The subject is also eligible if, in the judgement of the Investigator, long-
term IV antifungal therapy is not feasible or desirable due to clinical (isolate is resistant to or has a 
high MIC and is unlikely to respond to antifungal SOC) or logistical circumstances or if other 
antifungal alternatives are not appropriate.  
 
A summary of eligible fungal diseases is listed below and a detailed description of diagnostic, 
refractoriness, intolerance, toxicity and relapse criteria is available in Table 5 in the full protocol:  
• 
Acute or chronic invasive candidiasis, including candidemia 
• 
Acute or chronic severe mucocutaneous candidiasis, including:  
o 
Esophageal candidiasis (EC)  
o 
Oropharyngeal candidiasis (OPC)  
o 
Chronic mucocutaneous candidiasis (CMC) 
o 
Vulvovaginal candidiasis (VVC) 
• 
Disseminated/invasive dimorphic fungi: 
o 
Coccidioidomycosis 
o 
Histoplasmosis 
o 
Blastomycosis 
• 
Chronic Pulmonary Aspergillosis (CPA) 
• 
Allergic Bronchopulmonary Aspergillosis (ABPA) 
• 
Invasive Pulmonary Aspergillosis (IPA) 
• 
Other emerging fungi including yeasts and molds (e.g., sachromycetes, scopulariopsis, 
mucorales) 
 
KEY Exclusion Criteria: 
Subject will be excluded from participation in the study if he/she meets any of the following KEY 
exclusion criteria at Screening and/or Baseline:  

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1. Subject has an invasive fungal disease with central nervous system involvement unless the subject is 
planned to receive combination therapy with ibrexafungerp and other antifungal. 
2. Subject has an inappropriately controlled fungal disease source (e.g., persistent catheters, devices, 
identified undrained abscess) that is likely to be the source of the fungal disease. 
3. Subject is hemodynamically unstable and/or requiring vasopressor medication for blood pressure 
support. 
4. Subject has abnormal liver test parameters: AST or ALT >10 x ULN and/or total bilirubin >5 x ULN. 
Note: Subjects with unconjugated hyperbilirubinemia with a diagnosis of Gilbert’s disease are not 
excluded. 
5. Subject is unlikely to survive 30 days.  
Study Drugs:  
Ibrexafungerp citrate drug product for oral administration will be supplied as compressed oral tablets 
containing 250 mg of ibrexafungerp active ingredient on a free base basis. In addition to the active 
ingredient, the oral tablet formulation also contains silicified microcrystalline cellulose, crospovidone, 
mannitol, colloidal silicon dioxide, magnesium stearate (non-bovine), and butylated hydroxyanisole. 
Ibrexafungerp is packaged in bottles containing 30 tablets. 
Ibrexafungerp tablets are to be stored at room temperature: between 15°C and 25°C with allowable limited 
excursions of up to 30°C. 
Randomized Treatment Groups: This is an open-label, non-comparator, single-arm study. All subjects 
will receive ibrexafungerp monotherapy except subjects with refractory or relapsing invasive pulmonary 
aspergillosis (IPA), mucormycosis or other molds with unpredictable ibrexafungerp activity, who will 
receive combination therapy. Combination therapy may also be administered to other subjects based on 
Investigator’s judgement and contingent on Sponsor approval. Subjects will receive ibrexafungerp on an 
inpatient or outpatient basis, as needed for each fungal disease. 
Ibrexafungerp Monotherapy for All fungal Diseases, Excluding VVC 
Subjects will receive ibrexafungerp monotherapy given as an initial loading dose of 750 mg (3 tablets of 
250 mg each) given BID (total daily dose = 1500 mg) during the first 2 days of treatment and then 
subsequent oral doses of 750 mg (3 tablets of 250 mg each) QD for up to 180 days, depending on fungal 
disease. Treatment beyond 180 days may be permitted under certain circumstances to be agreed upon by 
the Investigator and the Sponsor on a per-subject basis. Subjects may be considered for re-enrollment upon 
discussion with the sponsor.   
If subjects cannot swallow the whole tablet, the tablets may be split. In the event subjects experience 
gastrointestinal intolerance on the 750 mg QD dose, the tablets may be split and/or administered at 10 to 
20-minute intervals. The daily dose may also be given as 375 mg (1 and ½ tablets) BID for subjects 
experiencing gastrointestinal intolerance. 
Ibrexafungerp Monotherapy for VVC 
Subjects with VVC will receive ibrexafungerp monotherapy given as oral doses of 375 mg BID (total 
daily dose = 750 mg) every three days for a total of three dosing days (Day 1, Day 4 and Day 7). Subjects 
treated for VVC who have a recurrence may receive additional cycles of ibrexafungerp treatment similar 
to the initial regimen upon discussion with the Sponsor.   
Ibrexafungerp Combination Therapy 
Monotherapy with ibrexafungerp is not recommended for refractory or relapsing IPA or mucormycosis. 
All subjects enrolled for refractory or relapsing IPA or mucormycosis should receive ibrexafungerp given 

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as combination therapy. Subjects with IPA and intolerance to other SOC options can be considered for 
enrollment to receive ibrexafungerp monotherapy, upon discussion with the Sponsor. 
For subjects who have infections due to other emerging fungi, including yeasts and molds, but have no 
culture isolate available (to confirm susceptibility to ibrexafungerp), combination therapy should be 
considered and discussed with the Sponsor. Combination therapy will also be allowed for other subjects 
based on Investigator’s judgement and contingent on Sponsor approval.  
Acceptable antifungal therapy includes voriconazole, isavuconazole, posaconazole, or amphotericin B 
(AMB) at the doses recommended per their label. When used in combination with the azoles, the dose of 
ibrexafungerp should be reduced from 750 mg to 500 mg.  
The following combination options are allowed:  
• 
addition of ibrexafungerp to any ongoing antifungal therapy 
• 
replacement of one (toxic/ineffective) element of a two-antifungal combination therapy with 
ibrexafungerp 
• 
replacement of current monotherapy with a new combination, generally: 
o 
replacement of AMB monotherapy with an azole plus ibrexafungerp combination, or 
o 
replacement of an azole monotherapy with an AMB plus ibrexafungerp combination  
• 
continuation of an azole plus echinocandin combination where the subject could go home on an oral 
regimen by replacing the parenteral echinocandin with ibrexafungerp 
Study Blinding, Randomization and Stratification: This is an open-label study 
Study Evaluations 
Efficacy Evaluations: Efficacy evaluations will consist of clinical evaluations of the signs and symptoms 
of infection, mycological testing (including, but not limited to, fungal culture, KOH and other fungal 
stains, and T2 testing), imaging (e.g., CT, MRI, X-Ray or ultrasound) and serological testing (including, 
among others, ß-D-glucan levels, GM and fungal antibody titers) as applicable for each fungal disease. 
Additional procedures (esophagoscopy, spirometry, St. George’s Respiratory Questionnaire [SGRQ], 6-
Minute Walk test and Medical Research Council [MRC] Dyspnea Scale) will be conducted for selected 
fungal diseases. 
Efficacy will be assessed primarily in terms of Global Response at TOC for VVC (Day 17), EOT visit or 
Day 84 (CMC) or Day 90 (CPA and ABPA) whichever comes first, and at EOT for all other fungal 
diseases, as determined by an independent DRC. Global Response will be a composite global outcome 
composed of clinical (including radiological, when applicable) and mycological (including serological) 
responses. In addition to the primary endpoint, Global Response, Clinical Response and Mycological 
Response will be assessed as secondary endpoints at the disease specific primary time point and at 
additional time points, for the determination of efficacy by the independent DRC and the Investigator. 
Other secondary efficacy assessments will include recurrence and survival. Recurrence will be evaluated 
at the 6-Week FU visit after EOT for all subjects, except VVC subjects, who will be assessed for 
recurrence at the 25-Day FU visit. Survival will be determined on Day 30 for patients with invasive 
candidiasis and candidemia, and on Day 42 for all subjects. Additional disease-specific efficacy endpoints 
will be evaluated for selected fungal diseases at additional time points. 
Efficacy outcomes will be based on EORTC-MSG Consensus Criteria except for diseases not defined in 
the EORTC-MSG Consensus Criteria such as ABPA, CPA, CMC and VVC. The efficacy time points and 
outcome definitions for the primary and secondary endpoints are detailed in Table 16 in the full protocol. 
Criteria for the DRC assessment of response will be further detailed in the DRC Charter.  

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Phamacokinetic Evaluations: For subjects who are willing to participate in the PK sampling, up to three 
(3) blood samples will be collected at the following visits and sampling windows: Day 2 (one sample 
collected anytime post dosing), Days 3 to 5 (one sample collected predose on any of these days), and Days 
7 to 10 (one sample collected predose on any of these days). Additional blood PK samples will be collected 
when clinically indicated. 
Procedures for collecting, storing, and shipping plasma samples for PK are described in the study PK 
Manual. The sparse samples collected in this study will be analyzed using Population PK (Pop PK) 
analysis methods to estimate PK parameters (Cmax, AUC, clearance/fraction absorbed [CL/F]) as 
applicable. Further analysis of possible metabolites may be performed. 
Safety Evaluations: Safety will be evaluated throughout the study, including the following parameters: 
AEs, treatment discontinuations, general physical examination, vital signs, safety laboratory tests and 
concomitant medications. A final safety assessment will be conducted at the 35-Day FU visit (35 days 
after EOT) for VVC subjects and at the 6-Week FU (6 weeks after the EOT) for all other subjects. 
Statistical Analyses:  
All statistical analyses will be performed using SAS® version 9.3 or later. Descriptive statistics (i.e., 
number of subjects, mean, standard deviation, median, minimum, maximum) will be presented for all 
continuous variables; number and percentage of subjects will be presented for categorical variables. For 
parameters measured over time, observed data and changes from Baseline will be described for each time 
point.  
Outcome analyses will include results by fungal disease, disease category, enrollment reason, and when 
relevant and sufficient number of cases allow, by pathogen and other clinical or microbiological 
characteristics such as MIC, FKS mutations, etc.  Overall response will also be presented for all disease 
categories combined. Unless otherwise stated, data will be analyzed as is with no imputation. Details of 
the statistical analysis will be provided in a statistical analysis plan, which will be approved prior to final 
database lock. 
Sample Size Determination: This is an exploratory study and no formal sample size calculations will be 
performed. A total of 220 subjects are estimated to be adequate for an assessment of the safety and 
tolerability of ibrexafungerp in subjects with documented eligible fungal diseases that have been refractory 
to, resistant to, have relapsed after SOC or subjects have intolerance to or demonstrated toxicities resulting 
from an approved SOC antifungal treatment. 
Analysis Populations 
The study populations to be used in the analyses are defined as follows: 
• 
Intent-to-Treat Population: The intent-to-treat (ITT) population will include all subjects who are 
enrolled in the study and receive at least 1 dose of study drug.  
• 
Myco-ITT: The Myco-ITT population will include all ITT subjects with confirmed pathogens and 
who also had all necessary cultures or mycology tests to estimate mycological response. 
• 
Per-Protocol Population: The per-protocol (PP) population will include all ITT subjects who 
received enough drug to enable clinical efficacy judgment as determined by DRC, who have an EOT 
(TOC for VVC, CMC, CPA and ABPA) assessment and who have no major protocol violations. 
• 
Safety Population: The safety population will include all subjects who receive at least one dose of 
study medication and have at least one safety assessment post Baseline. 
• 
Pharmacokinetic Population: The PK population will include all enrolled subjects who provide at 
least one PK sample and no deviations significant enough to affect the interpretability of PK data. 
Efficacy Analysis 

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The primary efficacy endpoint is the percentage of subjects with Global Response (clinical, radiological 
and mycological) as determined by the DRC at TOC for VVC (Day 17), CMC (EOT or Day 84), CPA 
(EOT or Day 90) and ABPA (EOT or Day 90) (whichever comes first), and at EOT for all other diseases. 
Results will be presented separately for each disease category along with a 95% confidence interval (CI) 
for a single binomial proportion in the ITT, Myco-ITT and PP populations where sufficient cases are 
available. In addition, the number of subjects with a successful response across all disease categories will 
be summarized as a response rate and 95% CI. Secondary endpoints will be presented with 95% Cis for 
the ITT, Myco-ITT and PP populations using the same approach as for the primary endpoint. The 
estimated response rates and 95% CIs outlined will also be assessed relative to the external data described 
in the Study Design section above. 
The percentage of subjects surviving at the defined time points will be presented for the ITT, Myco-ITT 
and PP populations. A Kaplan Meier plot will also be produced summarizing the survival curve over time 
and the median time to death. A subject without a reported death will be censored at the point of last time 
the subject was known to be alive. 
For primary and overall secondary endpoints, presentations by pathogen will be conducted, if numbers 
allow. Data for all subjects will be presented by fungal disease, disease category, reason for enrollment 
and receipt of combination therapy (Yes/No).  
If data are missing and the subject has not been deemed a success or failure the outcome will be categorized 
as unknown / not evaluable. 
Data Review Committee: A DRC Charter will provide detailed criteria to be used for the baseline and 
outcome analysis of subjects in this study. The analysis criteria will be based on the definitions captured 
in Table 16 using EORTC-MSG Consensus Criteria as reference for all diseases except ABPA, CPA, 
CMC and VVC. Adaptations to the EORTC-MSG criteria adopted by the DRC will be documented in the 
DRC Charter. 
Pharmacokinetics:  
The concentration versus time data from the sparse PK samples collected in this study will be analyzed 
using a Pop PK model to estimate Cmax, AUC and CL/F, as applicable. The PK analysis will be conducted 
on the PK Population. Further analysis of possible metabolites may be performed. 
Safety Analysis 
All safety analyses will be conducted in the safety population; all safety variables will be listed. 
Incidence and severity of treatment-emergent AEs, AEs leading to discontinuation and SAEs and their 
relationship to treatment will be summarized. Also data on AEs leading to death, AEs of special interest, 
AEs leading to withdrawal and AEs by severity will be summarized. 
Early discontinuation of study drug treatment will be presented and will include the reasons for and timing 
of such discontinuations. Abnormal physical examinations associated with adverse events will be listed. 
Concomitant medications will be summarized. 
Laboratory evaluations will be summarized as observed values and changes from Baseline; shifts with 
respect to the laboratory reference range will be summarized. Vital signs will be summarized as observed 
values and changes from Baseline. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and presented by 
system organ class and preferred term. Concomitant medications will be classified based on the World 
Health Organization´s (WHO) Drug Dictionary terminology. 

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6.0 
Schematic of Study Design 
 
Figure 1 
Schematic of Study Design 
 
End of Treatment (EOT) 
(last dose of study drug, up to 180 days of treatment 
with ibrexafungerp) 
6-Week Follow-up 
(6 weeks after EOT) 
 
 
Screening 
(Day -1) 
Ibrexafungerp Loading Dose 
Baseline (Day 1) & Day 2 
 
Ibrexafungerp Maintenance Dose 
Day 3 to EOT 
Additional Follow-ups 
(3 and 6 months  
after EOT,  
for ABPA subjects only)
ALL FUNGAL DISEASES 
EXCEPT VVC 
VVC 
Ibrexafungerp Dosing 
Baseline (Day 1), Day 4 & Day 7 
End of Treatment (EOT) 
Day 7 
(last dose of study drug) 
Test of Cure (TOC) 
Day 17 
25-Day Follow-up 
(25 days after EOT) 
35-Day Follow-up 
(35 days after EOT) 
All subjects: Survival Status at study Day 42 (42 days 
after first dose of study drug) and at Day 30 for IC / 
candidemia 
Re enrollment of subjects after TOC (VVC) or EOT (all others) may be considered 
upon discussion with the sponsor 

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7.0 
Background Information and Scientific Rationale 
7.1 
Background Information 
Ibrexafungerp (formerly “SCY-078”) is a member of a new class of antifungal agents, the 
triterpenoids. It is a semi-synthetic triterpene derivative of the natural product enfumafungin. 
Ibrexafungerp is a structurally distinct glucan synthesis inhibitor (GSI) that inhibits the synthesis 
of the fungal cell wall polymer β-(1,3)-D-glucan. Time kill studies have demonstrated that 
ibrexafungerp has fungicidal in vitro activity against Candida spp. isolates similar to that observed 
with the echinocandins. 
Ibrexafungerp is being developed as the first oral and intravenous (IV) GSI for the treatment and 
prevention of fungal diseases caused by Candida, Aspergillus and other fungal species with the 
potential to provide the therapeutic advantages of both an IV and oral formulation. 
Fungal diseases caused by Candida spp., Aspergillus spp., Pneumocystis, dimorphic fungi, etc., 
have limited treatment options and represent a growing threat, particularly to patients with 
compromised immune systems, including patients receiving cancer chemotherapy, hematopoietic 
stem cell transplantation and solid organ transplantation, and patients with advanced human 
immunodeficiency virus (HIV)-infection. Invasive fungal diseases caused by Candida and 
Aspergillus species are of principal concern. Despite advances in medical care, the overall 
mortality rate of invasive fungal infections remains high, particularly in the most profoundly 
immunocompromised patient populations1,2,13.   
While four classes of antifungal agents are currently available to treat these infections, only 
flucytosine and azoles are available for oral therapy.  Concerns about flucytosine toxicity and rapid 
emergence of resistance on therapy, limits its clinical utility.  The emergence of resistance (clinical 
and mycological) to azoles and more recently to echinocandins3,4, and the toxicity associated with 
polyenes, signals the need for new agents that are well tolerated and that retain activity against 
resistant strains.  
Ibrexafungerp retains activity in vitro and in vivo against both azole-resistant and the majority of 
clinical isolates containing FKS gene mutations, which confer echinocandin resistance. Unlike 
echinocandins, ibrexafungerp is orally bioavailable, with in vitro and in vivo activity against 
Candida, Aspergillus and other fungal genera.  Ibrexafungerp offers an oral non-azole treatment 
alternative for these infections.  
This includes e.g. patients with Candida infections who are failing therapy clinically or for whom 
azole therapy is not advisable due to infection with an isolate with a high likelihood of azole non-
susceptibility (e.g. C. glabrata, C. krusei, C. auris), or other Candida spp. isolates with 
documented non-susceptibility to azoles based on MIC determination6. 

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Antifungal activity 
The spectrum and potency of activity of ibrexafungerp has been evaluated by numerous 
independent laboratories against an extensive panel of clinically relevant yeast and mold isolates 
using the Clinical and Laboratory Standards Institute (CLSI) and European Committee on 
Antimicrobial Susceptibility Testing (EUCAST) methods. Overall, the epidemiological studies 
have demonstrated that ibrexafungerp has potent, broad-spectrum activity against the majority of 
the clinical isolates tested. These studies have laid the foundation in support of the use of 
ibrexafungerp for the treatment of invasive fungal diseases. 
 
Activity against Candida spp. 
Ibrexafungerp has been evaluated against >2000 Candida isolates, including all clinically relevant 
species, more than 600 C. glabrata isolates and more than 250 C. auris isolates. These in vitro 
studies have demonstrated the broad range of anti-Candida spectrum of activity of ibrexafungerp. 
Additionally, ibrexafungerp demonstrated in vitro activity against pre-formed biofilms, which is a 
relevant feature when addressing catheter-related Candida infections. Studies conducted with 
azole- and echinocandin-resistant strains have shown that ibrexafungerp retains activity (i.e., no 
significant change in minimum inhibitory concentration [MIC] when compared to wild type) 
against >90% of azole-resistant strains and >70% of Candida strains with FKS mutations 
commonly associated with echinocandin resistance. Interestingly, although ibrexafungerp and the 
echinocandins share a similar mechanism of action (β-[1,3]-D-glucan synthesis inhibition), their 
clearly different molecular structure provides them with some differentiating characteristics in 
terms of microbiological activity. 
Ibrexafungerp was evaluated in vitro against approximately 190 clinical isolates of echinocandin-
resistant strains of Candida spp., with most isolates having mutations in the FKS gene. Overall, 
ibrexafungerp was active against the majority of the echinocandin-resistant strains tested. 
Significantly, ibrexafungerp was active against approximately 70% of the isolates containing the 
most commonly reported FKS mutation associated with echinocandin resistance in C. glabrata 
(S663P in FKS2 and S645P in FKS1). Selection of ibrexafungerp resistance in vitro occurs at a 
low frequency. A deletion at position F659 in FKS2 of C. glabrata was the predominant mutation 
observed in these studies; notably, ibrexafungerp did not select for mutations at positions S663 or 
S645. These results suggest that ibrexafungerp inhibits glucan synthase in a manner different from 
that of echinocandins. 
The in vitro studies also included a number of multidrug-resistant isolates. Consistent with the data 
described above, ibrexafungerp was active against >70% of these isolates. Ibrexafungerp has also 
demonstrated activity against life-threatening and multidrug-resistant C. auris strains recently 
highlighted as a clinical alert by the CDC due to the global emergence of this fungal disease with 
limited therapeutic options and high mortality. In a recent study, Ibrexafungerp demonstrated 
potent in vitro activity against >100 different C. auris isolates and results showed potent activity 

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of ibrexafungerp against all strains at concentrations indicative of potential clinically-relevant 
effect.5 
While the majority of surveillance and resistance studies included isolates obtained from patients 
with invasive infections, ibrexafungerp demonstrated potent activity against vaginal Candida 
isolates and was also shown to be active against pre-formed biofilms in vitro. 
 
Activity against Aspergillus spp.  
The spectrum and potency of activity of ibrexafungerp has been evaluated by several independent 
laboratories against a panel of clinically relevant Aspergillus isolates using CLSI and EUCAST 
methods. The studies included 41 A. fumigatus, 48 A. flavus, 21 A. niger, and 27 A. terreus wild-
type isolates as well as 16 azole-resistant isolates: 14 A. fumigatus, and one each A. niger, and A. 
terreus. In these studies, microbiological outcome is reported as MEC (minimum effective 
concentration). Overall, ibrexafungerp was active against all the Aspergillus strains evaluated with 
MEC values similar to those obtained for caspofungin. Furthermore, there were no significant 
differences in the ibrexafungerp MEC values obtained between the wild-type and azole-resistant 
strains. Details are provided in Table 1.  
Table 1 
In Vitro Activity of Ibrexafungerp and Caspofungin Against Aspergillus spp. 
Aspergillus spp 
N 
Microbiologic 
Outcomea 
Ibrexafungerp Caspofungin 
A. fumigatus 
 
 
 
 
WT 
41 
MEC Range 
0.008 – 0.5 
0.015 – 0.125 
Azole-R 
14 
0.03 – 0.5 
0.015 – 0.125 
A. flavus 
 
 
 
 
WT 
48 
MEC Range 
0.015 - 8 
0.015 – 0.125 
Azole-R 
NT 
 
 
As. terreus 
 
 
 
 
WT 
27 
MEC Range 
0.008 – 0.125 
0.015 – 0.125 
Azole-R 
1 
0.125 
0.03 
A. niger 
 
 
 
 
WT 
29 
MEC Range 
0.008 – 0.125 
0.015-0.06 
Azole-R 
1 
0.06 
0.06 
Abbreviations: Azole-R = azole-resistant; MEC = minimum effective concentration; 
NT = none tested; WT = wild type 
a: Values in μg/mL 
The potent in vitro activity of ibrexafungerp against Aspergillus species was confirmed in a recent 
study that included >500 clinical isolates. MEC50 and MEC90 values for the 311 isolates tested 
were <0.063 and 0.125 µg/mL, respectively. 
Ibrexafungerp was evaluated for in vitro activity against 172 Aspergillus strains, including cryptic 
species and some with Cyp51 A mutants. MIC and MEC values were determined following 
EUCAST 9.2 and CLSI M38A methodologies. All strains were obtained from clinical samples 
(respiratory, cutaneous, biopsies, exudates, abscesses and wounds) between 2000 and 2017, and 

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included WT and Cyp51A mutants. Ibrexafungerp showed good activity with low MEC90 for 
almost all the species tested, both for EUCAST and CLSI. Ibrexafungerp displayed similar activity 
against WT and azole-R strains of A. fumigatus. Isolates of Aspergillus alliaceus were the only 
ones showing reduced susceptibility to ibrexafungerp, with MEC90 >16 µg/L (EUCAST) and 16 
µg/L (CLSI). Overall, there was good agreement between results obtained using EUCAST and 
CLSI methodologies. 
The in vitro activity of ibrexafungerp was evaluated alone and in combination with amphotericin 
B, isavuconazole, or voriconazole against a panel of clinical A. fumigatus isolates, which included 
four wild-type A. fumigatus strains and 2 strains with elevated amphotericin B and azole MICs 
(one of which has a CYP51 mutation at F46Y). The combination of ibrexafungerp with all three 
antifungals demonstrated synergy in most wild-type strains tested, and although ibrexafungerp 
retained activity against azole resistant isolates, it showed no synergistic effect against these 
strains. One exception was the combination of ibrexafungerp and amphotericin B, which was 
synergistic against the CYP51 mutant resistant strain. 
 
Activity against Dimorphic Fungi 
Ibrexafungerp was evaluated for in vitro activity against isolates of Coccidioides spp., Blastomyces 
spp. and Histoplasma spp. Ibrexafungerp was evaluated against 15 clinical isolates each of 
Blastomyces dermatitidis and Histoplasma capsulatum, and against 5 clinical isolates of 
Coccidioides immitis. The results of this evaluation revealed that the respective MICs for these 
dimorphic fungi ranged from <0.125 to 0.25 ug/ml. 
 
Non-clinical models of invasive fungal diseases 
The antifungal efficacy of ibrexafungerp has been evaluated in several murine models of 
disseminated candidiasis and aspergillosis. In a disseminated C. albicans model, ibrexafungerp 
was more active than fluconazole at all doses. Murine models of ibrexafungerp in disseminated 
candidiasis caused by C. glabrata, C. auris, and C. tropicalis indicated activity across multiple 
Candida species. The plasma area under the concentration-time curve (AUC) necessary to achieve 
target efficacy in these models was estimated to be 15.4 ± 2.2 μM•h.  
In murine models of disseminated A. fumigatus infection, treatment with ibrexafungerp resulted in 
improved survival, similar to that achieved with voriconazole treatment groups.  
The data available from all of the in vitro and in vivo studies conducted to date provide significant 
support for the use of ibrexafungerp in the treatment of invasive fungal diseases. 
The efficacy of ibrexafungerp in combination with isavuconazole in the treatment of experimental 
invasive pulmonary aspergillosis in persistently neutropenic rabbits was evaluated and established 
the foundation for further clinical evaluation. A neutropenic New Zealand White rabbit model of 

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experimental invasive pulmonary aspergillosis was used. Treatment groups included rabbits 
receiving ibrexafungerp (formerly known as SCY-078, thus abbreviated here as “SCY”) at 
2,5 mg/kg/day IV (SCY2.5) and 7.5 mg/kg/day IV (SCY7.5), isavuconazole at 40 mg/kg/day 
orally (ISA40), the combination of SCY2.5 + ISA40, the combination of SCY7.5 + ISA40, or 
untreated control rabbits. Treatment started 24 hours after endotracheal administration of an A. 
fumigatus inoculum and continued QD for up to 12 days. Blood samples for galactomannan index 
(GMI) antigenemia and serum (1→3)-β-D-glucan (BDG) levels were obtained every other day. 
Rabbits treated with SCY2.5+ISA40 and SCY7.5+ISA40 had prolonged survival in comparison 
to those of SCY2.5-treated, SCY7.5-treated, ISA40-treated or untreated control rabbits (p<0.05). 
In addition, groups of SCY2.5+ISA40 and SCY7.5+ISA40 demonstrated lower pulmonary infarct 
scores in comparison to those of single therapy ISA40. These outcome variable data correlated 
directly with a significant decline of GMI antigenemia and serum BDG levels during therapy in 
comparison to progressive GMI and BDG levels of untreated control rabbits. These preclinical 
data indicate a synergistic response resulting from the co-administration of ibrexafungerp with an 
azole antifungal. 
 
