An Open-Label Study to Evaluate the Efficacy and Safety of APX001 in Patients With Candidemia and/or Invasive Candidiasis Caused by Candida Auris
Phase: PHASE2
Conditions: Candidemia, Invasive Candidiases, Candida Infection
Sponsor: Basilea Pharmaceutica

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Amplyx Pharmaceuticals, Inc 
 
Clinical Study Protocol APX001-203 
 
Page 3 of 79 
Confidential & Proprietary 
Version 4.0, 08 April 2020 
INVESTIGATOR AGREEMENT 
 
By signing below, I agree that: 
 
I have read this protocol. I approve this document and I agree that it contains all necessary details 
for carrying out the study as described. I will conduct this study in accordance with the design and 
specific provision of this protocol and will make a reasonable effort to complete the study within 
the time designated. I will provide copies of this protocol and access to all information furnished 
by Amplyx Pharmaceuticals, Inc. to study personnel under my supervision. I will discuss this 
material with them to ensure they are fully informed about the study product and study procedures. 
I will let them know that this information is confidential and proprietary to 
Amplyx Pharmaceuticals, Inc. and that it may not be further disclosed to third parties. I understand 
that the study may be terminated or enrollment suspended at any time by Amplyx Pharmaceuticals, 
Inc., with or without cause, or by me if it becomes necessary to protect the best interests of the 
study patients. 
 
I agree to conduct this study in full accordance with Food and Drug Administration Regulations, 
Institutional Review Board/Ethic Committee Regulations and International Council for 
Harmonisation Guidelines for Good Clinical Practices. 
 
 
 
 
 
 
 
 
Investigator’s Signature 
Date 
 
 
 
 
Investigator’s Printed Name 
 

 
Amplyx Pharmaceuticals, Inc 
 
Clinical Study Protocol APX001-203 
 
Page 4 of 79 
Confidential & Proprietary 
Version 4.0, 08 April 2020 
SYNOPSIS 
TITLE: An Open-Label Study to Evaluate the Efficacy and Safety of APX001 in Patients with 
Candidemia and/or Invasive Candidiasis Caused by Candida auris 
PROTOCOL NUMBER: APX001-203 
INVESTIGATIONAL PRODUCT: APX001 
PHASE: 2 
INDICATION: Treatment of patients with candidemia and/or invasive candidiasis caused by 
Candida auris  
OBJECTIVES: 
The primary objective of this study is to evaluate the efficacy and safety of APX001 for the 
treatment of adult patients aged 18 years and above, with candidemia and/or invasive candidiasis 
caused by Candida auris, who have limited antifungal treatment options.  
The secondary objectives of this study are to: 
 Evaluate the time to first negative blood culture 
 Evaluate the percentage of patients with successful Mycological Outcomes at End of Study 
Drug Treatment (EOST), and 2 and 4 weeks after EOST 
 Evaluate the percentage of patients with Treatment Success 2 and 4 weeks after EOST 
 Evaluate all-cause mortality at Study Day 30 
 Evaluate safety parameters, including number of patients with treatment-emergent adverse 
events (TEAEs) 
 Evaluate pharmacokinetic (PK) parameters of APX001 
BACKGROUND: 
Disseminated infections associated with Candida species (spp.) are a significant cause of 
morbidity and mortality. Candida auris is an emerging fungal pathogen which has caused invasive 
infections and hospital outbreaks on several continents. Since C. auris was first described in Japan 
in 2009, additional cases have been reported in South Korea, India, Kuwait, Kenya, South Africa 
and 
more 
recently 
in 
Colombia, 
Venezuela, 
Panama, 
Pakistan, 
the United Kingdom and the United States1-14. A whole genome sequencing study documented 
recent, near-simultaneous and independent emergence of C. auris clones on three different 
continents (Africa, Asia and South America), rather than spread of a single “clone” across the 
globe15.  
 
 

 
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Clinical Study Protocol APX001-203 
 
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Invasive C. auris infections are associated with high mortality and are difficult to identify using 
traditional yeast identification methods16. The fungus persists on patients’ skin and in the 
healthcare environment, allowing for transmission to occur between patients in healthcare 
facilities, and may be difficult to eliminate from the hospital environment16. 
C. auris is often multi-drug resistant. The majority of tested C. auris isolates are resistant to 
fluconazole, an important first-line antifungal agent1-6, 15. Furthermore, more than 40% of tested 
C. auris isolates from a recent global study were resistant to two or more major classes of 
antifungals16. 
APX001, a first-in-class small molecule drug candidate, is the water soluble phosphate prodrug of 
APX001A. APX001 is rapidly metabolized by circulating phosphatases in vivo to APX001A. 
APX001A has a novel mechanism of action targeting the conserved fungal enzyme 
glycosylphosphatidylinositol (GPI)-anchored wall transfer protein 1 (GWT1), which is required 
for the expression of GPI-anchored proteins on the fungal cell wall. Inhibition of GWT1 by 
APX001A compromises cell wall integrity, inhibits biofilm formation, blocks filamentation, 
enhances immunogenicity of unmasked β-glucan, and produces severe fungal growth defects. The 
closest mammalian ortholog of GWT1 is PIG-W, which has no demonstrable inhibition by 
APX001A. 
APX001A has broad in vitro activity against major fungal pathogens, including Candida, 
Cryptococcus, Aspergillus, Scedosporium, Fusarium, and members of the Mucorales order17-21. 
The susceptibility of Candida auris to APX001A has been tested in over 100 diverse isolates 
including strains resistant to fluconazole, the echinocandins, and/or amphotericin B22. In these 
tests, APX001A is the most mycologically active agent against C. auris with markedly lower MIC 
values than the other antifungals tested. The MIC50 and MIC90 for APX001A were 0.002 mg/L 
and 0.008 mg/L, respectively. In addition, APX001A was active against all four C. auris clades22. 
APX001 was evaluated in a disseminated C. auris infection model in immunocompromised 
mice23. Anidulafungin, an echinocandin, was chosen as a comparator for this model. The mice 
were sacrificed at 48 hours post-inoculation for determination of the lung, kidney, and brain fungal 
burdens after intraperitoneal dosing of APX001 (78 mg/kg BID, 78 mg/kg TID, 104 mg/kg BID) 
and anidulafungin (10 mg/kg BID) versus the vehicle control. Treatment with APX001 resulted 
in significantly better survival than anidulafungin. Both APX001 and anidulafungin demonstrated 
significant and equivalent decreases in kidney and lung colony forming units (CFU) at 48 hours; 
however, only APX001 demonstrated a reduction in brain fungal burden.  
In three completed Phase 1 clinical studies of APX001, the safety, tolerability, and PK of single 
ascending doses and multiple ascending doses administered intravenously (IV) and orally (PO) to 
healthy volunteers were studied. A total of 178 healthy volunteers were enrolled in the 
placebo-controlled Phase 1 studies of APX001. All APX001 doses studied in Phase 1 were 
considered well tolerated. No serious adverse events (SAEs) were reported, and most of the 
treatment-emergent adverse events (TEAEs) were mild, transitory, and required no intervention. 
No dose-limiting toxicities (DLTs) were observed and no TEAEs or safety laboratory test results 
met any of the a priori rules that prevented dose escalation to the next protocol-specified cohort. 
The maximum tolerated dose was not determined/reached in these Phase 1 studies. 
Pharmacokinetic parameters for maximum serum concentration and AUC in both single and 

 
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multiple APX001 IV and PO doses were linear and dose proportional. In both in vitro studies of 
APX001 and in a cohort embedded within the PO dose Phase 1 study, APX001 demonstrated a 
favorable drug-drug interaction profile. APX001A was shown to be a weak inducer of cytochrome 
P450 (CYP) 2B6; a moderate inducer of CYP1A2, CYP2C19, and CYP3A4; and a weak inhibitor 
of CYP2C9 and CYP2D6. The relative bioavailability of the PO formulation was 90% in healthy 
subjects. There was no evidence of an effect on the bioavailability of APX001 in the presence of 
food (high fat and high calorie). Most importantly, the target AUCs anticipated for efficacy against 
both yeast and molds have been achieved with both IV and PO dose formulations tested in Phase 1. 
In summary, APX001 is a promising new antifungal agent with a novel mechanism of action 
having broad spectrum activity against Candida spp., including Candida auris. Because APX001 
is a first-in-class drug candidate with a novel mechanism of action, no cross-resistance with other 
classes of antifungal drugs has been observed or is expected. 
POPULATION: 
This study will enroll male and female patients aged 18 years and above with an established 
diagnosis of candidemia and/or invasive candidiasis caused by Candida auris from a sample taken 
<120 hours (for patients with candidemia) or <168 hours (for patients with invasive candidiasis 
without candidemia) of inclusion in the study.  Patients will have limited or no treatment options 
due to resistance, contraindication, intolerance or lack of clinical response to standard of care 
antifungal therapy, as advocated by the relevant regional/country treatment guidelines (e.g. South 
Africa: The Federation of Infectious Diseases Societies of Southern Africa (FIDSSA), 2019 in 
press; CDC: Recommendations for treatment of Candida auris infections). Candida auris must be 
confirmed in culture from blood or other tissue, aspirate or fluid sampled from a normally sterile 
site, and all eligibility criteria must be met prior to qualification for the study and subsequent 
dosing. 
Inclusion Criteria 
Patients must meet all of the following criteria to be eligible for study entry: 
1. Male or female aged 18 years and above 
2. Limited or no treatment options due to resistance, contraindication, intolerance or lack of 
clinical response to standard of care antifungal therapy, as advocated by the relevant 
regional/country treatment guidelines   
3. Established mycological and clinical diagnosis of candidemia and/or invasive candidiasis from 
a sample taken <120 hours (for candidemia) or <168 hours (for invasive candidiasis without 
candidemia) before study qualification:  
a. Candidemia criteria 
i. ≥1 blood culture positive for yeast/Candida spp. identified as C. auris;   
plus: 
 

 
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Clinical Study Protocol APX001-203 
 
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ii. Clinical signs attributable to candidemia within the 120 hours prior to 
qualification for the study, to include at least one of the following: (a) fever 
(>38oC), or (b) hypothermia (<36oC), or (c) hypotension (SBP <90mmHg or 
decrease of >30mmHg); 
b. Invasive candidiasis criteria 
i. >1 specimen (e.g., tissue, aspirate/fluid) sampled aseptically from a normally 
sterile site culture positive for yeast/Candida spp. identified as C. auris; 
plus: 
ii. Clinical signs attributable to invasive candidiasis within the 168 hours prior to 
qualification for the study, to include at least one of the following: (a) fever 
(>38oC), or (b) hypothermia (<36oC), or (c) hypotension (SBP <90mmHg or 
decrease of >30mmHg), or (d) signs associated with organ/site infected with 
Candida (e.g. eye, intra-abdominal). 
4. Patients with single C. auris infection, or mixed Candida auris plus other Candida spp. (other 
than C. krusei) infection, are eligible for the study.  
5. Able to have pre-existing intravascular catheters removed and replaced (if necessary). 
6. Females of childbearing potential with male partners, and males with female partner(s) of 
childbearing potential, must agree to use 2 forms of highly effective contraception, 1 of which 
must be a barrier method, throughout the duration of the study and for 90 days following the 
last study drug administration. Acceptable barrier forms of contraception are condom and 
diaphragm. Acceptable non-barrier forms of contraception for this study are oral 
contraceptives (e.g. oral birth control pill, depot, patch, or injectable), abstinence, intrauterine 
device, and/or spermicide. 
Post-menopausal is defined as amenorrhea for >12 months without an alternative medical 
cause or documented surgical sterilization (e.g. bilateral salpingectomy, bilateral 
oophorectomy, or hysterectomy). 
True abstinence, when in line with the preferred and usual lifestyle of the patient, is considered 
a highly effective method only if defined as refraining from heterosexual intercourse during 
the 
entire 
period 
of 
risk 
associated 
with 
the 
study 
drug 
treatment. 
(Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods] and 
withdrawal are not acceptable methods of contraception) 
7. Females of childbearing potential must have a negative urine pregnancy test within 96 hours 
prior to Baseline (i.e. pre-dose on Study Day 1) 
8. Willing to participate in the study, willing to give written informed consent, and willing to 
comply with the study restrictions; where permitted by local regulations, written informed 
consent from a legal authorized representative (LAR) will be obtained for patients who are 
unable to give consent. 
9. Male patients must agree to abstain from sperm donation and use condoms with spermicide 
during sexual intercourse between Screening and at least 90 days after administration of the 
last dose of study drug.  Male patients must ensure non-pregnant female partner(s) of 

 
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Clinical Study Protocol APX001-203 
 
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childbearing potential comply with the contraception requirements in Inclusion Criterion 6 
(above).  
Exclusion Criteria 
Patients who meet any of the following criteria will not be eligible for the study: 
1. Blood culture, or any other culture, positive for C. krusei 
2. Life expectancy of 7 days in the opinion of the Investigator 
3. Severe or moderate hepatic impairment (Child-Pugh Score 6 points) at any time during 
2 weeks prior to dosing.  The Child-Pugh score of >6 is applicable to patients with hepatic 
dysfunction and cirrhosis only. 
4. Baseline neurological conditions such as abnormal movements or convulsive disorders 
5. Human immunodeficiency virus-infected patients who are receiving antiretroviral therapy that 
are moderate to strong inducers of CYP3A4, or who have detectable viremia, or who have had 
an active opportunistic infection within 6 months prior to Screening 
6. Alanine aminotransferase or aspartate aminotransferase 5  upper limit of normal (ULN) 
7. Total bilirubin 3  ULN, unless isolated hyperbilirubinemia or due to documented Gilbert’s 
disease. 
8. Female patient is pregnant or lactating 
9. Inappropriate fungal infection source control (e.g. persistent indwelling catheters or 
intravascular devices) 
10. Investigational drug administered within 30 days prior to dosing or five half-lives whichever 
is longer 
11. Concomitant use of medication that is a strong inducer of CYP enzymes (e.g. rifampin, 
carbamazepine, phenytoin, rifabutin, efavirenz, nevirapine, phenobarbital, modafinil, 
nafcillin, St. John's Wort, and enzalutamide) 
12. Any other condition or laboratory abnormality that, in the opinion of the Investigator, would 
put the patient at unacceptable risk for participation in the study or may interfere with the 
assessments included in the study 
13. Diagnosis of deep-seated Candida-related infections causing hardware associated septic 
arthritis, osteomyelitis, endocarditis, myocarditis, hepatosplenic candidiasis, or a central 
nervous system infection or site of infection that would require antifungal therapy to exceed 
the maximal duration of study drug treatment (i.e. 6 weeks [42 days]). 

 
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Clinical Study Protocol APX001-203 
 
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Dosing Criteria 
Patients must meet the following criteria to begin dosing: 
Confirmed diagnosis of candidemia and/or invasive candidiasis caused by C. auris 
(in a single or mixed Candida spp. infection) within <120 hours (for candidemia) or 
<168 hours (for invasive candidiasis without candidemia) of the indicative positive blood 
culture or indicative positive culture from a specimen sampled from a normally sterile site, 
plus confirmation that all other eligibility criteria are met, qualify the patient for dosing with 
APX001. The initiation of the first dose of APX001 must occur within 12 hours of 
qualification for the study. 
STUDY DESIGN AND DURATION: 
This is a multicenter, open-label, non-comparative, single-arm study to evaluate the efficacy and 
safety of APX001 for the treatment of candidemia and/or invasive candidiasis caused by C. auris 
in patients aged 18 years and over with limited antifungal treatment options. The Study Drug 
Treatment Period will be up to a maximum of 42 days (inclusive of the loading dose 
[Study Day 1]). There will be a Follow-up Period of 4 weeks (+4 days) after EOST. The total 
duration of participation in the study is up to approximately 10.5 weeks (inclusive of the Screening 
Period [168 hours prior to Baseline]). Patients must have had C. auris confirmed in culture 
<120  hours (for candidemia) or <168 hours (for invasive candidiasis without candidemia) prior 
to qualification and dosing in the study. 
  
Screening and Baseline procedures will be performed within no more than 120 hours 
(for candidemia) or 168 hours (for invasive candidiasis without candidemia) from the time that 
the SOC blood and/or tissue sample or aspirate/fluid positive for C. auris was collected, and any 
outstanding baseline procedures completed before the first dose of study medication.  
All patients (or the patient’s LAR) will sign an ICF before any protocol specified procedures that 
are not indicated by SOC may be conducted. Inclusion/exclusion criteria assessments, 
medical history, demographics, and Acute Physiology and Chronic Health Evaluation II score will 
be collected before dosing.  When an LAR is used for the initial consent, the patient will be 
consented during the study as soon as he/she is able to do so. 
On Study Day 1 (or over the first 24 hours if dosing starts in the evening), a 1000 mg APX001 
loading dose will be administered over 3 hours by IV infusion twice daily (BID). On Study Days 
2 and 3, a 600 mg APX001 maintenance dose will be administered over 3 hours by IV infusion 
once daily (QD).  On Study Day 4 and onward, the APX001 maintenance dose will be 
administered as either 600 mg APX001 IV infusion QD over 3 hours or 800 mg PO QD. Patients 
who have completed a minimum of 3 days of IV APX001, are clinically stable as determined by 
the Investigator, and are able to swallow tablets, may switch from IV to PO dosing on Study Day 4 
and onward. Study drug will be administered for 14 days after clearance of Candida organisms 
from the bloodstream (two consecutive negative blood cultures), and in accordance with clinical 
judgment as applicable for other infected sites, up a maximum of 42 days. 
 

