Clinical trial NCT03604705
Conditions: Candidemia
Sponsor: Basilea Pharmaceutica
Start date: 2018-10-03; Completion date: 2020-07-02
Enrollment: 21 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a multicenter, open-label, non-comparative, single-arm study to evaluate the efficacy and safety of APX001 for the first-line treatment for candidemia including suspected or confirmed antifungal-resistant candidemia in non-neutropenic patients 18 yeas of age and older.

Suspicion of antifungal-resistant candidemia is sufficient (documented resistance is not required for enrollment). The Study Drug Treatment Period of APX001 will be a maximum of 14 days. After completion of 14 days study drug therapy, if further antifungal treatment is indicated to complete treatment of candidemia in accordance with standard practice guidelines, fluconazole (unless susceptibility results warrant alternative antifungal therapy) may commence for up to a further 7 days. There will be a Follow up Period of 4 weeks (+4 days) after EOT. The total duration of participation in the study is up to approximately 7.5 weeks.

This study will be conducted at approximately 20 sites in the United States and globally.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: APX001
Intervention descriptions: intervention 1: APX001

Protocol documents:
Prot_000.pdf: 
 
 
CLINICAL STUDY PROTOCOL 
 
An Open-Label Study to Evaluate the Efficacy and Safety of 
APX001 in Non-Neutropenic Patients with Candidemia, with or 
without Invasive Candidiasis, Inclusive of Patients with Suspected 
Resistance to Standard of Care Antifungal Treatment 
 
Investigational Product: APX001 
Protocol Number: APX001-201 
EudraCT Number: 2017-003571-56 
 
 
Sponsor: 
Amplyx Pharmaceuticals, Inc. 
12730 High Bluff Drive, Suite 160 
San Diego, CA 92130 
USA 
Telephone: +1-858-345-1755 
Fax: +1-858-345-1346 
 
Amendment Number: 2.0 
Protocol Version Number: 3.0 
Date: 03 June 2019 
 
 
 
Confidentiality Statement 
The information in this document is confidential and is not to be disclosed without the written 
consent of Amplyx Pharmaceuticals, Inc. except to the extent that disclosure would be required 
by law and for the purpose of evaluating and/or conducting a clinical study for Amplyx 
Pharmaceuticals, Inc. You are allowed to disclose the contents of this document only to your 
Institutional Review Board and study personnel directly involved with conducting this protocol. 
Persons to whom the information is disclosed must be informed that the information is 
confidential and proprietary to Amplyx Pharmaceuticals, Inc. and that it may not be further 
disclosed to third parties. 


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SYNOPSIS 
TITLE: An Open-Label Study to Evaluate the Efficacy and Safety of APX001 in 
Non-Neutropenic Patients with Candidemia, with or without Invasive Candidiasis, Inclusive of 
Patients with Suspected Resistance to Standard of Care Antifungal Treatment 
PROTOCOL NUMBER: APX001-201 
INVESTIGATIONAL PRODUCT: APX001 
PHASE: 2 
INDICATION: Treatment of non-neutropenic patients with candidemia – inclusive of those 
patients with suspected or confirmed antifungal-resistant candidemia  
OBJECTIVES: 
The primary objective of this study is to evaluate the efficacy and safety of APX001 for the 
treatment of adult non-neutropenic patients ≥18 years of age with candidemia that may include 
patients with suspected or confirmed resistance to standard of care (SOC) antifungal treatment. 
The secondary objectives of this study are to: 
• Evaluate the time to first negative blood culture 
• Evaluate the percentage of patients with Mycological Outcomes at End of Study Drug 
Treatment (EOST), End of Antifungal Treatment (EOT), and 2 and 4 weeks after EOT 
• Evaluate the percentage of patients with Treatment Success at EOT, and 2 and 4 weeks after 
EOT 
• Evaluate overall survival 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. Candidemia is a common cause of healthcare-associated blood stream 
infections with approximately 50% of isolates identified as non-Candida albicans for which the 
Infectious Diseases Society of America (IDSA) revised clinical practice guidance in 2016. 
Recently, the Centers for Disease Control and Prevention released a clinical alert for the ongoing 
transmission of C. auris in healthcare facilities with most isolates identified in blood. Antifungal 
susceptibility testing revealed resistance to one or more classes of antifungals, including 
echinocandins, which have been first line empiric therapy for candidemia pending definitive 
speciation. 


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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 with broad spectrum activity versus major fungal 
pathogens including Candida spp. and Aspergillus spp., including isolates with resistance to 
azoles, echinocandins, and polyenes. APX001A targets 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 demonstrated broad in vitro antifungal activity against Candida spp., including 
activity against azole-resistant and echinocandin-resistant strains. APX001A has demonstrated 
synergy with echinocandins (Aspergillus) and azoles (Candida). In invasive fungal disease animal 
models, including those for Aspergillus spp. and Candida spp. that are resistant to azoles, 
APX001A has demonstrated high survival rates and reduced colony counts of fungi in the lungs 
of infected mice. The PK-pharmacodynamic (PD) driver for efficacy of APX001A was associated 
with area under the concentration-time curve (AUC)/minimal inhibitory concentration (MIC). 
In 2 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 166 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 
non-SAEs 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 either of the 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 the in vitro studies 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 activity against azole- and 
echinocandin-resistant Candida spp. 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. 


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POPULATION: 
This study will enroll male and female patients ≥18 years of age with a new diagnosis of 
candidemia (positive blood test for Candida spp.). Patients with a positive blood culture taken as 
SOC with yeast suspected to be Candida spp. or from a positive rapid diagnostic method may sign 
the Informed Consent Form (ICF) and undergo Screening procedures, but must have confirmed 
Candida spp. from blood culture and meet the eligibility criteria to be dosed. 
Inclusion Criteria 
Patients must meet all of the following criteria to be eligible for study entry: 
1. Male or female ≥18 years of age 
2. New diagnosis of candidemia based on a blood sample drawn within 96 hours of dosing with: 
a. Positive blood culture for Candida spp., including those Candida spp. with suspected 
(in the opinion of the Investigator) or documented resistance to at least 1 SOC systemic 
antifungal agent 
OR 
b. Positive result from a Sponsor-approved rapid diagnostic blood test for Candida spp. 
infection (a rapid diagnostic test may be used to begin eligibility assessments; however, a 
subsequent confirmatory blood culture is required prior to dosing of APX001) 
3. Able to have pre-existing intravascular catheters removed and replaced (if necessary) 
4. 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 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) 
5. 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) 
6. 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 


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Exclusion Criteria 
Patients who meet any of the following criteria will not be eligible for the study: 
1. Neutropenia defined as absolute neutrophil count <500 cells/µL 
2. Diagnosis of deep-seated Candida-related infections causing intraperitoneal Candidiasis, 
septic arthritis, osteomyelitis, endocarditis, myocarditis, meningitis, or central nervous system 
infection or site of infection that would require antifungal treatment to exceed maximal duration 
of study drug (14 days) 
3. Hepatosplenic Candidiasis 
4. Blood culture, or any other culture, positive for C. krusei 
5. Received >2 days (>48 hours) equivalent of prior systemic antifungal treatment at approved 
doses to treat the current episode of candidemia (e.g., 2 consecutive doses of an echinocandin) 
Note: ≤5 days (≤120 hours) equivalent of prior antifungal treatment is permitted for patients 
with candidemia caused by Candida spp. with documented resistance to the specific prior 
antifungal administered  
6. Life expectancy of <72 hours in the opinion of the Investigator 
7. Severe hepatic impairment (Child-Pugh Score >9 points) at any time during 2 weeks prior to 
dosing 
8. Patients receiving hemodialysis 
9. Known human immunodeficiency virus, active hepatitis B virus, or hepatitis C virus (HCV) 
infections (defined as hepatitis B surface antigen or HCV ribonucleic acid positivity) 
10. Alanine aminotransferase or aspartate aminotransferase ≥5 × upper limit of normal (ULN) 
11. Total bilirubin >3 × ULN, unless isolated hyperbilirubinemia or due to documented Gilbert’s 
disease 
12. Female patient is pregnant or lactating 
13. Inappropriate fungal infection source control (e.g., persistent indwelling catheters or 
intravascular devices) 
14. Investigational drug administered within 30 days prior to dosing 
15. Prior participation in this or any previous study of APX001 
16. 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) 
17. 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 


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Dosing Criteria 
Patients must meet the following criteria to begin dosing: 
1. Confirmed diagnosis of candidemia 
2. Received ≤2 days (≤48 hours) equivalent of prior systemic antifungal treatment at approved 
doses to treat the current episode of candidemia 
OR 
≤5 days (≤120 hours) equivalent of prior treatment for candidemia caused by Candida spp. 
with documented resistance to the specific prior antifungal administered 
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 first-line treatment for candidemia, including suspected or confirmed 
antifungal-resistant candidemia in non-neutropenic patients ≥18 years of age. Suspicion of 
antifungal-resistant candidemia is sufficient and subsequent documented resistance is not required 
for enrollment. The Study Drug Treatment Period will be up to a maximum of 14 days (inclusive 
of the loading dose [Study Day 1]). After completion of 14 days study drug therapy, if further 
antifungal treatment is indicated to complete treatment of candidemia in accordance with standard 
practice guidelines, fluconazole (unless susceptibility results warrant alternative antifungal 
therapy) may commence for up to a further 7 days. There will be a Follow-up Period of 4 weeks 
(+4 days) after EOT. The total duration of participation in the study is up to approximately 
7.5 weeks (inclusive of the Screening Period [≤96 hours prior to Baseline]).  
Patients with a yeast identified in a blood culture or a positive rapid diagnostic method are eligible 
to be consented and screened for the study. Patients must have at least 1 positive blood test for 
Candida spp. (or yeast suspected to be Candida) for a diagnosis of candidemia to be considered 
for enrollment into the study. Patients with a positive blood culture showing yeast suspected to be 
Candida must have identification of Candida spp. from positive blood culture confirmed prior to 
dosing. Screening and Baseline procedures and the start of APX001 study drug will be initiated 
within 96 hours from the time that the SOC blood sample for the Candida spp. positive culture or 
rapid diagnostic test was drawn. 
Patients with >2 days (>48 hours) equivalent of prior systemic antifungal treatment at approved 
doses to treat the current episode of candidemia within 96 hours before first dose will be excluded. 
However, patients with Candida infections proven to be resistant to the specific antifungal 
administered may have received ≤5 days (≤120 hours) equivalent of that prior treatment (results 
of susceptibility testing are required prior to enrollment). 
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. 
On Study Day 1 (or over the first 24 hours if started 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 
of study drug, 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 


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administered as either 600 mg APX001 IV infusion QD over 3 hours or 700 mg PO QD. Patients 
who have completed a minimum of 3 days of IV APX001, are clinically stable as determined by 
the Investigator, able to swallow tablets, and have no further growth of the infecting organism 
48 hours following the most recent blood culture, may switch from IV to PO dosing on Study 
Day 4 and onward. Study drug will be administered for a maximum of 14 days. At the 
Investigator’s discretion, patients requiring a longer duration of antifungal therapy will be 
switched to fluconazole (unless susceptibility results warrant alternative antifungal therapy), to 
adhere to the IDSA clinical practice guidelines for the treatment of Candidiasis.  
Candida spp. bloodstream infection will be monitored by daily blood culture during Study Drug 
Treatment until 2 consecutive blood cultures are negative, and at EOST, EOT, and 2 and 4 weeks 
after EOT, or Early Termination. Simultaneously drawn blood samples will be collected for 
Candida testing by T2 magnetic resonance (T2MR) assay at Baseline, during Study Drug 
Treatment, and EOST, or Early Termination. Other cultures, histopathology, and imaging tests to 
assess the site(s) and extent of candidemia infection at other sites will be conducted as clinically 
indicated, and the 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 (including neurological assessment), prior and concomitant 
medication reporting, and adverse event reporting. A 12-lead electrocardiogram (ECG) will be 
performed at Baseline (pre-dose), EOST, EOT, and 4 weeks after EOT, or Early Termination. A 
dilated fundoscopic examination will be performed at Screening for all patients and at EOST, 
EOT, and 4 weeks after EOT, or Early Termination for those patients who had positive 
fundoscopic findings at Screening, or as 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, EOST, EOT, and 2 and 4 weeks after 
EOT, or Early Termination. 
Plasma samples for PK (APX001 [prodrug] and APX001A [active moiety]) will be collected at 
Baseline (pre-dose), twice weekly during Study Drug Treatment, EOST, EOT, 2 weeks after EOT, 
or Early Termination. 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, vitreal 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, EOT, and 2 and 4 weeks after 
EOT, or Early Termination. 
The end of study will occur after the last visit of the last patient on the study. 


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A schematic representing the study’s design is included below. 
BC = blood culture; BID = twice daily; EOST = End of Study Drug Treatment; EOT = End of Antifungal Treatment; 
IV = intravenous(ly); PO = oral(ly); QD = once daily.  
DOSAGE FORMS AND ROUTE OF ADMINISTRATION: 
On Study Day 1 (or over the first 24 hours if started 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 of study drug, a 600 mg APX001 maintenance dose will be administered 
over 3 hours by IV infusion QD. 
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  
• 700 mg PO QD 


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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 
• Is demonstrated to have no further growth of the infecting organism for 48 hours following the 
most recent blood culture 
RATIONALE FOR DOSE AND SCHEDULE SELECTION: 
Dose 
In PK-PD studies, immunocompromised mice were infected with 1 of 3 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 (colony-forming units [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%. This is reassuring, 
as hospitalized patients with severe infections may exhibit a higher clearance of antifungal drugs 
and/or a patient may be infected with a Candida spp. with a particularly high MIC above the 
MIC90.  
In 2 Phase 1 studies in healthy volunteers, APX001 IV and PO formulations were safe and well 
tolerated. The majority of the 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 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. This IV dose 
regimen is identical to the IV dose regimen that will be used in this study. In the second Phase 1 
clinical study, a dose of APX001 1000 mg administered PO QD on Days 1 through 14 was safe 
and well tolerated. This PO-dose regimen is higher than the 700 mg PO dose that will be used in 
this study. 