Nonclinical experience 
The toxicity and toxicokinetic profile of ibrexafungerp following a once daily (QD) oral (gavage) 
administration to Sprague-Dawley rats for 26 weeks or to Beagle dogs for 39 weeks was assessed. 
Additionally, the reversibility of any changes following a 12-week period post dosing cessation 
was evaluated in both species. For each study, clinical assessments consisted of mortality, clinical 
observations, body weight, food consumption and ophthalmology. Electrocardiograms were also 
conducted in dogs. Blood and urine samples were collected for clinical pathology and blood 
plasma was analyzed for toxicokinetics. Following the end of the 26- or 39-week dosing period 
and the 12-week recovery periods, animals were euthanized and organ weights and macroscopic 
observations were recorded. Histopathological examination was performed on a comprehensive 
list of tissues from all animals. 
In rats, no new toxicities or target organs of toxicity were identified (compared to experience in 
shorter terms studies), and the no-observed-adverse-effect-level (NOAEL) was established, which 
corresponded to mean maximum concentration (Cmax) and AUC up to the last measurable 
concentration (AUClast) values on Day 182 of 3290 ng/mL and 73,700 hr•ng/mL in males, and 
4060 ng/mL and 87,300 hr•ng/mL in females, respectively. Likewise, in dogs, no new toxicities 
or target organs of toxicity were identified (compared to experience in shorter terms studies) and 
the NOAEL was established, which corresponded to mean Cmax and AUClast values on Day 273 of 
1600 ng/mL and 26,700 hr•ng/mL in males, and 2390 ng/mL and 46,100 hr•ng/mL in females, 
respectively. 

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Therefore, as no new toxicities were identified following daily oral dose administration to rats and 
dogs for up to 6 and 9 months, respectively, per ICH M3(R2) dose administration duration in the 
clinical setting for greater than 6 months is supported. 
The in vitro studies indicated that ibrexafungerp metabolism was predominantly oxidative, with 
cytochrome P450 (CYP) 3A being the primary enzyme involved in its oxidative metabolism. 
Strong inhibitors of CYP3A would be expected to increase plasma levels of ibrexafungerp and its 
concurrent administration should be avoided. 
Clinical experience 
To date, the oral formulations of ibrexafungerp have been evaluated in over 1,500 subjects and 
patients included in multiple Phase 1 and two Phase 2 studies. 
Ibrexafungerp was generally well tolerated following single oral doses of up to 1600 mg and 
multiple oral doses of up to 800 mg/day for 28 consecutive days in Phase 1 studies. Reported 
adverse events (AEs) after oral administration have been generally transient and primarily mild to 
moderate in intensity. The most frequently reported AEs have been mild gastrointestinal events 
(nausea, vomiting, diarrhea and abdominal pain). 
A Phase 2 study of oral ibrexafungerp as step-down therapy from IV echinocandin in patients with 
invasive candidiasis has been completed. This was a multicenter, randomized, open-label study in 
which, following three to ten days of IV echinocandin therapy, 21 subjects received either 
ibrexafungerp 500 mg QD with a 1000 mg loading dose (6 patients), ibrexafungerp 750 mg QD 
with a 1250 mg loading dose (7 patients) or standard of care (SOC) treatment (8 patients with 
either oral fluconazole 400 mg QD with an 800 mg loading dose or IV micafungin 100 mg QD for 
up to 28 days). Ibrexafungerp was well tolerated in this study with an AE profile typical of this 
population and comparable to the SOC. The results from this study also indicated that the higher 
dose of ibrexafungerp tested (750 mg QD) is predicted to achieve the target exposure at steady 
state in the majority of patients. 
Two Phase 2 studies of oral ibrexafungerp in patients with vulvovaginal candidiasis (VVC) have 
been completed. Both were multicenter, randomized, active-controlled, evaluator or double-blind 
studies of oral ibrexafungerp in adult female patients with VVC. The results from both studies 
were consistent with oral ibrexafungerp achieving high clinical cure and mycological eradication 
rates. Specifically, in the Phase 2b study DOVE (204) in subjects with acute VVC, a 600 mg single 
day dose (administered as 300 mg every 12 h) of ibrexafungerp resulted in a clinical cure rate of 
52% at day 10 (TOC) and 70% at Day 25 with mycological eradication achieved by 63% of 
subjects by day 10. In these studies, ibrexafungerp was well tolerated with the most common AEs 
being mild gastrointestinal events. The high clinical cure rates observed are supportive of the 
clinically relevant antifungal activity of ibrexafungerp in this form of Candida infection.  
According to the Infectious disease society of America (IDSA) treatment guidelines,6 patients with 
severe acute Candida vulvovaginitis, fluconazole, 150 mg, given every 72 hours for a total of 2 or 

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3 doses, is recommended. Based on the anticipation that the VVC patients that would need 
treatment in this study would have severe disease, 750 mg, given every 72 hours for a total of three 
doses is recommended in this protocol for acute VVC. 
A preliminary efficacy review of the 20 subjects who completed therapy under this study, SCY-
078-301, was conducted by an external expert panel (Data Review Committee, DRC). These 20 
patients suffered from a variety of conditions, including esophageal candidiasis, intra-abdominal 
abscesses, spondylodiscitis and oropharyngeal candidiasis, with the most common fungal species 
being C. glabrata, C. krusei, and C. albicans. Ibrexafungerp treatment ranged from seven to 90 
days, with a mean duration of ~37 days. Per DRC evaluation at end of treatment, 11 patients 
achieved a Complete or Partial Global Response and six patients a stable-disease response. Only 
two patients showed progression of disease and one patient’s outcome was considered 
indeterminate. 
Several drug-drug interaction studies have been conducted. Ketoconazole (a strong inhibitor of 
CYP3A) induces a significant (5-fold) increase in ibrexafungerp exposure while diltiazem (a 
moderate inhibitor of CYP3A) induces a mild to moderate (<3 fold) increase in ibrexafungerp 
exposure. Ibrexafungerp did not have any effect on rosiglitazone (a CYP2C8 substrate) exposure, 
had only a mild effect (less than a 0.5-fold increase) on the AUC of tacrolimus (a CYP3A and P-gp 
substrate) and had no effect on the Cmax of tacrolimus. 
Based on the cumulative in vivo animal efficacy data and animal and human safety data, the target 
plasma exposure for clinical efficacy and safety in invasive candidiasis is 15.4 μM•hr 
(11.2 μg•hr/mL). A simulation using a population PK model was performed based on pooled data 
from healthy volunteers and patients. This simulation was used to predict the percentage of patients 
with AUCs greater than or equal to this target efficacy and safety exposure and the simulated 
plasma time course of the planned oral dosing regimen for ibrexafungerp, which consists of a two-
day loading dose regimen of 750 mg BID administered on Day 1 and Day 2 followed by an oral 
maintenance dose of 750 mg QD starting on Day 3. The results of the simulation indicate that 
ibrexafungerp given 750 mg BID for two days followed by 750 mg QD results in over 80% of the 
population reaching or exceeding the exposure target of AUC0-24 ≥11.2 μg•hr/mL in the majority 
of subjects. The exposure achieved by this dose regimen was further confirmed in a Phase 1 study 
(SCY-078-111) in 16 healthy volunteers in which oral ibrexafungerp was administered at doses of 
750 mg BID on Days 1 and 2 followed by 750 mg QD on Days 3 – 7. The geometric mean AUC0-24 
on Day 1 was 16 μg•hr/mL, indicating that target exposures were achieved within the first day. In 
the same study, steady state was reported by Day 4 and the AUC0-24 on Day 7 was 28 μg•hr/mL, 
urine concentrations of ibrexafungerp of 10 of 16 subjects were above 0.5 μg /mL at Day 7.  
Additionally, based on a simulation using the population PK model, ibrexafungerp can be 
administered as 750 mg BID on Day 1 and Day 2 followed by 375 mg BID starting on Day 3. This 
alternative dosing regimen results in the same exposure (AUC) and Cavg with a minor reduction in 
Cmax, in comparison to the primary dosing regimen described above. 

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Ibrexafungerp has the potential to be an important addition to the anti-fungal treatment arsenal by 
providing potent activity against the full spectrum of Candida species, including difficult to treat 
organisms, and affording the added flexibility of oral step down and earlier hospital discharge. 
For additional information on ibrexafungerp, please refer to the Investigator’s Brochure. 
7.2 
Rationale for the Study 
This study is being conducted to evaluate the efficacy, safety and PK of ibrexafungerp in male and 
female subjects >18 years of age with documented severe fungal diseases for whom SOC 
antifungal treatment is not appropriate due to refractoriness, resistance, intolerance, relapse, 
toxicities, need for oral therapy or other reasons.  
Eligible subjects must be selected based on study criteria and be approved for selection by the 
Sponsor or Sponsor designee. 
Subjects must have a documented eligible fungal disease that has been refractory to, has relapsed 
after, or the subject has intolerance to or demonstrated toxicities resulting from an approved SOC 
antifungal treatment, or has an isolate resistant to, or that has a high MIC and is unlikely to respond 
to SOC antifungal treatment. Subjects are also eligible if, in the judgement of the Investigator, 
continued IV antifungal therapy is not feasible or desirable due to clinical or logistical 
circumstances or if other oral antifungal alternatives are not appropriate. Refractoriness, defined 
as persistent clinical, radiological or mycological evidence of fungal disease, and intolerance, 
including presence of, history of or anticipated toxicities (e.g. drug-to-drug interactions) associated 
with administration of SOC antifungal agents, will be determined by the Investigator. 
The primary efficacy endpoint of the study is Global Response (composite assessment of clinical, 
radiological and mycological responses) as determined by a Data Review Committee (DRC). The 
primary endpoint will be determined at the TOC visit for VVC, CMC, CPA and ABPA and at the 
EOT visit for all other fungal diseases.7,8 Clinical response will be evaluated by the signs and 
symptoms of the infection and/or imaging scans, if applicable. Mycological response will be 
assessed by mycological testing (fungal culture, KOH and other fungal stains, T2 testing) and/or 
serological testing (including GMI, Coccidioides titers, and β-D-glucan levels, among others),9 if 
applicable. Recurrence will be assessed at the 25-Day FU visit (25 days after EOT) for subjects 
with VVC and at the 6-Week FU visit (42 days after EOT) for all other subjects as a secondary 
efficacy endpoint. Recurrence is defined as Global Response at EOT (TOC for VVC) but re-
emergence of the baseline fungal disease (with the same fungal species and involving the same 
site) during the post treatment follow-up. 

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8.0 
Study Objectives 
8.1 
Primary Objectives 
The primary objectives listed below apply to all eligible fungal diseases: 
• To evaluate the efficacy of ibrexafungerp in the treatment of severe fungal diseases by a 
Data Review Committee (DRC) at the primary time point for the fungal disease 
• To evaluate the safety of ibrexafungerp 
8.2 
Secondary Objectives 
8.2.1 
Overall Secondary Objectives 
The overall secondary objectives listed below apply to all eligible fungal diseases: 
• To evaluate the efficacy of ibrexafungerp as determined by the DRC at other time points 
• To evaluate the efficacy of ibrexafungerp as determined by the Investigator 
• To determine the efficacy of ibrexafungerp by pathogen 
• To determine the efficacy of ibrexafungerp by fungal disease and disease category  
• To evaluate the efficacy of ibrexafungerp by recurrence of the baseline fungal disease 
• To evaluate the efficacy of ibrexafungerp by reason for enrollment (refractory, resistance, 
relapse, intolerance, toxicity, need for oral therapy)  
• To determine All-Cause Mortality (ACM)  
• To evaluate the pharmacokinetics (PK) of ibrexafungerp by population PK analysis 
8.2.2 
Disease-Specific Secondary Objectives 
• To evaluate the efficacy of ibrexafungerp as determined by other disease-specific endpoints 
(Table 2) 
9.0 
Study Endpoints 
9.1 
Primary Endpoints 
The primary endpoints listed below apply to all eligible fungal diseases: 

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• Efficacy as measured by the percentage of subjects with Global Response at TOC for 
VVC (Day 17), CMC (EOT or Day 84), CPA (EOT or Day 90) and ABPA (EOT or Day 
90) (whichever comes first) and at  
EOT for all other diseases as determined by a DRC  
• Safety as measured by: physical examination, vital signs, AEs, and laboratory tests 
9.2 
Secondary Endpoints 
9.2.1 
Overall Secondary Endpoints 
The overall secondary endpoints listed below apply to all eligible fungal diseases: 
• The percentage of subjects who achieve Global Response at additional time points as 
applicable for each disease, disease category and reason for enrollment (Table 16), as 
determined by the DRC and by the Investigator 
• The percentage of subjects who achieve Clinical Response by pathogen at time points 
applicable for each disease, disease category and reason for enrollment (Table 16), as 
determined by the DRC and the Investigator  
• The percentage of subjects who achieve Mycological Response by pathogen at time points 
applicable for each disease, disease category and reason for enrollment (Table 16), as 
determined by the DRC and the Investigator 
• The percentage of subjects who achieve Clinical Response by fungal disease, disease 
category and reason for enrollment at time points applicable for each disease (Table 16), 
as determined by the DRC and the Investigator 
• The percentage of subjects who achieve Mycological Response by fungal disease, disease 
category and reason for enrollment at time points applicable for each disease (Table 16), 
as determined by the DRC and the Investigator 
• The percentage of subjects with a recurrence of the baseline fungal disease at the 25-Day 
FU for VVC and at the 6-Week FU for all other diseases as determined by the DRC 
• ACM at Day 30 (Invasive candidiasis and candidemia) and Day 42 for all diseases 
• Time to death from any cause 
• Describe ibrexafungerp plasma concentrations  
9.2.2 
Disease-Specific Secondary Endpoints  
Disease-specific secondary endpoints, as assessed by the DRC (Table 2) 
 

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Table 2 
Disease -Specific Secondary Endpoints 
Disease-Specific Secondary Endpoints 
Acute Invasive candidiasis / Candidemia  
• Completion of study drug antifungal treatment (i.e. no recurrence, no use of other antifungal 
treatment, no discontinuation for any reason) 
Acute or Chronic Severe Mucocutaneous Candidiasis 
• Percentage subjects with mycological cure at Day 84 
• Percentage subjects with clinical response by Day 30 and Day 84 
• Percentage of subjects with continued symptom relief at 6-week FU  
Chronic Pulmonary Aspergillosis (CPA) disease-specific endpoints 
o Six-Minute Walk Test and MRC Dyspnea Score at Day 90 and Day 180 
o Weight change at Day 90 and Day 180 
o Improvement in inflammatory markers (CRP, plasma viscosity, albumin, platelet count, 
disease-specific immunoglobulin levels) at Day 90 and Day 180 
o Change in total IgG and Aspergillus IgG at Day 90 and Day 180, if elevated at Baseline 
o All-cause mortality at Day 90, Day 120 and Day 180 
o Recurrence at Day 180 
Allergic Bronchopulmonary Aspergillosis (ABPA) disease-specific endpoints:  
o Percentage of subjects who exhibit a Global Response at Day 42  
o Percentage of subjects with Clinical Improvement (as measured on a 4-point scale) at 
TOC, Day 90, Day 180, then every 3 months while on therapy, and 6-Month FU 
o Percent decline in total IgE (baseline IgE minus time point IgE/baseline IgE) at Day 42 
and Day 90 
o Number of subjects who experience an ABPA exacerbation at the 3-Month and 6-Month 
FUs  
o Time to first ABPA exacerbation 
o Change in lung function (FEV1 and FVC) at Day 42 
o Number of Asthma exacerbations and ABPA exacerbations at the 3-Month and 6-Month 
FUs 
o All-cause mortality at Day 90, Day 120 and Day 180 
Invasive Pulmonary Aspergillosis (IPA) disease-specific endpoint 
o The percentage of subjects who attain a GMI decrease including absolute and percent 
reduction from Baseline to Weeks 1, 2, 4 and 6, when feasible 
o Time to achieve a clinically meaningful GMI absolute and percent decrease 
o All-cause mortality at Day 84  

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Disseminated/invasive dimorphic fungal disease-specific endpoint 
o All-cause mortality at Day 84  
Other emerging fungi including yeasts and molds disease-specific endpoint 
o All-cause mortality at Day 84  
Abbreviations: CRP=c-reactive protein; FEV1 = forced expiratory volume during the first second; FVC = forced 
vital capacity; FU = Follow-up; GMI=galactomannan index; IgE=immunoglobulin E; MRC=Medical Research 
Council; TOC=test of cure  
10.0 Study Design 
10.1 
Overall Description of the Study 
This is a multicenter, open-label, non-comparator, single-arm study to evaluate the efficacy, safety 
and PK of ibrexafungerp in male and female subjects ≥18 years of age with documented severe 
fungal diseases for whom SOC antifungal treatment is not appropriate due to refractoriness, 
resistance, intolerance, relapse, toxicities, need for oral therapy or other reasons.  
Subjects must have a documented eligible fungal disease that has been refractory to, has relapsed 
after, or subject has intolerance to or demonstrated toxicities resulting from an approved SOC 
antifungal treatment as listed in Table 5 (Eligible Fungal Diseases), or has an isolate resistant to, 
or that has a high MIC and is unlikely to respond to antifungal SOC. Subjects are also eligible if, 
in the judgement of the Investigator, continued IV antifungal therapy is not feasible or desirable 
due to clinical or logistical circumstances or if other oral antifungal alternatives are not appropriate. 
Subjects should meet these and other study criteria to be considered for enrollment. Inclusion of 
each subject in the study must be approved by the Sponsor (or Sponsor designee) prior to initiation 
of study drug.  
The study will be conducted at approximately 40 sites globally and is planned to enroll and treat 
approximately 220 (+10%) subjects.  
Study Schedule 
For all subjects except VVC subjects, there will be a Screening visit, a Baseline visit (also 
considered Day 1), several scheduled visits depending on the subject’s fungal disease, an EOT 
visit and a follow-up visit 6 weeks after EOT.  For ABPA subjects there will be additional follow-
up visits 3 months and 6 months after EOT.  . For CMC, CPA and ABPA subjects there will be a 
TOC visit on EOT or Day 84 for CMC subjects or Day 90 for CAP and ABPA subjects, whichever 
comes first. Following Screening, eligible subjects will receive the study drug loading dose on 
Days 1 and 2 and the study drug maintenance dose from Day 3 up to EOT. A summary of the 
overall treatment and follow-up schedule for these subjects is provided in Table 3. 

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Table 3 
Summary of Overall Treatment and Follow-Up Schedule for All Subjects 
Except VVC Subjects 
Pre-study 
Activities 
Ibrexafungerp 
Loading Dose 
Ibrexafungerp 
Maintenance 
Dose 
TOC 
EOT 
6-
Week 
Follow
-Up 
Additional 
Follow-
Ups 
Screeninga 
(Days -1 [-
3]) 
Day 1a 
(Baseline) & 
Day 2 
Day 3 to EOT  
EOT or Day 84 
(CMC) 
EOT or Day 90 
(CPA and ABPA) 
whichever comes 
first 
Last dose of 
study drug 
(up to 180 
days from 
Day 1) 
6 
weeks 
(±7 
days) 
after 
EOT 
3 and 6 
months 
after EOT 
for ABPA 
subjects 
only 
Abbreviations: ABPA = allergic bronchopulmonary aspergillosis; CMC = chronic mucocutaneous candidiasis; CPA = chronic 
pulmonary aspergillosis; EOT = end of treatment; TOC = test of cure 
a: Screening and Baseline (Day 1) may occur on the same day. 
 
Subjects with VVC will have a Screening visit, a Baseline/Day 1 visit, and scheduled visits on 
Day 4, Day 7 (EOT), Day 17 (TOC), 25-day FU (Day 32) and 35-day FU (Day 42). VVC subjects 
will receive treatment every three days for a total of three dosing days (i.e., on Days 1, 4 and 7). 
The EOT and 35-Day FU visits may be a phone contact for asymptomatic subjects. A summary of 
the overall treatment and follow-up schedule for VVC subjects is provided in Table 4. 
 
Table 4 
Summary of Overall Treatment and Follow-Up Schedule for VVC Subjects 
Pre-study 
Activities 
Ibrexafungerp 
Dosing 
EOT 
(Phone/on 
site) 
TOC 
25-Day FU 
35-Day FU 
(Phone/on site) 
Screeninga 
(Day -1) 
Day 1a (Baseline) 
Day 4 and Day 7 
Day 7 (+1) 
Day 17 (±3) 
Day 32 (25 days 
after EOT; 32 days 
after first dose) 
Day 42 (35 days 
after EOT; 42 days 
after first dose) 
Abbreviations: EOT = end of treatment; FU = follow up; TOC = test of cure; VVC = vulvovaginal candidiasis 
a:  Screening and Baseline (Day 1) may occur on the same day. 
 
Study Treatments 
Eligible subjects (excluding VVC subjects) will receive ibrexafungerp monotherapy given as an 
initial loading dose of 750 mg BID during the first two days of treatment (Day 1 and Day 2) and 
then subsequent oral doses of 750 mg QD for up to 180 days depending on fungal disease. 
Ibrexafungerp given as combination therapy will be required for all subjects with refractory or 
relapsing IPA, mucormycosis and other molds with unpredictable ibrexafungerp activity based on 
Investigator’s judgement and contingent on Sponsor approval. The treatment duration may be 
extended beyond 180 days, if needed, for certain fungal diseases. Sponsor approval must be 
obtained for any extension of treatment beyond 180 days. For subjects receiving extended 
treatment, a 4-week visit schedule may be followed.  Subjects who have a recurrence after EOT 
may also be considered for re enrollment upon discussion with the sponsor. Subjects who are re 

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enrolled will follow the protocol defined visit schedule. 
Subjects with VVC will receive oral doses of 375 mg BID (total daily dose = 750 mg) every three 
days for a total of three dosing days (Day 1, Day 4 and Day 7).  Subjects treated for VVC who 
have a recurrence after TOC may receive additional cycles of ibrexafungerp treatment, similar to 
the initial regimen, upon discussion with the sponsor. 
 
Study Assessments 
Efficacy, PK and safety will be evaluated in this study. 
Efficacy evaluations will consist of clinical evaluations of the signs and symptoms of infection, 
mycological testing (including, but not limited to, fungal culture, KOH and other fungal stains, 
and T2 testing), imaging (e.g., CT, MRI, X-Ray or ultrasound) and serological testing (including, 
among others, ß-D-glucan levels, GM and fungal antibody titers) as applicable for each fungal 
disease. Additional procedures (esophagoscopy, spirometry, St. George’s Respiratory 
Questionnaire [SGRQ]6-Minute Walk Test and Medical Research Council [MRC] Dyspnea Scale) 
will be conducted for selected fungal diseases. 
Efficacy will be assessed primarily in terms of Global Response at TOC for VVC (Day 17), CMC 
(EOT or day 84), CPA (EOT or Day 90) and ABPA (EOT or Day 90) (whichever comes first), 
and at EOT for all other fungal diseases, as determined by an independent DRC. Global Response 
will be a composite global outcome composed of clinical (including radiological, when applicable) 
and mycological (including serological) responses. In addition to the primary endpoint, Global 
Response, Clinical Response and Mycological Response will be assessed as secondary endpoints 
at the primary time point for the determination of efficacy (TOC) for VVC, CMC, CPA and ABPA, 
and EOT for all other eligible fungal diseases) and at additional time points by the independent 
DRC and the Investigator. Efficacy outcome definitions and time points for each fungal disease 
are listed in Table 16 and will be defined in the DRC Charter. 
Other secondary efficacy assessments will include recurrence and survival. Recurrence will be 
evaluated at the 6-Week FU visit after EOT for all subjects, except VVC subjects, who will be 
assessed for recurrence at the 25-Day FU visit. Survival will be determined primarily on Day 30 
for IC/Candidemia and on Day 42 for all subjects. Additional disease-specific efficacy endpoints 
will be evaluated for selected fungal diseases at additional time points (Table 2). 
PK: The PK data obtained from this study will be part of the Population PK analyses that will be 
performed. For subjects who are willing to participate in the PK sampling, blood samples will be 
collected on Day 2 (one sample collected anytime post dosing), Days 3 to 5 (one sample collected 
predose on any of these days) and Days 7 to 10 (one sample collected predose on any of these 
days). Additional blood PK samples will be collected when clinically indicated. 
Subjects will be evaluated for safety throughout the study, including parameters such as physical 
exam, vital signs, AEs and concomitant medications, and safety laboratory tests (hematology, 

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blood chemistry and urinalysis). A final safety assessment will be conducted at the 35-Day FU 
visit (35 days after EOT) for VVC subjects and at the 6-Week FU (6 weeks after the EOT) for all 
other subjects. 
Results from the study will be analyzed against historical and concurrent SOC-treated subjects, 
who will be selected from literature reviews and other data resources. 
10.2 
Blinding, Randomization and Stratification 
This is an open-label study. 
10.3 
Study Duration 
Each subject is expected to complete the study, including all follow-up survival visits, within 
approximately 222 days from Baseline/Day 1. 
10.4 
Number of Centers 
Approximately 40 study centers will participate in the study worldwide. 
11.0 Study Population 
The study population will include male and female adult subjects ≥18 years of age with documented 
eligible severe fungal diseases for whom SOC antifungal treatment is not appropriate due to refractoriness, 
resistance, intolerance, relapse, toxicities, need for oral treatment, or other reasons. 
11.1 
Inclusion Criteria 
Subjects must fulfill all of the following criteria at Screening and/or Baseline to be eligible for 
study admission: 
1. 
Subject is a male or female adult ≥18 years of age on the day the study informed consent form 
(ICF) is signed. 
2. 
Subject has a documented eligible fungal disease that has been refractory or resistant to SOC, 
has relapsed after, or the subject has intolerance to or demonstrated toxicities resulting from 
an approved SOC antifungal treatment (as defined in Table 5). The subject is also eligible if, 
in the judgement of the Investigator, long-term IV antifungal therapy is not feasible or 
desirable due to clinical (isolate is resistant to or has a high MIC and is unlikely to respond to 
antifungal SOC) or logistical circumstances or if other antifungal alternatives are not 
appropriate.  
 

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Table 5 
Eligible Fungal Diseases 
 
Eligibility Criteria 
Fungal Disease 
Diagnostic Criteria 
Refractoriness/Resistance/Intolerancea/Toxicityb/Relapsec 
Criteria 
Acute or chronic invasive 
candidiasis, including 
candidemia  
• 
Histopathologic, cytopathologic, or direct microscopic 
examination of a specimen obtained by needle aspiration 
or biopsy from a normally sterile site showing yeast 
cells—for example, Candida species showing 
pseudohyphae or true hyphae 
OR 
• 
Recovery of a Candida spp. by culture of a sample 
obtained by a sterile procedure (including a freshly 
placed [<24 h ago] drain) from a normally sterile site 
showing a clinical or radiological abnormality consistent 
with an infectious disease process 
OR 
• 
Blood culture positive for Candida spp. 
OR 
• 
Alternative approved diagnostic method such as T2 
testing or ß-D-glucan levels (two consecutive positive 
test results), and at least one of the following: 
temperature ≥38°C or <36°C, systolic blood pressure <90 
mmHg or a decrease of >30 mmHg from normal 
baseline, local signs or symptoms or radiologic findings 
of invasive candidiasis  
For acute invasive candidiasis, including candidemia 
refractoriness is defined as meeting one or more of the 
following criteria: 
• 
Persistence of mycological evidence of Candida infection 
after >3 days of SOC antifungal therapy. Acceptable 
mycological evidence for this study includes:  
o 
Persistently positive culture from a normally sterile site  
o 
Persistently positive T2 test 
o 
ß-D-glucan with elevated values equal to or increasing 
from Baseline (i.e., before start of SOC antifungal 
therapy) 
• 
Antifungal susceptibility results indicating that the Candida 
isolate is not susceptible to the SOC antifungal therapy 
being administered, indicating a high risk of therapeutic 
failure 
• 
Antifungal susceptibility results or local epidemiology 
indicating high risk of antifungal resistance with increased 
risk of therapeutic failure to SOC (e.g., Candida auris)  
For chronic disseminated candidiasis refractoriness is defined 
as any of the following: 
• 
Persistent clinical manifestations such as debilitating fever 
after 12 weeks of initiating SOC antifungal treatment 
• 
Lack of changes in radiological imaging lesions >12 weeks 
after starting SOC antifungal treatment 

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Eligibility Criteria 
Fungal Disease 
Diagnostic Criteria 
Refractoriness/Resistance/Intolerancea/Toxicityb/Relapsec 
Criteria 
Acute or chronic severe 
mucocutaneous 
candidiasis, including:  
• 
Esophageal 
candidiasis (EC)  
• 
Oropharyngeal 
candidiasis (OPC)  
• 
Chronic 
mucocutaneous 
candidiasis (CMC) 
• 
Vulvovaginal 
candidiasis (VVC) 
• 
EC: Clinical manifestations and endoscopic findings 
consistent with EC plus potassium hydroxide (KOH) or 
fungal stain from biopsy or brushing indicating yeast 
infection. 
• 
OPC, CMC: Evidence of clinical manifestations and 
mycological documentation (positive fungal stain from 
biopsy or positive Candida spp. culture obtained from the 
affected site). 
• 
VVC: Evidence of clinical manifestations with total 
composite signs and symptoms score of 4 or more in the 
vulvovaginal signs and symptoms (VSS) Scale 
(Section 21.4 [Appendix D]) and a positive Candida spp. 
culture obtained from a vaginal sample. 
 