 
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Patients will be monitored by daily blood culture from signing informed consent, through dosing, 
during Study Drug Treatment until 2 consecutive blood cultures are negative for Candida spp., 
at EOST, and at 2 and 4 weeks after EOST, or Early Termination. For patients diagnosed with 
invasive candidiasis, relevant cultures, histopathology, and imaging tests to assess the site(s), 
extent, progress, and outcome of the Candida infection will be conducted as clinically indicated. 
All results should be recorded in the electronic Case Report Form. The management of 
intravascular catheters, intravascular devices, and, if applicable, any drains will be recorded, 
including any associated microbiology results. 
Patients will be monitored for safety throughout the duration of the study. Safety assessments will 
include vital signs, clinical laboratory assessments (serum chemistry, hematology, coagulation, 
and urinalysis), physical examinations, neurological assessments (twice weekly on treatment), 
prior and concomitant medication reporting, and adverse event reporting. A 12-lead 
electrocardiogram (ECG) will be performed at Baseline (pre-dose), EOST, and 4 weeks after 
EOST, or Early Termination. A dilated fundoscopic examination will be performed at least once 
during the baseline period, which exclusively for this assessment may be up to Day 3 of the study. 
Follow-up fundoscopic examinations are required at EOST, and 4 weeks after EOST, or Early 
Termination for those patients who had positive findings up to Day 3 (or more if clinically 
indicated). A urine pregnancy test (for females of childbearing potential only) will be performed 
at Screening and Baseline (pre-dose), every 30 days during treatment if required by local 
regulations, at EOST, and 2 and 4 weeks after EOST, or Early Termination. 
In the event of an inadequate response/failure on APX001 study treatment, the study drug may be 
discontinued and alternative antifungal treatment instituted.   
Plasma samples for PK (APX001 [prodrug] and APX001A [active moiety]) will be collected at 
Baseline (pre-dose), twice weekly during Study Drug Treatment, and at EOST, 2 weeks after 
EOST, or Early Termination. Plasma samples for PK will be collected at the same time as samples 
are collected for the study’s clinical laboratory assessments. Serum samples for 
(1,3)-β-D-glucan levels will be collected at Baseline (pre-dose) and EOST, or Early Termination 
(if applicable). 
Optionally, if body fluids are sampled as part of routine patient management 
(e.g. bronchoalveolar lavage, lumbar puncture, paracentesis, vitreous fluid collection, abscess 
drainage) within approximately 2 hours of blood sampling for PK, these samples may be stored 
for future analysis of APX001 and APX001A levels. 
The evaluation of treatment outcome will be assessed at EOST, and 2 and 4 weeks after EOST, or 
Early Termination. 
The end of study will occur after the last visit of the last patient on the study. 
A schematic representing the study’s design is included on the following page. 

 
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Clinical Study Protocol APX001-203 
 
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DOSAGE FORMS AND ROUTE OF ADMINISTRATION: 
On Study Day 1 (or over the first 24 hours if dosing starts in the evening), a 1000 mg APX001 
loading dose will be administered over 3 hours by IV infusion BID.  
On Study Days 2 and 3, a 600 mg APX001 maintenance dose will be administered over 3 hours 
by IV infusion QD. 
The infusion volume for both the 1000 mg and the 600 mg APX001 doses will be 250 mL. 
On Study Day 4 and onward, an APX001 maintenance dose will be administered as either: 
• 600 mg APX001 IV infusion QD over 3 hours, or  
• 800 mg PO QD 
CRITERIA FOR SWITCHING FROM INTRAVENOUS TO ORAL DOSE: 
Patients who have completed a minimum of 3 days of APX001 IV administration may be eligible 
for PO switch on Study Day 4 and onward. Patients must meet all of the following criteria to 
switch from IV to PO dosing of APX001: 
• Is clinically stable, as determined by the Investigator 
• Is able to swallow tablets 
RATIONALE FOR DOSE AND SCHEDULE SELECTION: 
Dose 
In pharmacokinetic/pharmacodynamic (PK-PD) studies, immunocompromised mice were 
infected with one of three spp. of Candida (C. albicans, C. glabrata, or C. auris) and groups of 
animals were dosed with APX001 at different dose fractionations. The AUC/MIC ratio was 
determined to be the PK-PD variable that best correlated with antifungal efficacy as assessed by 
fungal burden (CFUs) in the kidney. The probability of target attainment (PTA) was calculated 
separately for each Candida spp. tested. The PTA calculation used the APX001A free drug AUC 
level at the stasis endpoint divided by the MIC required to inhibit the growth of 90% of organisms 
(MIC90) of each of the Candida spp. tested. 
The AUC level was estimated from a population PK model derived primarily from the Phase 1 
PK data. The stasis endpoint was defined as the quantity of Candida spp. in CFUs just prior to 
APX001 administration compared to CFUs at the endpoint of assessment (i.e. 24 hours for 
C. albicans; 96 hours for C. glabrata and C. auris). The MIC data for the Candida strains tested 
were obtained from recent surveillance data. 
Using the AUC at the stasis endpoint, along with the MIC90 from the surveillance data and the 
predicted exposure at the dose regimen to be used in this study, the PTA for the 3 Candida spp. 
tested was shown to be approximately 100%. Further, sensitivity analyses were conducted to 
evaluate the PTA under different scenarios including increased variability of PK parameters and 
higher Candida spp. MIC90 values. For both scenarios the PTA remained >90%.  
 

 
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In two Phase 1 studies in healthy volunteers, APX001 IV and PO formulations were safe and well 
tolerated. The majority of TEAEs were mild, transitory, and resolved without intervention. 
No  DLTs were observed. Specifically, in the first-in-human Phase 1 clinical study, a loading dose 
regimen of APX001 1000 mg IV 2-hour infusion BID on Day 1, followed by a maintenance dose 
of APX001 600 mg IV 1-hour infusion QD on Days 2 through 7, was safe and well tolerated. In 
an additional Phase 1 study of APX001, a dose regimen consisting of a loading dose of APX001 
1000 mg IV 3-hour infusion BID on Day 1, followed by a maintenance dose of APX001 600 mg 
IV 3-hour infusion QD on Days 2 through 7, and then APX001 800 mg orally QD on Days 8 
through 42 was also safe and well tolerated. 
Schedule 
To ensure the safety and tolerability of APX001 dosing for 42 days, this study will use an APX001 
dose and infusion duration already studied in Phase 1 for 42 days of therapy inclusive of IV and 
PO investigational drug therapy. The loading dose regimen of APX001 1000 mg IV BID over a 
3-hour infusion followed by APX001 600 mg IV QD over a 3-hour infusion has been designed to 
optimize patient safety and tolerability during the study. At Study Day 4 and onward, provided 
the protocol-defined criteria for a PO switch are met, the patient may be switched to oral APX001 
800 mg QD. Study drug will be administered for 14 days after clearance of Candida organisms 
from the bloodstream, and in accordance with clinical judgment as applicable for other infected 
sites, up to a maximum of 42 total days combined IV and PO APX001 therapy.  
 
EFFICACY ENDPOINTS:  
The primary efficacy parameter is percentage of patients with Treatment Success at EOST as 
determined by the Data Review Committee (DRC). 
The secondary efficacy parameters include the following: 
• Time to first negative blood culture 
• Percentage of patients with successful Mycological Outcomes at EOST, and at 2 and 4 weeks 
after EOST 
• Percentage of patients with Treatment Success at EOST as determined by the investigator 
• Percentage of patients with Treatment Success 2 and 4 weeks after EOST, as determined by 
the investigator and the DRC 
• All-cause mortality at Study Day 30 
• Number of patients with TEAEs 
The exploratory efficacy parameters include the following: 
• Change in serum (1,3)-β-D-glucan levels from Baseline (pre-dose) to EOST 
 
 

 
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EFFICACY ASSESSMENTS: 
At End of Study Drug Treatment (EOST): 
Treatment Success is defined as meeting all of the following criteria: 
• Two consecutive blood cultures negative for Candida spp., and/or for patients with a 
deep-seated site of infection, at least one negative tissue culture or aspirate/fluid culture 
o For patients with a deep-seated site of infection involving visceral organs from which 
a tissue culture is not obtainable, resolution of the attributable clinical signs of infection 
recorded at Baseline, and, as applicable, radiological improvement associated with the 
site of infection is required 
• Alive at EOST 
• No concomitant use of any other systemic antifungal therapies through EOST  
Note: administration of another systemic antifungal immediately following EOST for suspected or documented 
Candida infection at any site does not constitute a treatment success at EOST 
Treatment Failure is defined as any case that does not meet the criteria for Treatment Success. 
Successful Mycological Outcomes: 
• Eradication is defined as a negative blood (and/or other infection site) culture(s) for 
Candida spp. in the absence of concomitant antifungal therapy through EOST 
• Presumed Eradication (applicable to invasive candidiasis) is defined as clinical resolution of 
invasive Candida spp. infection where tissue samples are unavailable (supported by evidence 
of resolution/improvement in the diagnostic parameters used at Baseline) 
Both of the above definitions are in the absence of concomitant or additional systemic antifungal 
therapy. 
At Follow-up (2 Weeks and 4 Weeks After End of Study Drug Treatment [EOST]): 
• Treatment Success (sustained) is defined as having met the criteria for Treatment Success at 
EOST with no change during the follow-up period 
• Relapse is defined as re-occurrence of Candida in blood culture, or from other infection sites 
during the Follow-up Period, or diagnostic parameters indicative of recurrence or late spread 
of the Candida infection 
• Other: 
o Death 
o Unavailable for follow-up, or unevaluable at follow up for other reasons 
Additional DRC assessment categories are provided in the DRC Charter 
Mycological Recurrence is defined as mycologically confirmed infection based on blood culture 
(or other specimen(s) cultured from a normally sterile site), with the same Baseline Candida spp. 
during the 4 weeks after EOST. 

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SAFETY VARIABLES: 
Safety parameters include the following: 
•
Evaluation of adverse events at Screening, Baseline, during Study Drug Treatment, at EOST,
and 2 and 4 weeks after EOST, or Early Termination
Infusion site reactions should be graded according to the current version of the Common 
Terminology Criteria for Adverse Events
•
Vital signs (temperature, blood pressure, heart rate, respiratory rate, oxygen saturation, 
and weight) collected at Screening, Baseline (pre-dose), daily on Study Days 1 through 4 and 
twice weekly thereafter during Study Drug Treatment for outpatients (daily while inpatient), 
at EOST, and 2 and 4 weeks after EOST, or Early Termination. Height will be collected (from 
the patient’s medical record) at Baseline
•
Clinical laboratory assessments (serum chemistry, hematology, coagulation, and urinalysis) 
will occur at Screening, Baseline (pre-dose), twice weekly during Study Drug Treatment, 
at EOST, and 2 and 4 weeks after EOST, or Early Termination. If clinically indicated and at 
the discretion of the Investigator, or if a suspected adverse event is identified, clinical 
laboratory assessments may be conducted at any time during the study and compared to 
Baseline.
•
Physical examination, including a neurological assessment at Baseline (pre-dose), 
during Study Drug Treatment (neurological assessments twice weekly), at EOST, and 2 and 
4 weeks after EOST, or Early Termination
•
ECGs at Baseline (pre-dose), EOST, and 4 weeks after EOST, or Early Termination
WITHDRAWAL CRITERIA: 
Study drug dosing may be discontinued for any of the following reasons: 
•
The patient withdraws consent or requests discontinuation from the study for any reason
•
Occurrence of any medical condition or circumstance that exposes the patient to substantial 
risk and/or does not allow the patient to adhere to the requirements of the protocol
•
Occurrence of significant drug-induced liver injury (DILI) [Appendix D]
•
Any SAE, clinically significant adverse event, severe laboratory, intercurrent illness, or other 
medical condition that indicates to the Investigator that continued participation is not in the 
best interest of the patient
•
Pregnancy
•
Requirement of prohibited concomitant medication
•
Patient failure to comply with protocol requirements or study-related procedures
•
Termination of the study by the Sponsor or a regulatory authority

 
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Patients who discontinue study drug due to withdrawal of consent, death, or loss to follow-up will 
discontinue study participation. Patients who fail on study treatment and start alternative 
antifungals will be assessed for safety 4 weeks after stopping study medication.  Patients who 
discontinue study drug for other reasons will enter the follow-up phase of the study. 
The study may be discontinued for any of the following reason: five or more subjects in study 
(cumulative) experience a same grade 2 (or higher) related AE (laboratory or systemic) which is coded 
in the same high-level group term per MedDRA coding, throughout the duration of study; 
a recommendation from the DSMB based on other safety signals; lack of Investigational Product 
availability; inability to enroll the study; or decision by a regulatory authority or the sponsor. 
INDEPENDENT DATA REVIEW COMMITTEE: 
To ensure standardization of interpretation regarding the validity of study patients, the medical 
management, and response to treatment in this open-label study, a panel of recognized experts in 
the field of fungal infectious diseases will constitute a DRC. The DRC serves to provide 
independent oversight to confirm eligibility for efficacy analysis, to confirm the diagnosis of 
C. auris candidemia and/or invasive candidiasis at study entry, and to adjudicate efficacy outcome. 
The DRC assessments for each patient will be recorded in the database and used in the primary 
efficacy analysis of the study. The DRC members will not be Principal Investigators in the study. 
Guidelines for the DRC are described in the DRC Charter. 
DATA AND SAFETY MONITORING BOARD: 
A Data and Safety Monitoring Board (DSMB) comprised of members with pertinent expertise 
will review the accumulating data from the study periodically as set forth in the DSMB Charter, 
or more frequently at the request of the DSMB. The DSMB will advise the Sponsor on the 
continuing safety of the study patients and those yet to be recruited to the study, as well as the 
continuing validity and scientific merit of the study. At any time, the independent DSMB may 
temporarily suspend enrollment until any significant safety concerns are resolved or terminate the 
study to ensure patient safety, if in the opinion of the DSMB, further dosing would pose an 
inappropriate safety risk. Guidelines for what constitutes inappropriate safety risks are described 
in the DSMB Charter. 
ANALYSIS POPULATIONS: 
Intent-to-Treat Population/Safety Population 
The Intent-to-Treat Population/Safety Population will include all patients who have received at 
least 1 dose of APX001.  
Modified Intent-to-Treat Population 
The Modified Intent-to-Treat (MITT) Population will include all patients who satisfy the 
following criteria: 
• Received at least 1 dose of study drug 

 
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• Have a confirmed diagnosis of candidemia and/or invasive candidiasis caused by C. auris 
within 120 hours (for candidemia) or 168 hours (for invasive candidiasis without candidemia) 
of study qualification 
Per-Protocol Population 
The Per-Protocol Population will include all patients in the MITT Population who satisfy the 
following criteria: 
• Meet the protocol’s key inclusion and exclusion criteria 
• Receive at least 80% of the intended doses 
• Have no major protocol violations 
Pharmacokinetic (PK) Population 
The PK Population will include all patients who receive any amount of study drug and have 
evaluable PK data. 
 
STATISTICAL ANALYSES: 
Efficacy Analyses 
The primary population for efficacy analysis will be the MITT Population. 
The efficacy endpoints will be summarized descriptively. The percentage of patients with 
Treatment Success at EOST (as assessed by the DRC) will be summarized. The same summary 
will be repeated for the Per-Protocol Population. 
For the secondary efficacy endpoints, the percentage of patients with Treatment Success 2 and 
4 weeks after EOST will be summarized. Similarly, the proportion of patients with successful 
Mycological Outcomes at EOST, and 2 and 4 weeks after EOST will be summarized. 
A descriptive summary of overall survival at Study Day 30 and time to first negative blood culture 
will also be provided. 
Safety Analyses 
All safety analyses will be performed on the Safety Population. Safety data will be subject to 
clinical review and summarized by appropriate descriptive statistics. A DSMB will be assigned to 
monitor safety on an ongoing basis throughout the study.  
Pharmacokinetic Analysis 
Pharmacokinetic analysis of plasma concentration data will be performed using validated software 
in order to derive the population mean (and variance) values of specific PK parameters. 
Plasma concentrations will be summarized descriptively by treatment group and time point of 
collection. Summary statistics in the tabulation will include n, mean, standard deviation, 
CV% median, minimum, and maximum. Pharmacokinetic parameters will be estimated using 
population PK analysis methods, which will be described in a separate data analysis plan. 
Results of the PK analysis will be reported separately. 