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Schedule 
To ensure the safety and tolerability of APX001 dosing for 14 days, this study will use an APX001 
dose and infusion duration already studied in Phase 1 for 14 days of therapy inclusive of IV and 
PO investigational drug therapy. The loading dose 1000 mg IV BID over a 3-hour infusion 
followed by 600 mg IV QD over a 3-hour infusion will optimize patient safety and tolerability on 
study. At Study Day 4, provided a patient meets the protocol-defined criteria for a PO switch, then 
the switch will occur to PO APX001 dose at 700 mg QD for no more than 14 days of combined 
IV and PO APX001 therapy. 
Step-Down Therapy 
The IDSA clinical practice guidelines for treatment of Candidiasis recommend that the total 
duration of therapy for candidemia is 14 days after documented clearance of Candida spp. from 
the bloodstream (i.e., first consecutive negative blood culture) and resolution of symptoms 
attributable to candidemia. Hence, the duration of antifungal treatment required to treat patients 
with candidemia in this study will be driven by the time to clearance of candidemia. In 
3 randomized controlled trials in candidemia and invasive Candidiasis, the median time to 
bloodstream infection clearance after receiving appropriate antifungal therapy was 2 to 3 days. 
Therefore, patients enrolled in this study may need a few additional days of fluconazole therapy 
(unless susceptibility results warrant alternative antifungal therapy) for a total duration of 
antifungal treatment of approximately 16 to 17 days. Likewise, any patients who have deep-seated 
sites of infections diagnosed after enrollment, while they can continue to receive APX001 study 
drug treatment per protocol, will require additional days of fluconazole therapy. 
If appropriate, additional antifungal drug therapy with fluconazole (unless susceptibility results 
warrant alternative antifungal therapy) can be administered beyond 14 days of APX001. The 
recommended dose of fluconazole is 800 mg QD on the first day followed by 400 mg QD, for a 
maximum of 7 days. 
EFFICACY ENDPOINTS:  
The primary efficacy parameter is 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 Mycological Outcomes at EOST, EOT, and 2 and 4 weeks after 
EOT 
• Percentage of patients with Treatment Success at EOT, and 2 and 4 weeks after EOT as 
determined by the DRC 
• Overall survival at Study Day 30 
• Number of patients with TEAEs 


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The exploratory efficacy parameters include the following: 
• Change in serum (1,3)-β-D-glucan levels from Baseline (pre-dose) to EOST 
• Correlation of blood culture and T2MR assay Candida spp. results from Baseline (pre-dose) 
through EOST 
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. 
• Alive at EOST 
• No concomitant use of any other systemic antifungal therapies through EOST 
Treatment Failure is defined as any case that does not meet the criteria for Treatment Success. 
Mycological Outcome: 
• Eradication is defined as a negative blood culture(s) for Candida spp. in the absence of 
concomitant antifungal therapy through EOST. 
At End of Antifungal Treatment (EOT): 
After completion of 14 days study drug therapy, if further antifungal treatment is indicated to 
complete treatment of candidemia in accordance with standard practice guidelines, fluconazole 
(unless susceptibility results warrant alternative antifungal therapy) may commence for up to a 
further 7 days. If applicable, an assessment of efficacy will also be made at the end of this 
antifungal treatment at EOT. 
Treatment Success is defined as meeting all of the following criteria: 
• Two consecutive blood cultures negative for Candida spp.  
• Alive at EOT 
• No additional systemic antifungal therapies (except for protocol-allowed step-down treatment 
[e.g., fluconazole]) through EOT 
Treatment Failure is defined as any case that does not meet the criteria for Treatment Success. 
Mycological Outcome: 
• Eradication is defined as a negative blood culture(s) for Candida spp. in the absence of 
additional antifungal therapy (except for protocol-allowed step-down treatment [e.g., 
fluconazole]) through EOT. 
At Follow-up (2 Weeks and 4 Weeks After End of Antifungal Treatment): 
• Recurrence (mycological) is defined as a mycologically confirmed infection based on blood 
culture with the same Baseline Candida spp. during the 4 weeks after EOT. 


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• Relapse (DRC Assessment) is defined as re-occurrence of Candida in blood culture during the 
Follow-up Period, or diagnostic parameters indicative of recurrence or late spread of the 
Candida infection. 
SAFETY VARIABLES: 
Safety parameters include the following: 
• Evaluation of adverse events at Screening, Baseline, during Study Drug Treatment, at EOST, 
EOT, and 2 and 4 weeks after EOT, or Early Termination. 
Infusion site reactions should be graded according to the Common Terminology Criteria for 
Adverse Events v4.03. 
• Vital signs (temperature, blood pressure, heart rate, respiratory rate, oxygen saturation, and 
weight) collected at Screening, Baseline (pre-dose) daily on Study Days 2 through 4 and twice 
weekly thereafter during Study Drug Treatment, at EOST, EOT, and 2 and 4 weeks after EOT, 
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, 
EOST, EOT, and 2 and 4 weeks after EOT 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, EOST, EOT, and 2 and 4 weeks after EOT or Early Termination. 
• ECGs at Baseline (pre-dose), EOST, EOT, and 4 weeks after EOT, or Early Termination. 
WITHDRAWAL CRITERIA: 
Participation of a patient in this clinical study 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 
• 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 a regulatory authority 
 


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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 
candidemia 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 
• Have a confirmed diagnosis of candidemia within 96 hours of the start of treatment with 
APX001 
Per-Protocol Population 
The Per-Protocol Population will include all patients who satisfy the following criteria: 
• Received at least 1 dose of study drug 
• Have a confirmed diagnosis of candidemia within 96 hours of the start of treatment with 
APX001 
• Did not exceed prior antifungal treatment (per eligibility) 
• Meet the protocol’s key inclusion and exclusion criteria 
• Have no major protocol violations 


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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 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 at EOT, 
and 2 and 4 weeks after EOT will be summarized. Similarly, the percentage of patients with 
Mycological Outcomes at EOST, EOT, and 2 and 4 weeks after EOT 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 patient 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. 
SAMPLE SIZE DETERMINATION: 
A sample size of approximately 20 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. 
SITES: Approximately 20 sites in the United States and globally 
SPONSOR: 
Amplyx Pharmaceuticals, Inc. 
12730 High Bluff Drive, Suite 160 
San Diego, CA 92130 
Telephone: +1-858-345-1755 
Fax: +1-858-345-1346 


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TABLE OF CONTENTS 
Signature Page ............................................................................... Error! Bookmark not defined. 
Investigator Agreement .................................................................. Error! Bookmark not defined. 
Synopsis .......................................................................................................................................... 2 
Table of Contents .......................................................................................................................... 15 
List of Tables ................................................................................................................................ 20 
List of Figures ............................................................................................................................... 21 
List of Abbreviations and Definition of Terms............................................................................. 22 
1 Introduction and Background Information ............................................................................. 24 
1.1 
Rationale ........................................................................................................................ 25 
1.2 
Risk/Benefit ................................................................................................................... 25 
2 Study Objectives ..................................................................................................................... 27 
2.1 
Primary Objective ......................................................................................................... 27 
2.2 
Secondary Objectives .................................................................................................... 27 
3 Study Description.................................................................................................................... 28 
3.1 
Summary of Study Design ............................................................................................ 28 
3.2 
Study Indication(s) ........................................................................................................ 30 
4 Selection and Withdrawal of Subjects .................................................................................... 31 
4.1 
Inclusion Criteria ........................................................................................................... 31 
4.2 
Exclusion Criteria .......................................................................................................... 32 
4.3 
Dosing Criteria .............................................................................................................. 33 
4.4 
Withdrawal Criteria ....................................................................................................... 33 
5 Study Treatments .................................................................................................................... 34 
5.1 
Treatment Groups .......................................................................................................... 34 
5.2 
Rationale for Dosing ..................................................................................................... 34 
5.2.1 Dose ................................................................................................................... 34 
5.2.2 Schedule ............................................................................................................ 34 
5.2.3 Step-Down Therapy .......................................................................................... 34 
5.3 
Randomization and Blinding ......................................................................................... 35 
5.4 
Breaking the Blind ........................................................................................................ 35 
5.5 
Drug Supplies ................................................................................................................ 35 


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5.5.1 Formulation and Packaging ............................................................................... 35 
5.5.2 Study Drug Preparation and Dispensing ........................................................... 35 
5.5.3 Study Drug Administration ............................................................................... 35 
5.5.4 Treatment Compliance ...................................................................................... 36 
5.5.5 Storage and Accountability ............................................................................... 36 
5.6 
Prior and Concomitant Medications and/or Procedures ................................................ 36 
5.6.1 Excluded Medications and/or Procedures ......................................................... 36 
5.6.1.1 APX001A as a victim substrate for cytochrome P450 drug-drug 
interactions .......................................................................................... 36 
5.6.1.2 APX001A as a perpetrator of cytochrome P450 drug-drug 
interactions .......................................................................................... 37 
5.6.2 Prohibited Medications and/or Procedures ....................................................... 37 
5.6.3 Step-down Antifungal Therapy ......................................................................... 37 
5.6.4 Documentation of Prior and Concomitant Medication Use .............................. 38 
6 Study Procedures .................................................................................................................... 39 
6.1 
Informed Consent .......................................................................................................... 39 
6.2 
Eligibility (≤96 Hours Prior to Baseline) ...................................................................... 39 
6.3 
Screening (≤96 Hours Prior to Baseline) ...................................................................... 39 
6.4 
Treatment Period ........................................................................................................... 40 
6.4.1 Baseline (Day 1 Pre-Dose) ................................................................................ 40 
6.4.2 Study Drug Treatment ....................................................................................... 41 
6.4.3 End of Study Drug Treatment ........................................................................... 42 
6.4.4 End of Antifungal Treatment ............................................................................ 42 
6.5 
Follow-up (2 Weeks and 4 Weeks After End of Antifungal Treatment) ...................... 43 
6.5.1 Follow-up 2 Weeks After End of Antifungal Treatment (+2 Days) ................. 43 
6.5.2 Follow-up 4 Weeks After End of Antifungal Treatment (+4 Days) ................. 44 
6.6 
Early Termination Visit and Withdrawal Procedures ................................................... 45 
7 Efficacy Assessments .............................................................................................................. 46 
7.1 
Primary Efficacy Endpoint ............................................................................................ 46 
7.2 
Secondary Efficacy Endpoints ...................................................................................... 46 
7.3 
Exploratory Efficacy Endpoints .................................................................................... 46 
7.4 
Definitions for Efficacy Assessments ........................................................................... 46 
7.4.1 At End of Study Drug Treatment (EOST) ........................................................ 46 


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7.4.2 At End of Antifungal Treatment (EOT) ............................................................ 46 
7.4.3 At Follow-up (2 Weeks and 4 Weeks After End of Antifungal Treatment) ..... 47 
7.5 
Microbiological Assessments ........................................................................................ 47 
7.5.1 Blood Cultures ................................................................................................... 47 
7.5.2 Cultures From Other Sites of Infection ............................................................. 48 
7.5.3 Candida Spp. Testing by T2 Magnetic Resonance Assay ................................ 48 
7.5.4 Intravascular Catheter Management and Log ................................................... 48 
8 Safety Assessments ................................................................................................................. 49 
8.1 
Adverse Events .............................................................................................................. 49 
8.1.1 Adverse (Drug) Reaction .................................................................................. 49 
8.1.2 Unexpected Adverse Drug Reaction ................................................................. 49 
8.1.3 Assessment of Adverse Events by the Investigator .......................................... 50 
8.2 
Serious Adverse Events ................................................................................................. 51 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators ................................ 52 
8.4 
Expedited Reporting ...................................................................................................... 53 
8.5 
Stopping Rules .............................................................................................................. 53 
8.5.1 Study Stopping Rule .......................................................................................... 53 
8.5.2 Subject Stopping Rule ....................................................................................... 53 
8.6 
Pregnancy Reporting ..................................................................................................... 54 
8.7 
Clinical Laboratory Evaluations .................................................................................... 54 
8.8 
Vital Signs ..................................................................................................................... 54 
8.9 
APACHE II Score ......................................................................................................... 54 
8.10 Electrocardiograms ........................................................................................................ 54 
8.11 Physical Examinations .................................................................................................. 55 
8.12 Pharmacokinetics .......................................................................................................... 55 
8.13 Dilated Fundoscopic Examination ................................................................................ 55 
8.14 Imaging Tests ................................................................................................................ 55 
8.15 Other Cultures and Histopathology ............................................................................... 55 
8.16 Intravascular Catheter/Device Management Log .......................................................... 55 
9 Statistics .................................................................................................................................. 56 
9.1 
Analysis Populations ..................................................................................................... 56 
9.2 
Statistical Methods ........................................................................................................ 56 


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9.2.1 Analysis of Efficacy .......................................................................................... 56 
9.2.1.1 Primary efficacy analysis .................................................................... 56 
9.2.1.2 Secondary efficacy analysis ................................................................ 56 
9.2.2 Analysis of Safety ............................................................................................. 57 
9.2.2.1 Pharmacokinetic analysis .................................................................... 57 
9.2.3 Interim Analysis ................................................................................................ 57 
9.2.4 Independent Data Review Committee ............................................................... 57 
9.2.5 Data and Safety Monitoring Board ................................................................... 58 
9.2.6 Sample Size Determination ............................................................................... 58 
10 Data Management and Record Keeping ................................................................................. 59 
10.1 Data Management ......................................................................................................... 59 
10.1.1 Data Handling ................................................................................................... 59 
10.1.2 Computer Systems ............................................................................................. 59 
10.1.3 Data Entry ......................................................................................................... 59 
10.1.4 Medical Information Coding ............................................................................. 59 
10.1.5 Data Validation ................................................................................................. 59 
10.2 Record Keeping ............................................................................................................. 59 
11 Investigator Requirements and Quality Control ..................................................................... 60 
11.1 Ethical Conduct of the Study ........................................................................................ 60 
11.2 Institutional Review Board/Independent Ethics Committee ......................................... 60 
11.3 Informed Consent .......................................................................................................... 60 
11.4 Subject Card .................................................................................................................. 60 
11.5 Study Monitoring Requirements ................................................................................... 60 
11.6 Disclosure of Data ......................................................................................................... 61 
11.7 Retention of Records ..................................................................................................... 61 
11.8 Publication Policy ......................................................................................................... 62 
11.9 Financial Disclosure ...................................................................................................... 62 
11.10 Insurance and Indemnity ............................................................................................... 62 
11.11 Legal Aspects ................................................................................................................ 62 
12 Study Administrative Information .......................................................................................... 63 
12.1 Protocol Amendments ................................................................................................... 63 
12.2 Address List ................................................................................................................... 63 


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12.2.1 Sponsor .............................................................................................................. 63 
12.2.2 Contract Research Organization ........................................................................ 63 
12.2.3 Drug Safety ....................................................................................................... 63 
12.2.4 Biological Specimens ........................................................................................ 63 
12.2.5 Mycology Reference Laboratory ...................................................................... 64 
12.2.6 Pharmacokinetic Laboratory ............................................................................. 64 
13 References ............................................................................................................................... 65 
Appendix A: Schedule of Procedures ........................................................................................... 66 
Appendix B: Clinical Laboratory Analytes .................................................................................. 69 
Appendix C: APACHE II Score Form.......................................................................................... 70 


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LIST OF TABLES 
Table 1. 
Infusion Site Reaction Adverse Event Severity Grading Table .................................. 50 
 


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LIST OF FIGURES 
Figure 1. Study Schematic.......................................................................................................... 28 
 


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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 
Clinical research associate 
CTA 
Clinical trial authorization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CVC 
Central venous catheter 
CYP 
Cytochrome P450 
DDI 
Drug-drug interaction 
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 
EOT 
End of Study Drug Treatment 
End of Antifungal Treatment 
FDA 
Food and Drug Administration 
FIH 
First-in-human 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal  
GPI 
Glycosylphosphatidylinositol  
GWT1 
GPI-anchored wall transfer protein 1 
HCV 
Hepatitis C virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IDSA 
IEC 
Infectious Diseases Society of America 
Independent Ethics Committee 
IFD 
Invasive fungal disease 
IRB 
Institutional Review Board 
IV 
Intravenous(ly)  
LAR 
Legal authorized representative 


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Abbreviation 
Definition 
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 
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. Candidemia is a common cause of healthcare-associated blood stream 
infections with approximately 50% of isolates identified as non-C. albicans for which the 
Infectious Diseases Society of America (IDSA) revised clinical practice guidance in 2016.1 
Recently, the Centers for Disease Control and Prevention released a clinical alert for the ongoing 
transmission of C. auris in healthcare facilities with most isolates identified in blood. Antifungal 
susceptibility testing revealed resistance to one or more classes of antifungals, including 
echinocandins, which have been first line empiric therapy for candidemia pending definitive 
speciation.1,2 
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 with broad spectrum activity versus major fungal 
pathogens including Candida spp. and Aspergillus spp., including isolates with resistance to 
azoles, echinocandins, and polyenes.3,4,5 APX001A targets 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.6,7 
The closest mammalian ortholog of GWT1 is PIG-W, which has no demonstrable inhibition by 
APX001A. 
APX001A has demonstrated broad in vitro antifungal activity against Candida spp., including 
activity against azole-resistant and echinocandin-resistant strains. APX001A has demonstrated 
synergy with echinocandins (Aspergillus)8,9 and azoles (Candida). In invasive fungal disease 
(IFD) animal models, including those for Aspergillus spp. and Candida spp. that are resistant to 
azoles, APX001A has demonstrated high survival rates and reduced colony counts of fungi in the 
lungs of infected mice.8,9 The pharmacokinetic (PK)-pharmacodynamic (PD) driver for efficacy 
of APX001A was associated with area under the concentration-time curve (AUC)/minimal 
inhibitory concentration (MIC). 
In 2 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 166 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 
non-SAEs were mild, transitory, and required no intervention. No dose-limiting toxicities (DLTs) 
were observed and no treatment-emergent adverse events (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 (MTD) was not determined/reached in either of the Phase 1 studies. 
Pharmacokinetic parameters for maximum serum concentration (Cmax) and AUC in both single 
and multiple APX001 IV and PO doses were linear and dose proportional. In both the in vitro 
studies and in a cohort embedded within the PO dose Phase 1 study, APX001 demonstrated a 
favorable drug-drug interaction (DDI) 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 is 
>90% in healthy subjects. There was no evidence of an effect on the bioavailability of APX001 in 