For EC and OPC, refractoriness is defined as meeting the 
following criteria: 
• 
Lack of clinical improvement or worsening of infection 
after receipt of SOC antifungal therapy for at least 7 
consecutive days 
For CMC, refractoriness is defined as meeting the following 
criteria:  
• 
Lack of clinical improvement or worsening of the 
mucocutaneous manifestations of CMC after receipt of 
SOC antifungal therapy for at least 21 consecutive days 
For VVC, refractoriness is defined as meeting any of the 
following criteria:  
• 
Lack of clinical improvement or worsening of the infection 
after receipt of SOC antifungal therapy with documentation 
of persistence of Candida spp. in a vaginal sample obtained 
after completion of SOC antifungal therapy 
• 
Recurrent VVC caused by Candida glabrata 
• 
Recurrent VVC caused by any Candida species with a MIC 
for fluconazole ≥ 16 µg/mL 

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Eligibility Criteria 
Fungal Disease 
Diagnostic Criteria 
Refractoriness/Resistance/Intolerancea/Toxicityb/Relapsec 
Criteria 
Disseminated/invasive 
dimorphic fungi: 
• 
Coccidioidomycosis 
• 
Histoplasmosis 
• 
Blastomycosis  
• 
Recovery in culture from a specimen obtained from the 
affected site, in a host with a temporally related illness 
consistent with a fungal infectious disease process 
OR 
• 
If a culture is negative or not obtained, histopathologic or 
direct microscopic demonstration of appropriate 
morphological forms for dimorphic fungi having truly 
distinctive appearance 
OR 
• 
Positive blood culture 
OR 
• 
Demonstration of fungal antibody in a two-dilution rise 
measured in two consecutive blood samples tested 
concurrently in the setting of a temporally related 
infectious disease process 
For disseminated/invasive dimorphic fungi, refractoriness is 
defined as meeting any of the following criteria: 
• 
Relapse after therapy with a SOC antifungal agent (azole or 
amphotericin B) 
• 
Intolerance, anticipated intolerance including high risk for 
drug interactions, or current or past toxicity to administered 
antifungal 
• 
Failure of current therapy as judged by lack of decline in 
fungal serology titers or persistence of signs and symptoms 
after a minimum of 1 month of SOC antifungal therapy 
• 
Isolate with a MIC indicating a high probability of 
therapeutic failure for the intended antifungal agent (e.g., 
fluconazole MIC > 8 µg/mL) 

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Eligibility Criteria 
Fungal Disease 
Diagnostic Criteria 
Refractoriness/Resistance/Intolerancea/Toxicityb/Relapsec 
Criteria 
Chronic Pulmonary 
Aspergillosis (CPA) 
CPA diagnosed according to the European Respiratory Society 
2016 guideline, including: 
• 
Thoracic imaging (preferably by CT) consistent with 
CPA, such as: 
o 
Aspergilloma 
o 
Chronic cavitary pulmonary aspergillosis 
o 
Subacute invasive aspergillosis (1-3 months) 
AND 
• 
Direct evidence of Aspergillus infection or an 
immunological response to Aspergillus spp. 
o 
Percutaneous biopsy showing fungal hyphae on 
microscopy or growing Aspergillus spp. from a 
pulmonary lesion, OR 
o 
Respiratory samples showing hyphae consistent with 
Aspergillus and/or growing Aspergillus spp. and/or 
with a positive Aspergillus PCR 
AND 
o 
High Aspergillus IgG in a serum sample 
AND 
• 
Active mycobacterial infection ruled out 
• 
Disease present for at least 3 months 
• 
Disease requires antifungal treatment for CPA, in the 
opinion of the Investigator 
For CPA, refractoriness is defined as meeting any of the 
following criteria: 
• 
Suboptimal clinical response (per the Investigator’s 
judgment) of CPA signs and symptoms after receipt of SOC 
antifungal therapy for at least 6 weeks, including: 
o 
Significant hemoptysis 
o 
Weight loss 
o 
Persistent fatigue 
o 
Productive cough 
• 
Presence of new or worsened CPA signs and symptoms 
(expected to respond to antifungal treatment) while 
receiving SOC antifungal therapy for at least 6 weeks 
• 
Persistence of azole-resistant Aspergillus spp. positive 
sputum or BAL cultures after at least 3 months of SOC 
antifungal therapy 
• 
Radiologic evidence of lack of improvement, such as: 
o 
New cavities 
o 
Increased peri-cavity infiltrates 
o 
New fungal ball 
 

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Eligibility Criteria 
Fungal Disease 
Diagnostic Criteria 
Refractoriness/Resistance/Intolerancea/Toxicityb/Relapsec 
Criteria 
Allergic 
Bronchopulmonary 
Aspergillosis (ABPA) 
• 
Presence of all of the following: (1) asthma; (2) 
immediate cutaneous hyperreactivity on Aspergillus skin 
test or serum A. fumigatus-specific IgE > 0.35 kUA/L; 
and (3) elevated serum total IgE > 1,000 IU/mL (2.4 
mg/L).  
AND  
• 
Presence of two of the following features: (1) 
precipitating antibodies against A. fumigatus in serum; 
(2) fixed or transient radiographic pulmonary opacities; 
(3) peripheral blood eosinophil count > 1,000 cells/µL; 
(4) bronchiectasis on chest HRCT scan, (5) infection 
with azole-resistant but ibrexafungerp-susceptible 
Aspergillus spp.  
 Not responsive, intolerant or demonstrated toxicity to SOC 
glucocorticoids or azole therapy as judged by the Investigator 
Invasive Pulmonary 
Aspergillosis (IPA) 
 
Mycological evidence: 
• Histopathologic, cytopathologic, or direct microscopic 
examination of a specimen obtained by needle aspiration 
or biopsy from a normally sterile site showing hyphae 
forms accompanied by evidence of associated lung 
damage 
OR 
• Recovery of an Aspergillus spp. by culture of a sample 
obtained by a sterile procedure from a normally sterile 
site (excluding BAL) showing a clinical or radiological 
abnormality consistent with a pulmonary invasive 
aspergillosis  
OR 
• Alternative approved diagnostic method from serum or 
BAL, such as PCR or GMI test (for serum GMI: two 
consecutive positive test results; for BAL, one positive 
test) 
For IPA, refractoriness is defined as meeting the following 
criteria: 
• Suboptimal response (per the Investigator’s judgment) to an 
approved SOC antifungal treatment for IPA (i.e., 
voriconazole, isavuconazole, posaconazole, or amphotericin 
B at the doses recommended per their label), defined as 
radiological, serological or clinical signs of lack of response 
or increased fungal burden, such as any of the following: 
o 
Increased size or number of radiologic infiltrates not 
associated with resolution of neutropenia 
o 
Increased GMI levels 
o 
Lack of clinically meaningful reduction in serum GMI 
levels compared to a sample obtained prior to initiation 
of an acceptable antifungal therapy after at least 7 days 
of antifungal therapy 
 
Monotherapy with ibrexafungerp is not recommended for 
refractory or relapsing IPA. All subjects enrolled for refractory 
or relapsing IPA should receive combination antifungal therapy. 

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Eligibility Criteria 
Fungal Disease 
Diagnostic Criteria 
Refractoriness/Resistance/Intolerancea/Toxicityb/Relapsec 
Criteria 
PLUS  
Clinical evidence 
• At least one of the following clinical signs or symptoms: 
temperature ≥38°C or <36°C, systolic blood pressure <90 
mmHg or a decrease of >30 mmHg from normal baseline, 
local signs or symptoms  
AND 
• radiologic findings compatible with pulmonary invasive 
aspergillosis (Chest CT or MRI) 
PLUS  
Subject Risk Factors, such as: 
• Recent history of neutropenia, or 
• Allogeneic stem cell transplant recipient, or 
• Prolonged (>3 weeks) corticosteroid therapy, or 
• Recent treatment with other recognized T-cell 
immunosuppressant, such as cyclosporine, TNF-α 
blockers, specific monoclonal antibodies or nucleoside 
analogues during the past 90 days 
• Other underlying condition known to have increased risk 
for invasive aspergillosis (e.g. influenza, pneumonia) 
The following combination options are allowed:  
• addition of ibrexafungerp to any ongoing antifungal 
• replacement of one (toxic/ineffective) element of a two 
antifungal combination therapy with ibrexafungerp 
• replacement of current monotherapy with a new 
combination, generally: 
o 
replacement of amphotericin B monotherapy with an 
azole plus ibrexafungerp combination, or 
o 
replacement of an azole monotherapy with an 
amphotericin B plus ibrexafungerp combination  
• continuation of an azole plus echinocandin combination 
where the subject could go home on an oral regimen by 
replacing the parenteral echinocandin with ibrexafungerp 
 
Subjects with IPA and intolerance to other standard of care 
options can be considered for enrollment to receive 
ibrexafungerp monotherapy, upon discussion with the Sponsor. 

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Eligibility Criteria 
Fungal Disease 
Diagnostic Criteria 
Refractoriness/Resistance/Intolerancea/Toxicityb/Relapsec 
Criteria 
Other emerging fungi 
including yeasts and 
molds (e.g., 
sachromycetes, 
scopulariopsis) 
 
• Histopathologic, cytopathologic, or direct microscopic 
examination of a specimen obtained by needle aspiration 
or biopsy from a normally sterile site showing fungal 
cells.  
OR 
• Recovery of a fungal species by culture of a sample 
obtained by a sterile procedure from a normally sterile 
site, wound or lesion consistent with known 
pathophysiology of the organism  
AND 
• Radiological imaging showing evidence consistent with 
an infectious disease process 
AND 
• Fungus (genus species) is known to be generally 
susceptible to ibrexafungerp in vitro 
OR 
• Fungal susceptibility of the isolate showing MICs for 
ibrexafungerp ≤ 4 ug/mL 
For other emerging fungi, refractoriness is defined as meeting 
any of the following criteria: 
• Subject intolerant of available therapeutic options 
• Suboptimal response per the Investigator’s judgement 
• Limited or no therapeutic options available 
For subjects without culture isolate available (to confirm 
susceptibility to ibrexafungerp), combination therapy should be 
considered and discussed with the Sponsor. 

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Eligibility Criteria 
Fungal Disease 
Diagnostic Criteria 
Refractoriness/Resistance/Intolerancea/Toxicityb/Relapsec 
Criteria 
Abbreviations: ABPA=allergic bronchopulmonary aspergillosis; ALT= alanine aminotransferase; AST=aspartate aminotransferase; BAL=bronchoalveolar 
lavage; CMC=chronic mucocutaneous candidiasis; CPA=chronic pulmonary aspergillosis; CT=computerized tomography; EC=esophageal candidiasis; 
GMI=galactomannan index; HRCT= high resolution computerized tomography; Ig=immunoglobulin; IPA=invasive pulmonary aspergillosis; 
MIC=minimum inhibitory concentration; MRI=magnetic resonance imaging; OPC=oropharyngeal candidiasis; PCR= polymerase chain reaction; 
SOC=standard of care; TNF = tumor necrosis factor; VSS=vulvovaginal signs and symptoms; VVC=vulvovaginal candidiasis. 
a: Intolerance for any of the eligible diseases above is defined as presence or history of administration-related AEs (e.g., infusion reaction, hypersensitivity 
reactions, etc.) to the standard antifungal being administered or intended for treatment of the current fungal disease. 
b: Toxicity for any of the eligible diseases above is defined as the degree to which a substance (antifungals) can damage an individual as well as cause a 
negative effect on a substructure of an individual such as a system or organ. The toxicity should be of a severity or prognosis such that, as per the 
Investigator´s judgement, it is in the best interest of the subject to modify his/her antifungal therapy. Example of toxicities include: 
• 
Nephrotoxicity defined as elevation of serum creatinine level by 2 times the baseline value or any value above the upper limit of normal (ULN), in a 
repeat test at least 24 hours apart.  
• 
Hepatotoxicity defined as elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >5 times ULN. 
• 
Other events not related to the subject’s condition and that started after initiation of the standard antifungal agent, such as visual disturbances, cutaneous 
reactions, neurological reactions, histamine reactions, etc. 
• Drug-drug interactions of the standard antifungal agent with other therapies being received by the subject, which are either associated with a 
documented toxicity or are likely to result in toxicity. 
c:  Relapse is defined as deterioration or worsening of a fungal disease after an initial improvement to therapy. 
 
 
 

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3. Subject is able to tolerate medication orally or through a nasogastric (NG) tube or 
percutaneous endoscopic gastrostomy (PEG) tube. 
4. Subject and/or legal guardian is/are able to understand and sign a written ICF, which must 
be obtained prior to treatment and any study-related procedures. 
5. Subject and/or legal guardian is able to understand and sign a consent or authorization 
form, which shall permit the use, disclosure and transfer of the subject’s personal health 
information. (e.g., in the US, a Health Insurance Portability and Accountability Act 
[HIPAA] authorization form).  
6. Subject and/or legal guardian is able to understand and follow all study-related procedures 
including study drug administration.  
7. Subject is not pregnant and is highly unlikely to become pregnant or to impregnate a partner 
since he/she meets at least one of the following criteria:  
a. Subject is a female subject who is not of reproductive potential and is eligible 
without requiring the use of contraception. A female subject who is not of 
reproductive potential is defined as one who: (1) has reached natural menopause 
(defined as 6 months of spontaneous amenorrhea with serum follicle-stimulating 
hormone levels in the postmenopausal range as determined by the local laboratory, 
or 12 months of spontaneous amenorrhea); (2) is 6 weeks post-surgical bilateral 
oophorectomy with or without hysterectomy; or (3) has undergone bilateral tubal 
ligation. Spontaneous amenorrhea does not include cases for which there is an 
underlying disease that causes amenorrhea (i.e., anorexia nervosa). 
b. Subject is a male subject who is not of reproductive potential and is eligible without 
requiring the use of contraception. A male subject who is not of reproductive 
potential is defined as one who has undergone a successful vasectomy. A successful 
vasectomy is defined as (1) microscopic documentation of azoospermia, or (2) a 
vasectomy more than 2 years ago with no resultant pregnancy despite sexual 
activity post vasectomy.  
c. Subject is a male or female subject who is of reproductive potential and agrees to 
remain abstinent if it is the subject’s preferred method of contraception, or, if 
sexually active, use (or have their partner use) 2 acceptable methods of 
contraception starting from the time of consent through 28 days after the 
completion of study therapy. Acceptable methods of birth control are hormonal 
contraception (including but not limited to oral, injectable or implantable methods), 
intrauterine device, diaphragm with spermicide, condom, and vasectomy. 
Hormonal contraception (including but not limited to oral, injectable or implantable 
methods), must not be used alone as a method of contraception because it is 
unknown if the effect of ibrexafungerp may reduce the efficacy of hormonal 
contraceptives.  

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Periodic 
abstinence 
(calendar, 
symptothermal, 
post-ovulation 
methods), 
withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea 
method (LAM) are NOT acceptable methods of contraception. 
NOTE: Women of childbearing potential must have a negative urine or serum pregnancy 
test (β-human chorionic gonadotropin) prior to enrollment (performed by the site’s local 
laboratory). 
11.2 
Exclusion Criteria 
A subject will be excluded from participation in the study if he or she meets any of the following 
exclusion criteria at Screening and/or Baseline: 
1. Subject has an invasive fungal disease with central nervous system involvement unless the 
subject is planned to receive combination therapy with ibrexafungerp and other antifungal. 
2. Subject has an inappropriately controlled fungal disease source (e.g., persistent catheters, 
devices, identified undrained abscess) that is likely to be the source of the fungal disease. 
3. Subject is hemodynamically unstable and/or requiring vasopressor medication for blood 
pressure support. 
4. Subject has abnormal liver test parameters: AST or ALT >10 x ULN and/or total bilirubin >5 
x ULN. 
Note: Subjects with unconjugated hyperbilirubinemia with a diagnosis of Gilbert’s disease 
are not excluded.  
5. Subject is unlikely to survive 30 days. 
6. Subject has any other condition or laboratory abnormality that, in the judgment of the 
Investigator, would put the subject at unacceptable risk for participation in the study or may 
interfere with the assessments included in the study. 
7. Subject requires treatment with the prohibited medications.  
8. Subject has known hypersensitivity to ibrexafungerp. 
9. Subject is pregnant or lactating.  
10. Subject has received any other investigational drug (i.e., new chemical entity) within at least 
30 days (or 5 and a half half-lives of the investigational product) before signing the ICF. 
11. Subject is an employee of SCYNEXIS, Inc., the Investigator, or contract research organization 
involved in the study, or an immediate family member (partner, offspring, parents, siblings, 
or sibling’s offspring) of an employee involved in the study. 

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12. Subject or legal representative is/are unable to provide written informed consent for any 
reason. 
13. Subject is unlikely to comply with protocol requirements. 
11.3 
Discontinuation Criteria 
A subject may be discontinued from the study or study drug for any of the following reasons: 
• Withdrawal of consent by the subject and/or subject’s legal guardian; 
• Investigator or Sponsor decision that withdrawal is in the subject’s best interest; 
• Deterioration of the clinical condition or delayed response requiring, in opinion of the 
Investigator, alternative therapy; 
• Occurrence of an AE that, in the opinion of the Investigator, warrants discontinuation of 
the subject from the study drug; 
• Pregnancy; 
• Lost to follow up (every attempt should be made to contact the subject). 
The reason for a subject’s discontinuation of treatment or withdrawal from the study will be clearly 
documented in the source documents and on the electronic case report form (eCRF). 
For VVC subjects, all TOC procedures should be performed for subjects who discontinue from 
the study before the TOC visit, and all 25-Day FU procedures should be performed for subjects 
who discontinue from the study after the TOC visit but before the 25-Day FU visit.  
For all other fungal diseases, at the time of discontinuation, all EOT procedures should be 
performed for subjects who discontinue from treatment on or before the EOT visit and the 6-Week 
FU visit should also be completed. All 6-Week FU procedures should be performed for subjects 
who discontinue from the study after the EOT visit and on or before the 6-Week FU visit. All 
follow up visits should be completed for discontinued subjects regardless of need for additional 
antifungal therapy. 
11.4 
Replacement of Discontinued Subjects 
Subjects who discontinue early from randomized treatment will not be replaced. 
12.0 Study Treatments 
12.1 
Study Treatment Groups 
This is an open-label, non-comparator, single-arm study. All subjects will receive ibrexafungerp 
monotherapy except subjects with refractory or relapsing invasive pulmonary aspergillosis (IPA), 
who will receive combination therapy. Combination therapy may also be administered to other 

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subjects based on Investigator’s judgement and contingent on Sponsor approval. Subjects will 
receive ibrexafungerp on an inpatient or outpatient basis, as needed for each fungal disease. 
12.1.1 
Ibrexafungerp Monotherapy for All Fungal Diseases, Excluding VVC 
Subjects will receive ibrexafungerp monotherapy given as an initial loading dose of 750 mg (3 
tablets of 250 mg each) given BID (total daily dose = 1500 mg) during the first 2 days of treatment 
and then subsequent oral doses of 750 mg (3 tablets of 250 mg each) QD for up to 180 days, 
depending on fungal disease.  
Table 6 
Ibrexafungerp Monotherapy Dosing Regimen (Excluding VVC) 
 
Treatment Days 
Ibrexafungerp Dosing Regimen 
Total Ibrexafungerp 
Daily Dose 
Loading Dose 
 
Study Days 1 and 2 
750 mg BID: 
750 mg (3 tablets x 250 mg) AM 
750 mg (3 tablets x 250 mg) PM 
1500 mg 
Maintenance Dose 
Study Day 3 to EOT 
750 mg QD: 
750 mg (3 tablets x 250 mg) 
750 mg 
Alternative 
Maintenance Dose 
Study Day 3 to EOT 
375 mg BID: 
375 mg (1.5 tablets x 250 mg) AM 
375 mg (1.5 tablets x 250 mg) PM 
750 mg 
Abbreviations: AM = morning; BID = twice a day; EOT = end of treatment; PM = evening; QD = once a day; 
VVC = vulvovaginal candidiasis 
Treatment beyond 180 days may be permitted under certain circumstances to be agreed upon by 
the Investigator and the Sponsor on a per-subject basis. Subjects with a recurrence after TOC 
(VVC) or EOT (all other diseases) may be considered for re-enrollment upon discussion with the 
Sponsor.   
If subjects cannot swallow the whole tablet, the tablets may be split. In the event subjects 
experience gastrointestinal intolerance on the 750 mg QD dose, the tablets may be split and/or 
administered at 10 to 20-minute intervals. The daily dose may also be given as 375 mg (1 and ½ 
tablets) BID for subjects experiencing gastrointestinal intolerance. 
12.1.2 
Ibrexafungerp Monotherapy for VVC  
Subjects with VVC will receive ibrexafungerp monotherapy given as oral doses of 375 mg BID 
(total daily dose = 750 mg) every three days for a total of three dosing days (Day 1, Day 4 and 
Day 7). Subjects treated for VVC who have a recurrence after TOC may receive additional cycles 
of ibrexafungerp treatment similar to the initial regimen, upon discussion with the sponsor. 

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Table 7 
Ibrexafungerp Monotherapy Dosing Regimen for VVC 
Treatment Days 
Ibrexafungerp Dosing Regimen 
Total Ibrexafungerp 
Daily Dose 
Study Day 1 
375 mg (1 ½ tablets x 250 mg) AM 
375 mg (1 ½ tablets x 250 mg) PM 
750 mg 
Study Day 4 
375 mg (1 ½ tablets x 250 mg) AM 
375 mg (1 ½ tablets x 250 mg) PM 
750 mg 
Study Day 7 
375 mg (1 ½ tablets x 250 mg) AM 
375 mg (1 ½ tablets x 250 mg) PM 
750 mg 
Abbreviations: AM = morning; PM = evening; VVC = vulvovaginal candidiasis 
12.1.3 
Ibrexafungerp Combination Therapy 
Monotherapy with ibrexafungerp is not recommended for refractory or relapsing IPA.  All subjects 
enrolled for refractory or relapsing IPA, mucormycosis or other molds with unpredictable 
ibrexafungerp activity should receive ibrexafungerp given as combination therapy. Subjects with 
IPA and intolerance to other SOC options can be considered for enrollment to receive 
ibrexafungerp monotherapy, upon discussion with the Sponsor. 
For subjects who have infections due to other emerging fungi, including yeasts and molds, but 
have no culture isolate available (to confirm susceptibility to ibrexafungerp), combination therapy 
should be considered and discussed with the Sponsor. Combination therapy will also be allowed 
for other subjects based on Investigator’s judgement and contingent on Sponsor approval.  
Acceptable antifungal therapy includes voriconazole, isavuconazole, posaconazole, fluconazole or 
amphotericin B (AMB) at the doses recommended per their label. When used in combination with 
the azoles, the dose of ibrexafungerp should be reduced from 750 mg to 500 mg. 
 