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TABLE OF CONTENTS 
1 INTRODUCTION AND BACKGROUND INFORMATION .......................................... 26 
1.1 
Rationale ...................................................................................................................... 27 
1.2 
Risk/Benefit ................................................................................................................. 28 
2 STUDY OBJECTIVES ......................................................................................................... 28 
2.1 
Primary Objective ........................................................................................................ 28 
2.2 
Secondary Objectives .................................................................................................. 28 
3 STUDY DESCRIPTION ...................................................................................................... 29 
3.1 
Summary of Study Design .......................................................................................... 29 
3.2 
Study Indication(s) ...................................................................................................... 32 
4 SELECTION AND WITHDRAWAL OF SUBJECTS ..................................................... 32 
4.1 
Inclusion Criteria ......................................................................................................... 32 
4.2 
Exclusion Criteria ........................................................................................................ 34 
4.3 
Dosing Criteria ............................................................................................................ 35 
4.4 
Withdrawal Criteria ...................................................................................................... 35 
5 STUDY TREATMENTS ...................................................................................................... 36 
5.1 
Treatment Groups ........................................................................................................ 36 
5.2 
Rationale for Dosing ................................................................................................... 36 
5.3 
Randomization and Blinding ....................................................................................... 37 
5.4 
Breaking the Blind ....................................................................................................... 37 
5.5 
Drug Supplies .............................................................................................................. 37 
5.5.1 Formulation and Packaging ............................................................................. 37 
5.5.2 Study Drug Preparation and Dispensing ........................................................... 38 
5.5.3 Study Drug Administration ................................................................................ 38 
5.5.4 Treatment Compliance ...................................................................................... 39 
5.5.5 Storage and Accountability .............................................................................. 39 
5.6 
Prior and Concomitant Medications and/or Procedures .............................................. 40 
5.6.1 Excluded Medications and/or Procedures ....................................................... 40 
5.6.1.1 APX001A as a Victim Substrate for Cytochrome P450 Drug-drug 
Interactions ........................................................................................ 40 
5.6.1.2 APX001A as a Perpetrator of Cytochrome P450 Drug-drug 
Interactions ........................................................................................ 40 

 
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5.6.2 Prohibited Medications and/or Procedures ...................................................... 40 
5.6.3 Documentation of Prior and Concomitant Medication Use ............................ 41 
6 STUDY PROCEDURES ...................................................................................................... 41 
6.1 
Informed Consent ........................................................................................................ 41 
6.2 
Eligibility ..................................................................................................................... 41 
6.3 
Screening ..................................................................................................................... 42 
6.4 
Treatment Period (up to 6 Weeks) ............................................................................... 42 
6.4.1 Baseline (Day -1 or Day 1, Pre-Dose) ............................................................. 42 
6.4.2 Study Drug Treatment (6 Weeks) ................................................................. 43 
6.4.3 End of Study Drug Treatment (6 Weeks) ...................................................... 45 
6.5 
Follow-up (2 Weeks and 4 Weeks After End of Study Drug Treatment) ...................... 46 
6.5.1 Follow-up 2 Weeks After End of Study Drug Treatment ............................... 46 
6.5.2 Follow-up 4 Weeks After End of Study Drug Treatment .................................. 47 
6.5.3 Early Termination Visit and Withdrawal Procedures ...................................... 47 
7 EFFICACY ASSESSMENTS .............................................................................................. 48 
7.1 
Primary Efficacy Endpoint .......................................................................................... 48 
7.2 
Secondary Efficacy Endpoints .................................................................................... 48 
7.3 
Exploratory Efficacy Endpoint .................................................................................... 48 
7.4 
Definitions for Efficacy Assessments .......................................................................... 49 
7.4.1 At End of Study Drug Treatment ...................................................................... 49 
7.4.2 At Follow-Up (2 Weeks and 4 Weeks After End of Study Drug Treatment 
[EOST]) ........................................................................................................... 49 
7.5 
Microbiological Assessments ...................................................................................... 50 
7.5.1 Blood Cultures ................................................................................................. 50 
7.5.2 Cultures from Other Sites of Infection ............................................................ 50 
7.5.3 Intravascular Catheter Management and Log .................................................. 51 
8 SAFETY ASSESSMENTS ................................................................................................... 51 
8.1 
Adverse Events ............................................................................................................ 51 
8.1.1 Adverse (Drug) Reaction ................................................................................. 52 
8.1.2 Unexpected Adverse Drug Reaction ............................................................... 52 
8.1.3 Assessment of Adverse Events by the Investigator ......................................... 52 
8.2 
Serious Adverse Events ............................................................................................... 54 

 
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8.3 
Serious Adverse Event Reporting − Procedures for Investigators .............................. 55 
8.4 
Expedited Reporting .................................................................................................... 56 
8.5 
Stopping Rules ............................................................................................................ 56 
8.5.1 Study Stopping Rule ........................................................................................ 56 
8.5.2 Subject Stopping Rule ..................................................................................... 56 
8.6 
Pregnancy Reporting ................................................................................................... 57 
8.7 
Clinical Laboratory Evaluations .................................................................................. 57 
8.8 
Vital Signs ................................................................................................................... 57 
8.9 
APACHE II Score ....................................................................................................... 58 
8.10 Electrocardiograms ...................................................................................................... 58 
8.11 Physical Examinations ................................................................................................ 58 
8.12 Pharmacokinetics ........................................................................................................ 58 
8.13 Dilated Fundoscopic Examination .............................................................................. 58 
8.14 Imaging Tests ............................................................................................................... 59 
9 STATISTICS ......................................................................................................................... 59 
9.1 
Analysis Populations ................................................................................................... 59 
9.2 
Statistical Methods ...................................................................................................... 60 
9.2.1 Analysis of Efficacy ........................................................................................ 60 
9.2.1.1 Primary Efficacy Analysis ................................................................ 60 
9.2.1.2 Secondary Efficacy Analysis ............................................................ 60 
9.2.1.3 Analysis of Safety ............................................................................. 60 
9.2.1.4 Pharmacokinetic Analysis ................................................................. 61 
9.2.2 Interim Analysis ............................................................................................... 61 
9.2.3 Independent Data Review Committee (DRC) ................................................. 61 
9.2.4 Data and Safety Monitoring Board (DSMB) ................................................... 62 
9.2.5 Sample Size Determination ............................................................................. 62 
10 DATA MANAGEMENT AND RECORD KEEPING....................................................... 62 
10.1 Data Management ........................................................................................................ 62 
10.1.1 Data Handling .................................................................................................. 62 
10.1.2 Computer Systems ........................................................................................... 62 
10.1.3 Data Entry ....................................................................................................... 62 

 
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10.1.4  Medical Information Coding ........................................................................... 63 
10.1.5  Data Validation ................................................................................................ 63 
10.2  Record Keeping ........................................................................................................... 63 
11  INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL ............................. 63 
11.1  Ethical Conduct of the Study ....................................................................................... 63 
11.2  Institutional Review Board/Independent Ethics Committee ....................................... 64 
11.3  Informed Consent ........................................................................................................ 64 
11.4  Patient Card ................................................................................................................. 64 
11.5  Study Monitoring Requirements ................................................................................... 65 
11.6  Disclosure of Data ....................................................................................................... 65 
11.7  Retention of Records ................................................................................................... 65 
11.8  Publication Policy ........................................................................................................ 66 
11.9  Financial Disclosure ...................................................................................................... 66 
11.10 Insurance and Indemnity ............................................................................................. 66 
11.11 Legal Aspects .............................................................................................................. 66 
12  STUDY ADMINISTRATIVE INFORMATION ............................................................... 67 
12.1  Protocol Amendments ................................................................................................. 67 
12.2  Address List ................................................................................................................. 67 
12.2.1  Sponsor ............................................................................................................ 67 
12.2.2  Contract Research Organization ...................................................................... 67 
12.2.3  Drug Safety ..................................................................................................... 67 
12.2.4  Biological Specimens ...................................................................................... 68 
12.2.5  Mycology Reference Laboratory ..................................................................... 68 
12.2.6  Pharmacokinetic Laboratory ........................................................................... 68 
13  REFERENCES ...................................................................................................................... 69 
APPENDIX A:  SCHEDULE OF PROCEDURES.................................................................. 72 
APPENDIX B:  CLINICAL LABORATORY ANALYTES .................................................. 75 
APPENDIX C:  APACHE II SCORE FORM .......................................................................... 76 
APPENDIX D:  DRUG-INDUCED LIVER INJURY CRITERIA ........................................ 78 

 
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LIST OF FIGURES 
Figure 1. 
APX001-203 Study Schematic ........................................................................ 31 

 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
Abbreviation 
Definition 
APACHE  
Acute Physiology and Chronic Health Evaluation  
AUC 
Area under the concentration-time curve 
AUCinf 
Area under the concentration-time curve from time 0 to infinity 
BID 
Twice daily 
CFR 
Code of Federal Regulations 
CFU 
Colony-forming units 
Cmax 
Maximum serum concentration 
CRA 
CRP 
Clinical research associate 
C-reactive protein 
CTA 
Clinical trial authorization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CVC 
Central venous catheter 
CYP 
Cytochrome P450 
DDI 
Drug-drug interaction 
DILI 
Drug-induced liver injury 
DLT 
Dose-limiting toxicity 
DRC 
Data Review Committee 
DSMB 
Data and Safety Monitoring Board 
ECG 
Electrocardiogram  
eCRF 
Electronic Case Report Form 
EDC 
Electronic data capture 
EOST 
End of Study Drug Treatment 
FDA 
Food and Drug Administration 
FIH 
First-in-human 
GCP 
Good Clinical Practice 
GFR 
GI 
Glomerular filtration rate 
Gastrointestinal  
GPI 
Glycosylphosphatidylinositol  
GWT1 
GPI-anchored wall transfer protein 1 
HCV 
Hepatitis C virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 

 
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Abbreviation 
Definition 
ICH 
International Council for Harmonisation 
IDSA 
Infectious Diseases Society of America 
IEC 
Independent Ethics Committee 
IFD 
Invasive fungal disease 
IRB 
Institutional Review Board 
IV 
Intravenous(ly)  
LAR 
MDRD 
Legal authorized representative 
Modification of Diet in Renal Disease 
MIC 
Minimal inhibitory concentration 
MIC90 
Minimal inhibitory concentration required to inhibit the growth of 
90% of organisms tested 
MITT 
Modified Intent-to-Treat 
MTD 
Maximum tolerated dose 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic  
PO 
Oral(ly) 
PTA 
Probability of target attainment 
QD 
Once daily 
SAE 
Serious adverse event 
SOC 
Standard of care 
spp. 
Species  
T2MR 
T2 magnetic resonance 
TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
 

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1 
INTRODUCTION AND BACKGROUND INFORMATION 
Disseminated infections associated with Candida species (spp.) are a significant cause of 
morbidity and mortality. Candida auris is an emerging fungal pathogen which has caused invasive 
infections and hospital outbreaks on several continents. Since C. auris was first described in Japan 
in 2009, additional cases have been reported in South Korea, India, Kuwait, Kenya, South Africa 
and more recently in Colombia, Venezuela, Panama, Pakistan, the United Kingdom and the United 
States1-14. A whole genome sequencing study documented recent, near-simultaneous and 
independent emergence of C. auris clones on three different continents (Africa, Asia and South 
America), rather than spread of a single “clone” across the globe15. 
Invasive C. auris infections are associated with high mortality and are difficult to identify using 
traditional yeast identification methods16.The fungus persists on patients’ skin and in the healthcare 
environment, allowing for transmission to occur between patients in healthcare facilities, and may 
be difficult to eliminate from the hospital environment16. 
C. auris is often multi-drug resistant. The majority of tested C. auris isolates are resistant to
fluconazole, an important first-line antifungal agent1-6, 15. Furthermore, more than 40% of tested
C. auris isolates from a recent global study were resistant to two or more major classes of
antifungals16.
APX001, a first-in-class small molecule drug candidate, is the water soluble phosphate prodrug of 
APX001A. APX001 is rapidly metabolized by circulating phosphatases in vivo to APX001A. 
APX001A has a novel mechanism of action targeting the conserved fungal enzyme 
glycosylphosphatidylinositol (GPI)-anchored wall transfer protein 1 (GWT1), which is required 
for the expression of GPI-anchored proteins on the fungal cell wall. Inhibition of GWT1 by 
APX001A compromises cell wall integrity, inhibits biofilm formation, blocks filamentation, 
enhances immunogenicity of unmasked β-glucan, and produces severe fungal growth defects. The 
closest mammalian ortholog of GWT1 is PIG-W, which has no demonstrable inhibition by 
APX001A. 
APX001A has broad in vitro activity against major fungal pathogens, including Candida, 
Cryptococcus, Aspergillus, Scedosporium, Fusarium, and members of the Mucorales order17-21. 
The susceptibility of Candida auris to APX001A has been tested in over 100 diverse isolates 
including strains resistant to fluconazole, the echinocandins, and/or amphotericin B22. In these 
tests, APX001A is the most mycologically active agent against C. auris with markedly lower MIC 
values than the other antifungals tested. The MIC50 and MIC90 for APX001A were 0.002 mg/L 
and 0.008 mg/L, respectively. In addition, APX001A was active against all four C. auris clades22. 
APX001 was evaluated in a disseminated C. auris infection model in immunocompromised 
mice23. Anidulafungin, an echinocandin, was chosen as a comparator for this model. The mice 
were sacrificed at 48 hours post-inoculation for determination of the lung, kidney, and brain fungal 
burdens after intraperitoneal dosing of APX001 (78 mg/kg BID, 78 mg/kg TID, 104 mg/kg BID) 
and anidulafungin (10 mg/kg BID) versus the vehicle control. Treatment with APX001 resulted in 
significantly better survival than anidulafungin. Both APX001 and anidulafungin demonstrated 

 
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significant and equivalent decreases in kidney and lung colony forming units (CFU) at 48 hours; 
however, only APX001 demonstrated a reduction in brain fungal burden.  
 
In three completed Phase 1 clinical studies of APX001, the safety, tolerability, and PK of single 
ascending doses and multiple ascending doses administered intravenously (IV) and orally (PO) to 
healthy volunteers were studied. A total of 178 healthy volunteers were enrolled in the 
placebo-controlled Phase 1 studies of APX001. All APX001 doses studied in Phase 1 were 
considered well tolerated. No serious adverse events (SAEs) were reported, and most of the 
treatment-emergent adverse events (TEAEs) were mild, transitory, and required no intervention. 
No dose-limiting toxicities (DLTs) were observed and no TEAEs or safety laboratory test results 
met any of the a priori rules that prevented dose escalation to the next protocol-specified cohort. 
The maximum tolerated dose was not determined/reached in these Phase 1 studies. 
Pharmacokinetic parameters for maximum serum concentration and AUC in both single and 
multiple APX001 IV and PO doses were linear and dose proportional. In both in vitro studies of 
APX001 and in a cohort embedded within the PO dose Phase 1 study, APX001 demonstrated a 
favorable drug-drug interaction profile. APX001A was shown to be a weak inducer of cytochrome 
P450 (CYP) 2B6; a moderate inducer of CYP1A2, CYP2C19, and CYP3A4; and a weak inhibitor 
of CYP2C9 and CYP2D6. The relative bioavailability of the PO formulation was 90% in healthy 
subjects. There was no evidence of an effect on the bioavailability of APX001 in the presence of 
food (high fat and high calorie). Most importantly, the target AUCs anticipated for efficacy against 
both yeast and molds have been achieved with both IV and PO dose formulations tested in Phase 1. 
 
In summary, APX001 is a promising new antifungal agent with a novel mechanism of action 
having broad spectrum activity against Candida spp., including Candida auris. Because APX001 
is a first-in-class drug candidate with a novel mechanism of action, no cross-resistance with other 
classes of antifungal drugs has been observed or is expected. 
 
1.1 
Rationale 
 
The need for improved treatment of infections caused by the emerging and increasingly prevalent 
pathogen Candida auris is high, particularly given its resistance to fluconazole, and reduced 
susceptibility to other triazoles.  A number of isolates have demonstrated raised MICs to multiple 
classes of antifungal agents, raising the possibility of pandrug resistance.  Outbreaks of C. auris 
infection have been associated with treatment failure and in some cases with death.  APX001 has 
potent activity against C. auris isolates in vitro and in vivo, which in combination with its 
demonstrated favourable tissue penetration, pharmacokinetic and pharmacodynamic properties 
supports its preliminary clinical investigation for the treatment of C. auris infection.     
 

 
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1.2 
Risk/Benefit 
 
Subjects participating in this study will receive a drug in clinical development without regulatory 
approval for treatment of fungal diseases. Administration of APX001 in a concentration of 
1000 mg IV BID will be administered on Day 1, 600 mg IV QD will be administered on Days 2 
through 3, and then subsequently 600 mg IV or 800 mg PO QD will be administered throughout 
the Study Drug Treatment Period. This treatment may have advantages over standard of care 
(SOC) therapy against certain resistant fungal diseases, where SOC treatment might show no or 
limited therapeutic effectiveness, furthermore APX001 has a differentiated safety profile, 
is available as IV and oral formulation and may have fewer drug-drug interactions than SOC. Since 
the efficacy of APX001 has not yet been proven in patients, no additional protection of APX001 
in this concentration can be assured. Potential adverse events associated with APX001 were headache, 
dizziness, fatigue, nausea and vomiting. For more information on APX001 safety profile please refer to the 
Investigator’s Brochure. Subjects participating in this clinical study will receive more intense health 
monitoring as detailed in the schedule of procedures. 
 
2 
STUDY OBJECTIVES 
 
2.1 
Primary Objective 
 
The primary objective of this study is to evaluate the efficacy and safety of APX001 for the 
treatment of adult patients aged 18 years and above, with candidemia and/or invasive candidiasis 
caused by Candida auris, who have limited antifungal treatment options. 
 
2.2 
Secondary Objectives 
 
The secondary objectives of this study are to: 
• Evaluate the time to first negative blood culture 
• Evaluate the percentage of patients with successful Mycological Outcomes at End of 
Study Drug Treatment (EOST), and at 2 and 4 weeks after EOST 
• Evaluate the percentage of patients with Treatment Success 2 and 4 weeks after EOST 
• Evaluate all-cause mortality at Study Day 30 
• Evaluate safety parameters, including number of patients with treatment-emergent 
adverse events (TEAEs) 
• Evaluate pharmacokinetic (PK) parameters of APX001

 
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3 
STUDY DESCRIPTION 
 
3.1 
Summary of Study Design 
 
This is a multicenter, open-label, non-comparative, single-arm study to evaluate the efficacy and 
safety of APX001 for the treatment of candidemia and/or invasive candidiasis caused by C. auris 
in patients aged 18 years and over who have limited antifungal treatment options. The Study Drug 
Treatment Period will be up to a maximum of 42 days (inclusive of the loading dose 
[Study Day 1]). There will be a Follow-up Period of 4 weeks (+4 days) after EOST. The total 
duration of participation in the study is up to approximately 10.5 weeks (inclusive of the Screening 
Period [168 hours prior to Baseline]). Patients must have had C. auris confirmed in culture 
<120 hours (for candidemia) or <168 hours (for invasive candidiasis without candidemia) prior to 
qualification and dosing in the study.  
 
Screening and Baseline procedures will be performed within no more than 120 hours 
(for candidemia) or 168 hours (for invasive candidiasis without candidemia) from the time that the 
SOC blood and/or tissue sample or aspirate/fluid positive for C. auris was collected, and any 
outstanding baseline procedures completed before the first dose of study medication.  
 