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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 activity against azole- and 
echinocandin-resistant Candida spp. Because APX001 is 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 IFDs remains high, particularly with the growing number of 
immunocompromised patients, such as hematopoietic stem cell and solid organ transplant 
recipients, who are at particular risk for developing these infections and in whom treatment can be 
complex. Species of Candida and Aspergillus are well recognized as the 2 major causes of fungal 
diseases in these patients, although other emerging fungi, such as non-C. albicans (e.g., 
C. glabrata and C. auris), Fusarium spp., Scedosporium spp., and Mucorales fungi, are 
contributing to the need to find new and better strategies for managing these infections. Existing 
antifungal agents can be difficult to use, are often poorly tolerated, or have become increasingly 
ineffective due to the rise of drug resistant fungal strains. 
1.2 
Risk/Benefit 
The safety, tolerability, and PK of single and multiple doses of APX001 administered by IV 
infusion and PO in healthy volunteers were studied in 2 Phase 1 studies, APX001-101 and 
APX001-102. 
Study APX001-101 was a first-in-human (FIH) Phase 1, randomized, placebo-controlled study to 
investigate the safety, tolerability, and PK of single and multiple doses of APX001 administered 
by IV infusion in healthy subjects. A final Clinical Study Report has been issued for this study. 
No severe or SAEs have been reported and most of the adverse events were mild, transitory, and 
resolved with no intervention. There were no clinically relevant changes from baseline in 
laboratory safety tests. The AUC from time 0 to infinity (AUCinf) and Cmax were linear and dose 
proportional.  
All doses of APX001 were safe and well tolerated, and the majority of TEAEs were mild, 
transitory, and resolved without intervention. Single IV doses of APX001 up to 350 mg over a 
3-hour infusion and single IV doses of 1000 mg over 0.5-, 1-, 2-, and 3-hour infusions were well 
tolerated. Shorter infusion periods (i.e., 1000 mg over 0.5 to 2 hours) appeared to have similar 
toleration compared to 3-hour infusion periods. Multiple IV doses of APX001 up to 600 mg once 
daily (QD), for 14 consecutive days, were well tolerated by the majority of subjects; however, the 
total number of TEAEs related to gastrointestinal (GI) and nervous system disorders increased 
when the dose was increased from 300 mg to 600 mg. A loading dose of 1000 mg administered 
twice daily (BID) on Day 1 followed by a maintenance dose of 600 mg QD for 6 consecutive days 
was well tolerated. 
Study APX001-102 was a Phase 1, randomized, placebo-controlled study to investigate the safety, 
tolerability, and PK of single and multiple PO doses of APX001 and to investigate the absolute 
bioavailability of APX001, the effect of food on APX001, and the DDI potential of APX001. 


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A final Clinical Study Report has been issued for this study. No severe or SAEs were reported and 
most of the adverse events were mild, transitory, and resolved with no intervention. There were no 
clinically relevant changes from baseline in laboratory safety tests. The AUCinf and Cmax were 
linear and dose proportional. There was no impact of food on the PK of APX001A exposures 
(single dose of 400 mg). In cohort 3 (1000 mg, QD for 14 days), there was an increase in the 
number of subjects reporting adverse events; however, the intensity of reported events did not 
increase with multiple doses. 
All doses of APX001 were safe and well tolerated, and the majority of TEAEs were mild, 
transitory, and resolved without intervention. The single IV doses of 200 mg APX001 and single 
PO doses in the dose range of 100 mg to 500 mg were well tolerated. Multiple PO doses of 500 mg 
and 1000 mg of APX001 administered QD for 14 consecutive days were well tolerated by the 
majority of subjects; however, the number of moderate TEAEs, primarily those related to GI 
disorders, increased when the PO dose of APX001 increased from 500 mg to 1000 mg. Dosing 
under fed conditions improved tolerability by decreasing TEAEs related to GI (nausea, vomiting) 
and nervous system disorders (headache, fatigue).  
There were no deaths or SAEs reported during the study nor were there any withdrawals due to 
adverse events. There were no clinically significant findings with respect to laboratory safety tests, 
vital signs, electrocardiogram (ECG), physical examination, or weight. No DLTs were observed. 
No TEAEs or laboratory safety tests met any of the criteria to prevent dose escalation. The MTD 
was not reached in this study.  
Patients 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 700 mg PO 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. Since the efficacy of APX001 has not yet been proven in patients, no 
additional protection of APX001 in this concentration can be assured. Patients participating in this 
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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 non-neutropenic patients ≥18 years of age with candidemia that may include 
patients with suspected or confirmed resistance to SOC antifungal treatment. 
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 Mycological Outcomes at the End of Study Drug 
Treatment (EOST), End of Antifungal Treatment (EOT), and 2 and 4 weeks after EOT 
• Evaluate the percentage of patients with Treatment Success at EOT, and 2 and 4 weeks after 
EOT 
• Evaluate overall survival at Study Day 30 
• Evaluate safety parameters, including number of patients with TEAEs 
• Evaluate 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 first-line treatment for candidemia including suspected or confirmed 
antifungal-resistant candidemia in non-neutropenic patients ≥18 years of age. Suspicion of 
antifungal-resistant candidemia is sufficient and subsequent documented resistance is not required 
for enrollment. The Study Drug Treatment Period will be up to a maximum of 14 days (inclusive 
of the loading dose [Study Day 1]). After completion of 14 days study drug therapy, if further 
antifungal treatment is indicated to complete treatment of candidemia in accordance with standard 
practice guidelines, fluconazole (unless susceptibility results warrant alternative antifungal 
therapy) may commence for up to a further 7 days. There will be a Follow-up Period of 4 weeks 
(+4 days) after EOT. The total duration of participation in the study is up to approximately 
7.5 weeks (inclusive of the Screening Period [≤96 hours prior to Baseline]). 
This study will be conducted at approximately 20 sites in the United States and globally. 
A complete schedule of procedures for the study is found in Appendix A. 
Figure 1 presents a schematic for the study. 
Figure 1. Study Schematic 
 
BC = blood culture; BID = twice daily; EOST = End of Study Drug Treatment; EOT = End of Antifungal Treatment; 
IV = intravenous(ly); PO = oral(ly); QD = once daily. 


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Patients with a yeast identified in a blood culture or a positive rapid diagnostic method are eligible 
to be consented and screened for the study. Patients must have at least 1 positive blood test for 
Candida spp. (or yeast suspected to be Candida) for a diagnosis of candidemia to be considered 
for enrollment into the study. Patients with a positive blood culture showing yeast suspected to be 
Candida must have identification of Candida spp. from positive blood culture confirmed prior to 
dosing. Screening and Baseline procedures and the start of APX001 study drug will be initiated 
within 96 hours from the time that the SOC blood sample for the Candida spp. positive culture or 
rapid diagnostic test was drawn. 
Patients with >2 days (>48 hours) equivalent of prior systemic antifungal treatment at approved 
doses to treat the current episode of candidemia within 96 hours before first dose will be excluded. 
However, patients with Candida infections proven to be resistant to the specific antifungal 
administered may have received ≤5 days (≤120 hours) equivalent of that prior treatment (results 
of susceptibility testing are required prior to enrollment). 
All patients (or the patient’s legal authorized representative [LAR]) will sign an Informed Consent 
Form (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 (APACHE) II score will be collected before dosing. 
On Study Day 1 (or over the first 24 hours if started 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 of study drug, 
a 600 mg APX001 maintenance dose will be administered over 3 hours by IV infusion 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 700 mg PO QD. Patients who have completed a minimum 
of 3 days of IV APX001, are clinically stable as determined by the Investigator, able to swallow 
tablets, and have no further growth of the infecting organism 48 hours following the most recent 
blood culture, may switch from IV to PO dosing on Study Day 4 and onward. Study drug will be 
administered for a maximum of 14 days. At the Investigator’s discretion, patients requiring a 
longer duration of antifungal therapy will be switched to fluconazole (unless susceptibility results 
warrant alternative antifungal therapy), to adhere to the IDSA clinical practice guidelines for the 
treatment of Candidiasis.1 
Candida spp. bloodstream infection will be monitored by daily blood culture during Study Drug 
Treatment until 2 consecutive blood cultures are negative, and at EOST, EOT, and 2 and 4 weeks 
after EOT, or Early Termination. Simultaneously drawn blood samples will be collected for 
Candida testing by T2 magnetic resonance (T2MR) assay at Baseline, during Study Drug 
Treatment, and EOST, or Early Termination. Other cultures, histopathology, and imaging tests to 
assess the site(s) and extent of candidemia infection at other sites will be conducted as clinically 
indicated, and the results should be recorded in the electronic Case Report Form (eCRF). 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 (including neurological assessment), prior and concomitant 
medication reporting, and adverse event reporting. A 12-lead ECG will be performed at Baseline 
(pre-dose), EOST, EOT, and 4 weeks after EOT, or Early Termination. A dilated fundoscopic 
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EOT, or Early Termination for those patients who had positive fundoscopic findings at Screening, 
or as 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, EOST, EOT, and 2 and 4 weeks after EOT, or Early Termination. 
Plasma samples for PK (APX001 [prodrug] and APX001A [active moiety]) will be collected at 
Baseline (pre-dose), twice weekly during Study Drug Treatment, EOST, EOT, 2 weeks after EOT, 
or Early Termination. 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, vitreal 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, EOT, and 2 and 4 weeks after 
EOT, or Early Termination. 
The end of study will occur after the last visit of the last patient on the study. 
3.2 
Study Indication(s) 
APX001 is indicated for the treatment of non-neutropenic patients with candidemia, inclusive of 
those patients with suspected or confirmed antifungal-resistant candidemia.  


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4 
SELECTION AND WITHDRAWAL OF SUBJECTS  
This study will enroll male and female patients ≥18 years of age with a new diagnosis of 
candidemia (positive blood test for Candida spp.). Patients with a positive blood culture taken as 
SOC with yeast suspected to be Candida spp. or from a positive rapid diagnostic method may sign 
the ICF and undergo Screening procedures, but must have confirmed Candida spp. from blood 
culture and meet the eligibility criteria to be dosed. 
4.1 
Inclusion Criteria 
Patients must meet all of the following criteria to be eligible for study entry: 
1. Male or female ≥18 years of age 
2. New diagnosis of candidemia based on a blood sample drawn within 96 hours of dosing with: 
a. Positive blood culture for Candida spp., including those Candida spp. with suspected 
(in the opinion of the Investigator) or documented resistance to at least 1 SOC systemic 
antifungal agent 
OR 
b. Positive result from a Sponsor-approved rapid diagnostic blood test for Candida spp. 
infection (a rapid diagnostic test may be used to begin eligibility assessments; however, a 
subsequent confirmatory blood culture is required prior to dosing of APX001) 
3. Able to have pre-existing intravascular catheters removed and replaced (if necessary) 
4. 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 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) 
5. 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) 
6. 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 
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4.2 
Exclusion Criteria 
Patients who meet any of the following criteria will not be eligible for the study: 
1. Neutropenia defined as absolute neutrophil count <500 cells/µL 
2. Diagnosis of deep-seated Candida-related infections causing intraperitoneal Candidiasis, 
septic arthritis, osteomyelitis, endocarditis, myocarditis, meningitis, or central nervous system 
infection or site of infection that would require antifungal treatment to exceed maximal 
duration of study drug (14 days) 
3. Hepatosplenic Candidiasis 
4. Blood culture, or any other culture, positive for C. krusei 
5. Received >2 days (>48 hours) equivalent of prior systemic antifungal treatment at approved 
doses to treat the current episode of candidemia (e.g., 2 consecutive doses of an echinocandin) 
Note: ≤5 days (≤120 hours) equivalent of prior antifungal treatment is permitted for patients 
with candidemia caused by Candida spp. with documented resistance to the specific prior 
antifungal administered 
6. Life expectancy of <72 hours in the opinion of the Investigator 
7. Severe hepatic impairment (Child-Pugh Score >9 points) at any time during 2 weeks prior to 
dosing 
8. Patients receiving hemodialysis 
9. Known human immunodeficiency virus, active hepatitis B virus, or hepatitis C virus (HCV) 
infections (defined as hepatitis B surface antigen or HCV ribonucleic acid positivity) 
10. Alanine aminotransferase or aspartate aminotransferase ≥5 × upper limit of normal (ULN) 
11. Total bilirubin >3 × ULN, unless isolated hyperbilirubinemia or due to documented Gilbert’s 
disease 
12. Female patient is pregnant or lactating 
13. Inappropriate fungal infection source control (e.g., persistent indwelling catheters or 
intravascular devices) 
14. Investigational drug administered within 30 days prior to dosing 
15. Prior participation in this or any previous study of APX001 
16. 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) 
17. 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 


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4.3 
Dosing Criteria 
Patients must meet the following criteria to begin dosing: 
1. Confirmed diagnosis of candidemia 
2. Received ≤2 days (≤48 hours) equivalent of prior systemic antifungal treatment at approved 
doses to treat the current episode of candidemia 
OR 
≤5 days (≤120 hours) equivalent of prior treatment for candidemia caused by Candida spp. 
with documented resistance to the specific prior antifungal administered  
4.4 
Withdrawal Criteria 
Participation of a patient in this clinical study 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 
• 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 a regulatory authority 
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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5 
STUDY TREATMENTS 
5.1 
Treatment Groups 
All patients will be administered a 1000 mg APX001 loading dose BID 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 over 
3 hours QD or may be switched to 700 mg PO QD when/if the criteria for PO dosing are met 
(Section 5.5.3). 
5.2 
Rationale for Dosing 
5.2.1 
Dose 
In PK-PD studies, immunocompromised mice were infected with 1 of 3 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 (colony-forming units [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.  
In 2 Phase 1 studies in healthy volunteers, APX001 IV and PO formulations were safe and well 
tolerated. The majority of the TEAEs were mild, transitory, and resolved without intervention. No 
DLTs were observed. Specifically, in the FIH Phase 1 clinical study, a loading dose 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. This IV dose regimen is 
identical to the IV dose regimen that will be used in this study. In the second Phase 1 clinical study, 
a dose of APX001 1000 mg administered PO QD on Days 1 through 14 was safe and well tolerated. 
This PO-dose regimen is higher than the 700 mg PO dose that will be used in this study. 
5.2.2 
Schedule  
To ensure the safety and tolerability of APX001 dosing for 14 days, this study will use an APX001 
dose and infusion duration already studied in Phase 1 for 14 days of therapy inclusive of IV and 
PO investigational drug therapy. The loading dose 1000 mg IV BID over a 3-hour infusion 
followed by 600 mg IV QD over a 3-hour infusion will optimize patient safety and tolerability on 
study. At Study Day 4, provided a patient meets the protocol-defined criteria for a PO switch, then 
the switch will occur to PO APX001 dose at 700 mg QD for no more than 14 days of combined 
IV and PO APX001 therapy.  
5.2.3 
Step-Down Therapy 
The IDSA clinical practice guidelines for treatment of Candidiasis recommend that the total 
duration of therapy for candidemia is 14 days after documented clearance of Candida spp. from 
the bloodstream (i.e., first consecutive negative blood culture) and resolution of symptoms 
attributable to candidemia. Hence, the duration of antifungal treatment required to treat patients 


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with candidemia in this study will be driven by the time to clearance of candidemia. In 
3 randomized controlled trials in candidemia and invasive Candidiasis, the median time to 
bloodstream infection clearance after receiving appropriate antifungal therapy was 2 to 3 days. 
Therefore, patients enrolled in this study may need a few additional days of fluconazole therapy 
(unless susceptibility results warrant alternative antifungal therapy) for a total duration of 
antifungal treatment of approximately 16 to 17 days. Likewise, any patients who have deep-seated 
sites of infections diagnosed after enrollment, while they can continue to receive APX001 study 
drug treatment per protocol, will require additional days of fluconazole therapy. 
If appropriate, additional antifungal drug therapy with fluconazole (unless susceptibility results 
warrant alternative antifungal therapy) can be administered beyond 14 days of APX001. The 
recommended dose of fluconazole is 800 mg QD on the first day followed by 400 mg QD, for a 
maximum of 7 days. 
5.3 
Randomization and Blinding 
This is a non-randomized, open-label study. 
5.4 
Breaking the Blind 
This is an open-label study. 
5.5 
Drug Supplies 
5.5.1 
Formulation and Packaging 
APX001 Injection is formulated at a concentration of 20 mg/mL. Preparation and dilution 
instructions will be provided in the Pharmacy Manual. 
APX001 tablets are formulated at strengths of 100 mg and 200 mg white-coated tablets. The tablets 
are stored in high-density polyethylene bottles with a child-resistant container. 
All APX001 supplies will be labeled according to the requirements of local law and legislation, as 
well as current Good Manufacturing Practice and Good Clinical Practice (GCP) guidelines. 
5.5.2 
Study Drug Preparation and Dispensing 
Study drug will be delivered to the study site by an authorized delegate of the Sponsor. Site staff 
who have been delegated the task of drug dispensing by the Investigator will dispense the 
appropriate treatment.  
Additional details regarding study drug preparation and dispensing will be provided in the 
Pharmacy Manual. 
5.5.3 
Study Drug Administration 
On Study Day 1 (or over the first 24 hours if started 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 of study drug, a 600 mg APX001 maintenance dose will be administered 
over 3 hours by IV infusion QD. 