Table 8 
Ibrexafungerp – Azole Combination Therapy Dosing Regimen  
 
Treatment Days 
Additional 
Antifungal 
+ 
Ibrexafungerp Dosing Regimen 
Total Ibrexafungerp 
Daily Dose 
Loading Dose 
 
Study Days 1 and 2 
Per label 
+ 
500 mg BID: 
500 mg (2 tablets x 250 mg) AM 
500 mg (2 tablets x 250 mg) PM 
1000 mg 
Maintenance 
Dose 
Study Day 3 to EOT 
Per label 
+ 500 mg QD: 
500 mg (2 tablets x 250 mg) 
500 mg 
Abbreviations: AM = morning; EOT = end of treatment; PM = evening; QD = once a day 
The following combination options are allowed: 
• addition of ibrexafungerp to any ongoing antifungal therapy 
• replacement of one (toxic/ineffective) element of a two-antifungal combination therapy 
with ibrexafungerp 

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• replacement of current monotherapy with a new combination, generally: 
o replacement of AMB monotherapy with an azole plus ibrexafungerp combination, or 
o replacement of an azole monotherapy with an AMB plus ibrexafungerp combination  
• continuation of an azole plus echinocandin combination where the subject could go home 
on an oral regimen by replacing the parenteral echinocandin with ibrexafungerp 
12.1.4 Dietary Requirements 
Oral study drug should be taken with approximately 8 oz/240 mL of water, preferably with food. 
For subjects on continuous feeding via an NG or PEG tube, the drug should be crushed and 
administered with approximately 8 oz/240 mL of water. The tube should be closed at least one 
hour before drug administration and should be flushed with approximately 20 mL of water before 
and after drug administration. 
12.2 
Study Drugs 
12.2.1 Ibrexafungerp Description 
Study Drug Identifier: Ibrexafungerp  
Empirical Formula: 
C50H75N5O11 (citrate salt) 
Molecular Weight: 
922.18 (citrate salt) 
Physical Description: White to off-white solid 
Chemical Name: 
(1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-
2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-
pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-
dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-
phenanthro[1,2-c]pyran-7-carboxylic acid, citrate salt] 
 
Figure 2 
Chemical Structure of Ibrexafungerp Citrate 

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12.2.2 Formulation, Packaging and Labelling 
Ibrexafungerp citrate drug product for oral administration will be supplied as compressed oral 
tablets containing 250 mg of ibrexafungerp active ingredient on a free base basis. In addition to 
the active ingredient, the oral tablet formulation also contains silicified microcrystalline cellulose, 
crospovidone, mannitol, colloidal silicon dioxide, magnesium stearate (non-bovine), and butylated 
hydroxyanisole. Ibrexafungerp is packaged in bottles containing 30 tablets. 
Labels on the bottles of ibrexafungerp will include information as required by regional regulations 
and may include:  
• Sponsor information 
• Protocol number 
• Protocol visit number 
• Place to write the subject number 
• Route of administration 
• Lot number  
• Product name and potency 
• Contents, e.g. number of tablet count per bottle  
• Storage conditions 
• Name of manufacturer and date of manufacture 
• Caution statement according to local regulations: "Caution: New Drug – Limited by Law to 
Investigational Use Only” 
12.2.3 Storage and Stability 
The pharmacist or appropriate designee at each clinical research site will be responsible for the 
study drug. Ibrexafungerp tablets are to be stored at room temperature: between 15°C and 25°C 
with allowable limited excursions of up to 30°C. 
For long-term storage at the site, study drug supplies must be kept in a secure area (e.g., locked 
cabinet) and stored at room temperature. 
The site will be required to keep a temperature log to establish a record of compliance with these 
storage conditions. All study drug will be kept in a secure cabinet or room with access restricted 
to necessary clinic personnel. 
12.3 
Drug Accountability 
The Investigator or designee will inventory and acknowledge receipt of all shipments of the study 
drug. Drug accountability logs will be used to maintain accurate records of receipt, dispensing, 

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administration to each subject, and return of drug. A study monitor will periodically check the 
supplies of investigational products held by the site to verify accountability of all study drugs. At 
the conclusion of the study, after final drug accountability has been completed by the monitor, all 
unused study drug and all medication containers will be returned to the Sponsor or destroyed on 
site if the site has procedures in place for study drug destruction. 
Drug supplies will be maintained in a secure, limited-access storage area under the recommended 
storage conditions. 
The study drug supplied for this study is only for use in subjects who were properly consented and 
enrolled under this protocol. 
A study site designee (e.g., pharmacist, study nurse/coordinator) will: 
• Record the treatment in the drug accountability log. 
• Count the number of tablets per bottle before dispensing to subject. 
• Report and document any study medication issues such as contamination, crushed or broken 
tablets, incorrect labelling.  
o All product quality complaints should be reported to the Sponsor. 
• Collect and count the number of tablets remaining at the EOT visit. 
Review subject diary card and remaining study drug count, record any unused or remaining drug 
in the drug accountability log and eCRF, and note any discrepancies and reason for discrepancies. 
12.4 
Subject Compliance with Study Drug Dosing 
Subjects who are discharged from the hospital will be instructed to have the study medication 
(including empty bottles/units) with them at each visit. Compliance will be assessed based on 
remaining study drug as compared to what should have been taken and the subject diary where the 
subject will enter the details of dosing. Details of treatment including any missing dose will be 
recorded on the eCRF. Sites are encouraged to contact the medical monitor or Sponsor for concerns 
of compliance with the treatment regimen, especially for subjects who miss doses due to problems 
with tolerability. 
13.0 Non-Study Treatments 
13.1 
Prior and Concomitant Medications 
All medications (including prescription and over-the-counter medications, supplements, and 
herbal products) taken from 30 days before Baseline/Day 1 through TOC (Day 17) for VVC and 
EOT for all other fungal diseases will be recorded on the eCRF. Immunosuppressants (e.g., 

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chemotherapy, corticosteroids, T-Cell immunosuppressants) used up to 90 days prior to subject 
enrollment will be recorded on the eCRF. Antifungal medications administered for the treatment 
of the eligible fungal infection if received for ≥7 days in the preceding 6 months prior to enrollment 
will also be recorded on the eCRF. In individual cases, timelines beyond 6 months or treatments 
less than 7 days may be requested for the record as clinically relevant, as judged by the Investigator 
and the Sponsor. Only the use of other antifungal medications, antibiotics for any reason or 
medications to treat an AE will be recorded after EOT (TOC for VVC subjects) and through the 
last observation in the study (35-Day FU for VVC, 6-Month FU for ABPA and 6-Week FU for all 
other fungal diseases). Start and stop times of concomitant medications taken during antifungal 
therapy will be recorded on the eCRF. Subjects will also record any new concomitant medications 
taken between visits in the subject diary. 
See Section 13.2 and Section 13.3 for prohibited medications and medications to be administered 
with caution, respectively.  
13.2 
Prohibited Medications 
Medications not permitted include the following: 
• Non-study systemic or topical antifungal therapy except in subject subgroups where 
combination therapy is allowed or where an exception was granted by the Sponsor on a per-
subject basis 
• Other investigational drug(s) 
• Strong CYP3A4/5 inhibitors, CYP3A4/5 inducers, and select P-gp substrates (refer to 
Appendix B [Section 21.2] for the full list of prohibited medications). 
See Appendix B [Section 21.2] for the full list of prohibited medications 
13.3 
Medications to be Administered with Caution and Monitored as 
Appropriate 
CYP3A4 moderate substrates: In vitro, ibrexafungerp was an inhibitor of CYP3A mediated 
metabolism of midazolam but was only a weak inhibitor of metabolism of testosterone. The 
clinical significance of this inhibition is unknown; caution should be exercised when administering 
ibrexafungerp with drugs known to be CYP3A sensitive substrates with narrow therapeutic index. 
Subjects receiving sirolimus, tacrolimus, or warfarin are permitted for enrollment in the study and 
these medications may be administered with ibrexafungerp with close monitoring. The 
administration of either sirolimus or tacrolimus should be offset by no less than 2 hours with the 
administration of ibrexafungerp. At a minimum, blood levels of sirolimus and tacrolimus or 
prothrombin time/partial thromboplastin time/international normalized ratio for subjects on 
warfarin should be measured after the first dose of ibrexafungerp and when the subject has received 

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between 3 and 7 days of ibrexafungerp (at which time ibrexafungerp concentrations will have 
reached steady state). Dosing adjustments and subsequent monitoring of sirolimus, tacrolimus and 
warfarin should be undertaken in accordance with product prescribing information for the 
respective agents. 
Refer to Appendix B (Section 21.2) for further details. 
13.4 
Study Restrictions 
There are no study restrictions other than those described in Sections 11.2 (Exclusion Criteria), 
Section 12.1.4 (Dietary Requirements), Section 13.2 (Prohibited Medications) and Section 13.3 
(Medications to be Administered with Caution). 
14.0 Study Procedures 
The following sections provide a description of the individual study procedures to be performed 
during the conduct of the study. Detailed schedules of study assessments for VVC and for all other 
fungal diseases are provided in Section 15.0.  
Study days, weeks and months are counted relative to the first dose of study drug (Baseline 
[Day 1]). For follow-up visits, days, weeks and months are counted relative to the EOT visit. The 
Screening visit and Baseline (Day 1) visit may occur on the same day. 
14.1 General Procedures 
14.1.1 
Informed Consent 
Every study subject or legally authorized representative must provide written informed consent 
prior to participating in any screening evaluations or any other study activities (see Section 19.3). 
14.1.2 
Enrollment and ID Assignment 
At Screening, all subjects who have signed an ICF will receive an 8-digit subject identification 
(ID) number that will be composed of a 3-digit study number (301) and a 2-digit site number 
followed by a 3-digit sequentially assigned subject number starting at 001. Subject numbers will 
be sequentially assigned by the database upon entry by the site. For instance, if site 01 enters the 
first subject in the database, the subject ID will be 301-01-001. The second subject entered in the 
database will get the subject number 002 as entered by any site, so that if site 02 enters the second 
subject, the subject ID will be 301-02-002. This number will be unique to each subject and will be 
used to identify the subject throughout the study. Non-U.S. sites will have a 3-digit site 
identification number, instead of a 2-digit number for U.S. sites. 

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Subjects who are screen failures or who are not eligible for treatment will be recorded as such in 
the site’s subject screening log. The subject numbers assigned to eligible subjects will be recorded 
on the electronic Case Report Form (eCRF). Only one subject number will be assigned to each 
eligible subject. 
For subjects who signed an ICF (i.e., are assigned a subject number) but were NOT treated because 
they did not meet all of the inclusion/exclusion criteria, the Screening visit pages of the eCRF will 
be completed. The criteria that were not met for enrollment will be documented on the eCRF. 
All eligible subjects must be approved by the Sponsor (or Sponsor designee) for enrollment. An 
Eligibility Form will be used to request eligibility confirmation from the Sponsor or Sponsor designee. 
14.1.3 
Medical History and Demographics 
During the Screening visit, a complete medical history for the prior year will be recorded for each 
subject. The medical history will include previous and current medical diagnoses, as well as major 
surgical procedures and drug monitoring, if applicable. Subject demographics such as age, sex, 
race and ethnicity will also be collected. For subjects with ABPA, the number of Asthma and 
ABPA Exacerbations in the six months prior to enrollment should be recorded. For subjects with 
chronic pulmonary aspergillosis (CPA), the latest available result on the Six-Minute Walk Test 
and St. George’s Respiratory Questionnaire prior to Screening should be recorded on the eCRF.  
Data available to support inclusion / exclusion criteria collected as SOC prior to signature of the 
ICF will be collected as appropriate in the EDC. 
14.1.4 
Inclusion and Exclusion Criteria 
All inclusion and exclusion criteria will be reviewed to ensure that the subject qualifies for the 
trial at Screening and at Baseline/Day 1. 
14.1.5 
Pregnancy Test  
A urine or serum pregnancy test will be performed by the local laboratory for all female subjects 
of childbearing potential at Screening and will be repeated at EOT for all female subjects of 
childbearing potential, except those with VVC. Pregnancy tests may be conducted more often (e.g., 
on a monthly basis), per local regulations. 
14.1.6 
Prior and Concomitant Medications 
Refer to Section 13.0 and Section 21.2 for details. 

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14.1.7 
Study Drug Dispensing, Collection and Accountability Review 
For subjects who are not hospitalized, the study drug will be dispensed at Baseline/Day 1 and every 
14 days. Study drug will be collected for accountability review every 14 days up to EOT, at EOT 
and at unscheduled visits (see Section 12.4 for further details regarding treatment compliance 
evaluation). Any unused study drug will be re-dispensed to the subject. 
For VVC subjects, study drug will be dispensed at Baseline/Day 1 and will be collected at EOT 
(Day 7), when treatment compliance will be assessed. 
14.1.8 
Study Drug Dosing 
For all subjects except VVC subjects, study drug doses will be administered daily through EOT, 
as needed, depending on the fungal disease. Subjects with VVC will receive ibrexafungerp on 
Day 1 [Baseline], Day 4 and Day 7 [EOT]).  
Further details of the study treatment and dietary requirements for administration of ibrexafungerp 
monotherapy and combination therapy are provided in Section 12.1.1, Section 12.1.2 and 
Section 12.1.3. 
14.1.9 
Subject Diaries  
Non-hospitalized subjects will complete a subject diary up to their EOT visit. The subjects will 
record the date/time of study medication dosing, daily symptoms, other medical concerns or 
complaints, and concomitant medications. 
For all subjects except VVC subjects, diaries will be dispensed at Baseline/Day 1 and will be 
reviewed every 14 days during treatment up to EOT, at unscheduled visits, and at EOT, when they 
will be collected. For VVC subjects, diaries will be dispensed at Baseline/Day 1 and will be 
collected at TOC. 
14.2 Efficacy Procedures 
14.2.1 
Targeted Physical Examination, Including Clinical Evaluation of Signs 
and Symptoms  
A targeted examination of the fungal disease site, including the signs and symptoms of the fungal 
infection, will be conducted for all subjects, excluding VVC subjects, at Screening and 
Baseline/Day 1 (prior to treatment), and at the per-protocol visits displayed in Table 9. 

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Table 9 
Schedule of Visits for Targeted Physical Examinations by Fungal Disease 
(Excluding VVC) 
Study Days 
Every 14 
days during 
Txa 
D42 
cD84 
dD90 
D180 
EOT 
Unsch. 
Visits 
FU 1 
(6-WK) 
FU 2 & 
FU 3 
Allowable window 
±2 d 
±7 d 
±7 d  
±7 d 
±14 d 
±3 d 
AP 
± 7 d 
AP 
Acute or Chronic IC  
X 
X 
 
 
 
X 
X 
X 
 
EC, OPC 
X 
X 
 
 
 
X 
X 
X 
 
CMCc 
X 
X 
X 
 
 
X 
X 
X 
 
D/I DF  
X 
X 
X 
 
 
X 
X 
X 
 
CPAd 
Day 14  
X 
 
X 
Xb 
X 
X 
X 
 
ABPAd 
Day 14 
X 
 
X 
Xb 
X 
X 
X 
X  
IPA 
X 
X 
X 
 
 
X 
X 
X 
 
Other emerging fungi  
X 
X 
X 
 
 
X 
X 
X 
 
Abbreviations: ABPA=allergic bronchopulmonary aspergillosis; AP = as applicable; CMC=chronic mucocutaneous 
candidiasis; CPA=chronic pulmonary aspergillosis; D=day; DF=dimorphic fungi; D/I= disseminated/ invasive; 
EC=esophageal candidiasis; EOT=end of treatment; FU=follow up; FU 1=6-Week FU; FU 2=3-Month FU; FU 3=6-
Month FU; IC=invasive candidiasis; IPA=invasive pulmonary aspergillosis; OPC=oropharyngeal candidiasis; 
Tx=treatment; unsch.=unscheduled; VVC=vulvovaginal candidiasis; WK=week 
a: 
As clinically indicated for disease. 
b: Efficacy procedures for CPA and ABPA subjects will be performed every 3 months following Day 180 if the 
subject is still on treatment. 
c:    For CMC subjects, D84 is TOC visit unless EOT occurs first 
d:    For CPA and ABPA subjects, D90 is TOC visit unless EOT occurs first 
 
For subjects with VVC, targeted physical exams will be done at Screening, Baseline/Day 1 (prior 
to treatment), EOT (Day 7), TOC (Day 17 [±3]) and 25-Day FU visit (25 days after EOT). A 
targeted physical exam (vaginal examination) will also be conducted at the 35-Day FU visit (35 
days after EOT) if the subject is symptomatic. The EOT visit and the 35-Day FU visits will be a 
phone contact only if the subject is asymptomatic.  
Note: For subjects who are suspected to have a relapse of infection during the study follow-up 
period, evaluations relevant to the signs and symptoms of infection should be performed before 
starting non-study antifungal therapy. The results of these studies should be documented on the 
eCRF. Subjects who have a recurrence after TOC (VVC) or EOT (all other diseases), may be 
considered for re-enrollment upon discussion with the Sponsor. 
The signs and symptoms of fungal infection include, but are not limited to, the following: 
• General signs and symptoms: 
o Fever, defined as oral temperature ≥38.3°C (≥101°F) on one occasion or >37.8°C 
(>100°F) on two measurements at least 4 hours apart  
o Clinically significant hypothermia <36°C (<96.8°F) 
o Hypotension (systolic blood pressure <90 mmHg or a >30 mmHg decrease below 
normal baseline) 

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o Tachycardia 
o Local signs and symptoms of inflammation 
• Disease-specific signs and symptoms: 
o OPC: White patches or plaques on the tongue and other oral mucous membranes, 
redness or soreness in the affected areas, difficulty swallowing, cracking at the corners 
of the mouth (angular cheilitis) 
o EC: White plaques and/or ulcers on the lining of the esophagus or narrowing of the 
lumen, pain when swallowing, difficulty swallowing, heartburn 
o CMC: Extensive scaling, skin lesions, thickened nails 
o Other signs and symptoms of candidiasis and other fungal diseases, as applicable 
Subjects who are discharged from hospital during ibrexafungerp therapy will record their signs 
and symptoms daily on subject diaries, and the signs and symptoms will also be assessed by the 
site staff at the study visits. The site will assess whether the signs and symptoms recorded on the 
subject diary are related to the fungal disease. 
14.2.2 
Mycological Testing 
14.2.2.1 
Vulvovaginal Candidiasis 
Samples for fungal culture will be collected at Screening, EOT (Day 7), TOC (Day 17 [±3]) and 
25-Day FU (25 days after EOT; 32 days after first dose). Additional samples will be obtained, if 
applicable, at Baseline/Day 1 and at any unscheduled visits. For symptomatic subjects, samples 
will also be collected at the 35-Day FU visit (35 days after EOT; 42 days after first dose). 
14.2.2.2 
All Other Fungal Diseases Excluding Vulvovaginal Candidiasis 
Mycological samples will be obtained for all subjects at Screening and/or Baseline/Day 1 (prior to 
treatment), and as applicable for each subject and fungal disease while on therapy. In addition, 
samples will be collected at the per-protocol visits displayed in Table 10. 
 

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Table 10 
Schedule of Visits for Mycological Assessments by Fungal Disease (Excluding 
VVC) 
Study Days 
D42 
D84b 
D90c 
D180 
EOT 
Unsch. Visits 
FU 1 
(6-WK) 
FU 2 &  
FU 3 
Allowable window 
±7 d 
±7 d  
±7 d 
±14 d 
±3 d 
AP 
± 7 d 
AP 
Acute or Chronic IC  
X 
 
 
 
X 
 
X 
 
EC, OPC 
X 
 
 
 
X 
 
X 
 
CMCb 
X 
X 
 
 
X 
 
X 
 
D/I DF  
X 
X 
 
 
X 
 
X 
 
CPAc 
 
 
X 
Xa 
X 
 
X 
 
ABPA 
 
 
 
 
 
 
 
 
IPA 
X 
X 
 
 
X 
 
X 
 
Other emerging fungi 
X 
X 
 
 
X 
 
X 
 
Abbreviations: ABPA=allergic bronchopulmonary aspergillosis; AP = as applicable; CMC=chronic 
mucocutaneous candidiasis; CPA=chronic pulmonary aspergillosis; D=day; DF=dimorphic fungi; D/I= 
disseminated/ invasive; EC=esophageal candidiasis; EOT=end of treatment; FU=follow up; FU 1=6-Week FU; 
FU 2=3-Month FU; FU 3=6-Month FU; IC=invasive candidiasis; IPA=invasive pulmonary aspergillosis; 
OPC=oropharyngeal candidiasis; Tx=treatment; unsch.=unscheduled; VVC=vulvovaginal candidiasis; 
WK=week 
Note: Mycological response will be assessed by fungal culture, KOH and other fungal stains, T2 testing, and 
serological testing (including, GMI, Coccidioides titers, and β-D-glucan levels, among others [Section 14.2.4]), if 
applicable. 
a: 
Efficacy procedures for CPA subjects will be performed every 3 months following Day 180 if the subject is 
still on treatment. 
b:    For CMC subjects, D84 is TOC visit, unless EOT occurs first 
c:    For CPA and ABPA subjects, D90 is TOC visit unless EOT occurs first 
14.2.2.2.1 
Candida Infections Excluding VVC 
Blood cultures: Two sets of blood cultures will be collected at Screening and repeated daily or 
every other day until blood cultures are negative for at least 48 hours (if it is only possible to obtain 
1 set of blood cultures, a reason should be documented). Blood should be drawn peripherally 
[directly from a vein]; however, if this is not possible, blood may be drawn from a central IV 
catheter. Follow-up cultures will be performed as clinically indicated. 
Non-blood cultures: Follow-up cultures from subjects who have non-blood sites of Candida 
infection should be performed as clinically indicated. 
EC: Follow-up KOH or fungal stains and/or mycological cultures from biopsy or brushing 
indicating yeast infection will be performed as clinically indicated. 
OPC and CMC: Follow-up KOH or fungal stains and/or mycological cultures for Candida spp. 
obtained from the affected site will be performed as clinically indicated. 
Urine cultures: for subjects with urinary tract infections, urine samples for fungal cultures are 
recommended to be collected every 48-72 hours until negative. 

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For subjects diagnosed exclusively by T2 testing: 
• The diagnosis should be based on two consecutively positive T2 tests. 
• For subjects diagnosed based on positive T2 tests, in addition to Screening, samples for T2 
testing will be collected every 48 hours until negative. 
14.2.2.2.2 
Other Fungal Diseases 
Baseline mycological assessment (Screening) of the subject’s fungal disease will be performed 
according to best local practice using local laboratories, including suitable samples for fungal 
culture and isolation as well as samples from the infected site for histology and cytology. Outside 
of these time points, mycological assessment will be performed as clinically indicated and/or in 
line with standard clinical management for the subject’s specific fungal disease and anatomic site 
involved. The results of all mycological assessments, both culture and non-culture based 
(including negative results), performed during the study and relevant to the fungal infection will 
be recorded on the eCRF. 
14.2.2.3 
General Notes for Mycological Testing 
The study site’s local microbiology laboratory will perform identification and in vitro 
susceptibility testing as per their local standards. The Investigator should ensure that fungal 
isolates obtained from all cultures performed during the study period (and wherever possible, the 
isolate from the initial positive culture) are sent to the central microbiology laboratory, as described 
in the laboratory manual. The central microbiology laboratory will repeat the identification and 
perform in vitro susceptibility testing of the isolates as per CLSI M27-A4 and or EUCAST 
guidelines.10,11 Baseline isolated pathogens and subsequent isolates will be subjected to 
ibrexafungerp susceptibility testing. The central laboratory will include standard of care 
antifungals in the drug panels to determine resistance patterns. 
Further evaluation to identify the potential mechanism of resistance may be performed. Isolates 
may be maintained in a repository for potential future use, for subjects that provide consent for 
future use. 
Identification of the fungi isolate by local and central laboratory may be performed using 
acceptable methods such us culture, PCR, matrix-assisted laser desorption/ionization (MALDI-
TOF) or others that are approved for such use or are considered acceptable in the state of the art 
and current guidelines. 

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Table 11: 
Fungal Isolates to be Collect for the Study. 
Fungal isolate 
Definition 
When to Send to Central 
Laboratory 
Initial Isolate 
The isolate from the culture that resulted in 
the initial diagnosis of invasive fungal 
disease will be considered the “initial” 
isolate. All subjects except those diagnosed 
solely based on non-culture tests like T2, 
PCR or serological tests will have an isolate 
from an initial culture. 
End of Study for each 
subject. 
Screening 
Isolate 
Subjects with refractory or resistant fungal 
disease will have cultures that are positive 
after the initial positive culture (thereby 
qualifying the subjects as “refractory or 
resistant” for study eligibility). This will be 
referred to as the “Screening” Isolate. 
For subjects refractory or 
resistant to an echinocandin, 
the isolate should be sent at 
the time of enrollment per the 
laboratory manual 
instructions. 
Otherwise, screening isolates 
may be sent at End of Study 
for each subject. 
Study Isolate 
All fungal isolates recovered during study 
while the subject is receiving ibrexafungerp 
or during the follow-up window. 
End of Study for each 
subject. 
For subjects who are suspected to have a relapse of infection during the study follow-up period, 
cultures should be collected and other evaluations relevant to the signs and symptoms of infection 
should be performed before starting non-study antifungal therapy. Results of all mycological tests, 
including both culture and non-culture based (including negative results), relevant to the fungal 
infection under treatment should be documented on the eCRF. 
Sites should make every attempt to save the initial isolate for the study. However, it is not 
mandatory to have the initial isolate for enrollment. In the absence of baseline isolates, all post-
Baseline pathogens collected in the context of clinical failure and associated with the fungal 
disease will be stored and shipped to central laboratory for identification of fungal species and 
susceptibility testing. If the identities of the pathogens differ between the central and local 
laboratories, the central laboratory results will take precedence over the local results for all study 
purposes. 
 

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Other procedures and assessments will be performed as clinically indicated for the individual 
subject: 
• Suitable samples for fungal culture and isolation (blood/ tissue cultures). 
• Follow-up culture samples from non-bloodstream infections are not mandatory but, if 
obtained, results should be recorded. Histological or cytological findings are regarded as 
supportive evidence of invasive fungal disease and should be recorded, if available. 
• For outcome assessment of fungal blood stream infections, confirmed (two consecutive) 
negative blood cultures are required. 
• All isolates should be identified to species level. All baseline and EOT isolates will be 
stored and shipped for central retesting. The central laboratory results will be considered 
definitive. 
• Biopsy/biological fluid samples from the infected site for histology and cytology. 
14.2.3 
Imaging  
For subjects with fungal diseases where diagnosis and assessment of outcome are based on 
imaging, imaging scans (e.g., X-ray, ultrasound, computed tomography [CT], magnetic resonance 
imaging [MRI]) will be obtained for the assessment of infection. 
Imaging scans will be obtained for all subjects at Screening as applicable for each subject and 
fungal disease. Imaging scans will also be collected at the recommended per-protocol visits 
displayed in Table 12. In addition to the scheduled time points, imaging scans will be collected 
anytime during therapy, as clinically indicated. The window for EOT imaging may range from ± 3 
to ± 7 days, depending on the fungal disease. 
Data available to support patient eligibility collected as SOC prior to signature of the ICF will be 
collected as appropriate in the EDC.  Baseline radiological assessments for invasive fungal 
diseases should be performed ideally within 72 hours of Screening. However, assessments 
performed up to 7 days before/after the first administration of study medication may be used to 
confirm the diagnosis of the fungal disease if none exists within the ideal window. Radiological 
assessments should ideally be made by CT scan (HRCT if available) or MRI. The same radiologic 
methodology used at Baseline should be used for subsequent assessments. For lung, bone and 
abdominal infections, imaging at EOT is strongly recommended, since they are critical for 
outcome assessment. 
Bronchoscopic assessments should be performed as clinically indicated. When performing 
bronchoscopic examinations, samples obtained should be sent for the following tests: culture, 
histology/cytology and GM. If BAL samples are obtained at Baseline, an additional sample should 
be stored for shipping to the central laboratory. For other time points, any residual BAL sample 
after routine SOC testing is complete should be stored for shipping to the central laboratory. 
The results of these imaging studies should be documented on the eCRF. 

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Table 12  
Schedule of Visits for Recommended Imaging Assessments by Fungal Disease, 
if obtained for Routine Care (Excluding VVC) 
Study Days 
D42 
D84d 
D90e 
D180 
EOT 
Unsch. 
Visits 
FU 1 
(6-WK) 
FU 2 &  
FU 3 
Allowable window 
±7 d 
±7 d  
±7 d 
±14 d 
± 3 to ± 7 
AP 
± 7 d 
AP 
Acute or Chronic ICa 
X 
 
 
 
X 
 
X 
 
EC, OPCa 
X 
 
 
 
X 
 
X 
 
CMCa, d 
X 
X 
 
 
X 
 
X 
 
D/I DF  
X 
X 
 
 
X 
 
X 
 
CPAe 
 
 
X 
Xb 
X 
 
X 
 
ABPAe 
X 
 
X 
Xb 
X 
 
X 
X 
IPAc 
X 
X 
 
 
X 
 
X 
 
Other emerging fungia  
X 
X 
 
 
X 
 
X 
 
Abbreviations: ABPA=allergic bronchopulmonary aspergillosis; AP = as applicable; CMC=chronic 
mucocutaneous candidiasis; CPA=chronic pulmonary aspergillosis; D=day; DF=dimorphic fungi; D/I= 
disseminated/ invasive; EC=esophageal candidiasis; EOT=end of treatment; FU=follow up; FU 1=6-Week FU; FU 
2=3-Month FU; FU 3=6-Month FU; IC=invasive candidiasis; IPA=invasive pulmonary aspergillosis; 
OPC=oropharyngeal candidiasis; Tx=treatment; unsch.=unscheduled; VVC=vulvovaginal candidiasis; WK=week 
a: If applicable. 
b: Efficacy procedures for CPA and ABPA subjects will be performed every 3 months following Day 180 if the 
subject is still on treatment. 
c: For IPA subjects, a chest CT scan within -7 days of Baseline and ±3 to ±7 days of EOT is required. 
d: For CMC subjects, D84 is TOC unless EOT occurs first 
e: For CPA and ABPA subjects, D90 is TOC unless EOT occurs first 
14.2.4 
Serological Testing 
Serological tests will be obtained for all subjects, excluding VVC subjects, at Screening and at 
Baseline/Day 1 (prior to treatment), as applicable for each subject and fungal disease. Samples 
will also be collected at the recommended per protocol visits displayed in Table 13. 
 