All patients (or the patient’s LAR) will sign an ICF before any protocol specified procedures that 
are not indicated by SOC may be conducted. Inclusion/exclusion criteria assessments, 
medical history, demographics, and Acute Physiology and Chronic Health Evaluation II score will 
be collected before dosing.  When an LAR is used for the initial consent, the patient will be 
consented during the study as soon as he/she is able to do so. 
 
On Study Day 1 (or over the first 24 hours if dosing starts in the evening), a 1000 mg APX001 
loading dose will be administered over 3 hours by IV infusion twice daily (BID). On Study Days 2 
and 3, a 600 mg APX001 maintenance dose will be administered over 3 hours by IV infusion once 
daily (QD).  On Study Day 4 and onward, the APX001 maintenance dose will be administered as 
either 600 mg APX001 IV infusion QD over 3 hours or 800 mg PO QD. Patients who have 
completed a minimum of 3 days of IV APX001, are clinically stable as determined by the 
Investigator, and are able to swallow tablets, may switch from IV to PO dosing on Study Day 4 
and onward. Study drug will be administered for 14 days after clearance of Candida organisms 
from the bloodstream, and in accordance with clinical judgment as applicable for other infected 
sites, up to a maximum of 42 days.  
 
Patients will be monitored by daily blood culture from signing informed consent, through dosing, 
during Study Drug Treatment until 2 consecutive blood cultures are negative for Candida spp., 
at EOST, and at 2 and 4 weeks after EOST, or Early Termination. For patients diagnosed with 
invasive candidiasis, relevant cultures, histopathology, and imaging tests to assess the site(s), 
extent, progress, and outcome of the Candida infection will be conducted as clinically indicated. 
All results should be recorded in the electronic Case Report Form. The management of 
intravascular catheters, intravascular devices, and, if applicable, any drains will be recorded, 
including any associated microbiology results. 

 
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Patients will be monitored for safety throughout the duration of the study. Safety assessments will 
include vital signs, clinical laboratory assessments (serum chemistry, hematology, coagulation, 
and urinalysis), physical examinations, neurological assessments (twice weekly on study 
treatment), prior and concomitant medication reporting, and adverse event reporting. A 12-lead 
electrocardiogram (ECG) will be performed at Baseline (pre-dose), EOST, and 4 weeks after 
EOST, or Early Termination. A dilated fundoscopic examination will be performed at least once 
during the baseline period, which exclusively for this assessment may be up to Day 3 of the study. 
Follow-up fundoscopic examinations are required at EOST, and 4 weeks after EOST, or Early 
Termination for those patients who had positive findings up to Day 3 (or more if clinically 
indicated). A urine pregnancy test (for females of childbearing potential only) will be performed 
at Screening and Baseline (pre-dose), every 30 days during treatment if required by local 
regulations, at EOST, and 2 and 4 weeks after EOST, or Early Termination. 
 
In the event of an inadequate response/failure on APX001 study treatment, the study drug may be 
discontinued and alternative antifungal treatment instituted.  
 
Plasma samples for PK (APX001 [prodrug] and APX001A [active moiety]) will be collected at 
Baseline (pre-dose), twice weekly during Study Drug Treatment, and at EOST, 2 weeks after 
EOST, or Early Termination. Plasma samples for PK will be collected at the same time as samples 
are collected for the study’s clinical laboratory assessments. Serum samples for  
(1,3)-β-D-glucan levels will be collected at Baseline (pre-dose) and EOST, or Early Termination 
(if applicable). 
 
Optionally, if body fluids are sampled as part of routine patient management (e.g. bronchoalveolar 
lavage, lumbar puncture, paracentesis, vitreous fluid collection, abscess drainage) within 
approximately 2 hours of blood sampling for PK, these samples may be stored for future analysis 
of APX001 and APX001A levels. 
 
The evaluation of treatment outcome will be assessed at EOST, and 2 and 4 weeks after EOST, or 
Early Termination. 
 
The end of study will occur after the last visit of the last patient on the study. 
 
A schematic representing the study’s design follows. 
 

 
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Figure 1. 
APX001-203 Study Schematic 
 
 

 
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3.2 
Study Indication(s) 
 
APX001 is indicated in this study for the treatment of patients with candidemia and/or invasive 
candidiasis caused by Candida auris. 
 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS 
 
This study will enroll male and female patients aged 18 years and above with an established 
diagnosis of candidemia and/or invasive candidiasis caused by Candida auris from a sample taken 
<120 hours (for patients with candidemia) or <168 hours (for patients with invasive candidiasis 
without candidemia) of enrollment in the study.  Patients with a blood culture, or specimen 
sampled from a normally sterile site, positive for yeast suspected to be Candida auris who also 
have limited antifungal treatment options may sign the Informed Consent Form (ICF) and undergo 
Screening procedures for the study.  However, Candida spp. must be confirmed in culture from 
blood or other tissue, aspirate or fluid sampled from a normally sterile site, and all eligibility 
criteria must be met prior to qualification for the study and subsequent dosing. 
 
4.1 
Inclusion Criteria 
 
Patients must meet all of the following criteria to be eligible for study entry: 
1. 
Male or female aged 18 years and above 
2. 
Limited or no treatment options due to resistance, contraindication, intolerance or lack of 
clinical response to standard of care antifungal therapy, as advocated by the relevant 
regional/country treatment guidelines 
3. 
Established mycological and clinical diagnosis of candidemia and/or invasive candidiasis 
from a sample taken <120 hours (for candidemia) or <168 hours (for invasive candidiasis 
without candidemia) before study qualification: 
a. 
Candidemia criteria 
i. 
≥1 blood culture positive for yeast/Candida spp. identified as C. auris; 
plus: 
ii. 
Clinical signs attributable to candidemia within the 120 hours prior to 
qualification for the study, to include at least one of the following: (a) fever 
(>38oC), or (b) hypothermia (<36oC), or (c) hypotension (SBP <90mmHg 
or decrease of >30mmHg); 
b. 
Invasive candidiasis criteria 
i. 
>1 specimen (e.g., tissue, aspirate/fluid) sampled aseptically from a 
normally sterile site culture positive for yeast/Candida spp. identified as 
C. auris; 
plus: 

 
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ii. 
Clinical signs attributable to invasive candidiasis within the 168 hours prior 
to qualification for the study, to include at least one of the following: 
(a) fever (>38oC), or (b) hypothermia (<36oC), or (c) hypotension  
(SBP <90mmHg or decrease of >30mmHg), or (d) signs associated with 
organ/site infected with Candida (e.g. eye, intra-abdominal). 
4. 
Patients with single C. auris infection, or mixed Candida auris plus other Candida spp. 
(other than C. krusei) infection, are eligible for the study. 
5. 
Able to have pre-existing intravascular catheters removed and replaced (if necessary) 
6. 
Females of childbearing potential with male partners, and males with female partner(s) of 
childbearing potential, must agree to use 2 forms of highly effective contraception, 1 of which 
must be a barrier method, throughout the duration of the study and for 90 days following the 
last study drug administration. Acceptable barrier forms of contraception are condom and 
diaphragm. Acceptable non-barrier forms of contraception for this study are oral 
contraceptives (e.g. oral birth control pill, depot, patch, or injectable), abstinence, intrauterine 
device, and/or spermicide. 
 
Post-menopausal is defined as amenorrhea for >12 months without an alternative medical 
cause or documented surgical sterilization (e.g. bilateral salpingectomy, bilateral 
oophorectomy, or hysterectomy). 
 
True abstinence, when in line with the preferred and usual lifestyle of the patient, is considered 
a highly effective method only if defined as refraining from heterosexual intercourse during 
the entire period of risk associated with the study drug treatment. (Periodic abstinence 
[e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not 
acceptable methods of contraception)  
7. 
Females of childbearing potential must have a negative urine pregnancy test within 96 hours 
prior to Baseline (i.e. pre-dose on Study Day 1) 
8. 
Willing to participate in the study, willing to give written informed consent, and willing to 
comply with the study restrictions; where permitted by local regulations, written informed 
consent from a legal authorized representative (LAR) will be obtained for patients who are 
unable to give consent. 
9. 
Male patients must agree to abstain from sperm donation and use condoms with spermicide 
during sexual intercourse between Screening and at least 90 days after administration of the 
last dose of study drug.  Male patients must ensure non-pregnant female partner(s) of 
childbearing potential comply with the contraception requirements in Inclusion Criterion 6 
(above). 
 

 
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4.2 
Exclusion Criteria 
 
Participants who meet any of the following criteria will not be eligible for the study: 
1. Blood culture, or any other culture, positive for C. krusei 
2. Life expectancy of 7 days in the opinion of the Investigator 
3. Severe or moderate hepatic impairment (Child-Pugh Score 6 points) at any time during 
2 weeks prior to dosing.  The Child-Pugh score of >6 is applicable to patients with hepatic 
dysfunction and cirrhosis only. 
4. Baseline neurological conditions such as abnormal movements or convulsive disorders 
5. Human immunodeficiency virus-infected patients who are receiving antiretroviral therapy that 
are moderate to strong inducers of CYP3A4, or who have detectable viremia, or who have had 
an active opportunistic infection within 6 months prior to Screening 
6. Alanine aminotransferase or aspartate aminotransferase 5  upper limit of normal (ULN) 
7. Total bilirubin 3  ULN, unless isolated hyperbilirubinemia or due to documented Gilbert’s 
disease. 
8. Female patient is pregnant or lactating 
9. Inappropriate fungal infection source control (e.g. persistent indwelling catheters or 
intravascular devices) 
10. Investigational drug administered within 30 days prior to dosing or five half-lives whichever 
is longer 
11. Concomitant use of medication that is a strong inducer of CYP enzymes (e.g. rifampin, 
carbamazepine, phenytoin, rifabutin, efavirenz, nevirapine, phenobarbital, modafinil, nafcillin, 
St. John's Wort, and enzalutamide) 
12. Any other condition or laboratory abnormality that, in the opinion of the Investigator, would 
put the patient at unacceptable risk for participation in the study or may interfere with the 
assessments included in the study 
13. Diagnosis of deep-seated Candida-related infections causing hardware associated septic 
arthritis, osteomyelitis, endocarditis, myocarditis, hepatosplenic candidiasis, or a central 
nervous system infection or site of infection that would require antifungal therapy to exceed 
the maximal duration of study drug treatment (i.e. 6 weeks [42 days])   
 

 
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4.3 
Dosing Criteria 
 
Participants must meet the following criteria to begin dosing: 
 
Confirmed diagnosis of candidemia and/or invasive candidiasis caused by C. auris (in a single or 
mixed Candida spp. infection) within <120 hours (for candidemia) or within <168 hours 
(for invasive candidiasis without candidemia) of the indicative positive blood culture or the 
indicative positive culture from a specimen sampled from a normally sterile site, plus confirmation 
that all other eligibility criteria are met, qualify the patient for dosing with APX001.  The initiation 
of the first dose of APX001 must occur within 12 hours of qualification for the study. 
 
4.4 
Withdrawal Criteria 
 
Study drug dosing may be discontinued for any of the following reasons: 
• The patient withdraws consent or requests discontinuation from the study for any reason 
• Occurrence of any medical condition or circumstance that exposes the patient to substantial 
risk and/or does not allow the patient to adhere to the requirements of the protocol 
• Occurrence of significant drug-induced liver injury (DILI) [Appendix D] 
• Any SAE, clinically significant adverse event, severe laboratory abnormality, intercurrent 
illness, or other medical condition that indicates to the Investigator that continued 
participation is not in the best interest of the patient 
• Pregnancy 
• Requirement of prohibited concomitant medication 
• Patient failure to comply with protocol requirements or study-related procedures 
• Termination of the study by the Sponsor or the regulatory authority 
• Patients who discontinue study drug due to withdrawal of consent, death, or loss to follow-
up will discontinue study participation.  Patients who fail on study treatment and start 
alternative antifungals will be assessed for safety 4 weeks after stopping study medication.   
Patients who discontinue study drug for other reasons will enter the follow-up phase of the 
study. 
If a patient withdraws prematurely from the study due to any of the above criteria or for any other 
reason, study staff should make every effort to contact the Sponsor prior to discontinuation, 
if possible, and to complete the full panel of assessments scheduled for the Early Termination Visit. 
The reason for patient withdrawal must be documented in the eCRF. 
 
In the case of patients lost to follow-up, attempts to contact the patient must be made and 
documented in the patient’s medical records. 
 
Withdrawn patients will not be replaced. 
 

 
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The study may be discontinued for any of the following reasons: five or more subjects in study 
(cumulative) experience a same Grade 2 (or higher) related AE (laboratory or systemic) which is 
coded in the same high-level group term per MedDRA coding, throughout the duration of study; 
a recommendation from the DSMB based on other safety signals; lack of Investigational Product 
availability; inability to enroll the study; or decision by a regulatory authority or the sponsor. 
 
5 
STUDY TREATMENTS 
 
5.1 
Treatment Groups 
 
All patients will be administered a 1000 mg APX001 loading dose BID on Study Day 1 (or over 
the first 24 hours if dosing starts in the evening) followed by a 600 mg APX001 maintenance dose 
QD on Study Day 2 and Study Day 3. From Study Day 4 onwards, the APX001 maintenance dose 
will be administered as either 600 mg APX001 IV infusion QD or may be switched to 800 mg PO 
QD when/if the criteria for oral dosing are met (Section 5.5.3). 
 
5.2 
Rationale for Dosing 
 
In pharmacokinetic/pharmacodynamic (PK-PD) studies, immunocompromised mice were infected 
with one of three spp. of Candida (C. albicans, C. glabrata, or C. auris) and groups of animals 
were dosed with APX001 at different dose fractionations. The AUC/MIC ratio was determined to 
be the PK-PD variable that best correlated with antifungal efficacy as assessed by fungal burden 
(CFUs) in the kidney. The probability of target attainment (PTA) was calculated separately for 
each Candida spp. tested. The PTA calculation used the APX001A free drug AUC level at the 
stasis endpoint divided by the MIC required to inhibit the growth of 90% of organisms (MIC90) of 
each of the Candida spp. tested. 
 
The AUC level was estimated from a population PK model derived primarily from the Phase 1 PK 
data. The stasis endpoint was defined as the quantity of Candida spp. in CFUs just prior to APX001 
administration compared to CFUs at the endpoint of assessment (i.e. 24 hours for C. albicans; 
96 hours for C. glabrata and C. auris). The MIC data for the Candida strains tested were obtained 
from recent surveillance data. 
 
Using the AUC at the stasis endpoint, along with the MIC90 from the surveillance data and the 
predicted exposure at the dose regimen to be used in this study, the PTA for the 3 Candida spp. 
tested was shown to be approximately 100%. Further, sensitivity analyses were conducted to 
evaluate the PTA under different scenarios including increased variability of PK parameters and 
higher Candida spp. MIC90 values. For both scenarios the PTA remained >90%.  
 

 
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Tablets are to be administered at the same time each day, whole, and taken by mouth with water 
within 30 minutes of being removed from the refrigerator. No splitting or crushing of tablets is 
allowed. 
 
5.5.4 
Treatment Compliance 
 
Study drug will be administered at the study site. Compliance with treatment dosing will be 
monitored and recorded by site personnel. If patients are discharged home with study treatment, 
compliance will be documented in a dosing diary. 
 
 
5.5.5 
Storage and Accountability 
 
APX001 Injection will be stored at -20C and tablets will be stored at 2 to 8C in a secured location 
(locked) with access restricted to authorized personnel only. Detailed storage and handling 
instructions will be described in the study-specific Pharmacy Manual. Storage temperature will be 
monitored and recorded. Further details for storage and accountability of study drug will be 
provided in the Pharmacy Manual. 
 
Upon receipt of study drug, the Investigator or designee will conduct a complete inventory of all 
study drug and ensure no damage occurred during shipment. 
 
The Investigator will maintain adequate records documenting the receipt, use, loss, or other 
disposition of study drug. Drug accountability logs will identify the study drug code number and 
account for the disposition on a participant-by-participant basis, including specific dates and 
quantities. The drug accountability logs will be signed by the individual who dispenses the study 
drug and copies will be provided to the Sponsor. 
 
All used and unused supplies will be appropriately inventoried and verified by the clinical research 
associate (CRA). 
 
Any unused study drug will be returned to the Sponsor or destroyed on site per local standard 
operating procedure after monitoring has occurred. 
 

 
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5.6 
Prior and Concomitant Medications and/or Procedures 
 
5.6.1 
Excluded Medications and/or Procedures 
 
5.6.1.1 
APX001A as a Victim Substrate for Cytochrome P450 Drug-drug Interactions 
 
APX001A is metabolized by multiple CYP enzymes. Patients who are receiving or will receive 
strong inducers of multiple CYP enzymes (e.g., rifampin, carbamazepine, phenytoin, rifabutin) are 
excluded from participating in the study. Concomitant use of multiple medications that are strong 
inhibitors of different CYP pathways may increase levels of APX001A, which in consequence 
may potentially affect the safety risk of APX001 administration. Caution should be advised when 
co-administering medications that are strong inhibitors of CYP enzymes. 
 
5.6.1.2 
APX001A as a Perpetrator of Cytochrome P450 Drug-drug Interactions 
 
APX001A was shown to be a weak inducer of CYP2B6; a moderate inducer of CYP1A2, 
CYP2C19, and CYP3A4; and a weak inhibitor of CYP2C9 and CYP2D6. The potential clinical 
significance of any APX001A DDI will depend on the extent of induction or inhibition and 
therapeutic margin of the specific victim substrate or substrates. 
 
Co-administration of drugs that are metabolized by the CYP enzymes in this study should be 
approached with caution and the need for increased frequency of drug monitoring 
(where applicable) should be considered, especially for CYP substrates that have a narrow 
therapeutic window. 
 