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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 700 mg PO QD. Patients who have completed a minimum 
of 3 days of IV APX001, are clinically stable as determined by the Investigator, able to swallow 
tablets, and have no further growth of the infecting organism 48 hours following the most recent 
blood culture, may switch from IV to PO dosing on Study Day 4 and onward. Study drug will be 
administered for a maximum of 14 days (inclusive of the loading dose [Study Day 1]).  
Tablets are to be administered at the same time each day, whole, and taken by mouth with water. 
No splitting or crushing of tablets is allowed. 
If antifungal treatment is indicated for longer than 14 days, fluconazole may commence at the 
Investigator’s discretion (unless susceptibility results warrant alternative antifungal therapy) for 
up to a further 7 days of therapy, to adhere to IDSA clinical practice guidelines for the treatment 
of Candidiasis.1 
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 are located 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 patient-by-patient 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. 
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 and thus any single CYP enzyme that is 
inhibited or induced is unlikely to result in clinically significant changes in the levels of APX001A. 


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However, patients who are receiving or will receive strong inducers of multiple CYP enzymes 
(e.g., rifampin, carbamazepine, phenytoin, rifabutin, efavirenz, nevirapine, phenobarbital, 
modafinil, nafcillin, St. John's Wort, and enzalutamide) are excluded from participating in the 
study.  
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.  
Considering the magnitude of CYP inhibition/induction effects of APX001A, a review of drugs 
commonly used as part of the SOC for patients with candidemia indicates that clinically significant 
DDIs are unlikely to occur. Nonetheless, 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) considered, especially for CYP substrates that 
have a narrow therapeutic window.  
5.6.2 
Prohibited Medications and/or Procedures 
Eligible patients are prohibited from receiving >2 days (>48 hours) equivalent of antifungal 
treatment in the 96 hours prior to starting study treatment. The exception to this rule applies only 
to patients whose candidemia is caused by Candida spp. with laboratory-confirmed resistance to 
the specific antifungal administered, for whom ≤5 days (≤120 hours) equivalent of prior antifungal 
treatment is permitted. Once on study, patients may not receive concomitant systemic antifungal 
therapy for the treatment of candidemia while they are receiving APX001.  
Patients cannot have received any investigational drug within 30 days prior to dosing. 
5.6.3 
Step-down Antifungal Therapy 
The IDSA clinical practice guidelines for treatment of Candidiasis recommend that the total 
duration of therapy for candidemia is 14 days after documented clearance of Candida spp. from 
the bloodstream (i.e., first consecutive negative blood culture) and resolution of symptoms 
attributable to candidemia. Hence, the duration of antifungal treatment required to treat patients 
with candidemia in this study will be driven by the time to clearance of candidemia. In 
3 randomized controlled trials in candidemia and invasive Candidiasis, the median time to 
bloodstream infection clearance after receiving appropriate antifungal therapy was 2 to 3 days. 
Therefore, patients enrolled in this study may need a few additional days of fluconazole therapy 
for a total duration of antifungal treatment of approximately 16 to 17 days. Likewise, any patients 
who have deep-seated sites of infections diagnosed after enrollment, while they can continue to 
receive APX001 study drug treatment per protocol, will require additional days of fluconazole 
therapy. 
If appropriate, additional antifungal drug therapy with fluconazole (unless susceptibility results 
warrant alternative antifungal therapy) can be administered beyond 14 days of APX001. The 
recommended dose of fluconazole is 800 mg QD on the first day followed by 400 mg QD, for a 
maximum of 7 days. 


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5.6.4 
Documentation of Prior and Concomitant Medication Use 
All prior medications received by the patient 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. 


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6 
STUDY PROCEDURES 
6.1 
Informed Consent 
Written informed consent will be obtained from all patients (or the patient’s LAR) prior to any 
study-specific procedures being performed. Patients with a positive blood culture taken as SOC 
with yeast suspected to be Candida spp. or a positive rapid diagnostic method may sign the ICF 
and undergo Screening procedures, but must have a confirmed Candida spp. blood culture to be 
dosed. Only those patients who have transient loss of capacity (e.g., septic shock, mechanical 
ventilation, sedation) can have a LAR sign consent. These patients, upon return of their capacity, 
will then be consented and allowed to make their own informed medical decisions. Patients with 
permanent loss of capacity will not be eligible for study participation. 
6.2 
Eligibility (≤96 Hours Prior to Baseline) 
The following blood cultures drawn as SOC, prior to informed consent, will determine study 
eligibility: 
• Collect blood culture and confirm positive for Candida spp.  
• Collect blood sample for rapid diagnostic test positive for candidemia (if a rapid diagnostic 
test is available and used routinely for diagnosis of candidemia; the test must be 
Sponsor-approved and subsequent confirmatory blood culture is also required) 
Screening is triggered by the early identification of Candida spp. (or yeast) in blood drawn as SOC 
within a 96-hour window prior to first dose. Isolates of Candida spp. from the SOC culture must 
be submitted to the mycology reference laboratory for confirmation of identification and 
susceptibility testing. 
6.3 
Screening (≤96 Hours Prior to Baseline) 
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 dilated fundoscopic examination 
• Perform clinical laboratory assessments (serum chemistry, hematology, coagulation, and 
urinalysis) 
• Perform urine pregnancy test (for females of childbearing potential only) 


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• Collect blood cultures for Candida spp. (2 consecutive sets [1 aerobic and 1 anaerobic blood 
culture bottle per set] of blood cultures from 2 separate sites [1 from a central venous catheter 
(CVC) and 1 peripheral venipuncture, or 2 peripheral venipunctures, if a CVC is not 
applicable]) 
• Collect other cultures and histopathology from other sites, as clinically indicated to assess the 
site(s) and extent of candidemia infection 
• Perform imaging tests as clinically indicated to assess the site(s) and extent of candidemia 
infection  
• Record prior/concomitant medications 
• Record adverse events 
6.4 
Treatment Period 
6.4.1 
Baseline (Day 1 Pre-Dose) 
Baseline procedures are to be completed pre-dose on the same day as 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) 
• 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  
• Intravascular catheter management and log of the line changes; any indwelling intravascular 
catheters should be removed and catheter tips cultured prior to starting APX001 dosing; 
entrance site tissue should also be cultured if it appears infected 
• 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, the body site that corresponds to the entry site of candidemia 
(e.g., central venous catheter entry site), and a neurological examination.  
• Collect blood culture for Candida spp. and blood for Candida spp. testing by T2MR assay  
• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]) 
• Collect other cultures and histopathology from other sites, as clinically indicated to monitor 
the site(s) and extent of candidemia infection 
• Perform imaging tests, as clinically indicated to monitor the site(s) and extent of candidemia 
infection 


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• Collect serum samples for analysis of (1,3)-β-D-glucan 
• Record concomitant medications 
• Record adverse events 
6.4.2 
Study Drug Treatment  
During Study Drug Treatment, twice weekly visits are required with a maximum window of 
±2 days. 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.  
The following procedures will be performed during the period of Study Drug Treatment: 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight; collect twice weekly (daily Days 2 to 4 while inpatient) 
• Intravascular catheter management log; all changes to be recorded until EOT while inpatient, 
and as clinically indicated thereafter or for outpatients 
• Perform clinical laboratory assessments (serum chemistry, hematology, coagulation, and 
urinalysis); collect twice weekly 
• Perform urine pregnancy test (for females of childbearing potential only); every 30 days if 
required by local regulations 
• Perform focused, symptom-based physical examination including a neurological examination, 
once weekly  
• Collect blood cultures for Candida spp. and blood for Candida spp. testing by T2MR assay; 
daily on Days 2 through 4 (minimum), continuing until 2 negative blood culture results on 
2 consecutive tests are reported 
• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]); collect 
twice weekly 
o Optional: If body fluids are sampled as part of routine patient management 
(e.g., bronchoalveolar lavage, lumbar puncture, paracentesis, vitreal 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 
• Collect other cultures and histopathology from other sites, as clinically indicated to monitor 
the site(s) and extent of candidemia infection 
• Perform imaging tests as clinically indicated to monitor the site(s) and extent of candidemia 
infection 
• Administer study drug; administered as a 3-hour IV loading dose BID on 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 a maximum of 14 days (inclusive of the loading dose [Study Day 1]) 


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• Record concomitant medications 
• Assess adverse events 
6.4.3 
End of Study Drug Treatment  
The EOST occurs after completion of APX001 dosing. The following procedures will be 
performed at EOST: 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight 
• Intravascular catheter management log 
• Perform dilated fundoscopic examination (only required in those patients who had positive 
fundoscopic findings at Screening, or as clinically indicated) 
• 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 focused, symptom-based physical examination including a neurological examination 
• Collect blood culture for Candida spp. and blood for Candida spp. testing by T2MR assay  
• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]) 
o Optional: If body fluids are sampled as part of routine patient management 
(e.g., bronchoalveolar lavage, lumbar puncture, paracentesis, vitreal 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. 
• Collect other cultures and histopathology from other sites, as clinically indicated to monitor 
the site(s) and extent of candidemia infection 
• Perform imaging tests as clinically indicated to monitor the site(s) and extent of candidemia 
infection 
• Collect serum sample for analysis of (1,3)-β-D-glucan  
• Evaluate treatment outcome 
• Record concomitant medications 
• Assess adverse events 
6.4.4 
End of Antifungal Treatment  
After completion of 14 days study drug therapy, if further antifungal treatment is indicated to 
complete treatment of candidemia in accordance with standard practice guidelines, fluconazole 
(unless susceptibility results warrant alternative antifungal therapy) may commence for up to a 
further 7 days. If applicable, an assessment of efficacy will also be made at the end of this 
antifungal treatment.  


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The EOT for patients completing the study is ≤7 days after completion of 14 days of APX001 
dosing. If EOT is within 48 hours of EOST, asterisked procedures (*) do not need to be repeated, 
unless clinically indicated. The following procedures will be performed at EOT: 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight 
• Intravascular catheter management log 
• Perform dilated fundoscopic examination (only required in those patients who had positive 
fundoscopic findings at Screening, or as clinically indicated)* 
• 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 focused, symptom-based physical examination including a neurological examination* 
• Collect blood culture for Candida spp.  
• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]) 
o Optional: If body fluids are sampled as part of routine patient management 
(e.g., bronchoalveolar lavage, lumbar puncture, paracentesis, vitreal 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. 
• Collect other cultures and histopathology from other sites, as clinically indicated to monitor 
the site(s) and extent of candidemia infection 
• Perform imaging tests as clinically indicated to monitor the site(s) and extent of candidemia 
infection* 
• Evaluate treatment outcome 
• Record concomitant medications 
• Assess adverse events 
6.5 
Follow-up (2 Weeks and 4 Weeks After End of Antifungal Treatment) 
6.5.1 
Follow-up 2 Weeks After End of Antifungal Treatment (+2 Days) 
The following procedures will be performed at the Follow-up visit 2 weeks (+2 days) after EOT: 
• 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) 


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• Perform focused, symptom-based physical examination including a neurological examination 
• Collect blood culture for Candida spp. 
• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]) 
• Collect other cultures and histopathology from other sites, as clinically indicated to monitor 
the site(s) and extent of candidemia infection 
• Perform imaging tests as clinically indicated to monitor the site(s) and extent of candidemia 
infection 
• Evaluate treatment outcome 
• Record concomitant medications 
• Assess adverse events 
6.5.2 
Follow-up 4 Weeks After End of Antifungal Treatment (+4 Days) 
The following procedures will be performed at the Follow-up visit 4 weeks (+4 days) after EOT: 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight 
• Intravascular catheter management log as clinically indicated 
• Perform dilated fundoscopic examination (only required in those patients who had positive 
fundoscopic findings at Screening, or as clinically indicated) 
• 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 focused, symptom-based physical examination including a neurological examination 
• Collect blood culture for Candida spp. 
• Collect other cultures and histopathology from other sites, as clinically indicated to monitor 
the site(s) and extent of candidemia infection 
• Perform imaging tests as clinically indicated to monitor the site(s) and extent of candidemia 
infection 
• Evaluate treatment outcome 
• Record concomitant medications 
• Assess adverse events 
 
 
 


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6.6 
Early Termination Visit and Withdrawal Procedures 
For patients who are withdrawn from the study prior to completion, all EOT procedures will be 
performed at an Early Termination Visit. These procedures include the following: 
• Record vital signs, including temperature, blood pressure, heart rate, respiratory rate, oxygen 
saturation, and weight 
• Intravascular catheter management log  
• Perform dilated fundoscopic examination (only required in those patients who had positive 
fundoscopic findings at Screening, or as clinically indicated) 
• 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 focused, symptom-based physical examination including a neurological examination 
• Collect blood culture for Candida spp. and blood for Candida spp. testing by T2MR assay  
• Collect plasma sample for PK (APX001 [prodrug] and APX001A [active moiety]) 
• Collect other cultures and histopathology from other sites, as clinically indicated to monitor 
the site(s) and extent of candidemia infection 
• Perform imaging tests as clinically indicated to monitor the site(s) and extent of candidemia 
infection  
• Collect serum sample for analysis of (1,3)-β-D-glucan 
• Evaluate treatment outcome 
• Record concomitant medications 
• Assess adverse events 


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7 
EFFICACY ASSESSMENTS 
7.1 
Primary Efficacy Endpoint 
The primary efficacy parameter is 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 Mycological Outcomes at EOST, EOT, and 2 and 4 weeks after 
EOT 
• Percentage of patients with Treatment Success at EOT, and 2 and 4 weeks after EOT as 
determined by the DRC 
• Overall survival at Study Day 30 
• Number of patients with TEAEs 
7.3 
Exploratory Efficacy Endpoints 
The exploratory efficacy parameters include the following: 
• Change in serum (1,3)-β-D-glucan levels from Baseline (pre-dose) to EOST 
• Correlation of blood culture and T2MR assay Candida spp. results from Baseline (pre-dose) 
through EOST 
7.4 
Definitions for Efficacy Assessments 
7.4.1 
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. 
• Alive at EOST 
• No concomitant use of any other systemic antifungal therapies through EOST 
Treatment Failure is defined as any case that does not meet the criteria for Treatment Success. 
Mycological Outcome: 
• Eradication is defined as a negative blood culture(s) for Candida spp. in the absence of 
concomitant antifungal therapy through EOST. 
7.4.2 
At End of Antifungal Treatment (EOT) 
After completion of 14 days study drug therapy, if further antifungal treatment is indicated to 
complete treatment of candidemia in accordance with standard practice guidelines, fluconazole 
(unless susceptibility results warrant alternative antifungal therapy) may commence for up to a 