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Table 13 
Schedule of Visits for Recommended Serological Assessments by Fungal 
Disease (Excluding VVC) 
Study Days 
D3- 
D5 
D7-
D10 
Every 14 
days 
during Tx 
D42 
D84 
D90 D180 EOT Unsch. 
Visits 
FU 1 
(6-WK) 
FU 2 & 
FU 3 
Allowable window 
±2 d 
±2 d 
±2 d 
±7 d 
±7 d  ±7 d ±14 d ±3 d 
AP 
± 7 d 
AP 
Acute or Chronic IC  
 
 
 
 
 
 
 
 
 
 
 
EC, OPC 
 
 
 
 
 
 
 
 
 
 
 
CMC 
 
 
 
 
 
 
 
 
 
 
 
D/I DFa  
 
 
Day 14 
X 
X 
 
 
 
 
 
 
CPAb 
 as applicable  
 
 
X 
Xc 
X 
 
X 
 
ABPAd 
 as applicable  
X 
 
X 
Xc 
X 
 
X 
X 
IPAe 
X 
X 
X 
X 
 
 
 
 
 
 
 
Other emerging fungia  
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: ABPA=allergic bronchopulmonary aspergillosis; AP = as applicable; CMC=chronic 
mucocutaneous candidiasis; CPA=chronic pulmonary aspergillosis; D=day; DF=dimorphic fungi; D/I= 
disseminated/ invasive; EC=esophageal candidiasis; EOT=end of treatment; FU=follow up; FU 1=6-Week FU; 
FU 2=3-Month FU; FU 3=6-Month FU; IC=invasive candidiasis; IPA=invasive pulmonary aspergillosis; 
OPC=oropharyngeal candidiasis; Tx=treatment; unsch.=unscheduled; VVC=vulvovaginal candidiasis; WK=week 
a: Serological tests will be conducted as clinically indicated. 
b: Change in total IgG and Aspergillus-specific IgG will be evaluated if elevated at Baseline. 
c: Efficacy procedures for CPA and ABPA subjects will be performed every 3 months following Day 180 if the 
subject is still on treatment.  
d: Serum samples will be collected for total IgE . 
e: Serum samples will be collected for GM determination at Week 1, Week 2, Week 4 and Week 6. 
 
For subjects diagnosed exclusively by ß-D-glucan tests: 
• The diagnosis should be based on two consecutively positive ß-D-glucan tests.  
• Samples for ß-D-glucan testing will be collected every 72 hours until negative. 
For subjects with CPA: 
• Serum samples will be collected at Day 90 and Day 180 for Ig, Aspergillus-specific IgG 
and total IgG. 
For subjects with ABPA: 
• Serum samples will be collected for total IgE at Day 42, Day 90, Day 180 and every 3 
months following Day 180 while receiving study medication, at EOT and at the 3-Month 
FU and 6-Month FU visits. 
For subjects with invasive aspergillosis, including IPA: 
• A single value of ≥ 0.7 or two consecutive values each of ≥ 0.5 - < 0.7 (i.e., from two 
separate blood draws) will be considered a positive result unless deemed false positive due 
to the presence of known interacting agents. Subjects with serum GM meeting the 

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protocol-defined requirements drawn within 10 days prior to first dose of study medication 
are eligible for enrollment. 
• BAL for GM specimens may be processed locally, but an additional aliquot of BAL fluid 
will be collected for shipment to the central laboratory as well, when feasible. A single GM 
value ≥1 will be considered a positive result unless deemed false positive due to the 
presence of known interacting agents. For the current invasive aspergillosis episode, the 
results available for all previous GM determinations in the preceding 3 months (e.g. before 
enrollment) will be collected on the eCRF.  
For subjects with IPA: 
• Serum samples will be collected at Week 1, Week 2, Week 4 and Week 6 for GM 
determination. 
 
14.2.5 
Esophagoscopy 
Esophagoscopies will be conducted at Screening in all subjects who have EC. Results of the most 
recent esophagoscopy that confirmed the diagnosis must be available for Screening. A repeat 
esophagoscopy is not required at Screening if the subject’s signs and symptoms of EC have 
persisted since initial diagnosis. A repeat esophagoscopy is required at EOT for all subjects, if this 
complies with SOC. Additional esophagoscopies are recommended at the Day 42 and 6-Week FU 
visits only if symptoms have recurred and following local standard practices. Esophagoscopies 
should be performed at any unscheduled visits, if clinically indicated per local standard practices. 
Results from all esophagoscopies conducted during the subject’s participation in the study should 
be included in the study database. 
14.2.6 
Spirometry 
A spirometry test will be conducted at Screening or Baseline/Day 1 (prior to treatment) for all 
ABPA subjects. A repeat spirometry will be conducted at Day 42. 
14.2.7 
St. George’s Respiratory Questionnaire (SGRQ) 
For subjects with CPA, the latest available result on the St. George’s Respiratory Questionnaire 
prior to Screening should be recorded on the eCRF as part of their medical history. Additionally, 
subjects with CPA will be administered the St. George’s Respiratory Questionnaire at Screening 
or Baseline/Day 1 (prior to treatment), Day 90, Day 180, every 3 months while on therapy beyond 
Day 180, at EOT and at the 6-Week FU visits. 

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14.2.8 Six-Minute Walk Test and Medical Research Council (MRC) Dyspnea Scale 
For CPA subjects, the latest available result on the Six-Minute Walk Test prior to Screening should 
be recorded on the eCRF as part of their medical history. Additionally, subjects with CPA will 
undergo a Six-Minute Walk Test at Screening or Baseline/Day 1 (prior to treatment), Day 90, and 
Day 180. Subject’s disability will be graded using the MRC Dyspnea Scale at the same time points. 
14.2.9 Recurrence 
Recurrence will be assessed at the 25-Day FU visit (25 days after EOT, 32 days after first dose) 
for subjects with VVC and at the 6-Week FU (42 days after EOT) for all other subjects as a 
secondary efficacy endpoint. For CPA subjects, recurrence will also be assessed at Day 180. 
14.2.10 Survival  
Survival status (collected as ACM) will be recorded at Day 30 for IC/candidemia subjects and at 
Day 42 for all diseases. ACM will be also recorded at Day 84 for subjects with IPA, 
disseminated/invasive dimorphic fungi and other emerging fungi, and at Day 90, Day 120 and Day 
180 for subjects with CPA and ABPA. Information on survival status on Days 42, 84, 90, 120 and 
180 will be collected for all subjects, irrespective of when treatment was discontinued. If the 
subject has died, the date and cause of death along with the reporting of SAE details will be 
recorded on the eCRF. 
14.2.11 
Assessment of Efficacy 
Efficacy procedures will depend on each fungal disease. Efficacy will be assessed primarily in 
terms of Global Response at TOC for VVC, CMC, CPA and ABPA, and at EOT for all other 
fungal diseases. Global Response at other time points and Clinical Response and Mycological 
Response will also be assessed as secondary endpoints. In addition, secondary efficacy 
assessments will include disease-specific endpoints for selected fungal diseases. See Section 14.2 
for detailed efficacy procedures and Section 18.4.1 for a detailed discussion of efficacy 
assessments. 
The following study procedures will be performed to assess treatment outcome for all subjects: 
• Clinical signs and symptoms of fungal disease (Section 14.2.1) 
• Mycological testing (including, but not limited to, fungal cultures, T2 testing, KOH and 
other fungal stains) (Section 14.2.2) 
• Radiological assessments including esophagoscopy and other imaging scans, as applicable 
(e.g., X-ray, ultrasound, CT and MRI) (Section 14.2.3 and Section 14.2.5) 
• Serological testing (including, but not limited to, GM, Coccidioides titers, or ß-D glucan 
levels) (Section 14.2.4) 

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Additional procedures (i.e., spirometry, SGRQ, 6-Minute Walk Test and MRC Dyspnea Scale) 
will be conducted for selected fungal diseases. See Section 14.2.6, Section 14.2.7 and 
Section 14.2.8, respectively. 
14.3 Safety Procedures 
14.3.1 
Vital Signs  
Vital signs, including blood pressure (systolic and diastolic), heart rate, respiratory rate, weight 
and body temperature, will be measured at Screening, Baseline/Day 1, EOT and unscheduled visits 
as appropriate. For CPA subjects, weight will also be determined at the Day 180 visit. 
14.3.2 
General Physical Examination  
A general physical exam will be done at Screening and EOT. A general physical exam will also 
be conducted at the 6-Week FU for all subjects, except VVC subjects. The physical examination 
will include an abbreviated assessment of general appearance, skin, eyes, heart, chest and 
abdomen. 
14.3.3 
Clinical Laboratory Safety Assessments  
Clinical laboratory tests will include hematology, blood chemistry and urinalysis.  
For all fungal diseases except VVC, samples for clinical laboratory tests will be collected at 
Screening, every 14 days up to EOT if clinically indicated, at EOT, at the 6-Week FU if clinically 
indicated, and at unscheduled visits if clinically indicated. If indicated, these may be done more 
frequently as follow-up to a laboratory abnormality.  
In addition to the above, if still on treatment, CPA subjects will have blood drawn on Day 90 and 
Day 180 for albumin, platelet count, CRP and plasma viscosity assessment. 
For VVC subjects, safety labs will be collected at Screening, EOT (Day 7) and 25-Day FU (32 
days after first dose). Safety labs will be repeated at any unscheduled visit, if applicable.  

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The following laboratory parameters will be determined: 
Hematology  
 White blood cell (WBC) counta 
 Hemoglobin 
 Red blood cell (RBC) count  
 Hematocrit 
 Platelet countb 
 C-reactive proteinb 
 
 Plasma viscosityb 
a: Differential WBC count will include percentages for segmented neutrophils, lymphocytes, 
monocytes, eosinophils and basophils, and absolute counts for neutrophils, lymphocytes, 
monocytes, eosinophils and basophils. 
b: On Day 90 and Day 180 for CPA subjects only. 
Blood Chemistry 
 Sodium 
 Glucose 
 Potassium 
 Albumina 
 Alkaline Phosphatase 
 Aspartate aminotransferase (AST/SGOT) 
 Chloride  
 Alanine aminotransferase (ALT/SGPT) 
 Blood urea nitrogen (BUN) 
 Gamma glutamyl transferase (GGT) 
 Creatinine 
 Lactate dehydrogenase (LDH) 
 Total creatine phosphokinase (CPK) 
 Bilirubin (total, direct, and indirect) 
 Total protein 
 Prothrombin (PT) and international 
normalized ratio (INR) 
a: On Day 90 and Day 180 for CPA subjects only if still on treatment. 
 

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Urinalysis 
 Appearance (clarity, color) 
 Glucose  
 Specific gravity 
 Ketones  
 pH 
 Protein  
 Blood 
 Leukocytes  
 Bilirubin  
 Urobilinogen  
 
Reflex Microscopic Evaluation 
 Bacteria 
 Mucous 
 Casts 
 RBC 
 Crystals 
 WBC 
 Epithelial cells 
 
14.3.4 
Adverse Events 
All AEs will be collected and evaluated from the time the informed consent is signed throughout 
the duration of the study and up to the last observation in the study. AEs and SAEs will be reviewed 
at all scheduled and unscheduled study visits from the time the informed consent is signed. See 
Section 16.0 for details regarding safety assessment and monitoring. 
14.4 Pharmacokinetic Procedures 
For subjects who are willing to participate in the PK sampling, up to three (3) blood samples should 
be collected at the following visits and sampling windows: Day 2 (one sample collected anytime 
post dosing), Days 3 to 5 (one sample collected predose on any of these days), and Days 7 to 10 
(one sample collected predose on any of these days). Additional blood PK samples will be 
collected when clinically indicated. 
Procedures for collecting, storing, and shipping plasma samples for PK are described in the study 
PK Manual. The sparse samples collected in this study will be analyzed using Population PK (Pop 
PK) analysis methods to estimate PK parameters (Cmax, AUC, clearance/fraction absorbed [CL/F]) 
as applicable. Further analysis of possible metabolites may be performed. 

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In addition to blood samples, other fluid and tissue samples may be collected for ibrexafungerp 
PK determination when clinically indicated. Tissue samples collected as part of SOC procedures 
(e.g., biopsies) may be sent for drug concentration analysis, when available. 

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15.0 Study Schedules 
Detailed schedules of all study visits and procedures for all subjects (except VVC subjects) are presented in Table 14 and detailed 
schedules of all study visits and procedures for VVC subjects are presented in Table 15. 
Table 14 
Schedule of Treatment Visits and Procedures (All Fungal Diseases Except VVC) 
|PROCEDURE 
Visit 
Screena 
BL/ 
D1a 
D2 
(PK 
Only) 
D3-
D5 
D7-
D10 
Study Day 
14 and 
then 
Every 14 
days 
during Tx  
D42 D84t 
 
D90u 
 
D120 D180 EOT Unsch. 
Visits 
FU 1b 
(6-
WK) 
FU 2- 
FU 3b 
Days (allowable window) 
-1 (-3) Prior to 
Tx 
 
±2 d 
±2 d  
±2 d 
±7 d ±7 d  ±7 d ±14 d ±14 d ±3 d 
AP 
± 7d 
AP 
GENERAL 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Enrollment and ID Assignment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History and Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Tests 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Prior and Concomitant Medications 
X -------------------------------------------------------------------------------------------------------------------------X 
 
Study Drug Dispensingc 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Study Drug Collection and 
Accountability Review 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
 
 
Study Drug Dosing 
 
X 
X 
X--------------------------------------------------------------------------Xd 
 
 
 
Subject Diary Dispensing and 
Collection 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
 
 
EFFICACY 
 
Targeted PE including S&Sv 
X 
X 
 
 
 
X 
Xd 
Xd 
Xe,f 
 
Xe,f 
Xd 
 
Xd 
Xf 
Mycological Testingg,j 
Xd 
Xd 
 Xd  
Xd 
Xe 
 
Xe 
Xd 
 
Xd 
 
Imagingh 
Xd,r 
 
 
 
 
 
Xd 
Xd 
Xe,f 
 
Xe,f 
Xd,i 
 
Xd,i 
 
Serological Testingj,k 
Xd 
Xd 
 
 Xd  
Xd 
Xd 
Xe,f 
 
Xe,f 
Xd 
 
Xd 
Xf 
Esophagoscopyl 
Xm 
 
 
 
 
 
Xl 
 
 
 
 
Xl 
Xl  
Xl 
 
Spyrometry 
Xf 
Xf 
 
 
 
 
Xf 
 
 
 
 
 
 
 
 
SGRQ 
Xe 
Xe 
 
 
 
 
 
 
Xe 
 
X e 
Xe 
 
Xe 
 
6-Minute Walk Test 
Xe 
Xe 
 
 
 
 
 
 
Xe 
 
Xe 
 
 
 
 
MRC Dyspnea Scale 
Xe 
Xe 
 
 
 
 
 
 
Xe 
 
X e 
 
 
 
 

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|PROCEDURE 
Visit 
Screena 
BL/ 
D1a 
D2 
(PK 
Only) 
D3-
D5 
D7-
D10 
Study Day 
14 and 
then 
Every 14 
days 
during Tx  
D42 D84t 
 
D90u 
 
D120 D180 EOT Unsch. 
Visits 
FU 1b 
(6-
WK) 
FU 2- 
FU 3b 
Days (allowable window) 
-1 (-3) Prior to 
Tx 
 
±2 d 
±2 d  
±2 d 
±7 d ±7 d  ±7 d ±14 d ±14 d ±3 d 
AP 
± 7d 
AP 
Assessment of Recurrence 
 
 
 
 
 
 
 
 
 
 
Xe 
 
 
X 
 
Subject Status (alive/ deceased) 
 
 
 
 
 
 
X 
Xo 
Xe,f 
Xe, f 
Xe, f 
 
 
 
 
Assessment of Efficacy 
 
 
 
 
 
 
Xd 
Xd 
Xd 
 
Xd 
Xd 
 
Xd 
Xf 
SAFETY 
 
Vital Signs 
X 
X 
 
 
 
 
 
 
 
 
Xp 
X 
X 
 
 
General Physical exam 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
Clinical Laboratory Safety Assessments  
X 
 
 
 
 
X n 
X n 
X n 
X n, e 
Xn 
X n,e 
X 
Xn 
Xn 
 
AEs 
X------------------------------------------------------------------------------------------------------------------------------------X 
PHARMACOKINETIC 
 
PK Assessmentsq 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE = adverse event; ABPA = allergic bronchopulmonary aspergillosis; AP = as applicable; CPA=chronic pulmonary aspergillosis; d = day; D = Day; 
EC=esophageal candidiasis; eCRF=electronica case report form; EOT = End of Treatment; FU = Follow-up; ID = identification; IPA = invasive pulmonary aspergillosis; 
MRC = Medical Research Council; PK=pharmacokinetic; Screen. = Screening; S&S = signs and symptoms; SGRQ = St. George’s Respiratory Questionnaire; Tx = 
treatment; Unsch. = unscheduled; W = Week. 
Note: Study days, weeks and months are counted relative to the first dose of study drug (Baseline [Day 1]). For FU visits, weeks, months and years are counted relative to the 
EOT visit. 
a. 
Screening and Baseline (Day 1) may occur on the same day. 
b. 
FU visits will occur 6 weeks (6-Week FU = FU 1), 3 months (3-Month FU = FU 2) and 6 months (6-Month FU = FU 3) after the EOT visit. FU visits FU 2 and FU 3 will be 
conducted for ABPA subjects only. 
c. 
For subjects who are not hospitalized. 
d. 
As applicable based on fungal disease. 
e. 
For CPA subjects. Efficacy procedures for CPA subjects will be performed every 3 months following Day 180 if the subject is still on treatment. 
f. 
For ABPA subjects. Efficacy procedures for ABPA subjects will be performed every 3 months following Day 180 if the subject is still on treatment.  
g. 
For urinary tract infections, urine samples for fungal cultures are recommended to be collected every 48-72 hours until negative. 
h. 
In addition to the scheduled time points, imaging scans will be collected anytime during therapy, as clinically indicated. 
i. 
The window for EOT imaging may range from ± 3 to ± 7 days, depending on fungal disease.  
j. 
For subjects diagnosed exclusively by ß-D-glucan tests, the diagnosis should be based on two consecutively positive T2 or ß-D-glucan tests. For those subjects diagnosed 
based on positive T2 tests, samples for T2 testing will be collected every 48 hours until negative. For those subjects diagnosed based on positive ß-D-glucan tests, samples 
for ß-D-glucan testing will be collected every 72 hours until negative. 
k. 
For disseminated/invasive dimorphic fungi subjects, serological tests may be conducted at other time points, as clinically indicated. 
l. 
For EC subjects only. A repeat esophagoscopy is required at EOT for all subjects, if allowable per SOC practice. Additional esophagoscopies are recommended at the Day 
42 and 6-Week FU visits only if symptoms have recurred and following local standard practices.  Esophagoscopies should be performed at any unscheduled visits, if 
clinically indicated per local standard practices. 

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|PROCEDURE 
Visit 
Screena 
BL/ 
D1a 
D2 
(PK 
Only) 
D3-
D5 
D7-
D10 
Study Day 
14 and 
then 
Every 14 
days 
during Tx  
D42 D84t 
 
D90u 
 
D120 D180 EOT Unsch. 
Visits 
FU 1b 
(6-
WK) 
FU 2- 
FU 3b 
Days (allowable window) 
-1 (-3) Prior to 
Tx 
 
±2 d 
±2 d  
±2 d 
±7 d ±7 d  ±7 d ±14 d ±14 d ±3 d 
AP 
± 7d 
AP 
m. 
For subjects who have EC, results of the most recent esophagoscopy that confirmed the diagnosis must be available for Screening. A repeat esophagoscopy is not required at 
Screening if the subject’s signs and symptoms of EC have persisted since initial diagnosis. 
n. 
If clinically indicated. 
o. 
For IPA subjects, subjects with disseminated/invasive dimorphic fungi and subjects with other emerging fungi. 
p. 
At Day 180, weight will be determined for CPA subjects only. No other vital sign measurements will be collected for CPA or any other subjects. 
q. 
Sparse PK samples for Population PK analysis will be collected during the following time windows on Day 2 (anytime post dosing); between Days 3 to 5 (predose) and 
between Days 7 to 10 (predose). Additional blood PK samples will be collected when clinically indicated. The time of dosing and sample collection must be recorded on the 
subject diary and eCRF. In addition to blood samples, other fluid and tissue samples may be collected for ibrexafungerp PK determination when clinically indicated.  Tissue 
samples collected as part of SOC procedures (e.g., biopsies) may be sent for drug concentration analysis, when available. 
r. 
Baseline radiological assessments for invasive fungal disease should be performed ideally within 72 hours of Screening. However, assessments performed up to 7 days 
before/after the first administration of study medication may be used to confirm the diagnosis of the fungal disease if none exists within the ideal window. 
s. 
Pregnancy tests may be conducted more often (e.g., on a monthly basis), per local regulations. 
t. 
For CMC D84 is TOC unless EOT occurs first 
u. 
For CPA and ABPA D90 is TOC unless EOT occurs first 
v. 
Targeted Physical Examinations (clinical evaluation of signs and symptoms) should be performed if subject comes in for PK assessments 

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Table 15 
Schedule of Treatment Visits and Study Procedures for VVC 
Study Visit/ 
Day 
Screena 
BL/ 
Day 1a 
D4 
EOT 
D7 
TOC 
D17 
25-
DAY 
FU 
D32b 
35-
DAY 
FUc 
D42 
Unsch 
Visits 
Study Procedures 
-1 (-3) 
Prior 
to Tx 
 
Phone/ 
On-sitec 
± 3 
days 
 
Phone/ 
On-
sitec 
 
GENERAL 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Subject Enrollment and ID 
Assignment 
X 
 
 
 
 
 
 
 
Medical History and 
Demographics 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
 
 
Pregnancy Test 
X 
 
 
 
 
 
 
 
Prior and Concomitant 
Medications 
X------------------------------------------------------------X 
X 
Study Drug Dispensing 
 
X 
 
 
 
 
 
 
Study Drug Collection and 
Review 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Diary Dispensing and 
Collection 
 
X 
 
 
X 
 
 
 
EFFICACY 
 
Targeted PE including 
Clinical Evaluation of Signs 
and Symptoms of Infection  
X 
X 
 
X 
X 
X 
If 
applic.d 
 
Mycological Testing (fungal 
culture) 
X 
If 
applic. 
 
X 
X 
X 
If 
applic.d 
If 
applic. 
Assessment of Recurrence 
 
 
 
 
 
X 
 
 
Subject Status (alive/ 
deceased) 
 
 
 
 
 
 
X 
 
Assessment of Efficacy 
 
 
 
X 
X 
X 
X 
 
SAFETY 
 
Vital Signs 
X 
X 
 
X 
 
 
 
X 
General Physical exam 
X 
 
 
X 
 
 
 
 
Clinical Laboratory Safety 
Assessments  
X 
 
 
X 
 
X 
 
If 
applic. 
Adverse events 
X------------------------------------------------------------------------X 
PHARMACOKINETIC 
 
PK Assessmentse 
 
 
Xe 
Xe 
 
 
 
 
Abbreviations: applic. = applicable; BL = Baseline; D = day; eCRF = electronic case report Form; 
EOT = end of treatment; FU = Follow-up; ID = identification; PE = physical exam; PK = 
pharmacokinetic; Screen = Screening; TOC = test of cure; Tx = treatment; Unsch. = unscheduled. 
a. Screening and Baseline/ Day 1 can occur on the same day. 
b. The 25-Day FU visit will occur on study Day 32 (i.e., 32 days after the first dose of study 
drug and 25 days after EOT). 
c. The 35-Day FU visit will occur on study Day 42 (i.e., 42 days after the first dose of study 

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Study Visit/ 
Day 
Screena 
BL/ 
Day 1a 
D4 
EOT 
D7 
TOC 
D17 
25-
DAY 
FU 
D32b 
35-
DAY 
FUc 
D42 
Unsch 
Visits 
Study Procedures 
-1 (-3) 
Prior 
to Tx 
 
Phone/ 
On-sitec 
± 3 
days 
 
Phone/ 
On-
sitec 
 
drug and 35 days after EOT). This will be a telephone call and only a full on-site visit if the 
subject is symptomatic. 
d. Vaginal examination and samples for mycological testing to be done if the subject is still 
symptomatic. 
e. For subjects who give consent, sparse PK samples for Population PK analysis should be 
collected during the following time windows between Days 3 to 5 (predose) and between 
Days 7 to 10 (predose). The time of dosing and sample collection must be recorded on the 
subject diary and eCRF. Additional PK samples will be collected when clinically indicated. 
16.0 Safety Assessments and Monitoring 
16.1 
Definition of an Adverse Event 
An AE is 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 a study drug/study intervention, whether or not 
related to the study drug/study intervention. 
Any laboratory abnormality that is deemed to be clinically significant in the opinion of the 
Investigator will be considered an AE and should be recorded in the eCRF, whether or not 
it is related to the study drug. For non-fungal infection-related AEs (e.g., bacterial sepsis, 
bacterial intra-abdominal abscess) the positive cultures related to the AE should also be 
recorded on the eCRF. 
Stable chronic conditions that are present prior to clinical trial enrollment and do not 
worsen are not considered AEs and will be accounted for in the subject’s medical history. 
The following can be considered AEs: 
• An exacerbation of a pre-existing illness 
• An increase in frequency or intensity of a pre-existing episodic event or condition 
• A condition detected or diagnosed after the initiation of treatment with study 
medication, even though it may have been present prior to the start of the study 
• Continuous persistent disease or symptoms present at Baseline (Day 1) that worsen 
after signing the informed consent or following the initiation of treatment with 
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The following are not considered AEs: 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction or 
transfusion); the condition that leads to the procedure is an AE 
• Pre-existing disease or conditions present or detected at the start of the study that 
do not worsen 
• Situations where an untoward medical occurrence has not occurred (e.g., 
hospitalizations for cosmetic surgery or elective surgery or social/convenience 
admissions) 
• The disease being studied or signs or symptoms associated with the disease, unless 
more severe than expected for the subject’s condition or a worsening of the disease 
being studied 
16.2 
Definition of a Serious Adverse Event 
A SAE is defined as an AE meeting one of the following outcomes: 
• Death 
• Life-threatening event 
• Inpatient hospitalization or prolongation of existing hospitalization 
• Persistent or significant disability/incapacity or substantial disruption of the ability 
to conduct normal life functions 
• Congenital anomaly or birth defect 
Any other important medical event that may not result in one of the above outcomes may 
be considered a SAE when, based upon appropriate medical judgment, the event may 
jeopardize the participant and may require medical or surgical intervention to prevent one 
of the outcomes listed above. 
A life-threatening AE is any AE that places the subject, in the view of the Investigator, at 
immediate risk of death from the AE as it occurred. It does not include an AE that, had it 
occurred in a more severe form, might have caused death. 
16.3 
Events of Clinical Interest 
The following are considered events of clinical interest (ECIs) if they occur after dosing, 
and must be reported by the site when it becomes aware of the ECI: 
• 
ALT or AST >8 x ULN, if new compared to Baseline, confirmed by repeat testing 
• 
ALT or AST >5 x ULN for more than 2 weeks and if new compared to Baseline, 
confirmed by repeat testing 

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• 
ALT or AST >3 x ULN and total bilirubin >2 x ULN and if new compared to 
Baseline, confirmed by repeat testing 
• 
ALT or AST >3 x ULN, confirmed by repeat testing, with the appearance of 
fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, 
and/or eosinophilia (>5%)] 
16.4 
Overdose 
This refers to the administration of a quantity of a medicinal product given per 
administration or cumulatively, which is above the maximum recommended dose 
according to the authorized product information.  
An overdose can occur if a subject has taken, accidentally or intentionally, a drug 
administered in a dose exceeding the protocol-specified dose. An overdose must be 
reported within 24 hours of the site becoming aware of the overdose if such overdose 
occurs with an associated SAE. If an overdose occurs without an associated SAE, the 
overdose must be reported within 5 working days and documented in the subject diary and 
in the subject medical record. 
16.5 
Pregnancy 
Female subjects who become pregnant should be immediately discontinued from the study 
and followed up to determine the outcome of the pregnancy. The pregnancy must be 
reported to the Sponsor within 24 hours of the site becoming aware of the pregnancy. If 
the pregnancy ends for any reason before the anticipated date, the Investigator should 
notify the Sponsor. At the completion of the pregnancy, the Investigator will document the 
outcome of the pregnancy. If the outcome of the pregnancy meets the criteria for immediate 
classification as an SAE (i.e., postpartum complication, spontaneous abortion, stillbirth, 
neonatal death or congenital anomaly), the Investigator should follow the procedures for 
reporting an SAE. 
16.6 
Unexpected Adverse Event 
An AE is considered “unexpected” if it is not listed in the Investigator’s Brochure or is of 
greater specificity or severity than those that have been observed with the particular study 
drug being tested. For example, under this definition, hepatic necrosis would be unexpected 
(by virtue of greater severity) if the Investigator’s Brochure referred only to elevated 
hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis 
would be unexpected (by virtue of greater specificity) if the Investigator’s Brochure listed 
only cerebral vascular accidents. "Unexpected," as used in this definition, also refers to 
AEs that are mentioned in the Investigator’s Brochure as occurring with a class of drugs or 

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as anticipated from the pharmacological properties of the drug but are not specifically 
mentioned as occurring with the particular drug under investigation. 
16.7 
Grading of Adverse Events 
The severity (or intensity) of an AE refers to the extent to which it affects the subject’s 
daily activities and will be classified by the Investigator as mild, moderate or severe using 
the following criteria: 
• Mild: Awareness of sign or symptom, but easily tolerated. Not likely to require 
medical attention. 
• Moderate: Discomfort enough to cause some interference with daily activity. May 
require medical intervention. 
• Severe: Intense enough to disrupt daily activities. Likely requires medical 
intervention. 
Clarification of the difference in meaning between “severe” and “serious” 
The term “severe” is often used to describe the intensity (severity) of a specific event (as 
in mild, moderate or severe myocardial infarction); the event itself, however, may be of 
relatively minor medical significance (such as severe headache). This is not the same as 
“serious”, which is based on the outcome or action criteria usually associated with events 
that pose a threat to life or functioning. Seriousness (not severity) serves as a guide for 
defining regulatory reporting obligations. 
16.8 
Causality Assessment 
The Investigator will assess causality (i.e., whether there is a reasonable possibility that the 
study drug caused the event) for all AEs and SAEs. The relationship will be characterized 
using the following classification: 
• Related: The temporal relationship of the AE with the study drug makes causality 
possible and less likely due to another cause such as other drugs, a surgical 
intervention or an underlying disease. 
• Not related: The temporal relationship of the AE with the study drug makes 
causality improbable and can be due to another cause such as other drugs, a surgical 
intervention or an underlying disease. 