Refer to http://medicine.iupui.edu/clinpharm/ddis/main-table/ for an exhaustive list of CYP 
enzyme inducers and inhibitors. 
 
5.6.2 
Prohibited Medications and/or Procedures 
 
Once on study, patients may not receive concomitant systemic anti-fungal therapy for the treatment 
of candidemia and/or invasive candidiasis. 
 
Subjects cannot have received any investigational drug within 30 days (or five half-lives whichever 
is longer) prior to dosing. 
 

 
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5.6.3 
Documentation of Prior and Concomitant Medication Use 
 
All prior medications received by the participant within 14 days prior to study drug administration 
and any concomitant medications used throughout the duration of the study will be recorded in the 
source documents and on the appropriate eCRF. The medication name, route of administration, 
dose, frequency, indication, and duration of treatment (start and stop dates) will be recorded. 
 
6 
STUDY PROCEDURES 
 
6.1 
Informed Consent 
 
Written informed consent will be obtained from all participants prior to any study-specific 
procedures being performed. C. auris must be confirmed in culture prior to patient qualification 
for the study and dosing with study medication. Only those patients who have transient loss of 
capacity (e.g. mechanical ventilation, sedation) can have an LAR sign consent on their behalf.  
These patients will be allowed to make their own informed medical decisions and undergo the 
consent process if and when they are able to do so.  Patients with permanent loss of capacity are 
not eligible for study participation. 
 
6.2 
Eligibility 
 
The following cultures drawn or sampled as SOC, prior to informed consent, will determine study 
eligibility: 
• Blood culture positive for Candida spp. confirmed to be C. auris  
• Tissue, aspirate or fluid sampled from a normally sterile site, culture positive for Candida spp. 
confirmed to be C. auris 
 
Limited antifungal treatment options are also a requirement for study eligibility. 
Limited treatment options may be due to one or more of the following factors: 
• Resistance of C. auris to antifungal drug(s) in question 
• Patient unable to tolerate antifungal treatment 
• Antifungal contraindicated for given patient 
• Inadequate response to antifungal treatment, including refractory and relapsing C. auris 
infection 
 
Screening may start on confirmation of Candida auris candidemia or invasive candidiasis in a 
patient with limited antifungal treatment options. 
 

 
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6.3 
Screening 
 
Screening procedures must occur within a 120-hour window (for patients with candidemia) or 
168-hour window (for patients with invasive candidiasis without candidemia) prior to qualification 
for the study. 
 
The following procedures will be performed at Screening: 
• Obtain informed consent 
• Review inclusion/exclusion criteria 
• Record medical history 
• Record demography information 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight 
• Intravascular catheter management and log of the line changes, to include any catheter tip 
culture results 
• Perform clinical laboratory assessments (serum chemistry, hematology, coagulation, and 
urinalysis) 
• Perform urine pregnancy test (for females of childbearing potential only) 
• Collect blood cultures (daily) 
• Collect other cultures and histopathology from other sites, as clinically indicated 
• Perform imaging tests as clinically indicated to assess the site(s) and extent of invasive 
candidiasis infection at study baseline 
• Record prior/concomitant medications 
• Record adverse events 
 
6.4 
Treatment Period (up to 6 Weeks) 
 
6.4.1 
Baseline (Day -1 or Day 1, Pre-Dose) 
 
Baseline procedures are to be completed predose and within 12 hours of the first dose of study 
drug (Day 1). The following procedures will be performed at Baseline (Day 1 Pre-dose): 
• Confirm inclusion/exclusion criteria 
• Perform APACHE II score calculation (Appendix C) 
• Collect blood culture for Candida spp. 
• Collect other cultures and histopathology from other sites, as clinically indicated 

 
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• Perform imaging investigations as clinically indicated to define the site(s) and extent of 
invasive candidiasis infection 
• Intravascular catheter management and log of the line changes; any indwelling intravascular 
catheters should be removed and catheter tips cultured within 24 hours of starting APX001 
dosing; entrance site tissue should also be cultured if it appears infected 
• Implementation of other fungal infection control measures, as clinically indicated 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight; height will be collected (from the patient’s medical record) at Baseline 
only 
• Perform clinical laboratory assessments (serum chemistry, hematology, coagulation and 
urinalysis) 
• Perform 12-lead ECG 
• Perform urine pregnancy test (for females of childbearing potential only) 
• Perform complete physical examination including an assessment of general appearance, 
skin, eyes, heart, chest, abdomen, and the body site that corresponds to the entry site of 
candidemia (e.g., central venous catheter entry site) and/or the site of invasive candidiasis, 
if applicable, and a neurological examination (cranial nerve, sensory and motor examination, 
reflex and gait testing, coordination assessment) 
• Perform dilated fundoscopic examination. This exam should be performed at least once 
during the baseline period, which exclusively for this assessment may be up to Day 3 of the 
study. 
• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]). 
Plasma samples for PK will be collected at the same time as samples are collected for the 
study’s clinical laboratory assessments. 
• Collect serum sample for analysis of (1,3)-β-D-glucan 
• Record concomitant medications 
• Record adverse events 
 
6.4.2 
Study Drug Treatment (6 Weeks) 
 
Day 1 dose 
Prior to the initiation of the first APX001 dose, a diagnosis of candidemia and/or invasive 
candidiasis caused by C. auris (in a single or mixed Candida spp. infection) must be confirmed 
within 120 hours (for candidemia) or 168 hours (for invasive candidiasis without candidemia) of 
formal qualification for the study. The initiation of the first dose of APX001 must occur within 
12 hours of qualification for the study. 
• Study drug to be administered as a 3-hour IV loading dose BID on Day 1 (or over the first 
24 hours if started in the evening).   

 
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Day 2 onwards (maximum to Day 42) 
• On Study Days 2 to 3, study drug to be administered over 3 hours by IV QD; on Day 4 and 
onward, oral administration of the study drug may be considered if the patient meets the 
IV to oral switch criteria 
• Study drug to be administered for a minimum of 14 days after clearance of Candida 
organisms from the bloodstream or other infected sites,  
• Maximum duration of study drug treatment is up to 6 weeks total (42 days, inclusive of the 
loading dose [Study Day 1]) 
 
The following procedures will be performed during the period of Study Drug Treatment: 
• For patients with candidemia (with or without invasive candidiasis) daily blood cultures are 
to be performed on Days 1 through 4 (minimum), continuing until 2 negative blood culture 
results are reported from 2 consecutive samples.   (Considered negative at least 48 hours after 
collection).  
• For patients with invasive candidiasis, with or without candidemia, appropriate material from the 
infected site(s) is to be sampled for culture or histopathology to monitor the progress of infection, 
as clinically indicated until mycological and/or clinical resolution. 
 
• Imaging tests are to be performed as clinically indicated to monitor the site(s), extent and 
progress of invasive candidiasis infection 
• Intravascular catheter management log; all changes are to be recorded until EOST while 
inpatient, and as clinically indicated thereafter or for outpatients 
• Daily vital signs, including temperature, blood pressure, heart rate, respiratory rate, 
oxygen saturation, and weight while an inpatient.  Measurements are to be continued 
twice weekly while on treatment as an outpatient. 
During Study Drug Treatment, twice weekly visits are required with a minimum window of 
2 days and a maximum window of 4 days. Subjects who are outpatients will be asked to record 
daily dosing on a diary and bring the diary and study drug bottles with them to every clinic visit. 
• Perform clinical laboratory assessments (serum chemistry, hematology, coagulation and 
urinalysis) twice weekly 
• Perform urine pregnancy test (for females of childbearing potential only); every 30 days if 
required by local regulations 
• Perform neurological examinations twice weekly 
• Perform focused, symptom-based physical examination, as clinically indicated, once weekly 

 
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• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]) twice 
weekly. Plasma samples for PK will be collected at the same time as samples are collected 
for the study’s clinical laboratory assessments. 
o Optional:  If body fluids are sampled as part of routine patient management 
(e.g., bronchoalveolar lavage, lumbar puncture, paracentesis, vitreous fluid collection, 
abscess drainage, etc.), within approximately 2 hours of blood sampling for PK, 
these samples may be stored for future analysis of APX001 levels 
• Record concomitant medications 
• Assess adverse events 
 
6.4.3 
End of Study Drug Treatment (6 Weeks) 
 
The EOST for patients completing the study is at least 14 days from the date of clearance of 
candidemia, as documented by the first of the two consecutive negative blood cultures up to a 
maximum of 6 weeks total (42 days, inclusive of the loading dose [Study Day 1]). For patients with 
a deep-seated site of infection amenable to sampling, EOST is after at least one negative tissue 
culture or aspirate/fluid, up to a maximum of 6 weeks total (42 days, inclusive of the loading dose 
[Study Day 1]). 
 
• For patients with a deep-seated site of infection involving visceral organs from which a tissue 
culture is not obtainable, EOST is after the resolution of the attributable clinical signs of 
infection recorded at Baseline, and, as applicable, radiological improvement associated with 
the site of infection, up to a maximum of 6 weeks total. 
 
The following procedures will be performed at EOST: 
• Collect blood cultures for Candida spp. 
• Collect other cultures and histopathology from other sites, as clinically indicated 
• Perform imaging tests as clinically indicated to monitor the site(s) and extent of invasive 
candidiasis infection 
• Perform dilated fundoscopic examination (only required in those patients who had baseline 
positive fundoscopic findings [up to Day 3], or as clinically indicated) 
• Intravascular catheter management log 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight 
• Perform clinical laboratory assessments (serum chemistry, hematology, coagulation and 
urinalysis) 
• Perform 12-lead ECG 
• Perform urine pregnancy test (for females of childbearing potential only) 
• Perform neurological examination 

 
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• Perform focused, symptom-based physical examination as clinically indicated 
• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]). 
Plasma samples for PK will be collected at the same time as samples are collected for the 
study’s clinical laboratory assessments. 
• Collect serum sample for analysis of (1,3)-β-D-glucan 
• Evaluate treatment outcome 
• Record concomitant medications 
• Assess adverse events 
 
6.5 
Follow-up (2 Weeks and 4 Weeks After End of Study Drug Treatment) 
 
6.5.1 
Follow-up 2 Weeks After End of Study Drug Treatment 
 
The following procedures will be performed at the follow-up visit 2 weeks after EOST: 
• Collect blood cultures for Candida spp. 
• Collect other cultures and histopathology from other sites, as clinically indicated 
• Perform imaging tests as clinically indicated to monitor the site(s) and extent of invasive 
candidiasis infection 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight 
• Intravascular catheter management log, as clinically indicated 
• Perform clinical laboratory assessments (serum chemistry, hematology, coagulation and 
urinalysis) 
• Perform urine pregnancy test (for females of childbearing potential only) 
• Perform neurological examination 
• Perform focused, symptom-based physical examination, as clinically indicated 
• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]). 
Plasma samples for PK will be collected at the same time as samples are collected for the 
study’s clinical laboratory assessments. 
• Evaluate treatment outcome 
• Record concomitant medications 
• Assess adverse events 
 

 
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6.5.2 
Follow-up 4 Weeks After End of Study Drug Treatment 
 
The following procedures will be performed at the follow-up visit 4 weeks after EOST: 
• Collect blood culture for Candida spp. 
• Collect other cultures and histopathology from other sites, as clinically indicated 
• Perform imaging tests as clinically indicated to monitor the site(s) and extent of invasive 
candidiasis infection 
• Perform dilated fundoscopic examination (only required in those patients who had baseline 
positive fundoscopic findings [up to Day 3] or as clinically indicated) 
• Intravascular catheter management log, as clinically indicated 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight 
• Perform clinical laboratory assessments (serum chemistry, hematology, and urinalysis) 
• Perform 12-lead ECG 
• Perform urine pregnancy test (for females of childbearing potential only) 
• Perform neurological examination 
• Perform focused, symptom-based physical examination, as clinically indicated 
• Evaluate treatment outcome 
• Record concomitant medications 
• Assess adverse events 
 
6.5.3 
Early Termination Visit and Withdrawal Procedures 
 
For patients who are withdrawn from the study prior to completion, all EOST procedures will be 
performed at an Early Termination visit. These procedures include the following: 
• Collect blood culture for Candida spp. 
• Collect other cultures and histopathology from other sites, as clinically indicated 
• Perform imaging tests as clinically indicated to monitor the site(s) and extent of invasive 
candidiasis infection 
• Perform dilated fundoscopic examination (only required in those patients who had baseline 
positive fundoscopic findings [up to Day 3], or as clinically indicated) 
• Intravascular catheter management log, as clinically indicated 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight 

 
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• Perform clinical laboratory assessments (serum chemistry, hematology, coagulation and 
urinalysis) 
• Perform 12-lead ECG 
• Perform urine pregnancy test (for females of childbearing potential only) 
• Perform neurological examination 
• Perform focused, symptom-based physical examination, as clinically indicated 
• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]) 
• Collect serum sample for analysis of (1,3)-β-D-glucan 
• Evaluate treatment outcome 
• Record concomitant medications 
• Assess adverse events 
 
7 
EFFICACY ASSESSMENTS 
 
7.1 
Primary Efficacy Endpoint 
 
The primary efficacy parameter is percentage of patients with Treatment Success at EOST as 
determined by the Data Review Committee (DRC). 
 
7.2 
Secondary Efficacy Endpoints 
 
The secondary efficacy parameters include the following: 
• Time to first negative blood culture 
• Percentage of patients with successful Mycological Outcomes at EOST, and at 2 and 
4 weeks after EOST 
• Percentage of patients with Treatment Success at EOST as determined by the investigator  
• Percentage of patients with Treatment Success 2 and 4 weeks after EOST, as determined by 
the investigator and by the DRC 
• All-cause mortality at Study Day 30 
• Number of patients with TEAEs 
 
7.3 
Exploratory Efficacy Endpoint 
 
The exploratory efficacy parameters include the following: 
• Change in serum (1,3)-β-D-glucan levels from Baseline (pre-dose) to EOST 
 

 
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7.4 
Definitions for Efficacy Assessments 
 
7.4.1 
At End of Study Drug Treatment 
 
Treatment Success is defined as meeting all of the following criteria: 
• Two consecutive blood cultures negative for Candida spp. and/or for patients with a 
deep-seated site of infection, at least one negative tissue culture or aspirate/fluid 
o 
for patients with a deep-seated site of infection involving visceral organs from which a 
tissue culture is not obtainable, resolution of the attributable clinical signs of infection 
recorded at Baseline, and, as applicable, radiological improvement associated with the 
site of infection is required  
• Alive at EOST 
• No concomitant use of any other systemic antifungal therapies through EOST 
Note: administration of another systemic antifungal immediately following EOST for suspected or documented 
Candida infection at any site does not constitute a treatment success at EOST 
Treatment Failure is defined as any case that does not meet the criteria for Treatment Success. 
 
Successful Mycological Outcome: 
• Eradication is defined as a negative blood (and/or other infection site) culture(s) for 
Candida spp. in the absence of concomitant antifungal therapy through EOST 
• Presumed Eradication (applicable to invasive candidiasis) is defined as clinical resolution of 
invasive Candida spp. infection where tissue samples are unavailable (supported by evidence 
of resolution/improvement in the diagnostic parameters used at Baseline) 
 
Both of the above definitions are in the absence of concomitant or additional systemic antifungal 
therapy. 
 
7.4.2 
At Follow-Up (2 Weeks and 4 Weeks After End of Study Drug Treatment [EOST]) 
• 
Treatment Success (sustained) is defined as having met the criteria for Treatment Success at 
EOST with no change during the follow-up period 
• 
Relapse is defined as re-occurrence of Candida in blood culture, or from other infection 
sites, during the Follow-up Period, or diagnostic parameters indicative of recurrence or late 
spread of the Candida infection 
• 
Other: 
o 
Death 
o 
Unavailable for follow-up, or unevaluable at follow up for other reasons 
Additional DRC assessment categories are provided in the DRC Charter 

 
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Mycological Recurrence is defined as mycologically confirmed infection based on blood culture 
(or other specimen(s) cultured from a normally sterile site), with the same Baseline Candida spp. 
during the 4 weeks after EOST.  
 
7.5 
Microbiological Assessments 
 
7.5.1 
Blood Cultures 
 
For patients with candidemia, Candida auris confirmed in blood culture is required for 
qualification into the study, which must occur within 120 hours of the collection of the indicative 
positive blood sample. The study site’s local microbiology laboratory will analyze blood and other 
cultures for Candida spp. Isolates of all Candida spp from SOC eligibility cultures must be submitted to the 
mycology reference laboratory for confirmation of identification and susceptibility testing. 
 
For all patients (candidemia or invasive candidiasis), once consent is obtained, the first blood 
collection should comprise two consecutive sets (1 aerobic and 1 anaerobic blood culture bottle in 
each set) of blood cultures from 2 separate IV sites (1 from a central venous catheter (CVC) and 
1 peripheral, or 2 peripherals if CVC is not applicable); a minimum of 1 set  (1 aerobic and 
1 anaerobic blood culture bottle in each set) of blood cultures is required thereafter.  
 
Blood cultures for Candida spp. will be performed during the Screening period (daily), 
at Baseline (pre-dose), during Study Drug Treatment, at EOST, and 2 and 4 weeks after EOST, 
or Early Termination. During the Study Drug Treatment Period, blood cultures are required daily 
on Study Days 1 through 4; thereafter, blood cultures during study drug treatment may be stopped 
after negative results on 2 consecutive blood culture tests are obtained.  
The study site’s local microbiology laboratory will analyze all blood cultures for Candida spp. 
The local microbiology lab will send all Candida isolates from blood cultures to the mycology 
reference laboratory for confirmation of identification and susceptibility testing. 
 
In the event that the study site uses a rapid diagnostic test for the diagnosis of candidemia, 
subsequent confirmatory blood cultures are required, and resulting isolates should be submitted to 
the mycology reference laboratory for confirmation of identification and susceptibility testing. 
Results from rapid diagnostic tests performed must be captured in the eCRF. 
 