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further 7 days. If applicable, an assessment of efficacy will also be made at the end of this 
antifungal treatment at EOT. 
Treatment Success is defined as meeting all of the following criteria: 
• Two consecutive blood cultures negative for Candida spp. 
• Alive at EOT 
• No additional systemic antifungal therapies (except for protocol-allowed step-down treatment 
[e.g., fluconazole]) through EOT 
Treatment Failure is defined as any case that does not meet the criteria for Treatment Success. 
Mycological Outcome: 
• Eradication is defined as a negative blood culture(s) for Candida spp. in the absence of 
additional 
antifungal 
therapy 
(except 
for 
protocol-allowed 
step-down 
treatment 
[e.g., fluconazole]) through EOT. 
7.4.3 
At Follow-up (2 Weeks and 4 Weeks After End of Antifungal Treatment) 
• Recurrence (mycological) is defined as a mycologically confirmed infection based on blood 
culture with the same Baseline Candida spp. during the 4 weeks after EOT. 
• Relapse (DRC Assessment) is defined as re-occurrence of Candida in blood culture during the 
Follow-up Period, or diagnostic parameters indicative of recurrence or late spread of the 
Candida infection. 
7.5 
Microbiological Assessments 
7.5.1 
Blood Cultures 
A blood culture positive for Candida spp. drawn within 96 hours of APX001 dosing is required 
for eligibility as part of SOC. During screening, 2 consecutive sets (1 aerobic and 1 anaerobic 
blood culture bottle per set) of blood cultures from 2 separate sites (1 from a CVC and 1 peripheral 
venipuncture, or 2 peripheral venipunctures, if a CVC is not applicable) are required before the 
initiation of APX001 dosing. The screening cultures may be drawn on the day of dosing. Blood 
cultures (minimum of 1 set) for Candida spp. will also be performed at Baseline (pre-dose), during 
Study Drug Treatment, at EOST, EOT, and 2 and 4 weeks after EOT, or Early Termination. During 
the Study Drug Treatment Period, daily blood cultures are required on Study Days 1 through 4; 
thereafter, blood cultures may be stopped after negative results on 2 consecutive days are obtained. 
Candida spp. isolates from the blood cultures performed at the local laboratory must be submitted 
to the mycology reference laboratory for confirmation of identification and susceptibility testing. 
If a Sponsor-approved rapid diagnostic test for candidemia is used to identify potentially eligible 
patients, subsequent confirmatory blood cultures are required prior to dosing. Likewise, 
Candida spp. isolates from these blood cultures are to be submitted to the mycology reference 
laboratory. Results from any further rapid diagnostic tests performed as per local SOC must be 
captured in the eCRF. 


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7.5.2 
Cultures From Other Sites of Infection 
Any Candida spp. cultured from a normally sterile site, from intravascular catheter tip(s), or from 
a sample indicative of deep-seated invasive Candidiasis discovered after dosing with APX001, 
should be sent to the mycology reference laboratory for confirmation of identification and 
susceptibility testing. 
7.5.3 
Candida Spp. Testing by T2 Magnetic Resonance Assay 
Each time a blood culture is collected for the protocol, an additional blood sample will be collected 
for Candida spp. testing by T2MR assay at Baseline, during Study Drug Treatment, and through 
EOST or Early Termination. A central laboratory will perform the T2MR assay. 
7.5.4 
Intravascular Catheter Management and Log 
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. 
Intravascular catheter management should be managed at the site level as per local SOC. 


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8 
SAFETY ASSESSMENTS 
8.1 
Adverse Events 
An adverse event is defined as any untoward medical occurrence in a clinical investigation patient 
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. Patients 
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.  
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 change 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. 
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 


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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 
• 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 
The severity of infusion site reactions adverse events will be graded using the definitions in 
Table 1. 
Table 1. 
Infusion Site Reaction Adverse Event Severity Grading Table 
Event 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Life-Threatening) 
Infusion/injection 
site reaction 
Tenderness with or 
without associated 
symptoms (e.g., 
warmth, erythema, 
itching) 
Pain; lipodystrophy; 
edema; phlebitis 
Ulceration or 
necrosis; severe 
tissue damage; 
operative 
intervention 
indicated 
Life-threatening 
consequences; 
urgent intervention 
indicated 
Infusion/injection site reaction is defined as a disorder characterized by an intense adverse reaction (usually immunologic) 
developing at the site of an infusion/injection. 
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. 


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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 
• 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 an 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 


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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 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators 
Initial Reports 
All SAEs occurring from the time of informed consent until 30 days following the last 
administration of study drug must be reported to Medpace Clinical Safety within 24 hours of the 
knowledge of the occurrence (this refers to any adverse event that meets any of the aforementioned 
serious criteria). All SAEs that the Investigator considers related to study drug occurring after the 
30-day Follow-up Period must be reported to the Sponsor. 
To report the SAE, the Investigator must complete the SAE form electronically in the electronic 
data capture (EDC) system for the study. When the form is completed, Medpace Clinical Safety 
personnel will be notified electronically and will retrieve the form. If the event meets seriousness 
criteria and it is not possible to access the EDC system, the Investigator should send an e-mail to 
Medpace Clinical Safety at Medpace-safetynotification@medpace.com or call the Medpace 
Clinical Safety SAE reporting line (phone number listed below), and fax the completed paper SAE 
form to Medpace Clinical Safety (fax number listed below) within 24 hours of awareness. When 
the EDC system becomes available, the SAE information must be entered within 24 hours of the 
system becoming available. 
Safety Contact Information: Medpace Clinical Safety 
Medpace SAE reporting line – USA: 
Telephone: +1-800-730-5779, dial 3 or +1-513-579-9911, dial 3 
Fax: +1-866-336-5320 or +1-513-570-5196 
e-mail: medpace-safetynotification@medpace.com 
 
Medpace SAE reporting line – Europe: 
Telephone: +49 89 89 55 718 44 
Fax: +49 89 89 55 718 104 
e-mail: medpace-safetynotification@medpace.com 


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Follow-up Reports 
The Investigator must continue to follow the patient until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the patient 
dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation 
(e.g., patient discharge summary or autopsy reports) to Medpace Clinical Safety via fax or e-mail. 
If it is not possible to access the EDC system, refer to the procedures outlined above for initial 
reporting of SAEs. 
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.  
Expedited reporting of suspected unexpected serious adverse reactions related to APX001 will not 
be necessary. Listings of cases related to APX001 will be included in the Development Safety 
Update Report. 
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. 
8.5.2 
Subject Stopping Rule 
Study treatment for an individual patient may be discontinued for lack of clinical and/or 
microbiological response, 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, EOT, and 2 and 4 weeks after EOT, 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 Medpace Clinical Safety 
within 24 hours of being notified. Medpace Clinical Safety 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 
Medpace Clinical Safety. 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 Screening, Baseline (pre-dose), twice weekly during Study Drug Treatment, at EOST, 
EOT, and 2 and 4 weeks after EOT, 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 2 
through 4, and twice weekly thereafter during Study Drug Treatment, at EOST, EOT, and 2 and 
4 weeks after EOT, or Early Termination. Height will be collected (from the patient’s medical 
record) at Baseline. 
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, EOT, and 4 weeks after EOT, or 
Early Termination. 


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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 focused, symptom-based physical examination to include a neurological examination will be 
performed once weekly during study treatment, EOST, EOT, and 2 and 4 weeks after EOT, 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, EOT, and 2 weeks after 
EOT, or Early Termination. 
Optionally, if body fluids are sampled as part of routine patient management (e.g., bronchoalveolar 
lavage, lumbar puncture, paracentesis, vitreal 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. 
8.13 
Dilated Fundoscopic Examination 
A dilated fundoscopic examination will be performed at Screening for all patients and at EOST, 
EOT, and 4 weeks after EOT, or Early Termination for those patients who had positive 
fundoscopic findings at Screening, or as clinically indicated. 
8.14 
Imaging Tests 
Imaging should be performed to assess the site(s) and extent of candidemia infection as clinically 
indicated. 
8.15 
Other Cultures and Histopathology 
Other cultures and histopathology should be performed to assess the site(s) and extent of 
candidemia infection as clinically indicated. 
8.16 
Intravascular Catheter/Device Management Log 
The management of intravascular catheters, intravascular devices, and, if applicable, any drains 
will be recorded, including any associated microbiology results. 


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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 within 96 hours of the start of treatment with 
APX001 
Per-Protocol Population 
The Per-Protocol Population will include all patients who satisfy the following criteria: 
• Received at least 1 dose of study drug 
• Have a confirmed diagnosis of candidemia within 96 hours of the start of treatment with 
APX001 
• Did not exceed prior antifungal treatment (per eligibility) 
• Meet the protocol’s key inclusion and exclusion criteria (to be defined in the study’s Statistical 
Analysis Plan) 
• Have no major protocol violations (to be defined in the study’s Protocol Deviation Plan) 
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 EOT and 2 and 4 weeks after EOT will be 
summarized. Similarly, the percentage of patients with Mycological Outcomes at EOST, EOT, 
and 2 and 4 weeks after EOT will be summarized. A descriptive summary of overall survival at 
Study Day 30 and time to first negative blood culture will also be provided. 


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9.2.2 
Analysis of Safety 
All safety analyses will be performed on the Safety Population. Safety data will be patient 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.  
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. 
9.2.2.1 
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. 
9.2.3 
Interim Analysis 
No interim analysis is planned for the study. 
9.2.4 
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 
candidemia 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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9.2.5 
Data and Safety Monitoring Board 
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. 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. 
9.2.6 
Sample Size Determination 
A sample size of approximately 20 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. 


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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. 
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.  


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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 patients. Compliance with this 
standard provides public assurance that the rights, safety, and well-being of study patients are 
protected, consistent with the principles that have their origin in the Declaration of Helsinki, and 
that the clinical study data are credible. 
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 patients. 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 patients, 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 patients 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 patient or patient’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 patient 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 
Subject Card 
On enrollment in 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. 
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. 


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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. Patients or their 
legal representatives may request their medical information be given to their personal physician or 
other appropriate medical personnel responsible for their welfare. 
Patient 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 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. 


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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 patient liability 
insurance for all patients 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 Medpace 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, unless immediate implementation of the change is necessary for patient safety. In this case, 
the situation must be documented and reported to the IRB within 5 working days. 
12.2 
Address List 
12.2.1 
Sponsor 
Amplyx Pharmaceuticals, Inc. 
12730 High Bluff Drive, Suite 160 
San Diego, CA 92130 
Telephone: +1-858-345-1755 
Fax: +1-858-345-1346 
12.2.2 
Contract Research Organization 
Medpace, Inc. 
5375 Medpace Way 
Cincinnati, OH 45227 
Telephone: +1-513-579-9911 
Fax: +1-513-579-0444 
12.2.3 
Drug Safety 
Medpace, Inc. 
5375 Medpace Way 
Cincinnati, OH 45227 
Telephone: +1-513-579-9911, dial 3 
Fax: +1-513-579-0444 
12.2.4 
Biological Specimens 
Medpace Reference Laboratories 
5365 Medpace Way 
Cincinnati, OH 45227 
Telephone: +1-800-749-1737 or +1-513-366-3270 
Fax: +1-800-705-2177 or +1-513-366-3273 
 
ARUP Laboratories 
500 Chiptea Way 
Salt Lake City, UT 84108 
Telephone: +1-800-522-2787 


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Medpace Central Laboratories BVBA 
Technologielaan 19 
Leuven B-3001 
Belgium 
Telephone: +32-16-4077752-3606 
Fax: +32-16-407781 
 
University of Alabama 
Division of Infectious Diseases 
1900 University Boulevard 
Birmingham, AL 35294-0006 
Telephone: +1-205-934-5191 
Fax: +1-205-934-5195 
12.2.5 
Mycology Reference Laboratory 
NTS Ventures 
737 Bolivar Road, Suite 4500 
Cleveland, OH 44115 
Telephone: +1-216-215-5758 
12.2.6 
Pharmacokinetic Laboratory 
PRA Health Sciences – Early Development Services, Bioanalytical Laboratory  
Amerikaweg 18 
9407 TK Assen 
The Netherlands 
Telephone: +0031 592 303424 
e-mail: EDSNL-SRO@prahs.com 


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13 
REFERENCES 
 
1. 
Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the 
management of candidiasis: 2016 update by the Infectious Diseases Society of America. 
Clin Infect Dis. 2016;62(4):e1-50. 
2. 
Tsay S, Welsh RM, Adams EH, et al. Notes from the field: ongoing transmission of 
candida auris in health care facilities - United States, June 2016-May 2017. MMWR 
Morb Mortal Wkly Rep. 2017;66(19):514-15. 
3.  
Castanheira M, Duncanson FP, Diekema DJ, et al. 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. 2012;56(1):352-7. 
4.  
Pfaller MA, Hata K, Jones RN, et al. 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. 2011;71(2):167-70. 
5.  
Pfaller MA, Duncanson F, Messer SA, et al. 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. 2011;55(11):5155-8. 
6.  
Watanabe NA, Miyazaki M, Horii T, et al. E1210, a new broad-spectrum antifungal, 
suppresses Candida albicans hyphal growth through inhibition of 
glycosylphosphatidylinositol biosynthesis. Antimicrob Agents Chemother. 
2012;56(2):960-71. 
7.  
McLellan CA, Whitesell L, King OD, et al. Inhibiting GPI anchor biosynthesis in fungi 
stresses the endoplasmic reticulum and enhances immunogenicity. ACS Chem Biol. 
2012;7(9):1520-8. 
8.  
Hata K, Horii T, Miyazaki M, et al. Efficacy of oral E1210, a new broad-spectrum 
antifungal with a novel mechanism of action, in murine models of candidiasis, 
aspergillosis, and fusariosis. Antimicrob Agents Chemother. 2011;55(10):4543-51. 
9.  
Wiederhold NP, Najvar LK, Fothergill AW, et al. The investigational agent E1210 is 
effective in treatment of experimental invasive candidiasis caused by resistant Candida 
albicans. Antimicrob Agents Chemother. 2015;59(1):690-2. 