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16.9 
Adverse Event Collection Timeframe 
For subjects who receive study drug, AEs will be collected and evaluated from the time the 
informed consent is signed throughout the duration of the study and up to the last 
observation in the study. 
All AEs reported by the subject or observed by members of the clinical staff will be 
evaluated by the PI or qualified designee. The PI will attempt, if possible, to establish a 
diagnosis based on presenting signs and symptoms. The nature of the AE, time of onset 
relative to study drug administration, duration, severity, and relationship to treatment 
should be determined. Details of any corrective treatment must be recorded in the eCRF. 
The PI will determine whether any changes have occurred in baseline signs and symptoms. 
All AEs and SAEs will be collected in the eCRF. 
For subjects who experience a severe AE or a SAE that is deemed related to the study drug, 
a blood sample should be drawn (if possible) for determination of the concentration of 
ibrexafungerp. 
16.10 Serious Adverse Event Reporting Requirements 
All SAEs must be reported within 24 hours of the site becoming aware of the SAE. Any 
event that is serious, study drug-related, and unexpected as assessed by the medical monitor 
or the Sponsor will be submitted to the regulatory authorities in accordance with national 
regulatory laws and regulations. The PI will be responsible for reporting all SAEs that 
require reporting to the local or central Institutional Review Board/Ethics Committee 
(IRB/EC) in accordance with its regulations and guidelines. 
16.11 Adverse Event and Serious Adverse Event Follow-up 
All AEs and SAEs will be followed up to resolution (the subject’s health has returned to 
his or her baseline status or all variables have returned to normal) or until an outcome is 
reached, stabilization occurs (the Investigator does not expect any further improvement or 
worsening of the event) or the event is otherwise explained, regardless of whether the 
subject is still participating in the study. All appropriate therapeutic measures should be 
undertaken and recorded. Where appropriate, medical tests and examinations will be 
performed to document resolution of the event(s). 
16.12 Serious Adverse Event Reporting – Procedures for Investigators 
Initial Reports and Follow-Up SAE Reports: To report an SAE, the SAE eCRF form within 
the Electronic Data Capture (EDC) system must be completed. All SAEs, whether or not 
deemed drug-related or expected, must be reported by the Investigator or qualified designee 
within 24 hours of first becoming aware of the event. The Investigator/qualified designee 

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will enter the required information regarding the SAE into the appropriate form, which will 
automatically result in distribution of the information to the appropriate Sponsor contact. 
In case of any technical issues in EDC system, the investigator will fill the Paper SAE 
form, sign it and send the scanned copy via email to the dedicated centralized email ID: 
safety.scynexis@awinsals.com or send via Fax +1 844-769-3213 within 24 hours of their 
awareness. Site can also reach out at AWINSA’s safety hotline +1 760-372-7230. 
Upon return of the availability of EDC system, the SAE information must be entered into 
the EDC system as soon as possible. The SAE form within the EDC system must be 
updated within 24 hours of knowledge/receipt of SAE follow-up information. 
Upon return of the availability of EDC system, the SAE information must be entered into 
the EDC system as soon as possible. The SAE form within the EDC system must be 
updated within 24 hours of knowledge/receipt of SAE follow-up information. 
 
16.13 Procedures for Emergency Unblinding 
This is an open-label study. 
17.0 Data 
Collection, 
Study 
Monitoring 
and 
Record 
Management 
17.1 
Data Collection and Reporting 
Data for this study will be collected using eCRFs. The Investigator and study site staff will 
receive training regarding the completion of the eCRF. Visit-specific data should be 
entered into the eCRF and be ready for review as soon as possible, but no later than 5 days 
after each visit/time point. 
All protocol-required information collected during the study must be entered by the 
Investigator or designated representative in the source documents and eCRF. All data entry, 
modification or deletion will be recorded indicating the individual subject, original value, 
the new value, the reason for change, who made the change, and when the change was 
made. All data changes will be clearly indicated with a means to locate prior values. The 
Investigator will maintain a list of individuals who are authorized to enter or correct data 
on the eCRFs. 
The Investigator or, if allowed per local regulations, a designated sub-investigator, 
following review of the data in the eCRF, will confirm the validity of each subject’s data 
by signing the eCRF. 

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17.2 
Study Monitoring 
Study progress will be monitored by the Sponsor or its representative as frequently as 
necessary to ensure adequate and accurate data collection, protocol compliance, and study 
conduct in accordance with accepted regulatory requirements. The Principal Investigator 
(PI) must make all the subject data available to the monitor for review during the planned 
site monitoring visits. Arrangements for monitoring visits will be made in advance, except 
in emergency cases. 
17.3 
Investigator Study Files 
The PI is responsible for maintaining all study-related documents in study files. The 
Sponsor will notify the PI when retention of study files is no longer necessary. The 
following documents will be kept in the study files or be readily accessible: 
• original protocol and all amendments; 
• signed agreement or protocol; 
• signed and dated study staff roles and responsibilities log; 
• copy of the current curriculum vitae of the PI and of all sub-investigators; 
• IRB/EC membership list and all IRB/EC approvals for the protocol and amendments, 
informed consent documentation and all updates, advertisements, and written 
information provided to subjects; all IRB/EC correspondence; documentation that the 
Investigator’s Brochure and subsequent revisions have been submitted to the IRB/EC; 
documentation that all SAEs and any periodic safety reports have been submitted to 
the IRB/EC; and annual IRB/EC renewals (as required); 
• updated laboratory certification and the laboratory’s normal values (covering the entire 
time interval of the study for all laboratory tests conducted during the study); 
• all confirmations of investigational drug receipt, drug accountability logs and drug 
return records; 
• a CD or DVD containing final subject CRF data; 
• all correspondence to or from the Sponsor or its designees; 
• blank informed consent form; 
• Investigator’s Brochure; 
• subject screening log; 
• subject list (contains subject initials and/or protocol-specific subject number); 
• all subjects’ original signed informed consents; and 
• monitoring visit log. 
17.4 
Retention of Records 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application and until there are no pending or contemplated marketing 
applications, or at least 2 years have elapsed since the formal discontinuation of the clinical 
development of the investigational product. These documents should be retained for a 

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longer period, however, if required by the applicable regulatory requirements or by an 
agreement with the Sponsor. 
The Sponsor will inform the PI/institution in writing of the need for record retention and 
will notify the PI/institution in writing when the trial-related records are no longer needed. 
An investigator who withdraws from the responsibility of maintaining study records or 
wishes to move them to a new location has the obligation to place them in safekeeping and 
to inform the Sponsor of their location. 
18.0 Analytical Plan 
All statistical analyses will be performed using SAS® version 9.3 or later.  
Descriptive statistics (i.e., number of subjects, mean, standard deviation, median, 
minimum, maximum) will be presented for all continuous variables; number and 
percentage of subjects will be presented for categorical variables. For parameters measured 
over time, observed data and changes from Baseline will be described for each time point.  
All analyses for ibrexafungerp will present the results by fungal disease, disease category 
and enrollment category.  Overall response will be presented for all disease categories 
combined.  
Unless otherwise stated, data will be analyzed as is with no imputation. Details of the 
statistical analysis will be provided in a statistical analysis plan, which will be approved 
prior to final database lock. 
18.1 
Sample Size Determination 
This is an exploratory study and no formal sample size calculations will be performed. A 
total of 220 subjects are estimated to be adequate for an assessment of the safety and 
tolerability of ibrexafungerp in subjects with documented eligible fungal diseases that have 
been refractory or resistant to, have relapsed after SOC, or subjects have intolerance to or 
demonstrated toxicities resulting from an approved SOC antifungal treatment.  
18.2 
Analysis Populations 
The study populations to be used in the analyses are defined as follows: 
• Intent-to-Treat Population: The intent-to-treat (ITT) population will include all 
subjects who are enrolled in the study and receive at least 1 dose of study drug.  
• MITT: the Myco-ITT population will include all ITT subjects with confirmed 
pathogens and who also had all necessary cultures or mycology tests to estimate 
mycological response. 

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• Per-Protocol Population: The per-protocol (PP) population will include all ITT 
subjects who receive enough study drug (ibrexafungerp) to enable clinical efficacy 
judgement as determined by the DRC, who have an EOT (TOC for VVC, CMC, CPA 
and ABPA) assessment and who have no major protocol violations. 
• Safety Population: The safety population will include all subjects who receive at least 
one dose of study medication and have at least one safety assessment post Baseline. 
• Pharmacokinetic Population: The PK population will include all enrolled subjects 
who provide at least one PK sample and no deviations significant enough to affect 
the interpretability of PK data.  
18.3 
Interim Analyses and Supplemental Analysis 
No interim analyses are planned for this study.  If subjects on long-term treatment (CMC, 
ABPA and CPA) are ongoing at the time of planned data base lock, their data up to TOC 
visit will be included in the analyses, and data collected after TOC will be reported in a 
Supplementary Analysis.   
18.4 
Efficacy 
18.4.1 Enrollment Categories 
The following enrollment categories as detailed in Table 5, will be utilized. Each subject’s 
enrollment reason will be assessed by the DRC and the Investigator: 
• Refractory 
• Intolerant 
• Resistant (includes step-down cases) 
• Toxicities 
• Relapse 
18.4.2 Efficacy Assessments 
Response will be assessed by the DRC and by the Investigator. The primary efficacy 
endpoint of the study is the percentage of subjects who achieve Global Response at TOC  
for VVC (Day 17), CMC (Day 84), CPA (Day 90), ABPA (Day 90) and at EOT for all 
other diseases, as determined by the DRC. In cases where EOT for CMC, CPA or ABPA 
subjects occurs before the planned TOC days, EOT will be TOC assessment. Secondary 
efficacy endpoints include the percentage of subjects who achieve Global Response, 
Clinical Response and Mycological Response by pathogen and by disease category (type 
of fungal disease) at several time points as assessed by the DRC and by the Investigator. 
The percentage of subjects with a recurrence, ACM and time to death will also be assessed. 
See Section 9.0 for detailed study endpoints and Section 14.2 for efficacy procedures.  

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Efficacy outcomes will be based on the definitions captured in Table 16 and Table 17. 
Criteria for the DRC assessment of response will be further detailed in the DRC Charter. 
Criteria for the Investigator is outlined in Section 18.4.5. 
18.4.2.1 
Efficacy Time Points and Outcome Definitions 
The efficacy time points and outcome definitions for the primary and secondary endpoints 
are detailed in Table 16.  
 

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Table 16  
Efficacy Time Points and Outcome Definitions for Primary and Secondary Endpoints 
Fungal disease  
Primary time point  
 (Secondary time points) 
Primary Outcome Definition  
Secondary Outcome Definitions 
(disease-specific outcome definitions, if not previously defined)a, e 
Acute or chronic 
invasive candidiasis, 
including candidemia  
EOT 
(EOT, Day 42, 6-Week 
FU) 
 
Global Response = Global 
Response based on MSG-
EORTC outcome response 
definitionsb, e 
Global Response (as defined) 
Clinical Response (including radiological outcome) and 
Mycological Response = Clinical and Mycological Responses 
based on MSG-EORTC outcome response definitionsb 
Acute or chronic severe 
mucocutaneous 
candidiasis, including:  
• Esophageal 
candidiasis (EC)  
• Oropharyngeal 
candidiasis (OPC)  
• Chronic 
mucocutaneous 
candidiasis (CMC) 
• Vulvovaginal 
candidiasis (VVC) 
For EC and OPC: 
EOT 
(EOT, Day 42, 6-Week 
FU) 
 
For EC and OPC: 
Global Response = Global 
Response based on MSG-
EORTC outcome response 
definitionsb 
For EC and OPC: 
Global Response (as defined) 
Clinical Response (including radiological outcome if done as 
SOC) and  
Mycological Response = Clinical and Mycological Responses 
based on MSG-EORTC outcome response definitionsb 
For CMC: 
TOC (Day 84 or EOT, 
whichever occurs first) 
(EOT, Day 42, Day 84, 
6-Week FU) 
 
 
For CMC: 
Global Response = Global 
Response based on MSG-
EORTC outcome response 
definitionsb 
For CMC: 
Global Response (as defined) 
Clinical Response (including radiological outcome) and 
Mycological Response = Clinical and Mycological Responses 
based on MSG-EORTC outcome response definitionsb 
For VVC: 
TOC (Day 17) 
(Day 17, 25-Day FU 
[Day 32], 35-Day FU 
[Day 42]) 
For VVC:  
Global Response = Clinical 
Success, defined as at least 50% 
reduction from baseline in total 
composite score, without use of 
additional antifungal 
For VVC: 
Global Response (as defined) 
Clinical Response = Clinical Cure, defined as complete resolution 
of all signs and symptoms (VSS = 0) without use of additional 
antifungal (Reference FDA guidelines 2016); Resolved VVC 
infection (score <3) 
Mycological Response = mycological eradication for the baseline 
pathogen 
Symptom resolution at FU (clinical cure, resolved infection, 
clinical success) 
Responder outcome (Clinical Cure and mycological eradication) 
at TOC and FU  

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Fungal disease  
Primary time point  
 (Secondary time points) 
Primary Outcome Definition  
Secondary Outcome Definitions 
(disease-specific outcome definitions, if not previously defined)a, e 
Disseminated/invasive 
dimorphic fungi: 
• Coccidioidomycosis 
• Histoplasmosis 
• Blastomycosis  
EOT 
(EOT, Day 42, Day 84, 
6-Week FU) 
 
Global Response = Global 
Response based on MSG-
EORTC outcome response 
definitionsb 
Global Response (as defined) 
Clinical Response (including radiological outcome) and 
Mycological Response = Clinical and Mycological Responses 
based on MSG-EORTC outcome response definitionsb 
Chronic Pulmonary 
Aspergillosis (CPA) 
TOC (Day 90 or EOT, 
whichever occurs first) 
(EOT, Day 90, Day 180, 
every 3 months while on 
Tx if beyond Day 180, 
6-Week FU)  
 
Global Response = Successful 
Overall CPA Response, 
defined as subjects who are 
judged to have shown 
improvement of the disease by 
clinical, radiological and 
mycological parameters and 
those that achieved stable 
disease after entering the study 
with a rapidly progressing 
condition. 
Global Response (as defined)  
Clinical Response = defined as a decrease in the St. George’s 
Respiratory Questionnaire (SGRQ) score by ≥4 points 
SGRQ outcomes will be categorized as follows: 
• Improvement: Decrease in SGRQ by ≥4 points 
• Stability: Change in SGRQ between: increase by <4 to 
decrease by <4  
• Deterioration: Increase in SGRQ by ≥4 point 
Radiological Response will be assessed using chest CT scan and 
will be categorized as: 
• Radiological Improvement: >30% decrease in volume of 
fungus ball AND/OR 20% decrease in cavity wall thickening 
AND/OR 20% improvement in pleural thickening. 
• Radiological Deterioration: >30% increase in volume of 
fungus ball AND/OR 20% increase in cavity wall thickening 
AND/OR 20% increase in pleural thickening. Subjects with 
measurements fulfilling any of the criteria for radiological 
deterioration will be classified as deteriorated, even if they also 
fulfil a criterion for improvement. 
• Radiological Stability: No notable change in radiological 
image. 
 
Mycological Response =  
reduction in Aspergillus IgG by ≥20% 
AND/OR 
negative sputum culture for Aspergillus 

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Fungal disease  
Primary time point  
 (Secondary time points) 
Primary Outcome Definition  
Secondary Outcome Definitions 
(disease-specific outcome definitions, if not previously defined)a, e 
Allergic 
Bronchopulmonary 
Aspergillosis (ABPA) 
 
TOC (Day 90 or EOT, 
whichever occurs first) 
(EOT, Day 90, Day 180, 
every 3 months while on 
Tx if beyond Day 180, 
6-Week FU)  
 
Global Response = Composite 
ABPA Response, defined as 
>75% improvement from 
Baseline in cough and dyspnea, 
partial (≥50%) or total clearance 
of chest radiographic lesions (if 
present prior to treatment 
initiation), AND decline in 
serum total IgE by ≥ 25%c,d 
Global Response (as defined) 
Clinical Response = >75% improvement from Baseline in cough 
and dyspnea AND partial (≥50%) or total clearance of chest 
radiographic lesions (if present prior to treatment initiation 
Mycological Response = decline in serum total IgE by ≥ 25%  
 
Disease-specific outcome definitions not previously defined: 
Clinical Improvement in cough and dyspnea is documented on a 
four point scale, as follows: 
1. no improvement or worsening;  
2. mild improvement (<25% reduction from Baseline); 
3. moderate improvement (25%-75% reduction from Baseline); 
and 
4. significant improvement (>75% reduction from Baseline). 
ABPA exacerbation: clinical and/or radiological worsening along 
with doubling of the serum total IgE over the previous Baseline 
value 
Asthma exacerbation: clinical worsening in cough and dyspnea 
with no radiological worsening or doubling of serum total IgE. 
Invasive Pulmonary 
Aspergillosis (IPA) 
 
EOT 
(EOT, Day 42, Day 84, 
6-Week FU) 
  
Global Response = Global 
Response based on MSG-
EORTC outcome response 
definitionsb 
Global Response (as defined) 
Clinical Response (including radiological outcome) and 
Mycological Response = Clinical and Mycological Responses 
based on MSG-EORTC outcome response definitionsb 
• Other emerging fungi 
including yeasts and 
molds (e.g., 
sachromycetes, 
scopulariopsis) 
EOT 
(EOT, Day 42, Day 84, 
6-Week FU) 
 
Global Response = Global 
Response based on MSG-
EORTC outcome response 
definitionsb 
Global Response (as defined) 
Clinical Response (including radiological outcome) and 
Mycological Response = Clinical and Mycological Responses 
based on MSG-EORTC outcome response definitionsb 
Abbrev: ABPA = allergic bronchopulmonary aspergillosis; CMC=chronic mucocutaneous candidiasis; CPA=chronic pulmonary aspergillosis; CT = 
computed tomography; EC=esophageal candidiasis; EOT=end of treatment; FDA = Food and Drug Administration; FU = Follow-up; Ig = immunoglobulin; 
IPA = invasive pulmonary aspergillosis; MSG-EORTC = Mycosis Study Group and European Organization for Research and Treatment of Cancer 

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Fungal disease  
Primary time point  
 (Secondary time points) 
Primary Outcome Definition  
Secondary Outcome Definitions 
(disease-specific outcome definitions, if not previously defined)a, e 
Consensus Criteria; OPC=oropharyngeal candidiasis; SGRQ = St. George’s Respiratory Questionnaire; TOC = Test of Cure; Tx = treatment; 
VVC=vulvovaginal candidiasis. 
a: See disease-specific secondary endpoints in Section 9.2.2 for disease-specific time points. 
b: Segal BH, Herbrecht R, Stevens DA, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study 
Group and European Organization for Research and Treatment of Cancer Consensus Criteria. Clin Infect Dis. 2008;47(5):674–683. Doi:10.1086/590566 
c: Agarwal R, Dhooria S, Singh Sehgal I, et al. A randomized trial of itraconazole vs prednisolone in acute-stage allergic bronchopulmonary aspergillosis 
complicating asthma. Chest. 2018;153(3):656-664. Doi:10.1016/j.chest.2018.01.005. 
d: Agarwal R, Dhooria S, Singh Sehgal I, et al. A randomized trial of voriconazole and prednisolone monotherapy in acute-stage ABPA complicating 
asthma. Eur Respir J. 2018; in press. Doi:10.1183/13993003.01159-2018. 
e: When the MSG_EORTC criteria is not fully applicable for a specific case, the DRC will adjudicate outcome based on acceptable criteria, per their 
judgement. 
 
 

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As specified in Table 16, the EORTC-MSG12 outcome definitions will be used for the 
assessment of efficacy for all fungal diseases except for ABPA, CPA, CMC and VVC. 
EORTC-MSG general criteria for global responses to antifungal therapy are provided in 
Table 17.  
 
Table 17 
EORTC-MSG General Criteria for Global Responses to Antifungal 
Therapy with adaptations a and b 
Global Response 
Outcome Criteria 
Success 
Complete Response: Survival within the prespecified period of 
observation, resolution of all attributable symptoms and signs of 
disease and radiological abnormalities, and mycological evidence 
of eradication of disease 
a For subjects who were enrolled for step-down therapy and who 
were asymptomatic at baseline: no new symptoms or signs 
suggestive of disease and no new positive cultures. 
Partial Response: Survival within a prespecified period of 
observation, improvement in attributable symptoms and signs of 
disease and radiological abnormalities, and evidence of clearance 
of cultures or reduction of fungal burden, and no new positive 
cultures, as assessed by a quantitative and validated laboratory 
marker 
Failure 
Stable Response: Survival within a prespecified period of 
observation and minor or no improvement in fungal disease, but 
no evidence of progression, as determined on the basis of a 
composite of clinical, radiological and mycological criteria.  
Progression of Fungal Disease: Evidence of progressive fungal 
disease based on a composite of clinical, radiological and 
mycological criteria 
Death: Death during the prespecified period of evaluation, 
regardless of attribution 
b Not Evaluable 
Outcome cannot be assessed due to missing data 
a Definition added for subjects enrolled for step-down therapy 
b Category added for non-evaluable subjects due to missing data 

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When the MSG_EORTC criteria is not fully applicable for a specific case, the DRC will adjudicate 
outcome based on acceptable criteria, per their judgement. 
18.4.2.2 
Recurrence 
Recurrence is defined as Global Response at EOT but re-emergence of the baseline fungal 
disease during the post treatment follow-up. Re-emergence of the fungal disease is required 
to be with the same species and involving the same site that was initially identified at 
Baseline.  
Recurrence will be assessed at the 25-Day FU visit (25 days after EOT, 32 days after first 
dose) for subjects with VVC and at the 6-Week FU (42 days after EOT) for all other 
subjects as a secondary efficacy endpoint. For CPA subjects, recurrence will also be 
assessed at Day 180. 
18.4.2.3 
Survival 
Survival status (collected as ACM) will be recorded at Day 30 for IC/Candidemia and at 
Day 42 for all. ACM will be also recorded at Day 84 for subjects with IPA, 
disseminated/invasive dimorphic fungi and other emerging fungi, and at Day 90, Day 120 
and Day 180 for subjects with CPA and ABPA. 
Information on survival status on Day 30 (IC/Candidemia), Days 42, 84, 90, 120 and 180 
will be collected for all subjects, irrespective of when treatment was discontinued. If the 
subject has died, the date and cause of death along with the reporting of SAE details will 
be recorded on the eCRF. 
18.4.3 Efficacy Analyses 
The primary efficacy endpoint is the percentage of subjects with Global Response (clinical, 
radiological and mycological) as determined by the DRC at TOC for VVC (Day 17), CMC 
(EOT or Day 84), CPA and ABPA (EOT or Day 90) (whichever comes first), and at EOT 
for all other diseases. Results will be presented separately for each disease category along 
with a 95% confidence interval (CI) for a single binomial proportion in the ITT, Myco-ITT 
and PP populations where sufficient cases are available. In addition, the number of subjects 
with a successful response across all disease categories will be summarized as a response 
rate and 95% CI.  
Secondary endpoints will be presented with 95% CIs for the ITT, Myco-ITT and PP 
populations using the same approach as for the primary endpoint. 
The estimated response rates and 95% CIs outlined will also be assessed relative to the 
external data described in Section 10.1. 
The percentage of subjects surviving at the defined time points will be presented for the 
ITT, Myco-ITT and PP populations. A Kaplan Meier plot will also be produced 

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summarizing the survival curve over time and the median time to death. A subject without 
a reported death will be censored at the point of last time the subject was known to be alive. 
For primary and overall secondary endpoints, presentations by pathogen will be conducted, 
if numbers allow. 
Data for all subjects will be presented by fungal disease, disease category, reason for 
enrollment and receipt of combination therapy (Yes/No). If data are missing and the subject 
has not been deemed a success or failure the outcome will be categorized as unknown/not 
evaluable. 
18.4.4 Data Review Committee 
A DRC Charter will provide detailed criteria to be used for the baseline and outcome 
analysis of subjects in this study. The analysis criteria will be based on EORTC-MSG 
Consensus Criteria12 for all diseases except ABPA, CPA, CMC and VVC. Adaptations to 
the EORTC-MSG criteria adopted by the DRC will be documented in the DRC Charter. 
18.4.5 Investigator’s Assessment of Overall Response  
The Investigator will be asked to provide his/her opinion of the subject’s response as 
follows: 
 
Clinical Response (all non-radiological clinical symptoms and physical findings): 
1. Resolution of all attributable clinical symptoms and physical findings (i.e., 
resolution of all clinical symptoms and physical findings of fungal disease present 
at Baseline and/or resolution of those that appeared at a subsequent visit) 
2. Resolution of some attributable clinical symptoms and physical findings (i.e., 
resolution of some but not all clinical symptoms and/or physical findings of fungal 
disease present at Baseline and/or of those that appeared at a subsequent visit) 
3. No resolution of any attributable clinical symptoms and physical findings and/or 
worsening (i.e., no resolution or worsening of any clinical symptoms and/or 
physical findings of fungal disease present at Baseline and/or of those that appeared 
at a subsequent visit) 
4. Results not available/subject unevaluable (i.e., visit and/or assessment of clinical 
symptoms and physical findings of fungal disease was not performed at any time 
point) 
5. No attributable signs and symptoms at Screening (i.e., no clinical symptoms or 
physical findings of fungal disease present at Baseline) 
 
Radiological Response: 
 

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1. ≥90% improvement 
2. ≥50 to < 90% improvement 
3. ≥25 to < 50% improvement 
4. < 25% improvement 
5. No signs on radiological images at Screening  
6. Results not available (i.e., visit and/or radiological assessment was not performed 
at any time point) 
 
Mycological Response: 
1. Eradication (eradication of the original causative organism cultured or identified 
by histology/cytology/serology at Baseline) 
2. Presumed eradication (missing documentation of the eradication of the original 
causative organism at Baseline plus resolution of all or some clinical symptoms 
and physical findings of fungal disease present at Baseline and/or of those that 
appeared at a subsequent visit) 
3. Persistence (persistence of the original causative organism cultured or identified 
by histology/cytology at Baseline or emergence of a new causative organism) 
4. Presumed persistence (missing documentation of the persistence of the original 
causative organism at Baseline plus no resolution or worsening of any clinical 
symptoms and physical findings of fungal disease present at Baseline and/or of 
those that appeared at a subsequent visit) 
5. No mycological follow-up results available, for whatever reason (no diagnostic 
test done at any time point) 
6. No mycological evidence at Screening (up to Day 7) (any negative diagnostic 
test(s) obtained or not done at Baseline [from Screening up to Day 7, inclusive]) 
Mycological response will be confirmed by the DRC and will include central laboratory 
results. 
If relevant mycology findings occur after successful mycological response (proven or 
presumed eradication), an evaluation will be made as to whether the infection is recurrent 
(same species as at Baseline) or emergent (different species compared with Baseline). 
Subjects with recurrent or emergent infection will be classified as mycological failure from 
the visit onwards where positive cultures were reported, i.e. positive cultures before the FU 
Visit will be categorized as mycological failure and overall non-successful response on the 
primary efficacy assessment. 
18.5 
Pharmacokinetics 
18.5.1 Pharmacokinetic Assessments 
See Section 14.4 for details. 