7.5.2 
Cultures from Other Sites of Infection 
 
For patients with invasive candidiasis, a tissue culture or aspirate/fluid sample confirmed positive 
for Candida auris that has been collected aseptically from a normally sterile site is required for 
inclusion in the study. Study qualification will occur within 168 hours of a confirmed positive 
tissue culture or aspirate/fluid collection. Isolates of all Candida spp. from SOC eligibility cultures 
and baseline and follow-up cultures must be submitted to the mycology reference laboratory for 
confirmation of identification and susceptibility testing. Tissue culture or aspirate/fluid samples 

 
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for Candida spp. will be collected at Baseline (pre-dose), and where amenable to sampling during 
Study Drug Treatment, at EOST, and 2 and 4 weeks after EOST, or Early Termination. Collection 
of culture or aspirate/fluid samples may be stopped after at least one negative tissue culture or 
aspirate/fluid sample.  
 
The study site’s local microbiology laboratory will analyze all tissue cultures or aspirate/fluid 
samples for Candida spp. The local microbiology lab will send all Candida isolates from tissue 
cultures or aspirate/fluid cultures to the mycology reference laboratory for confirmation of 
identification and susceptibility testing. 
 
7.5.3 
Intravascular Catheter Management and Log 
 
If possible, all intravascular catheters should be removed and the catheter tips cultured by the local 
microbiology laboratory within 24 hours of APX001 dosing. The entrance site should also be 
cultured by the local microbiology laboratory if it appears infected. The local microbiology lab 
will send all Candida isolates from intravascular catheter or entrance site cultures to the mycology 
reference laboratory for confirmation of identification and susceptibility testing. Intravascular 
catheter management should be managed at the site level as per local SOC. 
 
8 
SAFETY ASSESSMENTS 
 
8.1 
Adverse Events 
 
An adverse event is defined as any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship with 
this treatment. An adverse event can therefore be any unfavorable and/or unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a study drug, whether or not related to the study drug. All adverse events, including observed 
or volunteered problems, complaints, or symptoms, are to be recorded on the appropriate eCRF. 
 
Adverse events, which include clinical laboratory test variables, will be monitored and 
documented from the time of informed consent until study participation is complete. 
Subjects should be instructed to report any adverse event that they experience to the Investigator. 
Beginning with Day 1 of study drug, Investigators should make an assessment for adverse events at 
each visit and record the event on the appropriate adverse event eCRF. 
 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate adverse event on the eCRF. 
Additionally, the condition that led to a medical or surgical procedure (e.g., surgery, endoscopy, 
tooth extraction, or transfusion) should be recorded as an adverse event, not the procedure. 

 
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Any medical condition already present at Screening should not be reported as an adverse event 
unless the medical condition or signs or symptoms present at Baseline changes in severity or 
seriousness at any time during the study. In this case, it should be reported as an adverse event. 
 
Clinically significant abnormal laboratory or other examination (e.g., ECG) findings that are 
detected during the study or are present at Screening and significantly worsen during the study 
should be reported as adverse events. The Investigator will exercise his or her medical and 
scientific judgment in deciding whether an abnormal laboratory finding or other abnormal 
assessment is clinically significant. Clinically significant abnormal laboratory values occurring 
during the clinical study will be followed until repeat tests return to normal, stabilize, or are no 
longer clinically significant. Any abnormal test that is determined to be an error does not require 
reporting as an adverse event. A laboratory finding that is abnormal but not clinically significant 
(e.g., does not warrant intervention) is not considered an adverse event. 
 
8.1.1 
Adverse (Drug) Reaction 
All noxious and unintended responses to a study drug related to any dose should be considered an 
adverse drug reaction. “Responses” to a study drug means that a causal relationship between a 
study drug and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be 
ruled out. 
Drug-induced liver injury is defined in Appendix D, and requires study drug withdrawal. 
 
8.1.2 
Unexpected Adverse Drug Reaction 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information. For APX001, the reference safety 
information is included in the Investigator’s Brochure (IB) currently in force. The reference safety 
information will be reviewed yearly and the periodicity of the review will be harmonized with the 
reporting period of the Development Safety Update Report. 
 
8.1.3 
Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each adverse event and will also categorize 
each adverse event as to its potential relationship to study drug using the categories of “yes” or 
“no.” 
 
Assessment of Severity: 
The severity of all adverse events should be graded according to the Common Terminology 
Criteria 
for 
Adverse 
Events 
(CTCAE) 
v4.03. 
These 
criteria 
can 
be 
found 
at 
http://ctep.cancer.gov/reporting/ctc.html. For those adverse events not listed in the CTCAE, 
the following grading system should be used: 
• Mild (CTCAE Grade 1): Transient symptoms, awareness of sign/symptom, but easily 
tolerated and no interference with patient’s daily activities 

 
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• Moderate (CTCAE Grade 2): Marked signs/symptoms that interfere with patient’s usual 
activities, but still acceptable 
• Severe (CTCAE Grade 3): Incapacitating  signs/symptoms which cause considerable 
interference with the patient’s daily activities, unacceptable 
• Life-threatening (CTCAE Grade 4):  Life threatening or disabling adverse  event 
• Death (CTCAE Grade 5):  Death-related adverse event 
 
Causality Assessment: 
 
The relationship of an adverse event to the administration of the study drug is to be assessed 
according to the following definitions: 
 
No (unrelated, not related, no relation) – The time course between the administration of study drug 
and the occurrence or worsening of the adverse event rules out a causal relationship and another 
cause (concomitant drugs, therapies, complications, etc.) is suspected. 
 
Yes (related) – The time course between the administration of study drug and the occurrence or 
worsening of the adverse event is consistent with a causal relationship and no other cause 
(concomitant drugs, therapies, complications, etc.) can be identified. 
 
The definition implies a reasonable possibility of a causal relationship between the event and the 
study drug. This means that there are facts (evidence) or arguments to suggest a causal relationship. 
 
The following factors should also be considered: 
 
• The temporal sequence from study drug administration- 
o The event should occur after the study drug is given. The length of time from study drug 
exposure to event should be evaluated in the clinical context of the event 
• Underlying, concomitant, intercurrent diseases- 
o Each report should be evaluated in the context of the natural history and course of the 
disease being treated and any other disease the patient may have 
• Concomitant drug- 
o The other drugs the patient is taking or the treatment the patient receives should be 
examined to determine whether any of them might be recognized to cause the event in 
question 
• Known response pattern for this class of study drug- 
o Clinical and/or preclinical data may indicate whether a particular response is likely to be 
a class effect 

 
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• Exposure to physical and/or mental stresses- 
o The exposure to stress might induce adverse changes in the recipient and provide a 
logical and better explanation for the event 
• The pharmacology and PK of the study drug- 
o The known pharmacologic properties (absorption, 
distribution, metabolism, 
and excretion) of the study drug should be considered 
 
8.2 
Serious Adverse Events 
 
An adverse event or adverse reaction is considered serious if, in the view of either the Investigator 
or Sponsor, it results in any of the following outcomes: 
• Death 
• A life-threatening adverse event 
o An adverse event or adverse reaction is considered “life-threatening” if, in view of either 
the Investigator or Sponsor, its occurrence places the patient at immediate risk of death. 
It does not include an event that, had it occurred in a more severe form, might have 
caused death 
• Requires hospitalization or prolongation of existing hospitalizations 
o Any hospital admission with at least 1 overnight stay will be considered an inpatient 
hospitalization. An emergency room visit without hospital admission will not be 
recorded as a SAE under this criterion, nor will hospitalization for a procedure scheduled 
or planned before signing of informed consent. However, unexpected complications 
and/or prolongation of hospitalization that occur during elective surgery should be 
recorded as adverse events and assessed for seriousness. Admission to the hospital for 
social or situational reasons (i.e., no place to stay, live too far away to come for hospital 
visits) will not be considered inpatient hospitalizations 
• A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions 
• A congenital anomaly/birth defect 
• An important medical event 
o Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed above. Examples of such medical 
events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalizations, or the development of drug dependency 
 

 
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8.4 
Expedited Reporting 
 
The Sponsor will comply with all country-specific regulations relating to safety reporting to the 
regulatory authority, Institutional Review Board (IRB)/Independent Ethics Committee (IEC), 
and Investigators. 
 
The Sponsor will report all relevant information about suspected unexpected serious adverse 
reactions that are fatal or life-threatening as soon as possible to the Food and Drug Administration 
(FDA), applicable competent authorities in all the Member States concerned, and to the 
Central Ethics Committee, and in any case no later than 7 days after knowledge by the Sponsor of 
such a case, and that relevant follow-up information will subsequently be communicated within 
an additional 8 days. 
 
All other suspected unexpected serious adverse reactions will be reported to the FDA, applicable 
competent authorities concerned, and to the Central Ethics Committee as soon as possible but 
within a maximum of 15 days of first knowledge by the Sponsor. 
 
The Sponsor will also inform all Investigators as required. 
 
8.5 
Stopping Rules 
 
8.5.1 
Study Stopping Rule 
 
At any time, the independent DSMB may temporarily suspend enrollment until any significant 
safety concerns are resolved or terminate the study to ensure patient safety, if in the opinion of the 
DSMB, further dosing would pose an inappropriate safety risk. Guidelines for what constitutes 
inappropriate safety risks are described in the DSMB Charter. 
 
Additionally, the study may be discontinued for any of the following reasons: five or more subjects 
in study (cumulative) experience a same Grade 2 (or higher) related AE (laboratory or systemic) 
which is coded in the same high-level group term per MedDRA coding, throughout the duration 
of study; lack of investigational product availability; inability to enroll the study; or decision by a 
regulatory authority or the sponsor. 
 
8.5.2 
Subject Stopping Rule 
 
Study treatment for an individual patient may be discontinued for any adverse event, SAE, 
laboratory abnormality, or intercurrent illness which, in the opinion of the Investigator, indicates 
that continued dosing in the study is not in the best interest of the patient. 
 

 
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8.6 
Pregnancy Reporting 
 
A urine pregnancy test will be performed at Screening and Baseline (pre-dose), every 30 days 
during treatment if required by local regulations, EOST, and 2 and 4 weeks after EOST, or Early 
Termination for all female patients of childbearing potential. If the patient or partner of a patient 
participating in the study becomes pregnant during the study or within 30 days of discontinuing 
study drug, the Investigator should report the pregnancy to 
y within 
24 hours of being notified. 
 will then forward the Exposure In Utero Form 
to the Investigator for completion. 
 
A patient becoming pregnant while on study drug will immediately be withdrawn from the study 
and Early Termination study procedures will be performed. 
 
The patient or partner should be followed by the Investigator until completion of the pregnancy. 
If the pregnancy ends for any reason before the anticipated date, the Investigator should notify 
. At the completion of the pregnancy, the Investigator will document the 
outcome of the pregnancy within 24 hours. 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. 
 
8.7 
Clinical Laboratory Evaluations 
 
Screening laboratory assessments to determine eligibility will be performed at the local laboratory 
and may have been collected as SOC within the previous 24 hours. Laboratory assessments 
collected after Screening will be sent to the central laboratory for analysis. 
 
Clinical laboratory assessments (serum chemistry, hematology, coagulation, and urinalysis) will 
occur at Baseline (pre-dose), twice weekly during Study Drug Treatment, at EOST, and at 2 and 
4 weeks after EOST, or Early Termination. If clinically indicated and at the discretion of the 
Investigator, or if a suspected adverse event is identified, clinical laboratory assessments may be 
conducted at any time during the study and compared to Baseline. See Appendix B for a complete 
list of clinical laboratory analytes. 
 
8.8 
Vital Signs 
 
Vital signs will include temperature, blood pressure, heart rate, respiratory rate, oxygen saturation, 
and weight and will be collected at Screening, Baseline (pre-dose), daily on Study Days 1 through 
4 and twice weekly thereafter during Study Drug Treatment for outpatients (daily while inpatient), 
EOST, and 2 and 4 weeks after EOST, or Early Termination. Height will be collected (from the 
patient’s medical record) at Baseline only. 
 

 
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8.9 
APACHE II Score 
 
The APACHE II score (Appendix C) will be determined at Baseline (pre-dose). 
 
8.10 
Electrocardiograms 
 
A 12-lead ECG will be obtained at Baseline (pre-dose), EOST, and 4 weeks after EOST,  
or Early Termination. 
 
8.11 
Physical Examinations 
 
A complete physical examination will be conducted at Baseline (pre-dose). Complete physical 
examination will include an assessment of general appearance, skin, eyes, heart, chest, abdomen, 
the body site that corresponds to the entry site of candidemia (e.g., central venous catheter entry 
site), if applicable, and a neurological examination. Components of the neurological examination 
include cranial nerve, sensory and motor examination, reflex and gait testing, and coordination 
assessment.  
 
A neurological examination will be performed twice weekly during study drug treatment.  
A focused, symptom-based physical examination will be performed once weekly during study 
treatment. Neurological and focused, symptom-based examinations will also be performed at 
EOST, and 2 and 4 weeks after EOST, or Early Termination.  
 
8.12 
Pharmacokinetics 
 
Plasma samples for PK (APX001 [prodrug] and APX001A [active moiety]) will be collected at 
Baseline (pre-dose), twice weekly during Study Drug Treatment, EOST, and 2 weeks after EOST, 
or Early Termination. 
 
Optionally, if body fluids are sampled as part of routine patient management (e.g., bronchoalveolar 
lavage, lumbar puncture, paracentesis, vitreous fluid collection, abscess drainage, etc.), within 
approximately 2 hours of blood sampling for PK, these samples may be stored for future analysis 
of APX001 levels. 
 
8.13 
Dilated Fundoscopic Examination 
 
A dilated fundoscopic examination will be performed at Baseline + 3 days. Thereafter, a dilated 
fundoscopic examination is only required in those patients who had positive fundoscopic findings 
at Baseline + 3 days, or as clinically indicated. 
 

 
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8.14 
Imaging Tests 
 
Imaging should be performed to assess the site(s) and extent of invasive candidiasis infection as 
clinically indicated. 
 
9 
STATISTICS 
 
9.1 
Analysis Populations 
 
Intent-to-Treat Population/Safety Population 
The Intent-to-Treat Population/Safety Population will include all patients who have received at 
least 1 dose of APX001.  
 
Modified Intent-to-Treat Population 
The Modified Intent-to-Treat (MITT) Population will include all patients who satisfy the 
following criteria: 
• Received at least 1 dose of study drug 
• Have a confirmed diagnosis of candidemia and/or invasive candidiasis caused by C. auris 
within 120 hours (for candidemia) or 168 hours (for invasive candidiasis without candidemia) 
of study qualification 
 
Per-Protocol Population 
The Per-Protocol Population will include all patients in the MITT Population who satisfy the 
following criteria: 
• Meet the protocol’s key inclusion and exclusion criteria  
• Receive at least 80% of the intended doses 
• Have no major protocol violations 
 
Pharmacokinetic (PK) Population 
• The PK Population will include all patients who receive any amount of study drug and have 
evaluable PK data. 
 

 
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9.2 
Statistical Methods 
 
Summary statistics will be presented. For continuous variables, the number of observations (n), 
mean, standard deviation, median, minimum, and maximum will be provided. For categorical 
variables, the frequency and percentage in each category will be displayed. 
 
9.2.1 
Analysis of Efficacy 
 
9.2.1.1 
Primary Efficacy Analysis 
 
The primary population for efficacy analysis will be the MITT Population. 
 
The efficacy endpoints will be summarized descriptively. The percentage of patients with 
Treatment Success at EOST will be summarized. The same summary will be repeated for the 
Per-Protocol Population. 
 
9.2.1.2 
Secondary Efficacy Analysis 
 
The percentage of patients with Treatment Success at 2 and 4 weeks after EOST will be 
summarized. Similarly, the proportion of patients with Mycological Outcomes eradication or 
presumed eradication at EOST, and recurrence or relapse 2 and 4 weeks after EOST will be 
summarized. A descriptive summary of overall survival at Study Day 30 and time to first negative 
culture will also be provided. 
 
9.2.1.3 
Analysis of Safety 
 
All safety analyses will be performed on the Safety Population. Safety data will be subject to 
clinical review and summarized by appropriate descriptive statistics. A DSMB will be assigned to 
monitor safety on an ongoing basis throughout the study. 
 
Analyses will be based on adverse events, vital signs, clinical laboratory assessments, and ECGs. 
Safety analyses will be descriptive and will be presented in tabular format with the appropriate 
summary statistics. 
 
A TEAE is defined as an adverse event started on or after the administration of study drug. 
The number and percentage of patients with TEAEs will be tabulated by system organ class, 
preferred term, and by severity and relationship to treatment. Serious adverse events and adverse 
events leading to discontinuation from study drug will be summarized. Listings will also be 
provided for SAEs and adverse events leading to discontinuation of study drug. 
 

 
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Descriptive statistics will be provided for clinical laboratory data for both actual values and 
changes from baseline over time. 
 
Descriptive statistics will be provided for vital sign data presented as both actual values and 
changes from baseline over time. 
 
Abnormal physical examination findings will be listed. 
Descriptive statistics will be provided for ECG interval data and presented as both actual values 
and changes from baseline. 
 
9.2.1.4 
Pharmacokinetic Analysis 
 
Pharmacokinetic analysis of plasma concentration data will be performed using validated software. 
Pharmacokinetic analysis of plasma concentration data will be performed using validated software 
in order to derive the population mean (and variance) values of specific PK parameters.  
 
Plasma concentrations will be summarized descriptively by treatment group and time point of 
collection. Summary statistics in the tabulation will include n, mean, standard deviation, CV%, 
median, minimum, and maximum. Pharmacokinetic parameters will be estimated using population 
PK analysis methods, which will be described in a separate data analysis plan. Results of the PK 
analysis will be reported separately. 
 