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APPENDIX A: SCHEDULE OF PROCEDURES 
Procedure 
Eligibility 
Screening 
(≤96 
Hours of 
Baseline) 
[a] 
Treatment Period[b] 
Follow-up 
Early 
Termination 
Baseline 
(Day 1 
Pre-Dose) 
Study 
Drug 
Treatment 
(≤14 Days) 
End of 
Study 
Drug 
Treatment 
(EOST)[c] 
End of 
Antifungal 
Treatment 
(EOT)[e,f] 
Follow-up 
2 Weeks 
After EOT 
+2 Days 
Follow-up 
4 Weeks 
After EOT 
+4 Days 
Informed consent 
 
X[g] 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
 
X 
X 
 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
APACHE II score 
 
 
X 
 
 
 
 
 
 
Vital 
signs/temperature[h] 
 
X 
X 
X 
X 
X 
X 
X 
X 
Intravascular 
catheter/device 
management log 
(including any drains, if 
applicable) 
 
X[i] 
X[i] 
X 
X 
X[j] 
X[k] 
X[k] 
X 
Dilated fundoscopic 
examination 
 
X 
 
 
X[l] 
X[d,l] 
 
X[l] 
X[l] 
Clinical safety 
laboratory tests[m] 
 
X 
X 
X 
X 
X[d] 
X 
X 
X 
12-lead 
electrocardiogram 
 
 
X 
 
X 
X[d] 
 
X 
X 
Urine pregnancy test (for 
females of childbearing 
potential only) 
 
X 
X 
X[n] 
X 
X[d] 
X 
X 
X 
Physical examination[o] 
 
 
X 
X 
X 
X[d] 
X 
X 
X 
Blood sample for 
Candida spp. culture and 
testing by T2MR 
assay[r,s] 
X 
X[q] 
X[p,q] 
X[p,q] 
X[p,q] 
X[q] 
X[q] 
X[q] 
X[p,q] 
 


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APPENDIX A: SCHEDULE OF PROCEDURES (CONTINUED) 
Procedure 
Eligibility 
Screening 
(≤96 
Hours of 
Baseline) 
[a] 
Treatment Period[b] 
Follow-up 
Early 
Termination 
Baseline 
(Day 1 
Pre-Dose) 
Study 
Drug 
Treatment 
(≤14 Days) 
End of 
Study 
Drug 
Treatment 
(EOST)[c] 
End of 
Antifungal 
Treatment 
(EOT)[e,f] 
Follow-up 
2 Weeks 
After EOT 
+2 Days 
Follow-up 
4 Weeks 
After EOT 
+4 Days 
Blood samples for rapid 
diagnostic test[t] 
X 
 
 
 
 
 
 
 
 
Pharmacokinetic 
sample[u] 
 
 
X 
X 
X 
X 
X 
 
X 
Other cultures and 
histopathology[k,v] 
 
X 
X 
X 
X 
X 
X 
X 
X 
Imaging tests[k,v] 
 
X 
X 
X 
X 
X[d] 
X 
X 
X 
Serum sample[w] 
 
 
X 
 
X 
 
 
 
X 
Evaluation of treatment 
outcome 
 
 
 
 
X 
X 
X 
X 
X 
Study drug 
administration[x] 
 
 
 
X 
 
 
 
 
 
Fluconazole treatment[y] 
 
 
 
 
 
X 
 
 
 
Prior/concomitant 
medications 
 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event 
evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
a. 
To be completed within 96 hours from blood sampling time for culture positive for Candida spp. 
b. 
During Study Drug Treatment, twice weekly visits are required with a maximum window of ±2 days. 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. 
c. 
End of Study Drug Treatment (EOST) occurs after completion of APX001 dosing. 
d. 
Assessments performed at EOST do not need to be repeated at End of Antifungal Treatment (EOT), if <48 hours apart, unless clinically indicated. 
e. 
The EOST may be the same as EOT for those patients that do not have a step-down (i.e., fluconazole or other protocol approved step-down). 
f. 
The EOT occurs up to a maximum of 21 days after Baseline (includes up to 14 days of APX001 administration and up to 7 days of fluconazole administration or other 
protocol approved step-down). 
g. 
To be obtained prior to the initiation of any protocol-specific procedure outside of SOC. 
h. 
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 2 to 4, and twice weekly thereafter during Study Drug Treatment, EOST, EOT, and 2 and 4 weeks after EOT, or Early Termination. Height will be 
collected (from the patient’s medical record) at Baseline. 
i. 
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. 
j. 
Intravascular catheters logged until EOT. 


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k. 
As clinically indicated. If obtained, results should be recorded in the eCRF. 
l. 
Only required in those patients who had positive fundoscopic findings at Screening, or as clinically indicated. 
m. 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, hematology, 
coagulation, and urinalysis) will be collected at Baseline (pre-dose), twice weekly during Study Drug Treatment, at EOST, EOT, and 2 and 4 weeks after EOT, 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. 
n. 
Urine pregnancy test (for females of childbearing potential only) every 30 days if required by local regulations. 
o. 
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 focused, 
symptom-based physical examination to include a neurological examination will be performed once weekly during study drug treatment, EOST, EOT, and 2 and 4 weeks after 
EOT, or Early Termination. 
p. 
Each time a blood culture is collected, an additional blood sample will be drawn for subsequent analysis of the correlation of blood culture and T2MR assay Candida spp. 
results from Baseline (pre-dose) through EOST or Early Termination. A central laboratory will perform the T2MR assay.  
q. 
Two consecutive sets of blood cultures during screening within 96 hours before the initiation of APX001 study treatment; 1 set thereafter. 
r. 
All Candida spp. isolates must be submitted to the mycology reference laboratory for confirmation of identification and susceptibility testing. 
s. 
During Study Drug Treatment, daily blood cultures on Study Days 1 through 4 (minimum), continuing until 2 consecutive blood cultures negative for Candida spp. are 
reported. 
t. 
Optional rapid diagnostic test, if available and used routinely for candidemia diagnosis; test (e.g., T2MR assay) must be Sponsor-approved; a subsequent confirmatory blood 
culture must also be performed to confirm Candida spp. 
u. 
Plasma samples for PK (APX001 [prodrug] and APX001A [active moiety]) will be collected at Baseline (pre-dose), twice weekly during Study Drug Treatment, EOST, EOT, 
2 weeks after EOT, or Early Termination. Optional: If body fluids are sampled as part of routine patient management (e.g., bronchoalveolar lavage, lumbar puncture, 
paracentesis, vitreal 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.  
v. 
Other cultures, histopathology, and imaging tests to assess the site(s) and extent of candidemia infection, if applicable. If performed, these will be analyzed at the local study 
site. 
w. Serum samples for (1,3)-β-D-glucan levels will be collected at Baseline (pre-dose) and EOST, or Early Termination (if applicable). 
x. 
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 a maximum of 14 days (inclusive of the loading dose [Study Day 1]). 
y. 
After completion of 14 days study drug therapy, if further antifungal treatment is indicated to complete treatment of candidemia in accordance with standard practice 
guidelines, fluconazole (unless susceptibility results warrant alternative antifungal therapy) may commence for up to a further 7 days. 
APACHE = Acute Physiology and Chronic Health Evaluation; BID = twice daily; eCRF = electronic Case Report Form; EOST = End of Study Drug Treatment; EOT = End of 
Antifungal 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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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 
Calcium 
Chloride 
Creatine kinase 
Creatinine 
Estimated glomerular filtration rate 
Gamma-glutamyl transferase 
Glucose 
Inorganic phosphorus 
Lactate dehydrogenase 
Lipase 
Potassium 
Sodium 
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 
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) 


Amplyx Pharmaceuticals, Inc. 
Clinical Study Protocol APX001-201 
Confidential & Proprietary 
 
Version 3.0, 03 June 2019 
70 
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 APX001-201 
Confidential & Proprietary 
 
Version 3.0, 03 June 2019 
71 
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 

SAP_001.pdf: 
 
 
Statistical Analysis Plan 
(SAP) 
 
An Open-Label Study to Evaluate the Efficacy and Safety of 
APX001 in Non-Neutropenic Patients with Candidemia, with 
or without Invasive Candidiasis, Inclusive of Patients with 
Suspected Resistance to Standard of Care Antifungal 
Treatment 
 
Protocol Number: APX001-201 
EudraCT Number: 2017-003571-56 
Phase: 2 
 
Protocol Version: V3.0, 3 June 2019 
SAP Version: V1.0, 27 April 2020 
 
Sponsor:  
Amplyx Pharmaceuticals, Inc. 
12730 High Bluff Drive, Suite 160 
San Diego, CA 92130 
USA 
 
 
Confidentiality Statement 
 
This document is confidential. It contains proprietary information belonging to Amplyx 
Pharmaceuticals, Inc.. Any viewing or disclosure of such information that is not authorized in 
writing by Amplyx Pharmaceuticals, Inc. is strictly prohibited. Such information may be used 
solely for the purpose of reviewing or performing this study. 


Amplyx Pharmaceuticals, Inc. 
Protocol Number APX00 1-201 
CONFIDENTIAL
SAP APPROVAL FORM 
Document Title: 
Protocol Number: 
Statistical Analysis Plan
APX00l-201 
Statistical Analysis Plan
Version 1.0, 27 April 2020 
Study Title: 
An Open-Label Study to Evaluate the Efficacy and Safety of
APX0O 1 in Non-Neutropenic Patients with Candidemia, with or 
without Invasive Candidiasis, Inclusive of Patients with Suspected
Resistance to Standard of Care Antifungal Treatment 
Protocol Version: 
V3.0, 3 June 2019 
SAP Version: 
Vl .0, 27 April 2020
This Statistical Analysis Plan has been reviewed and approved by:
Approved by: 
MeiE
Michael Hodges, MD 
Chief Medical Officer 
Amplyx Pharmaceutical, Inc.
//- /Vlo(;f-20
 
Date 
11-May-2020
Date
11th May 2020 
Date 
Page 2 of28 


Amplyx Pharmaceuticals, Inc.   
 CONFIDENTIAL 
     Statistical Analysis Plan 
Protocol Number APX001-201 
 Version 1.0, 27 April 2020 
Page 3 of 28 
TABLE OF CONTENTS 
SAP APPROVAL FORM..................................................................................................2
TABLE OF CONTENTS ..................................................................................................3
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................6
1.
INTRODUCTION ..........................................................................................7
2.
STUDY OVERVIEW .....................................................................................7
2.1.
Study Objectives ...............................................................................................7
2.1.1.
Primary Objective .............................................................................................7
2.1.2.
Secondary Objectives .......................................................................................7
2.2.
Study Design .....................................................................................................7
3.
SAMPLE SIZE DETERMINATION .........................................................13
4.
INDEPENDENT DATA REVIEW COMMITTEE (DRC) ......................13
5.
DATA SAFETY MONITORING BOARD (DSMB) .................................13
6.
STUDY ENDPOINTS ..................................................................................13
6.1.
Primary Efficacy Endpoints ............................................................................13
6.2.
Secondary Efficacy Endpoints ........................................................................13
6.3.
Exploratory Efficacy Endpoints .....................................................................14
6.4.
Definitions for Efficacy Assessments .............................................................14
6.4.1.
At End of Study Drug Treatment (EOST) ......................................................14
6.4.2.
At End of Antifungal Treatment (EOT) .........................................................14
6.4.3.
At Follow-up (2 Weeks and 4 Weeks After End of Antifungal Treatment) ..15
6.5.
Microbiological Assessments .........................................................................15
6.5.1.
Blood Cultures ................................................................................................15
6.5.2.
Cultures from Other Sites of Infection ...........................................................15
6.5.3.
Candida Spp. Testing by T2 Magnetic Resonance Assay ..............................15
6.5.4.
Intravascular Catheter Management and Log .................................................15
6.6.
Safety Endpoints .............................................................................................16
6.6.1.
Adverse Events ...............................................................................................16
6.6.2.
Clinical Laboratory Evaluations .....................................................................16
6.6.3.
Vital Signs ......................................................................................................18
6.6.4.
APACHE II Score ...........................................................................................18


Amplyx Pharmaceuticals, Inc.   
 CONFIDENTIAL 
     Statistical Analysis Plan 
Protocol Number APX001-201 
 Version 1.0, 27 April 2020 
Page 4 of 28 
6.6.5.
Electrocardiograms .........................................................................................18
6.6.6.
Physical Examinations ....................................................................................18
6.6.7.
Pharmacokinetics ............................................................................................18
6.6.8.
Dilated Fundoscopic Examination ..................................................................18
6.6.9.
Imaging Tests ..................................................................................................18
6.6.10.
Other Cultures and Histopathology ................................................................19
6.6.11.
Intravascular Catheter/Device Management Log ...........................................19
7.
STATISTICAL METHODOLOGY ...........................................................19
7.1.
General Considerations ...................................................................................19
7.1.1.
Summary Statistics .........................................................................................19
7.1.2.
Handling of Dropouts and Missing Data ........................................................19
7.1.3.
Baseline Definition .........................................................................................19
7.2.
Analysis Populations ......................................................................................20
7.2.1.
Enrolled Population ........................................................................................20
7.2.2.
Intent-to-Treat (ITT) Population/Safety Population .......................................20
7.2.3.
Modified Intent-to-Treat (MITT) Population .................................................20
7.2.4.
Per-Protocol (PP) Population ..........................................................................20
7.3.
Patient Data and Study Conduct .....................................................................20
7.3.1.
Patient Disposition ..........................................................................................20
7.3.2.
Protocol Deviations ........................................................................................21
7.3.3.
Demographic and Baseline Characteristics ....................................................21
7.3.4.
Baseline Infection Characteristics ..................................................................21
7.3.5.
Medical History ..............................................................................................22
7.3.6.
Prior and Concomitant Medications ...............................................................22
7.3.6.
Dosing and Extent of Exposure ......................................................................22
7.3.6.1.
Study Drug .....................................................................................................22
7.3.6.2.
Overall Antifungal Treatment ........................................................................23
7.4.
Efficacy Analysis ............................................................................................23
7.4.1.
Primary Efficacy Analysis ..............................................................................23
7.4.2.
Secondary Efficacy Analysis ..........................................................................24
7.4.2.1.
Treatment Outcome ........................................................................................24
7.4.2.2.
Mycological Outcome ....................................................................................24
7.4.2.3.
Time to First Negative Blood Culture ............................................................24


Amplyx Pharmaceuticals, Inc.   
 CONFIDENTIAL 
     Statistical Analysis Plan 
Protocol Number APX001-201 
 Version 1.0, 27 April 2020 
Page 5 of 28 
7.4.2.4.
Overall Survival at Study Day 30 ...................................................................24
7.4.2.5.
DRC Assessments ..........................................................................................25
7.4.3.
Exploratory Efficacy Analysis ........................................................................25
7.4.4.
Other Efficacy Data ........................................................................................25
7.5.
Safety Analysis ...............................................................................................25
7.5.1.
Adverse Events ...............................................................................................25
7.5.2.
Clinical Laboratory Tests ...............................................................................26
7.5.3.
Vital Signs ......................................................................................................27
7.5.4.
Electrocardiograms .........................................................................................27
7.5.5.
Physical Examinations ....................................................................................27
7.5.6.
Other Safety Assessments ...............................................................................27
7.6.
Pharmacokinetic Analyses ..............................................................................27
8.
INTERIM ANALYSIS .................................................................................28
9.
CHANGES FROM PROTOCOL-SPECIFIED STATISTICAL
ANALYSES ...................................................................................................28
10.
PROGRAMMING SPECIFICATIONS .....................................................28


Amplyx Pharmaceuticals, Inc.   
 CONFIDENTIAL 
     Statistical Analysis Plan 
Protocol Number APX001-201 
 Version 1.0, 27 April 2020 
Page 6 of 28 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
AE
Adverse event
ALT
Alanine transaminase
ALP
Alkaline phosphatase
APACHE
Acute Physiology and Chronic Health Evaluation
AST
Aspartate aminotransferase
ATC
Anatomical therapeutic chemical
BID
Twice daily
BMI
Body mass index
CSR
Clinical study report
CVC
Central venous catheter
DRC
Data Review Committee
DSMB
Data and Safety Monitoring Board
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EOST
End of Study Treatment
EOT
End of Antifungal Treatment
ICF
Informed Consent Form
ITT
Intent-to-Treat
IV
Intravenous(ly)
LAR
Legal authorized representative
LLN
Lower limit of normal
MedDRA
Medical Dictionary for Regulatory Activities
MITT
Modified Intent-to-Treat
PK
Pharmacokinetic(s)
PO
Oral(ly)
PP
Per-Protocol
QD
Once daily
SAE
Serious adverse event
SAP
Statistical analysis plan
SOC
Standard of care
spp.
Species
T2MR
T2 magnetic resonance
TEAE
Treatment-emergent adverse event
ULN
Upper limit of normal
WHO
World Health Organization


Amplyx Pharmaceuticals, Inc.                 CONFIDENTIAL                      Statistical Analysis Plan 
Protocol Number APX001-201 
                                        Version 1.0, 27 April 2020 
Page 7 of 28 
 
1. 
INTRODUCTION 
The purpose of this Statistical Analysis Plan (SAP) is to provide a description of the statistical 
methods to be implemented for the analysis of data from the study with protocol number APX001-
201 (Version 3.0, June 3, 2019).  The SAP will be finalized prior to database lock.  Any deviations 
from the SAP after database lock will be documented in the final Clinical Study Report (CSR). 
2. 
STUDY OVERVIEW 
2.1. 
Study Objectives 
2.1.1. 
Primary Objective 
The primary objective of this study is to evaluate the efficacy and safety of APX001 for the 
treatment of adult non-neutropenic patients 18 years of age with candidemia that may include 
patients with suspected or confirmed resistance to standard of care (SOC) antifungal treatment. 
2.1.2. 
Secondary Objectives 
The secondary objectives of this study are to: 
 Evaluate the time to first negative blood culture; 
 Evaluate the percentage of patients with Mycological Outcomes at the End of Study Drug 
Treatment (EOST), End of Antifungal Treatment (EOT), and 2 and 4 weeks after EOT; 
 Evaluate the percentage of patients with Treatment Success at EOT, and 2 and 4 weeks after 
EOT; 
 Evaluate overall survival at Study Day 30; 
 Evaluate safety parameters, including number of patients with Treatment-emergent adverse 
events (TEAEs); and 
 Evaluate Pharmacokinetic(s) (PK) parameters of APX001. 
2.2. 
Study Design 
This is a multicenter, open-label, non-comparative, single-arm study to evaluate the efficacy and 
safety of APX001 for the first-line treatment for candidemia including suspected or confirmed 
antifungal-resistant candidemia in non-neutropenic patients 18 years of age. Suspicion of 
antifungal-resistant candidemia is sufficient and subsequent documented resistance is not required 
for enrollment. The Study Drug Treatment Period will be up to a maximum of 14 days (inclusive 
of the loading dose [Study Day 1]). After completion of 14 days study drug therapy, if further 
antifungal treatment is indicated to complete treatment of candidemia in accordance with standard 
practice guidelines, fluconazole (unless susceptibility results warrant alternative antifungal 
therapy) may commence for up to a further 7 days. There will be a Follow-up Period of 4 weeks 
(+4 days) after EOT/EOST. The total duration of participation in the study is up to approximately 
7.5 weeks (inclusive of the Screening Period [96 hours prior to Baseline]). 