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18.5.2 Pharmacokinetic Analyses 
The concentration versus time data from the sparse PK samples collected in this study will 
be analyzed using a Pop PK model to estimate Cmax, AUC and CL/F, as applicable. 
The PK analysis will be conducted on the PK Population. 
Further analysis of possible metabolites may be performed. 
18.6 
Safety  
18.6.1 Safety Assessments 
Safety will be evaluated throughout the study, including the following parameters: AEs, 
treatment discontinuations, general physical examination, vital signs, safety laboratory 
tests and concomitant medications. Prior and concomitant medications are discussed in 
Section 13.1. Other safety procedures are described in Section 14.3.  
18.6.2 Safety Analyses 
All safety analyses will be conducted in the safety population; all safety variables will be 
listed. 
Incidence and severity of treatment-emergent AEs, AEs leading to discontinuation and 
SAEs and their relationship to treatment will be summarized. Also data on AEs leading to 
death, AEs of special interest, AEs leading to withdrawal and AEs by severity will be 
summarized. 
Early discontinuation of study drug treatment will be presented and will include the reasons 
for and timing of such discontinuations. Abnormal physical examinations associated with 
adverse events will be listed. Concomitant medications will be summarized. 
Laboratory evaluations will be summarized as observed values and changes from Baseline; 
shifts with respect to the laboratory reference range will be summarized. 
Vital signs will be summarized as observed values and changes from Baseline. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and 
presented by system organ class and preferred term. Concomitant medications will be 
classified based on the World Health Organization´s (WHO) Drug Dictionary terminology. 

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19.0 Ethics and Protection of Human Patients 
19.1 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, the ethical principles 
established by the Declaration of Helsinki (as amended in Fortaleza, Brazil, October 2013), 
the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines, the United States Code of Federal Regulations (CFR) sections that address 
clinical research studies, applicable European Union regulations and/or other national and 
local ethical and legal requirements, as applicable. 
19.2 
Institutional Review Board/Ethics Committee Review 
The PI or CRO must provide the IRB/EC with all appropriate materials, including a copy 
of the subject ICF. The study will not be initiated until the PI or CRO obtains written 
approval of the protocol and the subject ICF from the appropriate IRB/EC, and copies of 
these documents are received by the Sponsor. Appropriate reports on the progress of this 
study will be made by the PI to the IRB/EC, medical monitor, and Sponsor in accordance 
with applicable government regulations and in agreement with policy established by the 
Sponsor. 
19.3 
Informed Consent  
The ICH issued guidelines to provide protection for human subjects in clinical 
investigations. The ICH Tripartite Guideline for GCP establishes the general requirements 
for informed consent. Each subject will be provided with oral and written information in a 
language they can understand that describes the nature and duration of the study. Before 
undergoing screening, each subject must consent in writing to study participation. The 
subject will sign and personally date the subject ICF. The person rendering consent will 
also sign and personally date the subject ICF as the person who obtained the consent of the 
subject. In the case of a minor, according to the local definition (e.g., below 16 or 18 years 
of age), a parent or legal representative should also sign and date the ICF. Additional local 
regulatory requirements may be applicable for participation of subjects below the age of 
consent. The original signed subject ICF will be retained with the study center’s records. 
Each subject will receive a copy of his or her signed subject ICF. In addition, the PI, or his 
or her designee, must document in the case history that informed consent was obtained 
before study participation.  

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19.4 
Future Use of Samples  
Fungal isolates collected during the study will be sent to a central laboratory and will be 
maintained for as long as they deem useful to conduct in vivo and/or in vitro testing of new 
or existing medication antifungals or analysis of mechanisms of action/resistance.  
Human biological samples collected from this study such us plasma or tissue for PK 
determination of ibrexafungerp or its metabolites and/or fungal pathogen identification will 
be maintained in a central repository for as long as deemed useful for the specified research 
purposes.  
All samples will be identified only by a coded number to maintain subject confidentiality. 
Researchers requesting samples or information from the repository must have a research 
protocol approved by an Institutional Review Board (IRB)/Ethics Committee (EC). Human 
biological samples will only be retained for subjects who provide consent for future use. 
19.5 
Subject Privacy and Subject Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records that leave the site 
will be identified only by a coded number to maintain subject privacy and confidentiality. 
All records will be kept in a locked file cabinet. All computer entry and networking 
programs will be performed with coded numbers only. Clinical information will not be 
released without written permission of the subject, except as necessary for monitoring by 
the medical monitor, IRB/EC, the Food and Drug Administration (FDA), the Sponsor or 
where required by law. All local privacy laws must be followed.  
19.6 
 Study Termination 
The PI, the Sponsor, the FDA, and the IRB/EC each reserve the right to terminate the study 
in the interest of subjects’ safety and welfare. The Sponsor reserves the right to terminate 
the study at any time for administrative reasons. 
19.7 
Financial Disclosure 
The financial interests of all Investigators from all participating clinical centers must be 
collected prior to study initiation and 1 year following the completion of the clinical trial. 

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20.0 References 
1. 
Schmiedel Y, Zimmerli S. Common invasive fungal diseases: an overview of 
invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia. 
Swiss Med Wkly. 2016; 146:w14281. 
2. 
Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of 
health care- associated infections. NEJM 2014;370:1198-208. 
3. 
Centers for Disease Control and Prevention [Internet]. Atlanta, GA: Centers for 
Disease Control and Prevention. Fungal Diseases: Invasive Candidiasis Statistics; 
[updated 2016 Dec 12; cited 2016 Dec 27]; [about 5 screens]. Available from: 
http://www.cdc.gov/fungal/diseases/candidiasis/invasive/statistics.html. 
4. 
Farmakiotis D, Kyvernitakis A, Tarrand JJ et al. Early initiation of appropriate 
treatment is associated with increased survival in cancer patients with Candida 
glabrata fungaemia: a potential benefit from infectious disease consultation. Clin 
Microbiol Infect [Internet]. 2015 [cited 2016 Dec 27];21(1):79-86. Available from: 
http://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)00020-
2/pdf. doi: 10.1016/j.cmi.2014.07.006. 
5. 
Larkin E, Hager C, Chandra J, Mukherjee PK, et al. The Emerging Candida auris: 
Characterization of Growth Phenotype, Virulence Factors, Antifungal Activity, and 
Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and 
Biofilm Formation. Antimicrob Agents Chemother. 2017 Feb 21. 
6. 
Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the 
Management of Candidiasis: 2016 Update by the Infectious Diseases Society of 
America. CID 2016:62(4):e1-50. 
7. 
Perfect JR, Marr KA, Walsh TJ, et al. Voriconazole Treatment for Less-Common, 
Emerging, or Refractory Fungal Infections. Clin Infect Dis 2003; 36 (9): 1122-1131. 
doi: 10.1086/374557. 
8. 
Kuse ER, Chetchotisakd P, da Cunha CA, et al. Micafungin versus liposomal 
amphotericin B for candidaemia and invasive candidosis: a phase III randomized 
double-blind trial. Lancet 2007; 369: 1519–27. 
9. 
Odabasi Z, Mattiuzzi G, Estey E, et al. β- d -Glucan as a Diagnostic Adjunct for 
Invasive Fungal Infections: Validation, Cutoff Development, and Performance in 
Patients with Acute Myelogenous Leukemia and Myelodysplastic Syndrome. Clin 
Infect Dis 2004; 39 (2): 199-205. doi: 10.1086/421944. 
10. 
CLSI. 2012. Reference method for broth dilution antifungal susceptibility testing of 
yeasts; 4th informational supplement. CLSI document M27-S4. Clinical and 
Laboratory Standards Institute, Wayne, PA. 
11. 
European Committee on Antimicrobial Susceptibility Testing (EUCAST) 
Guidelines. 
12. 
Segal BH, Herbrecht R, Stevens DA, et al. Defining responses to therapy and study 
outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and 

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European Organization for Research and Treatment of Cancer Consensus Criteria. 
Clin Infect Dis. 2008;47(5):674–683. doi:10.1086/590566. 
13. 
Andes DR, Safdar N, Baddley JW et al. Impact of Treatment Strategy on Outcomes 
in Patients with Candidemia and Other Forms of Invasive Candidiasis: A Patient-
Level Quantitative Review of Randomized Trials. Clinical Infectious Diseases 
2012;54:80:1110-22. 
 
 
 

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21.0 Appendices 
21.1 
Appendix A: Protocol Revision History 
21.1.1 Protocol Amendment 3 
Current Version and Date: Protocol Amendment 3 (Protocol Version 4.0) dated 
21 November 2022.  Revision to Protocol dated 13 AUGUST 2019 (Amendment 2) listed 
below. 
Amended to include the bolded text and delete the strikethrough text 
Protocol Amendment 3 
Main affected 
Protocol Sections 
Change and Rationale 
o Synopsis 
Updated based on changes listed in this Revision History 
o Background 
Updated with more recent information 
o Study Objectives 
o Study Endpoints 
Overall Description 
of the study 
Additions and clarifications as applicable for fungal diseases.  
Changes implemented throughout the document 
o Primary study 
objective  
 
 
o Primary endpoints 
To evaluate the efficacy of ibrexafungerp in the treatment of severe 
fungal diseases by a Data Review Committee (DRC) at the primary 
time point for the fungal disease 
 
Efficacy as measured by the percentage of subjects with Global 
Response at TOC for VVC (Day 17), CMC (EOT or Day 84), CPA 
(EOT or Day 90) and ABPA (EOT or Day 90) (whichever comes 
first) and at EOT for all other diseases as determined by a DRC 
o Overall secondary 
objectives and  
 
 
 
 
o Secondary 
endpoints 
o To determine the efficacy of ibrexafungerp by fungal disease and 
disease category 
o To evaluate the efficacy of ibrexafungerp by reason for 
enrollment (refractory, resistance, relapse, intolerance, 
toxicity, need for oral therapy)  
 
o ACM at Day 30 (Invasive candidiasis and candidemia) and 
Day 42 for all diseases 
o Disease specific 
secondary 
endpoints 
ADDED - Acute Invasive candidiasis / Candidemia  
o Completion of study drug antifungal treatment (i.e. no 
recurrence, no use of other antifungal treatment, no 
discontinuation for any reason) 
ADDED Acute or Chronic Severe Mucocutaneous Candidiasis 
o Percentage subjects with mycological cure at Day 84 
o Percentage subjects with clinical response by Day 30 and Day 
84 

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Protocol Amendment 3 
Main affected 
Protocol Sections 
Change and Rationale 
o Percentage of subjects with continued symptom relief at 6-
week FU 
Chronic Pulmonary Aspergillosis 
o ADDED Recurrence at Day 180 
o Study Treatments 
and overall 
Description of the 
Study 
Added allowance of re-enrollment in cases of recurrence 
Subjects who have a recurrence after TOC (VVC subjects) 
or EOT (other subjects), may be considered for re 
enrollment upon discussion with the sponsor 
Clarified combination therapy requirement 
 
Ibrexafungerp given as combination therapy will be required for 
all subjects with refractory or relapsing IPA, mucormycosis and 
other molds with unpredictable ibrexafungerp activity. 
o Study Population 
and enrollment 
reasons 
Clarification of enrollment reasons: 
Subject has a documented eligible fungal disease that has been 
refractory or resistant to SOC, has relapsed after, or the subject 
has intolerance to or demonstrated toxicities resulting from an 
approved SOC antifungal treatment (as defined in Table 5). The 
subject is also eligible if, in the judgement of the Investigator, 
long-term IV antifungal therapy is not feasible or desirable due 
to clinical (isolate is resistant to or has a high MIC and is 
unlikely to respond to antifungal SOC) or logistical 
circumstances or if other antifungal alternatives are not 
appropriate 
o Study Procedures 
Medical History and Imaging – added 
Data available to support inclusion/exclusion criteria 
collected as SOC prior to signature of the ICF will be 
collected as appropriate in the EDC 
Imaging – updated to remove central reading 
Radiological assessments should ideally be made by CT scan 
(HRCT if available) or MRI and all radiological images and 
local reports pertaining to the fungal disease will be forwarded to 
the central reading laboratory for independent review. 
Esophagoscopy – added 
A repeat esophagoscopy is required at EOT for all subjects, if 
this complies with SOC. 
Tissue simples - added 

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Protocol Amendment 3 
Main affected 
Protocol Sections 
Change and Rationale 
Tissue samples collected as part of SOC procedures (e.g., 
biopsies) may be sent for drug concentration analysis, when 
available. 
o Analytical Plan 
Clarified as follows: 
All analyses for ibrexafungerp will initially present the results by 
fungal disease, disease category and enrollment category.  
Overall response will be presented for all disease categories 
combined. 
o Sample size 
Increased from 200 to 220 (+10%) 
o Analysis 
Population 
Added Myco-ITT and clarified PP 
o Myco-ITT: the Myco-ITT population will include all ITT 
subjects with confirmed pathogens and who also had all 
necessary cultures or mycology tests to estimate mycological 
response. 
o Per-Protocol Population: The per-protocol (PP) population will 
include all ITT subjects who receive enough study drug 
(ibrexafungerp) to enable clinical efficacy judgement as 
determined by the DRC, who have an EOT (TOC for VVC, 
CMC, CPA and ABPA) assessment and who have no major 
protocol violations that would impact the assessment of efficacy. 
o Interim Analysis 
and Supplementary 
Analysis 
Added a clause for Supplemental Analyses 
No interim analyses are planned for this study.  If subjects on 
long-term treatment (CMC, ABPA and CPA) are ongoing at 
the time of planned data base lock, their data up to TOC visit 
will be included in the analysis, and data collected after TOC 
will be reported in a Supplementary Analysis.   
o Enrollment 
Categories 
Added Section 18.4.1 Enrollment Categories 
The following enrollment categories as detailed in Table 5, 
will be utilized. Each subject’s enrollment reason will be 
assessed by the DRC and the Investigator: 
o Refractory 
o Intolerant 
o Resistant (includes step-down cases – need for oral 
therapy) 
o Toxicities 
o Relapse 
o Efficacy 
Assessment 
Updated as follows: 
The primary efficacy endpoint of the study is the percentage of 
subjects who achieve Global Response at TOC for VVC (Day 
17), CMC (Day 84), CPA (Day 90), ABPA (Day 90) and at 

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Protocol Amendment 3 
Main affected 
Protocol Sections 
Change and Rationale 
EOT for all other diseases, as determined by the DRC. In cases 
where EOT for CMC, CPA or ABPA subjects occurs before 
the planned TOC days, EOT will be TOC assessment. 
o Efficacy 
Timepoints and 
Outcome 
Definitions for 
primary and 
secondary 
endpoints 
Primary Efficacy Timepoints changed as follows: 
CMC: TOC (Day 84 or EOT, whichever comes first) 
CPA: TOC (Day 90 or EOT, whichever comes first) 
ABPA: TOC (Day 90 or EOT, whichever comes first) 
Outcome definitions changed as follows: 
o EC and OPC 
Clinical Response (including radiological outcome if done as 
SOC) 
 
o VVC Primary Outcome Definition: 
Global Response = Clinical Success Improvement, defined as 
at least 50% reduction from baseline in complete or partial 
resolution of signs and symptoms with total composite score 
not >1, without use of additional antifungal 
 
o VVC Secondary Outcome Definition:  
Global Response (as defined) 
Clinical Response = Clinical Cure, defined as complete 
resolution of all signs and symptoms (VSS = 0) without use of 
additional antifungal (Reference FDA guidelines 2016); 
Resolved VVC infection (score <3) 
Mycological Response = mycological eradication for the 
baseline pathogen 
Symptom resolution at FU (clinical cure, resolved infection, 
clinical success) 
Responder outcome (Clinical Cure and mycological 
eradication) at TOC and FU 
 
EORTC-MSG table for General Criteria for Global Responses to 
Antifungal therapy (Table 17) – additions as follows: 
o Global Response - Success definition for step-down therapy 
added: 
For subjects who were enrolled for step-down therapy 
and who were asymptomatic at baseline: no new 
symptoms or signs suggestive of disease and no new 
positive cultures. 
o Partial Response: Survival within a prespecified period of 
observation, improvement in attributable symptoms and 
signs of disease and radiological abnormalities, and evidence 
of clearance of cultures or reduction of fungal burden, and 

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Protocol Amendment 3 
Main affected 
Protocol Sections 
Change and Rationale 
no new positive cultures, as assessed by a quantitative and 
validated laboratory marker 
o Added a category “Not Evaluable” 
Not Evaluable – Outcome cannot be assessed due to 
missing data 
o Added a statement: 
When the MSG_EORTC criteria is not fully applicable 
for a specific case, the DRC will adjudicate outcome 
based on acceptable criteria, per their judgement. 
o Survival 
Updated: 
Survival status (collected as ACM) will be recorded at Day 30 for 
IC/Candidemia and at Day 42 for all. 
Protocol Amendment 3 
Administrative and/or General Changes 
o Cover Page, 
headers and 
footers 
o Updated protocol version details. 
o Contact 
Information  
o Protocol 
Approvals 
o Updated contact and protocol approval details. 
o Spelling and 
typographic 
errors 
o Corrected throughout 
o Section 16.12 
SAE Reporting 
procedures for 
Investigators 
o Contact information for Pharmacovigilance Service Provider 
and SAE reporting process updated 
o References 
o Updated reference list. 
o Appendices 
o Added Protocol Amendment 3 under Revision History 
(Section 21.1.1) 
o Renumbered appendices accordingly. 
 
 
 

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21.1.2 Protocol Amendment 2 
Current Version and Date: Protocol Amendment 2 (Protocol Version 3.0) dated 
13 AUGUST 2019 
Revisions to Protocol dated 23 MAR 2017 (Amendment 1) listed below. 
 
Protocol Amendment 2 
Main Affected 
Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
Overall document 
Updated protocol organization to current template 
organization. 
o Synopsis 
o Updated based on major and minor/general changes listed in 
this Revision History. 
o Schematic of 
Study Design 
o Updated to reflect current study design. 
o Background 
Information 
o Updated to describe current ibrexafungerp knowledge. 
o Study Objectives 
o Study Endpoints 
o Rationale for the 
study 
o Overall 
Description of the 
Study 
o Revised study objectives and endpoints to account for all 
eligible diseases. 
o Added disease-specific objectives and endpoints for selected 
fungal diseases. 
o Overall 
Description of the 
Study 
o Updated to reflect current study design 
o Study Duration 
o Overall 
Description of the 
Study 
o Updated to a total study duration of approximately 222 days 
for each subject. 
o Inclusion Criteria  o Clarified that subjects must fulfill all inclusion criteria at 
Screening and/or Baseline (as applicable). 
o Added the following fungal diseases as eligible for inclusion 
in the study:  
 vulvovaginal candidiasis (VVC) 
 disseminated/invasive dimorphic fungi 
(coccidioidomycosis, histoplasmosis, blastomycosis) 
 chronic pulmonary aspergillosis (CPA) 
 allergic bronchopulmonary aspergillosis (ABPA) 
 invasive pulmonary aspergillosis (IPA) 
 other emerging fungi including yeasts and molds (e.g., 
sachromycetes, scopulariopsis) 

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Protocol Amendment 2 
Main Affected 
Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
o Added eligibility criteria for the above-listed fungal 
diseases. 
o Updated relapse and refractoriness criteria for eligible 
fungal diseases. 
o Added “and/or legal guardian” to inclusion criteria No. 5 
and No. 6. 
o Revised contraception wording. 
o Exclusion Criteria o Clarified that subjects will be excluded if they meet any of 
the exclusion inclusion criteria at Screening and/or Baseline 
(as applicable). 
o Revised exclusion criterion No. 1 to clarify that subjects will 
be excluded if they have an invasive fungal disease with 
central nervous system involvement, unless they are planned 
to receive combination therapy with ibrexafungerp and other 
antifungal. 
o Removed exclusion criteria for subjects with VVC and 
invasive fungal diseases of the bone and/or joint. 
o Removed exclusion criteria based on absolute neutrophil 
count and QTcF interval. 
o Discontinuation 
Criteria 
o Added instructions for discontinuation procedures to be 
conducted depending on time of discontinuation. 
o Study Treatments 
o Overall 
Description of the 
Study 
o Added a dedicated section (Study Treatment Groups) for 
study treatments, as per current protocol template, including 
subsections with detailed dosing instructions and dietary 
requirements for: 
 ibrexafungerp monotherapy for all fungal diseases 
except VVC 
 ibrexafungerp monotherapy for VVC, and 
 ibrexafungerp combination therapy for certain 
subgroups of subjects 
o Clarified that for subjects on continuous feeding via an NG 
or PEG tube, the tube should be flushed with approximately 
20 mL of water before and after drug administration. 
o Clarified that ibrexafungerp will be packaged in bottles 
containing 30 tablets and that ibrexafungerp should be 
stored at a maximum temperature of 25°C with allowable 
excursions to 30°C. 
o Non-Study 
Treatments 
o Developed a separate, dedicated section for non-study 
treatments, as per current protocol template. 
o Prior and 
Concomitant 
Medications 
o Revised the time period for recording prior and concomitant 
medications depending on fungal disease. 

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(Major changes shown as underlined font) 
o Clarified specific time period for recording prior use of 
immunosuppressants and antifungals. 
o Study Procedures 
o Reorganized study procedures as General Procedures, 
Efficacy Procedures, Safety Procedures and 
Pharmacokinetic Procedures to match new order in Schedule 
of Study Procedures. 
o Added clarification that study days, weeks and months are 
counted relative to the first dose of study drug (Baseline 
[Day 1]) and that, for follow-up visits, days, weeks and 
months are counted relative to the EOT visit. Clarified that 
Screening and Baseline/Day 1 may occur on the same day. 
o Informed Consent o Added “legally authorized representative” as potential 
person giving consent. 
o Enrollment and 
ID Assignment 
o Study Rationale 
o Overall 
Description of the 
Study 
o Appendix B 
o Added clarification that an Eligibility Form will be used to 
request eligibility confirmation from the Sponsor. 
o Name changed from “Enrollment Form” to “Eligibility 
Form”. 
o Included updated sample Eligibility Form in Appendix B. 
o Clarified that non-US sites will have a 3 digit ID number for 
their sites. 
o Clarified subject enrollment may also be approved by a 
Sponsor designee. 
o Medical History 
and 
Demographics 
o Added drug monitoring, if applicable, and details to be 
collected for ABPA and CPA subjects. 
o Pregnancy Test 
o Added urine testing in addition to serum testing as an option 
for pregnancy tests and a mandatory pregnancy test at EOT 
for all female subjects, except VVC subjects. 
o Clarified that pregnancy tests may be conducted more often 
(e.g., on a monthly basis), per local regulations. 
o Prior and 
Concomitant 
Medications 
o Separated AE and medication procedures to accommodate 
to the new organization of the Schedule of Study 
Procedures. 
o Cross-referred to Non-Study Treatments section and 
Appendix B, for clarity. 
o Study Drug 
Dispensing, 
Collection and 
Accountability 
Review 
o Clarified that, for non-hospitalized subjects excluding VVC 
subjects, study drug will be dispensed at Baseline/Day 1 and 
then collected and redispensed every 14 days up to EOT. 
Also clarified that any unused study drug will be 
redispensed to the subject. 

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Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
o Added dispensing and collection details for VVC (dispensed 
at Baseline/Day 1 and collected at EOT). 
o Study Drug 
Dosing 
o Added entire procedure with overall details for study drug 
dosing. 
o Subject Diaries 
o Clarified that, for all subjects except VVC subjects, diaries 
will be reviewed every 14 days up to EOT and collected and 
reviewed at EOT. 
o For VVC subjects, diaries will be collected at TOC. 
o Targeted Physical 
Exam 
o Added timepoints specific for each fungal disease. 
o Clarified that, if a relapse is suspected, the examination 
should occur before starting any new antifungal treatment. 
o Mycological 
Testing 
o Added timepoints and requirements specific for each fungal 
disease. 
o Added instructions for urinary tract infections. 
o Provided general requirements for baseline mycological, 
identification and susceptibility testing and testing during 
the study. 
o Added discussion regarding the requirements for fungal 
isolates and incorporated table to define Initial, Screening 
and Study Isolates. 
o Clarified that, if a relapse is suspected, samples for fungal 
culture should be collected before starting any new 
antifungal treatment. 
o Imaging 
o Added recommended timepoints and requirements specific 
for each fungal disease. 
o Clarified radiological requirements for enrollment and for 
the duration of the study. 
o Added requirements for bronchoscopies. 
o Serological 
o Added recommended timepoints and requirements specific 
for each fungal disease. 
o Esophagoscopy 
o Clarified timepoints and requirements for EC subjects. 
o Spirometry 
o Added as new procedure (required for ABPA subjects). 
o Saint George’s 
Respiratory 
Questionnaire 
o Added as new procedure (required for CPA subjects). 
o Six-Minute Walk 
Test and MRC 
Dyspnea Scale 
o Added as new procedures (required for CPA subjects). 
o Recurrence 
o Added as a procedure with timepoints and requirements 
specific for each fungal disease. 
o Survival 
o Added as a procedure with timepoints and requirements 
specific for each fungal disease. 

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Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
o Assessment of 
Efficacy 
o Updated based on current endpoints and added fungal 
diseases. 
o Moved outcome definitions to the efficacy portion of the 
Analytical Plan section of the protocol. 
o Vital Signs 
o Added weight to vital sign measurements. 
o Clarified that, for CPA subjects, weight will also be 
determined at the Day 180 visit. 
o General Physical 
Examination 
o Clarified that this procedure is not applicable for VVC 
subjects. 
o 12-Lead ECG 
o ECGs will no longer be conducted for the study. Removed 
ECG procedure throughout the study. 
o Clinical 
Laboratory Safety 
Assessments 
o Added timepoints and requirements specific for each fungal 
disease and for the determination of ECIs. 
o Adverse Events  
o Adverse Event 
Collection 
Timeframe 
o Separated AE and medication procedures to accommodate 
to the new organization of the Schedule of Study 
Procedures. 
o Clarified that all AEs will be collected from signature of the 
informed consent to the last observation in the study. 
o PK Procedures 
o Overall 
Description of the 
Study 
o Removed “optional” for Day 2 sampling to clarify that all 
PK sampling is optional (i.e., for consenting subjects only). 
o Added that additional blood PK samples will be collected 
when clinically indicated. 
o Clarified that, in addition to blood samples, other fluid and 
tissue samples may be collected for ibrexafungerp PK 
determination when clinically indicated. 
o Study Schedules 
o Overall 
Description of the 
Study 
o Developed two separate schedules: one for VVC and a 
separate one for all other fungal diseases. 
o Reorganized study procedures for both schedules as General 
Procedures, Efficacy Procedures, Safety Procedures and 
Pharmacokinetic Procedures. 
o For all diseases except VVC: added study visits for Day 42, 
Day 84, Day 90, Day 120, Day 180, 3-month FU and 6-
month FU and added spirometry, SGRQ, MRC Dyspnea 
Scale, 6-Minute Walk Test, Recurrence, Survival and Study 
Drug Dosing as study procedures based on revised endpoints 
and newly incorporated eligible fungal diseases. 
o For VVC: developed a schedule with VVC-specific 
procedures and the following VVC-specific visits: Day 4, 
EOT (Day 7), TOC (Day 17), 25-Day FU (32 days after first 
dose) and 35-day FU (42 days after first dose). 