9.2.2 
Interim Analysis 
 
No interim analysis is planned for the study. 
 
9.2.3 
Independent Data Review Committee (DRC) 
 
To ensure standardization of interpretation regarding the validity of study patients, the medical 
management, and response to treatment in this open-label study, a panel of recognized experts in 
the field of fungal infectious diseases will constitute a DRC. The DRC serves to provide 
independent oversight to confirm eligibility for efficacy analysis, to confirm the diagnosis of 
candidemia and/or invasive candidiasis at study entry, and to adjudicate efficacy outcome. 
The DRC assessments for each patient will be recorded in the database and used in the primary 
efficacy analysis of the study. The DRC members will not be Principal Investigators in the study. 
Guidelines for the DRC are described in the DRC Charter. 
 

 
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9.2.4 
Data and Safety Monitoring Board (DSMB) 
 
A DSMB comprised of members with pertinent expertise will review the accumulating data from 
the study periodically as set forth in the DSMB Charter, or more frequently at the request of the 
DSMB. The DSMB will advise the Sponsor on the continuing safety of the study patients and 
those yet to be recruited to the study, as well as the continuing validity and scientific merit of the 
study. The DSMB may recommend to the Sponsor that dosing in the study be suspended if, in the 
opinion of the DSMB, further dosing in the study would pose an inappropriate safety risk. 
Guidelines for what constitutes inappropriate safety risks are described in the DSMB Charter. 
 
9.2.5 
Sample Size Determination 
 
A sample size of approximately 15 patients will be recruited in this open-label study. No formal 
statistical assessment for sample size determination has been performed. This sample size is 
considered adequate to provide the necessary data to evaluate the efficacy and safety of APX001. 
 
10 
DATA MANAGEMENT AND RECORD KEEPING 
 
10.1 
Data Management 
 
10.1.1 
Data Handling 
 
Data will be recorded at the site on eCRFs and reviewed by the CRA during monitoring visits. 
The CRAs will verify data recorded in the EDC system with source documents. All corrections or 
changes made to any study data must be appropriately tracked in an audit trail in the EDC system. 
An eCRF will be considered complete when all missing, incorrect, and/or inconsistent data has 
been accounted for. 
 
10.1.2 
Computer Systems 
 
Data will be processed using a validated computer system conforming to regulatory requirements. 
 
10.1.3 
Data Entry 
 
Data must be recorded using the EDC system as the study is in progress. All site personnel must 
log into the system using their secure user name and password in order to enter, review, or correct 
study data. These procedures must comply with Title 21 of the Code of Federal Regulations 
(21 CFR Part 11) and other appropriate international regulations. All passwords will be strictly 
confidential. 
 

 
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10.1.4 
Medical Information Coding 
 
For medical information, the most recent versions of the following thesauri will be used: 
• Medical Dictionary for Regulatory Activities for medical history and adverse events 
• World Health Organization Drug Dictionary for prior and concomitant medications 
 
10.1.5 
Data Validation 
 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the downloaded data, will be applied to the data in order to ensure 
accurate, consistent, and reliable data. Data identified as erroneous, or data that are missing, will be 
referred to the investigative site for resolution through data queries. 
 
The eCRFs must be reviewed and electronically signed by the Investigator. 
 
10.2 
Record Keeping 
 
Records of patients, source documents, monitoring visit logs, eCRFs, inventory of study product, 
regulatory documents, and other Sponsor correspondence pertaining to the study must be kept in 
the appropriate study files at the site. Source data is defined as all information in original records 
and certified copies of original records of clinical findings, observations, or other activities in a 
clinical study necessary for the evaluation and reconstruction of the clinical study. Source data are 
contained in source documents (original records or certified copies). These records will be retained 
in a secure file for the period as set forth in the Clinical Study Agreement. Prior to transfer or 
destruction of these records, the Sponsor must be notified in writing and be given the opportunity 
to further store such records. 
 
11 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL 
 
11.1 
Ethical Conduct of the Study 
 
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve human subjects. Compliance with this 
standard provides public assurance that the rights, safety, and wellbeing of study subjects are 
protected, consistent with the principles that have their origin in the Declaration of Helsinki, and 
that the clinical study data are credible. 
 

 
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11.2 
Institutional Review Board/Independent Ethics Committee 
 
The IRB/IEC will review all appropriate study documentation in order to safeguard the rights, 
safety, and well-being of subjects. The study will only be conducted at sites where IRB/IEC 
approval has been obtained. The protocol, IB, ICF, advertisements (if applicable), 
written information given to the subjects, safety updates, annual progress reports, and any 
revisions to these documents will be provided to the IRB/IEC by the Investigator. 
 
Federal regulations and International Council for Harmonisation (ICH) require that approval be 
obtained from an IRB/IEC prior to participation of subjects in research studies. Prior to study onset, 
the protocol, any protocol amendments, ICFs, and any other written information regarding this 
study to be provided to a subject or subject’s legal guardian must be approved by the IRB/IEC. 
 
11.3 
Informed Consent 
 
The ICF and any changes to the ICF made during the course of the study must be agreed to by the 
Sponsor or designee and the IRB/IEC prior to its use and must be in compliance with all ICH GCP, 
local regulatory requirements, and legal requirements. 
 
The Investigator must ensure that each study patient is fully informed about the nature and 
objectives of the study and possible risks associated with participation and must ensure that the 
patient has been informed of his/her rights to privacy. The Investigator will obtain written informed 
consent from each patient before any study-specific activity is performed and should document in 
the source documentation that consent was obtained prior to enrollment in the study. The patient 
(or the patient’s LAR) will sign and date the ICF, and the original signed copy of the ICF must be 
maintained by the Investigator and is subject to inspection by a representative of the Sponsor, their 
representatives, auditors, the IRB/IEC and/or regulatory agencies. A copy of the signed ICF will 
be given to the patient. 
 
11.4 
Patient Card 
 
On qualification for the study, the patient will receive a patient card. The patient card will state 
that the patient is participating in a clinical research study, type of treatment administered, 
and contact details in case of an SAE. 
 

 
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11.5 
Study Monitoring Requirements 
 
It is the responsibility of the Investigator to ensure that the study is conducted in accordance with 
the protocol, ICH GCP, Directive 2001/20/EC, applicable regulatory requirements, and the 
Declaration of Helsinki and that valid data are entered into the eCRFs. 
 
To achieve this objective, the monitor’s duties are to aid the Investigator and, at the same time, 
the Sponsor in the maintenance of complete, legible, well organized, and easily retrievable data. 
Before the enrollment of any patient in this study, the Sponsor or their designee will review with 
the Investigator and site personnel the following documents: protocol, IB, eCRFs and procedures 
for their completion, informed consent process, and the procedure for reporting SAEs. 
 
The Investigator will permit the Sponsor or their designee to monitor the study as frequently as 
deemed necessary to determine that data recording and protocol adherence are satisfactory. 
During the monitoring visits, information recorded on the eCRFs will be verified against source 
documents and requests for clarification or correction may be made. After the eCRF data is entered 
by the site, the CRA will review the data for safety information, completeness, accuracy, 
and logical consistency. Computer programs that identify data inconsistencies may be used to help 
monitor the clinical study. If necessary, requests for clarification or correction will be sent to 
Investigators. The Investigator and his/her staff will be expected to cooperate with the monitor and 
provide any missing information, whenever possible. 
 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the investigational site by signature and date on the study-specific monitoring log. 
 
11.6 
Disclosure of Data 
 
Data generated by this study must be available for inspection by the FDA, the Sponsor or their 
designee, applicable foreign health authorities, and the IRB/IEC as appropriate. Subjects or their 
legal representatives may request their medical information be given to their personal physician or 
other appropriate medical personnel responsible for their welfare. 
 
Subject medical information obtained during the study is confidential and disclosure to third 
parties other than those noted above is prohibited. 
 
11.7 
Retention of Records 
 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator 
will keep records, including the identity of all participating patients (sufficient information to link 
records, e.g., eCRFs and hospital records), all original signed ICFs, copies of all eCRFs, SAE forms, 
source documents, and detailed records of treatment disposition. The records should be retained 
by the Investigator according to specifications in the ICH guidelines, local regulations, or as 

 
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specified in the Clinical Study Agreement, whichever is longer. The Investigator must obtain 
written permission from the Sponsor before disposing of any records, even if retention 
requirements have been met. 
 
If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor should 
be prospectively notified. The study records must be transferred to an acceptable designee, such 
as another Investigator, another institution, or to the Sponsor. 
 
11.8 
Publication Policy 
 
Following completion of the study, the data may be considered for publication in a scientific 
journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data 
pertaining to the study confidential. The Investigator must consult with the Sponsor before any 
study data are submitted for publication. The Sponsor reserves the right to deny publication rights 
until mutual agreement on the content, format, interpretation of data in the manuscript, and journal 
selected for publication are achieved. 
 
11.9 
Financial Disclosure 
 
Investigators are required to provide financial disclosure information to the Sponsor to permit the 
Sponsor to fulfill its obligations under 21 CFR Part 54. In addition, Investigators must commit to 
promptly updating this information if any relevant changes occur during the study and for a period 
of 1 year after the completion of the study. 
 
11.10 
Insurance and Indemnity 
 
In accordance with the relevant national regulations, the Sponsor has taken out subject liability 
insurance for all subjects who have given their consent to the clinical study. This cover is designed 
for the event that a fatality, physical injury, or damage to health occurs during the clinical study’s 
execution. 
 
11.11 
Legal Aspects 
 
The clinical study is submitted to the relevant national competent authorities in all participating 
countries to achieve a clinical trial authorization (CTA). 
 
The study will commence (i.e., initiation of study centers) when the CTA and favorable Ethics 
opinion have been received. 
 

 
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12 
STUDY ADMINISTRATIVE INFORMATION 
 
12.1 
Protocol Amendments 
 
Any amendments to the study protocol will be communicated to the Investigators by 
 or 
the Sponsor. All protocol amendments will undergo the same review and approval process as the 
original protocol. A protocol amendment may be implemented after it has been approved by the 
IRB/IEC, unless immediate implementation of the change is necessary for patient safety. In this 
case, the situation must be documented and reported to the IRB/IEC within 5 working days. 
 
12.2 
Address List 
 
12.2.1 
Sponsor 
 
Amplyx Pharmaceuticals, Inc.  
  
 
 
 
 
12.2.2 
Contract Research Organization 
 
 
 
 
 
 
 
12.2.3 
Drug Safety 
 
 
 
 
 
 
 

 
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12.2.4 
Biological Specimens 
 
 
 
 
 
 
 
 
 
 
 
 
 
12.2.5 
Mycology Reference Laboratory 
 
 
 
 
0 
 
12.2.6 
Pharmacokinetic Laboratory 
 
 
 
 
 

 
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13 
REFERENCES 
1. 
Chowdhary A, Sharma C, Duggal S, Agarwal K, Prakash A, Singh PK, et al. New clonal 
strain of Candida auris, Delhi, India. Emerg Infect Dis. 2013;19(10):1670-3.  
2. 
Chowdhary A, Kumar VA, Sharma C, Prakash A, Agarwal K, Babu R, et al. 
Multidrug-resistant endemic clonal strain of Candida auris in India. Eur J Clin Microbiol 
Infect Dis. 2014;33(6):919-26.  
3. 
Magobo RE, Corcoran C, Seetharam S, Govender NP. Candida auris-associated 
candidemia, South Africa. Emerg Infect Dis. 2014;20:1250-1.  
4. 
Magobo RE, Corcoran C, Govender NP. Molecular typing of multidrug-resistant Candida 
auris strains in Gauteng province, South Africa. Abstract presented at: ASLM; 2016 
December; South Africa. 2016.  
5. 
Vallabhaneni S. Investigation of the First Seven Reported Cases of Candida auris, a 
Globally 
Emerging 
Invasive, 
Multidrug-Resistant 
Fungus—United 
States,  
May 2013–August 2016. MMWR Morbidity and Mortality Weekly Report. 2016;65.  
6. 
Schelenz S, Hagen F, Rhodes JL, Abdolrasouli A, Chowdhary A, Hall A, et al. 
First hospital outbreak of the globally emerging Candida auris in a European hospital. 
Antimicrobial Resistance & Infection Control. 2016;5(1):35. 
7. 
Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H. Candida auris 
sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in 
a Japanese hospital. Microbiol Immunol. 2009;53(1):41-4.  
8. 
Kim M-N, Shin JH, Sung H, Lee K, Kim E-C, Ryoo N, et al. Candida haemulonii and 
closely related species at 5 university hospitals in Korea: identification, antifungal 
susceptibility, and clinical features. Clin Infect Dis. 2009;48(6):e57-e61. 
9. 
Lee WG, Shin JH, Uh Y, Kang MG, Kim SH, Park KH, et al. First three reported cases of 
nosocomial fungemia caused by Candida auris. J Clin Microbiol. 2011;49(9):3139-42.  
10. 
Emara M, Ahmad S, Khan Z, Joseph L, Al-Obaid Im, Purohit P, et al. Candida auris 
candidemia in Kuwait, 2014. Emerging infectious diseases. 2015;21(6):1091.  
11. 
CDC. Clinical Alert to U.S. Healthcare Facilities: Global Emergence of Invasive Infections 
Caused by the Multidrug-Resistant Yeast Candida auris 2016. Available from: 
http://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-alert.html.  
12. 
PHE. Guidance for the laboratory investigation, management and infection prevention and 
control 
for 
cases 
of 
Candida 
auris 
2016. 
Available 
from: 
https://www.gov.uk/government/collections/candida-auris. 

 
Amplyx Pharmaceuticals, Inc 
 
Clinical Study Protocol APX001-203 
 
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13. 
Tsay S. Mycotic Diseases Branch, Division of Foodborne, Waterborne, and Environmental 
Diseases. Epidemic Intelligence Service. Centers for Disease Control and Prevention. 
Atlanta, 
Georgia. 
Correspondence: 
S. 
Tsay, 
1600 
Clifton 
Rd 
NE,  
Mailstop C-09, Atlanta, GA 30329 (stsay@cdc.gov).  
14. 
Okinda N, Kagotho E, Castanheira M, Njuguna A, Omuse G, Makau P, et al. 2013. 
Candidemia at a referral hospital in sub-Saharan Africa: Emergence of Candida auris as a 
major pathogen. Poster presentation at: ECCMID 2013 
15. 
Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, et al. 
2016. Simultaneous emergence of multidrug resistant Candida auris on three continents 
confirmed by whole genome sequencing and epidemiological analyses. Clin Infect Dis. 
2016:ciw691.  
16. 
Tsay S, Kallen A, Jackson BR, Chiller TM. Approach to the investigation and management 
of patients with Candida auris, an emerging multidrug-resistant yeast.  Clin Infect Dis. 
2018:66(2):306–11. 
17. 
Castanheira M, Duncanson FP, Diekema DJ, Guarro J, Jones RN, Pfaller MA. 2012. 
Activities of E1210 and comparator agents tested by CLSI and EUCAST broth 
microdilution methods against Fusarium and Scedosporium species identified using 
molecular methods. Antimicrob Agents Chemother 56:352–357. doi:10.1128/AAC. 
05414-11.  
18. 
Miyazaki M, Horii T, Hata K, Watanabe NA, Nakamoto K, Tanaka K, Shirotori S, Murai 
N, Inoue S, Matsukura M, Abe S, Yoshimatsu K, Asada M. 2011. In vitro activity of E1210, 
a novel antifungal, against clinically important yeasts and molds. Antimicrob Agents 
Chemother 55:4652–4658. doi:10.1128/AAC.00291-11. 
19. 
Pfaller MA, Duncanson F, Messer SA, Moet GJ, Jones RN, Castanheira M. 2011. In vitro 
activity of a novel broad-spectrum antifungal, E1210, tested against Aspergillus spp. 
determined by CLSI and EUCAST broth microdilution methods. Antimicrob Agents 
Chemother 55:5155–5158. doi:10.1128/AAC.00570-11. 
20. 
Pfaller MA, Hata K, Jones RN, Messer SA, Moet GJ, Castanheira M. 2011. In vitro activity 
of a novel broad-spectrum antifungal, E1210, tested against Candida spp. as determined by 
CLSI 
broth 
microdilution 
method. 
Diagn 
Microbiol 
Infect 
Dis  
71:167–170. doi:10.1016/j.diagmicrobio.2011.05.001. 
21. 
Pfaller MA, Watanabe N, Castanheira M, Messer SA, Jones RN. 2011. Pre-clinical 
development of antifungal susceptibility test methods for the testing of the novel antifungal 
agent E1210 versus Candida: comparison of CLSI and European Committee on 
Antimicrobial 
Susceptibility 
Testing 
methods. 
J 
Antimicrob 
Chemother  
66:2581–2584. doi:10.1093/jac/dkr342. 

 
Amplyx Pharmaceuticals, Inc 
 
Clinical Study Protocol APX001-203 
 
Page 71 of 79 
Confidential & Proprietary 
Version 4.0, 08 April 2020 
22. 
Berkow EL, Lockhart SR. Activity of novel antifungal compound APX001A against a 
large collection of Candida auris. J Antimicrob Chemother. 2018 Nov 1;73(11): 
3060-3062. doi: 10.1093/jac/dky302. 
23. 
Hager CL, Larkin EL, Long L, Abidi FZ, Shaw KJ, Ghannoum MA. In Vitro and In Vivo 
Evaluation of the Antifungal Activity of APX001A/APX001 against Candida auris. 
Antimicrob 
Agents 
Chemother 
Feb 
2018, 
62 
(3) 
e02319-17;  
doi: 10.1128/AAC.02319-17. 
 