Amplyx Pharmaceuticals, Inc.                 CONFIDENTIAL                      Statistical Analysis Plan 
Protocol Number APX001-201 
                                        Version 1.0, 27 April 2020 
Page 8 of 28 
 
Patients with a yeast identified in a blood culture or a positive rapid diagnostic method are eligible 
to be consented and screened for the study. Patients must have at least 1 positive blood test for 
Candida species (spp.) (or yeast suspected to be Candida) for a diagnosis of candidemia to be 
considered for enrollment into the study. Patients with a positive blood culture showing yeast 
suspected to be Candida must have identification of Candida spp. from positive blood culture 
confirmed prior to dosing. Screening and Baseline procedures and the start of APX001 study drug 
will be initiated within 96 hours from the time that the SOC blood sample for the Candida spp. 
positive culture or rapid diagnostic test was drawn. 
Patients with >2 days (>48 hours) equivalent of prior systemic antifungal treatment at approved 
doses to treat the current episode of candidemia within 96 hours before first dose will be excluded. 
However, patients with Candida infections proven to be resistant to the specific antifungal 
administered may have received 5 days (120 hours) equivalent of that prior treatment (results 
of susceptibility testing are required prior to enrollment). 
All patients (or the patient’s legal authorized representative [LAR]) will sign an Informed Consent 
Form (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 (APACHE) II score will be collected before dosing. 
On Study Day 1 (or over the first 24 hours if started in the evening), a 1000 mg APX001 loading 
dose will be administered over 3 hours by intravenous (IV) infusion Twice daily (BID). On Study 
Days 2 and 3 of study drug, 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 700 mg oral (PO) QD. 
Patients who have completed a minimum of 3 days of IV APX001, are clinically stable as 
determined by the Investigator, able to swallow tablets, and have no further growth of the infecting 
organism 48 hours following the most recent blood culture, may switch from IV to PO dosing on 
Study Day 4 and onward. Study drug will be administered for a maximum of 14 days. At the 
Investigator’s discretion, patients requiring a longer duration of antifungal therapy will be switched 
to fluconazole (unless susceptibility results warrant alternative antifungal therapy), to adhere to 
the IDSA clinical practice guidelines for the treatment of Candidiasis. 
Candida spp. bloodstream infection will be monitored by daily blood culture during Study Drug 
Treatment until 2 consecutive blood cultures are negative, and at EOST, EOT, and 2 and 4 weeks 
after EOT, or Early Termination. Simultaneously drawn blood samples will be collected for 
Candida testing by T2 magnetic resonance (T2MR) assay at Baseline, during Study Drug 
Treatment, and EOST, or Early Termination. Other cultures, histopathology, and imaging tests to 
assess the site(s) and extent of candidemia infection at other sites will be conducted as clinically 
indicated, and the results should be recorded in the electronic Case Report Form (eCRF). 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 (including neurological assessment), prior and concomitant 
medication reporting, and adverse event reporting. A 12-lead electrocardiogram (ECG) will be 
performed at Baseline (pre-dose), EOST, EOT, and 4 weeks after EOT, or Early Termination. A 
dilated fundoscopic examination will be performed at Screening for all patients and EOST, EOT, 


Amplyx Pharmaceuticals, Inc.                 CONFIDENTIAL                      Statistical Analysis Plan 
Protocol Number APX001-201 
                                        Version 1.0, 27 April 2020 
Page 9 of 28 
 
and 4 weeks after EOT, or Early Termination for those patients who had positive fundoscopic 
findings at Screening, or as 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, EOST, EOT, and 2 and 4 weeks after EOT, or Early 
Termination. 
Plasma samples for PK (APX001 [prodrug] and APX001A [active moiety]) will be collected at 
Baseline (pre-dose), twice weekly during Study Drug Treatment, EOST, EOT, 2 weeks after EOT, 
or Early Termination. 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, vitreal 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, EOT, and 2 and 4 weeks after 
EOT, 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 below. 
 
BC = blood culture; BID = twice daily; EOST = End of Study Drug Treatment; EOT = End of Antifungal Treatment; IV = 
intravenous(ly); PO = oral(ly); QD = once daily. 
Table 1 presents the schedule of procedures of the study.


Amplyx Pharmaceuticals, Inc.                                                CONFIDENTIAL                                                  Statistical Analysis Plan 
Protocol Number APX001-201                                                                                                                         Version 1.0, 27 April 2020 
 
Page 10 of 28 
 
Table 1: Schedule of Procedures  
Procedure 
Eligibility 
Screening
(96 
Hours of 
Baseline) 
[a] 
Treatment Period[b] 
Follow-up 
Early 
Termination 
Baseline 
(Day 1 
Pre-Dose) 
Study 
Drug 
Treatment
(14 Days) 
End of 
Study 
Drug 
Treatment 
(EOST)[c] 
End of 
Antifungal 
Treatment 
(EOT)[e,f] 
Follow-up 
2 Weeks 
After EOT 
+2 Days 
Follow-up 
4 Weeks 
After EOT 
+4 Days 
Informed consent
 
X[g]
Inclusion/exclusion 
criteria
 
X
X
Medical history
 
X
Demographics
 
X
APACHE II score
 
X
Vital 
signs/temperature[h]
 
X
X
X
X
X
X
X
X
Intravascular 
catheter/device 
management log 
(including any drains, if 
applicable)
 
X[i]
X[i]
X
X
X[j]
X[k]
X[k]
X
Dilated fundoscopic 
examination
 
X
X[l]
X[d,l]
X[l]
X[l]
Clinical safety 
laboratory tests[m]
 
X
X
X
X
X[d]
X
X
X
12-lead 
electrocardiogram
 
X
X
X[d]
X
X
Urine pregnancy test (for 
females of childbearing 
potential only)
 
X
X
X[n]
X
X[d]
X
X
X
Physical examination[o]
 
X
X
X
X[d]
X
X
X
Blood sample for 
Candida spp. culture and 
testing by T2MR 
assay[r,s]
X
X[q]
X[p,q]
X[p,q]
X[p,q]
X[q]
X[q]
X[q]
X[p,q]


Amplyx Pharmaceuticals, Inc.                                                CONFIDENTIAL                                                  Statistical Analysis Plan 
Protocol Number APX001-201                                                                                                                         Version 1.0, 27 April 2020 
 
Page 11 of 28 
 
Table 1: Schedule of Procedures (Continued) 
Procedure 
Eligibility 
Screening
(96 
Hours of 
Baseline) 
[a] 
Treatment Period[b] 
Follow-up 
Early 
Termination 
Baseline 
(Day 1 
Pre-Dose) 
Study 
Drug 
Treatment
(14 Days) 
End of 
Study 
Drug 
Treatment 
(EOST)[c] 
End of 
Antifungal 
Treatment 
(EOT)[e,f] 
Follow-up 
2 Weeks 
After EOT 
+2 Days 
Follow-up 
4 Weeks 
After EOT 
+4 Days 
Blood samples for rapid 
diagnostic test[t]
X
Pharmacokinetic 
sample[u]
 
X
X
X
X
X
X
Other cultures and 
histopathology[k,v]
 
X
X
X
X
X
X
X
X
Imaging tests[k,v]
 
X
X
X
X
X[d]
X
X
X
Serum sample[w]
 
X
X
X
Evaluation of treatment 
outcome
 
X
X
X
X
X
Study drug 
administration[x]
 
X
Fluconazole treatment[y]
 
X
Prior/concomitant 
medications
 
X
X
X
X
X
X
X
X
Adverse event 
evaluation
 
X
X
X
X
X
X
X
X
a. 
To be completed within 96 hours from blood sampling time for culture positive for Candida spp. 
b. 
During Study Drug Treatment, twice weekly visits are required with a maximum window of 2 days. 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. 
c. 
End of Study Drug Treatment (EOST) occurs after completion of APX001 dosing. 
d. 
Assessments performed at EOST do not need to be repeated at End of Antifungal Treatment (EOT), if <48 hours apart, unless clinically indicated. 
e. 
The EOST may be the same as EOT for those patients that do not have a step-down (i.e., fluconazole or other protocol approved step-down). 
f. 
The EOT occurs up to a maximum of 21 days after Baseline (includes up to 14 days of APX001 administration and up to 7 days of fluconazole administration or other 
protocol approved step-down). 
g. 
To be obtained prior to the initiation of any protocol-specific procedure outside of SOC. 
h. 
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 2 to 4, and twice weekly thereafter during Study Drug Treatment, EOST, EOT, and 2 and 4 weeks after EOT, or Early Termination. Height will be 
collected (from the patient’s medical record) at Baseline. 
i. 
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. 
j. 
Intravascular catheters logged until EOT. 


Amplyx Pharmaceuticals, Inc.                                                CONFIDENTIAL                                                  Statistical Analysis Plan 
Protocol Number APX001-201                                                                                                                         Version 1.0, 27 April 2020 
 
Page 12 of 28 
 
k. 
As clinically indicated. If obtained, results should be recorded in the eCRF. 
l. 
Only required in those patients who had positive fundoscopic findings at Screening, or as clinically indicated. 
m. 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, hematology, 
coagulation, and urinalysis) will be collected at Baseline (pre-dose), twice weekly during Study Drug Treatment, at EOST, EOT, and 2 and 4 weeks after EOT, 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. 
n. 
Urine pregnancy test (for females of childbearing potential only) every 30 days if required by local regulations. 
o. 
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 focused, 
symptom-based physical examination to include a neurological examination will be performed once weekly during study drug treatment, EOST, EOT, and 2 and 4 weeks after 
EOT, or Early Termination. 
p. 
Each time a blood culture is collected, an additional blood sample will be drawn for subsequent analysis of the correlation of blood culture and T2MR assay Candida spp. 
results from Baseline (pre-dose) through EOST or Early Termination. A central laboratory will perform the T2MR assay.  
q. 
Two consecutive sets of blood cultures during screening within 96 hours before the initiation of APX001 study treatment; 1 set thereafter. 
r. 
All Candida spp. isolates must be submitted to the mycology reference laboratory for confirmation of identification and susceptibility testing. 
s. 
During Study Drug Treatment, daily blood cultures on Study Days 1 through 4 (minimum), continuing until 2 consecutive blood cultures negative for Candida spp. are 
reported. 
t. 
Optional rapid diagnostic test, if available and used routinely for candidemia diagnosis; test (e.g., T2MR assay) must be Sponsor-approved; a subsequent confirmatory blood 
culture must also be performed to confirm Candida spp. 
u. 
Plasma samples for PK (APX001 [prodrug] and APX001A [active moiety]) will be collected at Baseline (pre-dose), twice weekly during Study Drug Treatment, EOST, EOT, 
2 weeks after EOT, or Early Termination. Optional: If body fluids are sampled as part of routine patient management (e.g., bronchoalveolar lavage, lumbar puncture, 
paracentesis, vitreal 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.  
v. 
Other cultures, histopathology, and imaging tests to assess the site(s) and extent of candidemia infection, if applicable. If performed, these will be analyzed at the local study 
site. 
w. Serum samples for (1,3)-β-D-glucan levels will be collected at Baseline (pre-dose) and EOST, or Early Termination (if applicable). 
x. 
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 a maximum of 14 days (inclusive of the loading dose [Study Day 1]). 
y. 
After completion of 14 days study drug therapy, if further antifungal treatment is indicated to complete treatment of candidemia in accordance with standard practice 
guidelines, fluconazole (unless susceptibility results warrant alternative antifungal therapy) may commence for up to a further 7 days. 
APACHE = Acute Physiology and Chronic Health Evaluation; BID = twice daily; eCRF = electronic Case Report Form; EOST = End of Study Drug Treatment; EOT = End of 
Antifungal 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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3. 
SAMPLE SIZE DETERMINATION 
A sample size of approximately 20 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. 
4. 
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 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. 
5. 
DATA 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. 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. 
6. 
STUDY ENDPOINTS 
6.1. 
Primary Efficacy Endpoints 
The primary efficacy parameter is Treatment Success at EOST as determined by the Data Review 
Committee (DRC). 
6.2. 
Secondary Efficacy Endpoints 
The secondary efficacy parameters include the following: 
 Time to first negative blood culture; 
 Percentage of patients with Mycological Outcomes at EOST, EOT, and 2 and 4 weeks after 
EOT; 
 Percentage of patients with Treatment Success at EOT, and 2 and 4 weeks after EOT as 
determined by the DRC; 


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 Overall survival at Study Day 30; and 
 Number of patients with TEAEs. 
6.3. 
Exploratory Efficacy Endpoints 
The exploratory efficacy parameters include the following: 
 Change in serum (1,3)-β-D-glucan levels from Baseline (pre-dose) to EOST; and 
 Correlation of blood culture and T2MR assay Candida spp. results from Baseline (pre-dose) 
through EOST. 
6.4. 
Definitions for Efficacy Assessments 
6.4.1. 
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.; 
 Alive at EOST; and 
 No concomitant use of any other systemic antifungal therapies through EOST. 
Treatment Failure is defined as any case that does not meet the criteria for Treatment Success. 
Mycological Outcome: 
 Eradication is defined as a negative blood culture(s) for Candida spp. in the absence of 
concomitant antifungal therapy through EOST. 
6.4.2. 
At End of Antifungal Treatment (EOT) 
After completion of 14 days study drug therapy, if further antifungal treatment is indicated to 
complete treatment of candidemia in accordance with standard practice guidelines, fluconazole 
(unless susceptibility results warrant alternative antifungal therapy) may be administered for up to 
a further 7 days. If applicable, an assessment of efficacy will also be made at the end of this 
antifungal treatment at EOT. 
Treatment Success is defined as meeting all of the following criteria: 
 Two consecutive blood cultures negative for Candida spp.; 
 Alive at EOT; and 
 No additional systemic antifungal therapies (except for protocol-allowed step-down treatment 
[e.g., fluconazole]) through EOT. 
Treatment Failure is defined as any case that does not meet the criteria for Treatment Success. 
Mycological Outcome: 
 Eradication is defined as a negative blood culture(s) for Candida spp. in the absence of 
additional 
antifungal 
therapy 
(except 
for 
protocol-allowed 
step-down 
treatment 
[e.g., fluconazole]) through EOT. 