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(Major changes shown as underlined font) 
o For all fungal diseases: removed 12-lead ECG for all fungal 
diseases including VVC. 
o Updated schedules based on changes made to the procedure 
descriptions and footnotes accordingly. 
o Definition of an 
Adverse Event 
o Clarified that for non-fungal infection-related AEs (e.g., 
bacterial sepsis, bacterial intra-abdominal abscess) the 
positive cultures related to the AE should also be recorded 
on the eCRF. 
o Events of Clinical 
Interest 
o Clarified that an event will be considered an ECI if it occurs 
after dosing. 
o Removed QTc elevations as ECIs. 
o Removed INR elevations as ECIs. 
o Causality 
Assessment 
o Clarified definition for Related AEs as those with a temporal 
relationship with the study drug that makes causality 
possible and less likely due to another cause. 
o AE Collection 
Timeframe 
o Clarified that blood samples should be drawn (if possible) to 
determine ibrexafungerp concentrations for subjects who 
experience a severe AE or a SAE if such AE is deemed 
related to the study drug therapy. 
o SAE Reporting 
Requirements 
o Clarified that the PI will be responsible for reporting SAEs 
that require reporting to both local and/or central IRBs. 
o Data Collection 
and Reporting 
o Clarified that, following review of the data in the eCRF, a 
designated sub-investigator may confirm the validity of each 
subject’s data if allowed per local regulations. 
o Analytical Plan 
o Clarified that all analyses for ibrexafungerp will initially 
present results by disease category, and will then present 
results for all disease categories combined. 
o Sample Size 
Determination 
o Overall 
Description of the 
Study 
o Increased sample size to a total of 200 subjects. 
o Analysis 
Populations 
o For the PK Population, added that in addition to including 
all enrolled subjects who provide at least one PK sample, 
this population will include subjects with no deviations 
significant enough to affect the interpretability of PK data. 
o The ITT Population was redefined to include all subjects 
who are enrolled in the study and receive at least 1 dose of 
study drug. 

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(Major changes shown as underlined font) 
o The PP Population was redefined to include all ITT subjects 
who receive at least 5 days (1 day for VVC) of study drug 
(ibrexafungerp), who have an EOT (TOC for VVC) 
assessment and who have no major protocol violations that 
would impact the assessment of efficacy. 
o Interim Analysis 
o Added section to clarify that no interims analyses are 
planned for the study. 
o Efficacy 
Assessments 
o Added this as an entire new section, based on current 
protocol template.  
o Efficacy 
Timepoints and 
Outcome 
Definitions 
o Included table of efficacy timepoints and outcome 
definitions for primary and secondary endpoints for each 
fungal disease, as follows: 
 Efficacy timepoint and outcome definitions for the 
primary efficacy endpoint 
 Efficacy timepoints and outcome definitions for the 
overall secondary endpoints 
 Outcome definitions for disease-specific secondary 
efficacy endpoints 
o Added EORTC-MSG table of General Criteria for Global 
Responses to Antifungal Therapy. 
o Recurrence 
o Survival 
o Added as new sections. 
o Efficacy Analyses o Updated to address changes in eligible fungal diseases and 
study endpoints. 
o Revised to clarify that results (percentage with 95% CIs) for 
the response rates of the primary and secondary endpoints 
will be presented separately for each disease category, 
across all disease categories and by pathogen (if numbers 
allow).  
o Clarified that the estimated response rates and 95% CIs 
outlined will also be assessed relative to external data. 
o Data for all subjects will be presented by disease category 
and then by disease category and receipt of combination 
therapy. 
o Revised confidence interval details to clarify that endpoints 
will be presented with 95% confidence intervals to fully 
outline the estimated responses and their uncertainty. 
o Described analyses for ACM and time to death. 
o Data Review 
Committee 
o Added as new section. 
o Provided summary description of guidelines to be used by 
the DRC. 

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Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
o Investigator’s 
Assessment of 
Overall Response 
o Incorporated general guidelines for assessment of clinical, 
radiological and mycological response by the investigators. 
o Pharmacokinetic 
Assessments 
o Safety 
Assessments 
o Added as new sections based on current protocol template. 
o Safety Analyses 
o Clarified that summary tables by severity will be provided 
for AEs leading to death, AEs of special interest, AE’s 
leading to withdrawal and AEs. 
o Removed ECG from safety variables. 
o Informed Consent o Added clarification that in the case of a minor, according to 
the local definition (e.g., below 16 or 18 years of age), a 
parent or legal representative should also sign and date the 
ICF and that additional local regulatory requirements may 
be applicable for participation of subjects below the age of 
consent. 
o Future Use of 
Samples 
o Added as new section based on current protocol template. 
o Prohibited 
Medications and 
Medications to be 
administered with 
Caution 
o Appendix B 
o Clarified that no antifungal treatment other than the study 
drug is allowed during the study except in subject subgroups 
where combination therapy is allowed or where an exception 
was granted by the Sponsor on a per-subject basis. 
o Clarified that no investigational drugs (i.e., new chemical 
entities) other than the study drug are allowed within at least 
30 days or five and a half half-lives of the investigational 
product before Screening and throughout the study. 
o Clarified that subjects exposed to prohibited medications 
may be allowed in the study when treatment options are 
limited, in discussion with the Sponsor based on a risk-
benefit analysis, and that additional ibrexafungerp PK and/or 
therapeutic drug monitoring may be needed in these cases. 
o Added fluconazole as a prohibited medication and clarified 
that fluconazole, itraconazole, posaconazole and 
voriconazole are prohibited except in subject subgroups 
where combination therapy is allowed or where an exception 
was granted by the Sponsor on a per-subject basis. 
o Updated windows for prohibited medications. 
o Updated medications to be taken with caution. 
o Removed CYPC8 Substrates as prohibited medications. 
o Added vinblastine and talinolol as prohibited P-gp 
substrates. 

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o Removed moderate CYP3A4 inhibitors and OATP1B3. 
substrates as medications to be administered with caution. 
o Clarified that the administration of either sirolimus or 
tacrolimus should be offset by no less than 2 hours with the 
administration of ibrexafungerp. 
o Clarified that at a minimum, blood levels of sirolimus and, 
tacrolimus or prothrombin time/partial thromboplastin 
time/international normalized ratio for subjects on warfarin 
should be measured after the first dose of ibrexafungerp 
and when the subject has received between 3 and 7 days of 
ibrexafungerp. 
o Added tacrolimus to the list of drugs for which dosing 
adjustments and subsequent monitoring should be 
undertaken in accordance with product prescribing 
information for the respective agents. 
o Appendix C 
o Updated the sample eligibility form and clarified that 
eligibility form provided is a sample form that may be 
modified as needed. 
o Appendix D 
o Added Vulvovaginal Signs and Symptoms (VSS) Scale. 
 
Protocol Amendment 2 
Minor, Administrative and/or General Changes 
o Global Changes 
o Changed “SCY-078” to “ibrexafungerp”. 
o Changed “Treatment Day” to “Day”. 
o Changed “Data Monitoring Committee” to “Data Review 
Committee”. 
o Changed “Week-6 FU” to “6-Week FU”. 
o Minor stylistic changes. 
o Cover Page, 
headers and 
footers 
o Updated protocol version details. 
o Contact 
Information  
o Protocol 
Approvals 
o Updated contact and protocol approval details. 
o Abbreviations 
o Updated list of abbreviations and abbreviations used in text. 
o References 
o Updated reference list. 
o Appendices 
o Moved Revision Histories to Appendix A. 

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Minor, Administrative and/or General Changes 
o Renumbered appendices accordingly. 
21.1.3 Protocol Amendment 1 
Current Version and Date: Protocol Amendment 1 (Protocol Version 2.0) dated 
23 Mar 2017 
 
Revisions to Protocol dated 30 Nov 2016 (original protocol) listed below: 
 
MAJOR CHANGES 
Main Affected 
Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
o Inclusion Criteria 
o Table of Eligible 
Fungal Diseases 
o Other sections as 
applicable 
Added clarification that subjects may be male or female and 
updated definition of eligible fungal diseases for clarity as 
follows: 
2. Subject has a documented eligible acute or chronic 
invasive candidiasis (including candidemia) and/or acute or 
chronic severe mucocutaneous candidiasis (excluding 
VVC) (as defined in Table 1) that is refractory to or 
intolerant of, or has toxicities associated with at least one 
approved Standard of Care (SoC) antifungal treatment. The 
subject is also eligible if, in the judgement of the 
investigator, long-term IV antifungal therapy is not feasible 
or desirable due to clinical or logistical circumstances or if 
other oral antifungal alternatives are not appropriate. 
Added requirements for alternative diagnostic criteria for 
invasive candidiasis, as follows: 
Or 
Alternative approved diagnostic method such as T2 or ß-D-
glucan (two consecutive positive test results) and at least 
one of the following: temperature ≥38°C or <36°C, systolic 
blood pressure  <90 mmHg or a decrease of >30 mmHg 
from normal baseline, local signs or symptoms or 
radiologic findings of invasive candidiasis 
Revised refractoriness criteria based on ß-D-glucan to clarify 
that elevated values (rather than persistently high values) equal 
to or increasing from baseline meet criteria for refractory 
invasive candidiasis including candidemia. 

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Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
 
Revised requirements for acceptable contraceptive methods 
and added definitions of male and female subjects who are not 
of reproductive potential, for clarity. Clarified women of 
childbearing potential must have a negative pregnancy test 
before enrollment. 
o Exclusion Criteria Added an exclusion criterion to clarify that subjects with 
invasive fungal disease of the bone and/or joint are excluded if 
they are expected to require treatment for more than 90 days. 
Added an exclusion criterion to clarify that subjects with 
vulvovaginal candidiasis are not eligible for the study except 
for subjects with chronic mucocutaneous candidiasis including 
vulvovaginal involvement. 
Deleted the exclusion criterion excluding subjects with a life 
expectancy < 3 days. 
Clarified that subjects with unconjugated hyperbilirubinemia 
with diagnosis of Gilbert’s disease are not excluded. 
Removed exclusion criterion that allowed neutropenic patients 
to participate in the study if they were expected to recover in 3-
5 days following initiation of G-CSF treatment. 
o Study Objectives 
o Other sections as 
applicable 
Efficacy objectives revised based on updated definitions of 
treatment outcomes (see Study Procedures, Efficacy 
Assessments). 
Efficacy exploratory objective simplified. 
Pharmacokinetic exploratory objective revised as follows: 
• To evaluate the pharmacokinetics (PK) of SCY-078 by 
population PK analysis 

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Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
o Study Endpoints  
o Other sections as 
applicable 
Efficacy endpoints revised based on updated definitions of 
treatment outcomes (see Study Procedures, Efficacy 
Assessments). 
Primary efficacy endpoint revised as follows: 
• Efficacy as measured by the percentage of subjects with 
global success (complete or partial global response) at EoT 
as determined by the DMC 
Efficacy endpoints revised to clarify that outcomes will be 
determined by the DMC. 
Primary safety endpoint added. 
Pharmacokinetic exploratory endpoint revised as follows: 
• SCY-078 plasma concentrations by population PK 
analysis 
o Study Procedures, 
Targeted Physical 
Examination, 
including Clinical 
Evaluation of 
Signs and 
Symptoms  
o Other sections as 
applicable 
Clinical evaluation of signs and symptoms included under 
targeted physical examination for convenience. 
Signs and symptoms of infection revised as follows: 
• General signs and symptoms: 
o Fever defined as oral temperature ≥38.3°C (≥101°F) on 
one occasion or >37.8°C (>100°F) on two measurements 
at least 4 hours apart 
o Clinically significant hypothermia <36°C (<96.8°F) 
o Hypotension (systolic blood pressure of <90 mmHg or a 
>30 mmHg decrease below normal baseline) 
o Tachycardia 
o Local signs and symptoms of inflammation 
• Disease-specific signs and symptoms: 
o OPC: White patches or plaques on the tongue and other 
oral mucous membranes; redness or soreness in the 
affected areas; difficulty swallowing; cracking at the 
corners of the mouth (angular cheilitis) 
o EC: White plaques and/or ulcers on the lining of the 
esophagus or narrowing of the lumen, pain when 
swallowing, difficulty swallowing; heartburn 
o CMC:  Extensive scaling, skin lesions, thickened nails 
• Other signs and symptoms of candidiasis 

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Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
o Study Procedures, 
Study-specific 
Testing, 
Mycological 
Testing 
o Other sections as 
applicable 
Clarified mycological testing procedures to be performed 
during the study for eligible fungal diseases, as follows: 
Blood cultures: […] Blood should be drawn peripherally 
[directly from a vein]; however, if this is not possible, blood 
may be drawn from a central IV catheter).  […] 
Non-blood cultures:  Follow-up cultures from subjects who 
have non-blood sites of Candida infection should be 
performed as clinically indicated. 
EC: Follow-up KOH or fungal stains and/or mycological 
cultures from biopsy or brushing indicating yeast infection 
will be performed as clinically indicated. 
OPC and CMC: Follow-up KOH or fungal stains and/or 
mycological cultures for Candida spp. obtained from the 
affected site will be performed as clinically indicated. 
 
Clarified that local identification and susceptibility testing may 
be done according to the local lab´s standards and that central 
testing will be done as per CLSI M27-A3 guidelines. 
o Study Procedures, 
Study-specific 
Testing, 
Radiological 
Testing and 
Esophagoscopy 
Study procedure identified as “Radiological Testing” changed 
to “Imaging” for clarity. 
Clarified that, for subjects whose diseases are assessed by 
imaging or esophagoscopy, imaging scans/esophagoscopies 
must be available at Screening and must be performed for End 
of Treatment. The remaining imaging scans/esophagoscopies 
may be done as clinically indicated. 

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MAJOR CHANGES 
Main Affected 
Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
o Study Procedures, 
Pharmacokinetic 
Assessments 
o Other sections as 
applicable 
PK sampling times and windows clarified, as follows: 
Up to three (3) blood samples will be collected at the 
following visits and sampling windows: Treatment Day 2 
(one sample collected anytime post dosing [optional]), 
Treatment Days 3 to 5 (one sample collected predose on any 
of these days), and Treatment Days 7 to 10 (one sample 
collected predose on any of these days) 
o Study Procedures, 
12-Lead 
Electrocardiogram 
o Other sections as 
applicable 
Visit 4 ECG assessment removed 
o Study Procedures, 
Efficacy 
Assessments 
o Other sections as 
applicable 
Updated definitions for the assessment of treatment outcomes 
for consolidation with other protocols in the SCY-078 
development program, as follows: 
Global outcome will be scored as global success (complete 
global response or partial global response) or global failure 
(stable disease or progressive disease) 
Global success: Global success is defined as a complete 
global response or a partial global response 
• Complete global response is defined as a complete 
clinical response (the resolution of all clinical signs and 
symptoms and/or radiological abnormalities from 
baseline attributable to Candida infection) and a 
mycological response (mycological clearance (direct 
and/or negative cultures [when obtainable] and/or 
normal serological results [when appropriate]) 
• Partial global response is defined as a partial clinical 
response (major improvement of all clinical signs and 
symptoms and/or radiological abnormalities from 
baseline attributable to Candida infection) and a 
mycological response (mycological clearance (direct 
and/or negative cultures [when obtainable] and/or 
normal serological results [when appropriate]) 
Global failure: Global failure is defined as either stable 
disease and/or progressive disease 

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Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
• Stable disease is defined as minor or no clinical 
improvement 
but 
without 
deterioration 
and/or 
unchanged serological response. 
• Progressive disease is defined as clinical deterioration 
necessitating alternative antifungal therapy or resulting 
in death, and/or worsened serological response, and/or 
persistence of fungal infection on the basis of culture, 
microscopic evaluation, or histopathological testing. 
Clinical success: clinical success is defined as a complete 
clinical response or a partial clinical response. 
Mycological success: mycological success is defined as a 
mycological response. 
Added definition of recurrence for completion and a summary 
list of the procedures that will be performed to assess treatment 
outcome. 
o Study Procedures, 
Subject 
Discontinuation 
Criteria 
Added pregnancy as a subject discontinuation criterion. 
o Dosing and Drug 
Accountability 
Procedures, Prior 
and Concomitant 
Medications & 
Prohibited 
Medications and 
Medications to be 
Administered 
with Caution 
o Appendix A 
Clarified that subjects will record all concomitant medications 
used in the subject diary.  
Clarified that all medications used from 28 days before 
enrollment through the EoT visit will be recorded and that only 
the use of antifungal medications, antibiotics for any reason or 
medications to treat an AE will be recorded after EoT and 
through the Week 6 Follow-up visit. 
Clarified that no antifungal medications other than the study 
drug are allowed during the study treatment. 
Revised requirements for the timing of sirolimus and 
tacrolimus administration. 
o Dosing and Drug 
Accountability 
Procedures, 
Dietary 
Requirements for 
Clarified that the study drug should be taken with 
approximately 8 oz/240 mL of water, preferably with food. For 
subjects on continuous feeding via an NG or PEG tube, the 
drug should be crushed and administered with approximately 8 
oz/240 mL of water and the tube should be flushed with 

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(Major changes shown as underlined font) 
Study Drug 
Administration 
o Other sections as 
applicable. 
approximately 8 oz/240 mL of water before and after drug 
administration. 
 
o Safety 
Assessments and 
Monitoring, 
Events of Clinical 
Interest 
Removed reporting timeframe requirement for and revised list 
of events of clinical interest for clarity, as follows: 
• QTc > 500 ms or a > 60 ms change from Baseline, 
confirmed by repeat testing 
• ALT or AST > 8 x ULN, if new compared to Baseline, 
confirmed by repeat testing 
ALT or AST > 5 x ULN for more than 2 weeks and if new 
compared to Baseline, confirmed by repeat testing 
• ALT or AST > 3 x ULN and either total bilirubin >2 x 
ULN or INR >1.5) and if new compared to Baseline, 
confirmed by repeat testing 
• ALT or AST > 3 x ULN, confirmed by repeat testing, with 
the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (> 5%) 
o Safety 
Assessments and 
Monitoring, 
Overdose 
Clarified that an overdose is any dose higher than the protocol-
specified dose and that overdoses should be reported within 24 
hours if associated with a serious adverse event and within 5 
working days otherwise.  
o Safety 
Assessment and 
Monitoring, AE 
Collection 
Timeframe 
o Other sections as 
applicable 
Clarified that AEs will be collected and evaluated from the time 
the informed consent is signed through the EoT and that, after 
the EoT and up to the last observation in the study (Week 6 
Follow-up), new AEs will be collected only if deemed related to 
the study drug, if they are SAEs, or if they are related to a fungal 
infection.   
o Safety 
Assessments and 
Monitoring, SAE 
Reporting 
Updated requirements and details for the reporting of serious 
adverse events. 

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MAJOR CHANGES 
Main Affected 
Protocol Sections 
Change and Rationale 
(Major changes shown as underlined font) 
o Analytical Plan, 
Sample Size 
Determination 
Updated the planned sample size to a total of 60 subjects.  
o Analytical Plan, 
Efficacy Analyses Revised confidence interval details to clarify that endpoints will 
be presented with 95% confidence intervals. 
o Ethics and 
Protection of 
Human Subjects, 
Declaration of 
Helsinki 
Revised language to include ICH GCP guidelines, US and EU 
regulations and other local requirements as applicable, in 
addition to the Declaration of Helsinki. 
o Appendix B, 
Enrollment Form 
Updated the Enrollment Form for the study. 
 
MINOR AND/OR GENERAL CHANGES 
o Abbreviations 
Updated list of abbreviations and abbreviations used in text. 
o Synopsis 
Updated based on major and minor/general changes listed in 
this Revision History 
Included only key inclusion and exclusion criteria for clarity 
and convenience. 
Revised storage conditions for SCY-078 tablets to clarify that 
tablets do not need to be protected from moisture. 
Additional revisions made (language added or removed) for 
consistency with the body of the protocol amendment. 
o Schematic of 
Study Design 
Clarified that the End of Treatment visit will occur following a 
maximum of 90 days of treatment with SCY-078 and that 
Survival visits will occur 42 and 84 days after 
Baseline/Treatment Day 1. 
o Background 
Information 
o Rationale for the 
Study 
Updated to reflect the latest, currently available data for SCY-
078. 
o Rationale for the 
Study 
o Study Design 
Updated to reflect major and minor/general changes listed in 
this Revision History. 

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MINOR AND/OR GENERAL CHANGES 
o Inclusion and 
Exclusion Criteria 
Reorganized inclusion and exclusion criteria from key, 
protocol-specific criteria to standard, general criteria, and 
renumbered criteria accordingly. 
o Study Procedures 
o Study Schedule 
Reorganized and updated description of study procedures for 
clarity and to ensure consistency with the Schedule of Visits 
and Procedures and vice versa. 
Added a ±2 day window to the every-14-day visit, the End of 
Treatment visit and the Week 6 Follow-up visit. 
o Ethics and 
Protection of 
Human Subjects, 
Financial 
Disclosure 
Clarified timing for collection of financial disclosure forms. 
o References 
Updated bibliographic cross references and citations. 
Miscellaneous 
Updated protocol date and version. 
The following changes were made for clarity and for internal 
consistency and consistency with other protocols in the 
SCY-078 development program 
• Changed “proportion” to “percentage” in Study Endpoints 
• Changed “microbiological” to “mycological” throughout 
• Changed “radiographic” to “radiological”  
• Changed “biochemistry” to “blood chemistry” for safety 
laboratory tests 
• Changed “patient(s)” to “subject(s)” 
• Changed “Data Review Committee (DRC)” to “Data 
Monitoring Committee (DMC)” 
• Changed “Week 6 (follow up)” to “Week 6 Follow-up” 
• Changed “Baseline” and “Treatment Day 1” to 
“Baseline/Treatment Day 1” 
Introduced minor typographical and grammatical edits and 
reworded language slightly as needed for clarity. 
 
 
 
 

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21.2 
Appendix B: Prohibited Medications and Medications to be 
Administered with Caution 
21.2.1 Prohibited Medications 
No antifungal treatment other than the study drug is allowed during the study except in 
subject subgroups where combination therapy is allowed or where an exception was 
granted by the Sponsor on a per-subject basis. 
No investigational drugs (i.e., new chemical entities) other than the study drug are allowed 
within at least 30 days or five and a half half-lives of the investigational product before 
Screening and throughout the study. 
Subjects exposed to prohibited medications may be allowed in the study when treatment 
options are limited, in discussion with the Sponsor based on a risk-benefit analysis. 
Additional ibrexafungerp PK and/or therapeutic drug monitoring may be needed in these 
cases. 
 
Strong CYP3A4/5 inhibitors and CYP3A4/5 inducers 
CYP 
Strong/Moderate Inhibitors 
Inducera 
3A4/5 
Reversible inhibitors:b 
• boceprevir 
• conivaptan 
• indinavir 
• ketoconazolec 
• lopinavir/ritonavir 
• mibefradil 
• fluconazolec 
 
• nefazodone 
• nelfinavir 
• telaprevir 
• telithromycin 
• itraconazolec 
• posaconazolec 
• voriconazolec 
• avasimibe 
• carbamazepine 
• phenytoin 
• rifampin 
• St. John’s wort 
Time-dependent inhibitors:a 
• clarithromycin 
• ritonavir 
• saquinavir 
a. 
The CYP3A4/5 inducers and strong time-dependent CYP3A4/5 inhibitors listed in this table are not permitted 
during the 14 days prior to enrollment and during study treatment. 
b. 
The reversible CYP3A4/5 inhibitors listed in this table are not permitted during 48 hours prior to the 
administration of ibrexafungerp (except for the antifungal drug administered for the eligible fungal disease), and 
during the study. 
c. 
No antifungal treatment other than the study drug is allowed during the study. Fluconazole, itraconazole, 
posaconazole and voriconazole are prohibited except in subject subgroups where combination therapy is allowed 
or where an exception was granted by the Sponsor on a per-subject basis. 

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P-glycoprotein (P-gp) substrates 
P-gp Drug Substratea 
digoxin, colchicine, vinblastine, talinolol 
a. 
The P-gp substrates listed in this table are not permitted during the administration of ibrexafungerp. 
 
21.2.2 Medications to be administered with Caution and Monitored as 
Appropriate 
CYP3A4 substrates 
CYP 
Substrates 
3A4 
In vitro, ibrexafungerp was an inhibitor of CYP3A mediated metabolism of midazolam, 
but was only a weak inhibitor of metabolism of testosterone. The clinical significance 
of this inhibition is unknown; caution should be exercised when administering 
ibrexafungerp with drugs known to be CYP3A sensitive substrates with narrow 
therapeutic index. 
Subjects receiving sirolimus, tacrolimus or warfarin are permitted for enrollment in the 
study and these medications may be administered concomitantly with ibrexafungerp 
with close monitoring. The administration of either sirolimus or tacrolimus should be 
offset by no less than 2 hours with the administration of ibrexafungerp. At a minimum, 
blood levels of sirolimus and tacrolimus or prothrombin time/partial thromboplastin 
time/international normalized ratio for subjects on warfarin should be measured after the 
first dose of ibrexafungerp and when the subject has received between 3 and 7 days of 
ibrexafungerp (at which time, ibrexafungerp concentrations will have reached steady 
state). Dosing adjustments and subsequent monitoring of sirolimus, tacrolimus and 
warfarin should be undertaken in accordance with product prescribing information for 
the respective agents.  
 
Sources: 
• 
FDA Draft Guidance for Industry. Drug Interaction Studies – Study Design, Data Analysis, 
and Implications for Dosing and Labeling. 2012. 
• 
Drug interactions in infectious disease by Stephen C. Piscitelli, Keith Rodvold (2007). 
• UCSF-FDA Transportal. 
 

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21.3 
Appendix C: Sample Eligibility Form 
 
Note: The eligibility form shown below is a sample form. This form may be modified as 
needed for specific fungal diseases and per local regulations. 
 
 
 
 
 

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21.4 
Appendix D: Vulvovaginal Signs and Symptoms Scale 
 
SIGNS: 
To be rated by the Investigator during the vulvovaginal examination 
Sign 
Absent 
0 
Mild 
1 
Moderate 
2 
Severe 
3 
Edema 
 
 
 
 
Erythema  
 
 
 
 
Excoriation 
or 
fissures 
 
 
 
 
Definitions: 
Absent: none 
Mild: slight 
Moderate: definitely noticeable 
Severe: marked, intense 
 
SYMPTOMS: 
To be rated by the subject  
Symptom 
Absent 
0 
Mild 
1 
Moderate 
2 
Severe 
3 
Burning 
 
 
 
 
Itching 
 
 
 
 
Irritation 
 
 
 
 
 
Definitions: 
Absent: I have no discomfort (i.e., burning, itching, irritation) 
Mild: I have some discomfort (i.e., burning, itching, irritation), but it does not bother me 
much 
Moderate: I have discomfort (i.e., burning, itching, irritation), which is annoying, but not 
enough to affect what I am doing 
Severe: I have discomfort (i.e., burning, itching, irritation), which is annoying enough to 
affect what I am doing