 
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APPENDIX A:  SCHEDULE OF PROCEDURES 
 
Procedure 
Eligibility 
Screening 
(120 or <168 
Hours of 
Baseline)[a] 
Treatment Period[b] 
Follow-up 
Early 
Termination 
Baseline 
(Day 1 
Pre-Dose) 
Study Drug 
Treatment 
(42 Days) 
End of Study 
Drug Treatment 
(EOST)[c] 
Follow-up 
2 Weeks 
After 
EOST +2 
Days 
Follow-up 
4 Weeks 
After 
EOST +4 
Days 
Informed consent 
 
X[d] 
 
 
 
 
 
 
Inclusion/exclusion criteria 
 
X 
X 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
APACHE II score 
 
 
X 
 
 
 
 
 
Vital signs/temperature[e] 
 
X 
X 
X 
X 
X 
X 
X 
Intravascular catheter/device 
management log (including 
any drains, if applicable)[f] 
 
X[g] 
X[g] 
X 
X 
X[h] 
X[h] 
X 
Dilated fundoscopic 
examination 
 
 
X* 
 
X[i] 
 
X[i] 
X[i] 
Clinical safety laboratory 
tests[j] 
 
X 
X 
X 
X 
X 
X 
X 
12-lead electrocardiogram 
 
 
X 
 
X 
 
X 
X 
Urine pregnancy test (for 
females of childbearing 
potential only) 
 
X 
X 
X[k] 
X 
X 
X 
X 
Physical examination[l] 
 
 
X 
X 
X 
X 
X 
X 
Blood sample for Candida 
auris spp. culture [m,o] 
X[p] 
X[m,p] 
X[m,n,o] 
X[n,o] 
X[n,o] 
X[n,o] 
X[n,o] 
X[n,o] 
Blood sample for rapid 
diagnostic test[p] 
X 
 
 
 
 
 
 
 
 
 

 
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APPENDIX A:  SCHEDULE OF PROCEDURES (CONT’D) 
 
Procedure 
Eligibility 
Screening 
(120 or <168 
Hours of 
Baseline)[a] 
Treatment Period[b] 
Follow-up 
Early 
Termination 
Baseline 
(Day 1 
Pre-Dose) 
Study Drug 
Treatment 
(42 Days) 
End of Study 
Drug Treatment 
(EOST)[c] 
Follow-up 
2 Weeks 
After 
EOST +2 
Days 
Follow-up 
4 Weeks 
After 
EOST +4 
Days 
Other cultures and 
histopathology[h,r] 
X[u] 
X[u] 
X 
X 
X 
X 
X 
X 
Imaging tests[h,r] 
X[u] 
X[u] 
X 
X 
X 
X 
X 
X 
Pharmacokinetic sample[q] 
 
 
X 
X 
X 
X 
 
X 
Serum sample[s] 
 
 
X 
 
X 
 
 
X 
Evaluation of treatment 
outcome 
 
 
 
 
X 
X 
X 
X 
Study drug administration[t] 
 
 
 
X 
 
 
 
 
Prior/concomitant medications 
 
X 
X 
X 
X 
X 
X 
X 
Adverse event evaluation 
 
X 
X 
X 
X 
X 
X 
X 
a. 
To be completed within 120 hours (for candidemia) or 168 hours (for invasive candidiasis without candidemia) from blood or tissue/fluid/aspirate sampling time for 
culture positive for Candida spp. 
b. For outpatients during Study Drug Treatment, twice weekly visits are required with a maximum window of 2 days. Patients will be asked to record daily 
dosing on a diary and to bring the diary and study drug bottles with them to every clinic visit. 
c. 
End of Study Drug Treatment (EOST) occurs after completion of APX001 dosing. 
d. To be obtained prior to the initiation of any protocol-specific procedure outside of SOC. 
e. 
Vital signs will include temperature, blood pressure, heart rate, respiratory rate, oxygen saturation, and weight. Vital signs will be collected at Screening, 
Baseline (pre-dose), daily on Study Days 1 to 4, and twice weekly thereafter for outpatients (daily while inpatient) during Study Drug Treatment, EOST, 
and 2 and 4 weeks after EOST, or Early Termination. Height will be collected (from the patient’s medical record) at Baseline. 
f. 
Intravascular catheters logged until EOST while inpatient, and as clinically indicated thereafter or for outpatients. 
g. If possible, all indwelling intravascular catheters should be removed and the catheter tips cultured prior to starting APX001 dosing. The entrance site should 
also be cultured if it appears infected. Any removed catheter tip should be sent for culture. 
h. As clinically indicated.  
i. 
(* Baseline dilated fundoscopy may be performed up to Day 3 of study) Only required in those patients who had positive fundoscopic findings up to Day 3 or 
as clinically indicated. 
 
 

 
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Footnotes from appendix above (cont’d) 
j. 
Screening laboratory assessments to determine eligibility will be performed at the local laboratory and may have been collected as SOC within the previous 
24 hours. Laboratory assessments collected after Screening will be sent to the central laboratory for analysis. Clinical safety laboratory assessments 
(serum chemistry [including testing for C-reactive protein], hematology, coagulation, and urinalysis) will be collected at Baseline (pre-dose), twice weekly 
during Study Drug Treatment, at EOST, and 2 and 4 weeks after EOST, or Early Termination. If clinically indicated and at the discretion of the Investigator, 
or if a suspected adverse event is identified, clinical laboratory assessments may be conducted at any time during the study and compared to Baseline. 
k. Urine pregnancy test (for females of childbearing potential only) every 30 days if required by local regulations. 
l. 
A complete physical examination will be conducted at Baseline (pre-dose). Complete physical examination will include an assessment of general appearance, 
skin, eyes, heart, chest, abdomen, the body site that corresponds to the entry site of candidemia (e.g. central venous catheter entry site) and/or site of invasive 
candidiasis, if applicable, and a neurological examination. Components of the neurological examination include cranial nerve, sensory and motor examination, 
reflex and gait testing, and coordination assessment. A neurological examination will be performed twice weekly during study drug treatment. A focused, 
symptom-based physical examination will be performed once weekly during study drug treatment, EOST, and 2 and 4 weeks after EOST, or Early Termination. 
m. Blood cultures (daily) during 120-hour (5-day) screening period:  after consent obtained the first blood collection to comprise two sets taken at one time, within 
120 hours before the initiation of APX001 study treatment; 1 set thereafter. 
n. All Candida spp. isolates must be submitted to the mycology reference laboratory for confirmation of identification and susceptibility testing.  
o. During Study Drug Treatment, daily blood cultures on Study Days 1 through 4 (minimum), continuing daily until 2 negative blood culture results on 
2 consecutive tests reported. 
p. Optional rapid diagnostic test, if available, for Candida diagnosis; test (e.g. T2MR or PCR); subsequent confirmatory blood cultures must also be performed. 
q. Plasma samples for PK (APX001 [prodrug] and APX001A [active moiety]) will be collected at Baseline (pre-dose), twice weekly during Study Drug 
Treatment, EOST, 2 weeks after EOST, or Early Termination. Plasma samples for PK will be collected at the same time as samples are collected for the study’s 
clinical laboratory assessments. Optional: If body fluids are sampled as part of routine patient management (e.g. bronchoalveolar lavage, lumbar puncture, 
paracentesis, vitreous fluid collection, abscess drainage), within approximately 2 hours of blood sampling for PK, these samples may be stored for future 
analysis of APX001 and APX001A levels.  
r. 
Other cultures, histopathology, and imaging tests to assess the site(s) and extent of invasive candidiasis infection, if applicable. If performed, these will be 
analyzed at the local study site. 
s. 
Serum samples for (1,3)-β-D-glucan levels will be collected at Baseline (pre-dose) and EOST, or Early Termination (if applicable). 
t. 
Study drug will be administered as an IV loading dose over 3 hours BID on Study Day 1 (or over the first 24 hours if started in the evening);  
on Study Days 2 and 3 study drug will be administered over 3 hours by IV QD; on Study Day 4 and onward, PO administration of the study drug may be 
considered if the patient meets the IV to PO switch criteria. Study drug will be administered for up to 42 days (inclusive of the loading dose [Study Day 1]) 
u. (i) Tissue cultures or aspirate/fluid aseptically sampled from normally sterile sites confirmed for C. auris, (ii) imaging diagnostic for invasive candidiasis, may 
be obtained up to 168 hours prior to qualification for the study.  
APACHE = Acute Physiology and Chronic Health Evaluation; BID = twice daily; eCRF = electronic Case Report Form; EOST = End of Study Drug Treatment; 
IV = intravenous(ly); PK = pharmacokinetic; PO = oral(ly); QD = once daily; SOC = standard of care; spp. = species; T2MR = T2 magnetic resonance. 
 
 

 
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Clinical Study Protocol APX001-203 
 
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APPENDIX B:  CLINICAL LABORATORY ANALYTES 
 
Standard Safety Chemistry Panel 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Amylase 
Aspartate aminotransferase 
Bicarbonate 
Bilirubin (total, direct, and indirect) 
Blood urea nitrogen 
C-Reactive Protein 
Calcium 
Chloride 
Creatinine 
Creatine kinase 
Gamma-glutamyl transferase 
Estimated glomerular filtration rate 
Inorganic phosphorus 
Glucose 
Lipase 
Lactate dehydrogenase 
Sodium 
Potassium 
Uric acid 
Total protein 
 
Uric acid 
 
Hematology 
Hematocrit 
Hemoglobin 
Platelets 
Red blood cell count 
White blood cell count and differential [1] 
1. Manual microscopic review is performed only if white blood cell count and/or 
differential values are out of reference range. 
 
 
Coagulation 
Prothrombin time 
International normalized ratio 
 
Urinalysis 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocyte esterase 
Microscopy [1] 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
 
1. Microscopy is performed only as needed based on positive dipstick test results. 
 
 
Other Tests 
Urine pregnancy test (females of childbearing potential only) 
 

 
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Clinical Study Protocol APX001-203 
 
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APPENDIX C:  APACHE II SCORE FORM 
 
  
  
High Abnormal Range 
Low Abnormal Range 
  
Physiologic Variable 
+4 
+3 
+2 
+1 
0 
+1 
+2 
+3 
+4 
1 
Temperature rectal (oC) 
41 
39-40.9 
38.5-38.9 
36.0-38.4 
34-35.9 
32-33.9 
30-31.9 
29.9 
2 
Mean arterial pressure = 
(2 x diastolic + 
systolic)/3 
160 
130-159 
110-129 
70-109 
50-69 
49 
3 
Heart rate  
(ventricular response) 
180 
140-179 
110-139 
70-109 
55-69 
40-54 
39 
4 
Respiratory rate  
(non-ventilated or 
ventilated) 
50 
35-49 
25-34 
12-24 
10-11 
6-9 
5 
5 
Oxygenation 
A-aDO2 or PaO2 
(mmHg) 
a)FiO2>0.5 record  
A-aDO2 
500 
350-499 
200-349 
200 
  
b)FiO2<0.5:record only 
PaO2 
70 
61-70 
55-60 
55 
6 
Arterial pH 
If no ABGs record 
serum HCO3 below 
7.7 
7.6-7.69 
7.5-7.59 
7.33-7.49 
7.25-7.32 
7.15-7.24 
7.15 
7 
Serum sodium 
180 
160-179 
155-159 
150-154 
130-139 
120-129 
111-119 
110 
8 
Serum potassium 
7 
6-6.9 
5.5-5.9 
3.5-5.4 
3-3.4 
2.5-2.9 
2.5 
9 
Serum creatinine 
(mg/dL) 
Double point for acute 
renal failure 
3.5 
2-3.4 
1.5-1.9 
0.6-1.4 
0.6 
10 
Hematocrit (%) 
60 
50-59.9 
46-49.9 
30-45.9 
20-29.9 
20 
11 
White blood count 
40 
20-39.9 
15-19.9 
3-14.9 
1-2.9 
1 
12 
Glasgow Coma Scale 
(see next page) 
(Score = 15 minus 
actual GCS) 
15 minus the GCS = 
A 
Total Acute Physiology 
Score (APS) 
Sum of the 12 individual variable points = 
* 
Serum HCO3  
(venous-mmol/L)  
Not preferred, use if no 
ABGs 
>52 
41-51.9 
32-40.9 
22-31.9 
18-21.9 
15-17.9 
15 

 
Amplyx Pharmaceuticals, Inc 
 
Clinical Study Protocol APX001-203 
 
Page 77 of 79 
Confidential & Proprietary 
Version 4.0, 08 April 2020 
APPENDIX C:  APACHE II SCORE FORM (CONT’D) 
 
Glasgow Coma Scale  
(Circle appropriate response) 
B   Age Points 
C  
Chronic Health Points 
Apache II 
Score (sum of 
A+B+C) 
Eyes open 
4 - spontaneously 
3 - to verbal 
2 - to painful 
stimuli 
1 - no response 
 
Motor response 
6 - to verbal 
command 
5 - localizes to 
pain 
4 - withdraws to 
pain 
3 - decorticate 
2 - decerebrate 
1 - no response 
Verbal - nonintubated 
5 - oriented and 
conversant 
4 - disoriented and 
talks 
3 - inappropriate 
words 
2 - incomprehensible 
sounds 
1 - no response 
 
Verbal - intubated 
5 - seems able to talk 
3 - questionable 
ability to talk 
1 - generally 
unresponsive 
Age 
44 
45-54 
55-64 
65-74 
75 
 
Points 
0 
2 
3 
5 
6  
If any of the 5 CHE categories below is 
answered with yes, give +5 points for non-
operative or emergency postoperative 
patients or +2 points for elective 
postoperative patients. 
   A APS 
points (from 
prior page) 
+ B Age 
points 
+ C Chronic 
Health points 
__________ 
= Total 
APACHE II 
Liver 
- Cirrhosis with PHT or 
encephalopathy 
Age points = 
Cardiovascular 
- Class IV angina or at 
rest or with minimal 
self-care activities 
Pulmonary 
- Chronic hypoxemia or 
hypercapnia or 
polycythaemia of PHT 
>40 mmHg 
Kidney 
- Chronic peritoneal or 
haemodialysis 
Immune 
- Immune compromised 
host 
Chronic Health Points =  
A-aDO2 = alveolar-arterial oxygen difference; ABG = arterial blood gases; APACHE = Acute Physiology and Chronic Health 
Evaluation; APS = acute physiology score; CHE = chronic health evaluation; FiO2 = fraction of inspired oxygen;  
GCS = Glasgow coma scale; HCO3 = bicarbonate; IV = intravenous; PaO2 = arterial partial pressure of oxygen;  
PHT = pulmonary hypertension. 
Source: Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med. 
1985;13(10);818–29 
 

 
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APPENDIX D:  DRUG-INDUCED LIVER INJURY CRITERIA 
 
For patients with normal liver transaminases and bilirubin at baseline: 
If patients with normal baseline liver indices develop new elevations of aspartate aminotransferase 
(AST) or alanine aminotransferase (ALT) or alkaline phosphatase (ALP) >3x upper limit of normal 
(ULN) or total bilirubin (TBL) >2xULN values during the study, repeat testing should be 
performed within 48 to 72 hours. Investigators should also ask the patient if he/she has symptoms. 
If there are persistent elevations (ALT or AST >3x ULN or TBL >2x ULN) upon repeat testing, 
then close observation (as described below) should be implemented and discontinuation of drug 
should be considered. 
Drug should be discontinued, and the patient followed until resolution of symptoms or signs in the 
following situations: 
• ALT or AST >8x ULN 
• ALT or AST >5x ULN for more than 2 weeks. 
• ALT or AST >3x ULN and (TBL >2x ULN or INR >1.5) 
• ALT or AST >3x ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
For patients with elevations in baseline transaminases or bilirubin: 
If patients with abnormal baseline liver indices develop elevations of AST or ALT >2 x baseline 
or TBL >2 x baseline values during the study, repeat testing should be performed within 
48 to 72 hours.  Investigators should also ask to the patient if he/she has symptoms. 
If there are persistent elevations (ALT or AST >2x baseline or TBL >2x baseline values) upon 
repeat testing, then close observation (as described below) should be implemented and 
discontinuation of drug should be considered. 
Drug should be discontinued, and the patient followed until resolution of symptoms or signs in the 
following situations: 
• If baseline measurements were <2x ULN, discontinue if ALT or AST increases to >5x baseline 
measurements. 
• If baseline average measurements >2x ULN, discontinue if ALT or AST increases to 
>3x  baseline measurements. 
• Discontinue if ALT or AST increase >2x baseline measurements AND the increase is 
accompanied by a concomitant increase in TBL to >2x baseline measurements or the INR 
concomitantly increases by >0.2. 
• For any patients who present with a constellation of syndromes indicative of liver disease as per 
the Investigator’s overall assessment (ie, fatigue, nausea, vomiting, right upper quadrant pain 
or tenderness, fever, rash, and/or eosinophilia [>5%]). 
 

 
Amplyx Pharmaceuticals, Inc 
 
Clinical Study Protocol APX001-203 
 
Page 79 of 79 
Confidential & Proprietary 
Version 4.0, 08 April 2020 
Close observation for suspected drug-induced liver injury includes the following: 
• Repeating liver enzyme (ALT, AST, and ALP) and TBL tests 2 or 3 times weekly. 
The frequency of repeat testing can decrease to once a week or less if abnormalities stabilize or 
the study drug has been discontinued and the patient is asymptomatic. 
• Obtaining a more detailed history of symptoms and prior or concurrent diseases. 
• Obtaining a history of concomitant drug use (including nonprescription medications and herbal 
and dietary supplement preparations), alcohol use, recreational drug use, and special diets. 
• Ruling out acute viral hepatitis types A, B, C, D, and E; autoimmune or alcoholic hepatitis; 
hypoxic/ischemic hepatopathy; and biliary tract disease. 
• Obtaining a history of exposure to environmental chemical agents. 
• Obtaining additional tests to evaluate liver function, as appropriate (eg, INR, direct bilirubin). 
• Considering gastroenterology or hepatology consultations.