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6.4.3. 
At Follow-up (2 Weeks and 4 Weeks After End of Antifungal Treatment) 
 Recurrence (mycological) is defined as a mycologically confirmed infection based on blood 
culture with the same Baseline Candida spp. during the 4 weeks after EOT. 
 Relapse (DRC Assessment) is defined as re-occurrence of Candida in blood culture during the 
Follow-up Period, or diagnostic parameters indicative of recurrence or late spread of the 
Candida infection. 
6.5. 
Microbiological Assessments 
6.5.1. 
Blood Cultures 
A blood culture positive for Candida spp. drawn within 96 hours of APX001 dosing is required 
for eligibility as part of SOC. During screening, 2 consecutive sets (1 aerobic and 1 anaerobic 
blood culture bottle per set) of blood cultures from 2 separate sites (1 from a central venous catheter 
[CVC] and 1 peripheral venipuncture, or 2 peripheral venipunctures, if a CVC is not applicable) 
are required before the initiation of APX001 dosing. The screening cultures may be drawn on the 
day of dosing. Blood cultures (minimum of 1 set) for Candida spp. will also be performed at 
Baseline (pre-dose), during Study Drug Treatment, at EOST, EOT, and 2 and 4 weeks after EOT, 
or Early Termination. During the Study Drug Treatment Period, daily blood cultures are required 
on Study Days 1 through 4; thereafter, blood cultures may be stopped after negative results on 
2 consecutive days are obtained. Candida spp. isolates from the blood cultures performed at the 
local laboratory must be submitted to the mycology reference laboratory for confirmation of 
identification and susceptibility testing. 
If a Sponsor-approved rapid diagnostic test for candidemia is used to identify potentially eligible 
patients, subsequent confirmatory blood cultures are required prior to dosing. Likewise, 
Candida spp. isolates from these blood cultures are to be submitted to the mycology reference 
laboratory. Results from any further rapid diagnostic tests performed as per local SOC must be 
captured in the eCRF. 
6.5.2. 
Cultures from Other Sites of Infection 
Any Candida spp. cultured from a normally sterile site, from intravascular catheter tip(s), or from 
a sample indicative of deep-seated invasive Candidiasis discovered after dosing with APX001, 
should be sent to the mycology reference laboratory for confirmation of identification and 
susceptibility testing. 
6.5.3. 
Candida Spp. Testing by T2 Magnetic Resonance Assay 
Each time a blood culture is collected for the protocol, an additional blood sample will be collected 
for Candida spp. testing by T2MR assay at Baseline, during Study Drug Treatment, and through 
EOST or Early Termination. A central laboratory will perform the T2MR assay. 
6.5.4. 
Intravascular Catheter Management and Log 
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. 
Intravascular catheter management should be managed at the site level as per local SOC. 


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6.6. 
Safety Endpoints 
Safety assessments will include adverse events, vital signs, clinical laboratory evaluations, 
physical examination, and ECGs. 
6.6.1. 
Adverse Events 
An adverse event is defined as any untoward medical occurrence in a clinical investigation patient 
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. 
6.6.2. 
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 Screening, Baseline (pre-dose), twice weekly during Study Drug Treatment, at EOST, 
EOT, and 2 and 4 weeks after EOT, 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. The 
following is a complete list of clinical laboratory analytes. 
Standard Safety Chemistry Panel 
Alanine aminotransferase
Albumin
Alkaline phosphatase
Amylase
Aspartate aminotransferase
Bicarbonate
Bilirubin (total, direct, and indirect)
Blood urea nitrogen
Calcium
Chloride
Creatine kinase
Creatinine
Estimated glomerular filtration rate
Gamma-glutamyl transferase
Glucose
Inorganic phosphorus
Lactate dehydrogenase
Lipase
Potassium
Sodium
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 
International normalized ratio
Urinalysis 


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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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6.6.3. 
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 2 
through 4, and twice weekly thereafter during Study Drug Treatment, at EOST, EOT, and 2 and 
4 weeks after EOT, or Early Termination. Height will be collected (from the patient’s medical 
record) at Baseline. 
6.6.4. 
APACHE II Score 
The APACHE II score will be determined at Baseline (pre-dose).  
6.6.5. 
Electrocardiograms 
A 12-lead ECG will be obtained at Baseline (pre-dose), EOST, EOT, and 4 weeks after EOT, or 
Early Termination. 
6.6.6. 
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 focused, symptom-based physical examination to include a neurological examination will be 
performed once weekly during study treatment, EOST, EOT, and 2 and 4 weeks after EOT, or 
Early Termination.  
6.6.7. 
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, EOT, and 2 weeks after 
EOT, or Early Termination. 
Optionally, if body fluids are sampled as part of routine patient management (e.g., bronchoalveolar 
lavage, lumbar puncture, paracentesis, vitreal 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. 
6.6.8. 
Dilated Fundoscopic Examination 
A dilated fundoscopic examination will be performed at Screening for all patients and at EOST, 
EOT, and 4 weeks after EOT, or Early Termination for those patients who had positive 
fundoscopic findings at Screening, or as clinically indicated. 
6.6.9. 
Imaging Tests 
Imaging should be performed to assess the site(s) and extent of candidemia infection as clinically 
indicated. 


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6.6.10. 
Other Cultures and Histopathology 
Other cultures and histopathology should be performed to assess the site(s) and extent of 
candidemia infection as clinically indicated. 
6.6.11. 
Intravascular Catheter/Device Management Log 
The management of intravascular catheters, intravascular devices, and, if applicable, any drains 
will be recorded, including any associated microbiology results. 
7. 
STATISTICAL METHODOLOGY 
7.1. 
General Considerations 
7.1.1. 
Summary Statistics 
Summary statistics will be presented in total. 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. 
For summary statistics, the mean and median will be displayed to one decimal place greater than 
the original value and the measure of variability (e.g. standard deviation) will be displayed to two 
decimal places greater than the original value. 
7.1.2. 
Handling of Dropouts and Missing Data 
Subjects who dropped out or had missing outcome data will be included in the denominator for 
efficacy analyses. A clinical failure occurring at an earlier time point will be carried forward to the 
subsequent visits.  
In cases of missing or incomplete dates (e.g. Adverse event [AE] and concomitant medications), 
the missing component(s) will be assumed as the most conservative value possible. For example, 
AEs with missing start dates, but with stop dates either overlapping into the treatment period or 
missing, will be counted as treatment-emergent, taking the worst-case approach. When partial 
dates are present in the data, both a partial start date and/or a partial stop date will be evaluated to 
determine whether it can be conclusively established that the AE started prior to the start of study 
drug or ended prior to the start of study drug. If the above cannot be conclusively established based 
on the partial and/or present dates, then the AE will be considered as treatment-emergent. Actual 
data values as they appear in the original eCRF will be presented in the data listings.  
Missing values for other variables will not be imputed and only observed values will be used in 
data analyses and summaries. 
7.1.3. 
Baseline Definition 
For microbiological data, baseline pathogen(s) are Candida spp. isolated from the last positive 
blood sample collected within 96 hours prior to the first dose of study drug. 
For all efficacy and safety endpoints, baseline is defined as the last measurement or assessment 
prior to the first dose of study drug. 


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7.2. 
Analysis Populations 
7.2.1. 
Enrolled Population 
The Enrolled Population is defined as all screened patients excluding screen failures. 
7.2.2. 
Intent-to-Treat (ITT) Population/Safety Population 
The ITT Population/Safety Population will include all patients who have received at least 1 dose 
of APX001. 
7.2.3. 
Modified Intent-to-Treat (MITT) Population 
The MITT Population will include all patients who satisfy the following criteria: 
 Receive at least 1 dose of study drug; and 
 Have a confirmed diagnosis of candidemia (blood culture positive for Candida spp.) within 96 
hours of the start of treatment with APX001 
The MITT Population will be the primary population used for the efficacy analysis.  
7.2.4. 
Per-Protocol (PP) Population 
The Per-Protocol Population will include all patients who satisfy the following criteria: 
 Received at least 1 dose of study drug; 
 Have a confirmed diagnosis of candidemia within 96 hours of the start of treatment with 
APX001; 
 Did not exceed prior antifungal treatment (per eligibility assessed by the DRC); 
 Meet the protocol’s key inclusion and exclusion criteria; and  
 Have no major protocol violations. 
Based on the above criteria, the validity listings will be provided to identify which patients to be 
excluded from the PP Population. After the study team’s review, the decision to exclude a patient 
from the PP Population will be finalized and a list of patients with major protocol deviations 
leading to exclusion from the PP Population will be finalized and documented. 
7.3. 
Patient Data and Study Conduct 
7.3.1. 
Patient Disposition 
Patient disposition will be summarized for the Enrolled Population and ITT Populations in total. 
The following patient disposition categories will be included in the summary: 
 Patients who received study drug; 
 Patients who did not receive study drug; 


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 Patients who completed 14 days of study drug; 
 Patients who did not complete 14 days of study drug (and reason); 
 Patients who took protocol-allowed step-down further antifungal treatment; 
 Patients who did not take protocol-allowed step-down further antifungal treatment; 
 Patients who completed the study; and 
 Patients who did not complete the study (and reason). 
For patients who did not complete 14 days of study drug and patients who did not complete study, 
a summary will be provided by reason of discontinuation. In addition, the total number of patients 
for each defined population will be tabulated. 
7.3.2. 
Protocol Deviations 
The number of patients with at least one reportable protocol deviation, and the number of patients 
with at least one reportable deviation in each category defined in the study protocol deviation plan 
will be presented in total based on the Enrolled Population and ITT Population. 
Protocol deviations will also be listed by patient. 
7.3.3. 
Demographic and Baseline Characteristics 
The following demographic and baseline characteristics will be summarized: 
 Age (years) and age categories (<65 years, ≥65 years); 
 Sex; 
 Race; 
 Ethnicity; 
 Height (cm); 
 Weight (kg); 
 Body mass index (BMI) (kg/m2);  
 APACHE II score and categories (<10, 10-19, 20-30, or >30); and 
 ICU vs. non-ICU. 
Demographic and Baseline characteristics will be summarized with descriptive statistics or counts 
and percentages of patients as appropriate in total for the Enrolled Population, ITT, MITT, and PP 
Populations. 
7.3.4. 
Baseline Infection Characteristics 
All baseline pathogens will be summarized with counts and percentages of patients in total for the 
MITT and PP Populations. 


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Details of organism identification and antifungal susceptibility results including MICs of all 
antimicrobials tested will be listed by patient. Both data from local and central microbiological 
laboratories will be listed. 
7.3.5. 
Medical History 
The primary underlying condition leading to candidemia and other medical history will be coded 
to system organ class (SOC) and preferred term (PT) using the Medical Dictionary for Regulatory 
Activities (MedDRA, Version 20.1).  
Counts and percentages of patients with primary underlying condition and other medical history 
by SOC and PT will be summarized in total based on the ITT and MITT Populations. 
All medical history will be listed by patient.  
7.3.6. 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded to anatomical therapeutic chemical (ATC) class 
and preferred term using the World Health Organization (WHO) Drug Dictionary (September 
2017 B3 Version).  
Prior medications are medications used before the first dose of study drug. Concomitant 
medications are medications that were taken on or after first dose of study drug. 
The number and percentages of patients who receive the following prior and concomitant 
medications will be summarized by ATC class and preferred term in total for the ITT and MITT 
Populations: 
 Prior medications;  
 Concomitant medications; 
 Prior antifungals; 
 Protocol-allowed step-down fluconazole or alternative concomitant antifungals; and 
 Additional concomitant antifungals except for protocol-allowed step-down antifungals. 
All prior and concomitant medications and procedures will be listed by patient. 
7.3.6. 
Dosing and Extent of Exposure 
7.3.6.1. 
Study Drug 
Days of exposure to study drug will be summarized for intravenous and oral dose in overall. Days 
of exposure to study drug will be calculated as the last dose date of study drug – first dose date of 
study drug + 1. Overall days of exposure to study drug will be summarized in total based on the 
ITT, MITT, and PP Populations with descriptive statistics and with counts and percentages of 
patients with exposure in the following categories: 
 ≤7 days; 
 >7 to ≤14 days; and 


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 >14 days 
For patients who switch from intravenous to oral dose, the compliance rate for oral dose will be 
calculated as the total amount of doses received divided by the total amount of doses expected then 
multiplied by 100. The total amount of expected doses is the number of medication days multiplied 
by the expected doses per day. Number of medication days is the total number of days from the 
date of the first oral dose of study drug to the date of the last oral dose of study drug. 
Percent compliance with oral study drug will be calculated using the following formula: 
%compliance =
total amount of doses received * 100
expected doses per day * total number of medication days 
The compliance rate for oral dose will be summarized with descriptive statistics in total for the 
ITT, MITT, and PP Populations. In addition, contingency tables will be provided to show the 
number and percentage of patients in each treatment group with compliance in the following 
categories: <80% and ≥80%. 
7.3.6.2. 
Overall Antifungal Treatment 
After completion of 14 days study drug therapy, if further antifungal treatment is indicated to 
complete treatment of candidemia in accordance with standard practice guidelines, fluconazole 
(unless susceptibility results warrant alternative antifungal therapy) may commence for up to a 
further 7 days. 
The overall duration of antifungal treatment (study drug + protocol-allowed step-down further 
antifungal treatment) is defined as the last dose date of step-down further antifungal treatment − 
first dose date of study drug + 1. If patient did not take any step-down further antifungal treatment, 
the duration of antifungal treatment will be the same as duration of study drug. 
The overall duration of antifungal treatment will be summarized in total based on the ITT, MITT, 
and PP Populations with descriptive statistics and with counts and percentages of patients with 
exposure in the following categories: 
 ≤14 days; 
 >14 to ≤21 days; and 
 >21 days 
The number and percentage of patients who took protocol-allowed step-down further antifungal 
treatment will also be tabulated based on the ITT, MITT, and PP Populations. 
7.4. 
Efficacy Analysis 
7.4.1. 
Primary Efficacy Analysis 
The primary efficacy endpoint is Treatment Success at EOST as determined by the DRC.  


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The number and percentage of patients with Treatment Success or Treatment Failure at EOST 
determined by the DRC will be summarized descriptively in total for the MITT Population. The 
95% two-sided exact binomial confidence interval will also be presented. 
Additional analyses of the primary efficacy endpoint will be performed for the PP Population in 
the same manner. 
7.4.2. 
Secondary Efficacy Analysis 
Descriptive statistics will be provided for secondary efficacy endpoints as the following. 
7.4.2.1. 
Treatment Outcome  
Number and percentage of patients in the MITT and PP Populations with treatment outcomes 
(Treatment Success and Treatment Failure) at EOT as determined by the DRC will be presented 
descriptively, along with the 95% two-sided exact binomial confidence interval. 
Number and percentage of patients in the MITT and PP Populations with treatment outcomes 
(Treatment Success Sustained, Clinical Relapse, and Other [Non-Relapse]) at 2 and 4 weeks after 
EOT as determined by the DRC will be presented descriptively, along with the 95% two-sided 
exact binomial confidence interval. 
Number and percentage of patients in the MITT and PP Populations with treatment outcomes 
(Treatment Success and Treatment Failure) at EOST and EOT as determined by the Investigator 
will be tabulated, along with the 95% two-sided exact binomial confidence interval. 
7.4.2.2. 
Mycological Outcome  
The number and percentage of patients in the MITT and PP Populations with Eradication at EOST 
and EOT will be summarized descriptively, along with the 95% two-sided exact binomial 
confidence interval. 
The number and percentage of patients in the MITT and PP Populations with Recurrence at 2 and 
4 weeks after EOT as determined by the Investigator will be summarized descriptively, along with 
the 95% two-sided exact binomial confidence interval. 
7.4.2.3. 
Time to First Negative Blood Culture  
Time to first negative blood culture is defined as the number of days from first dose date of study 
drug to the date of first negative blood culture plus 1. 
Time to first negative blood culture will be summarized in total using descriptive statistics for the 
MITT and PP Population. 
In addition, the Kaplan-Meier estimate of the median time to first negative blood culture and the 
associated 95% confidence interval will be presented. Patients without a negative blood culture at 
post-baseline visits will be censored at the last assessment date.   
7.4.2.4. 
Overall Survival at Study Day 30  
Overall survival at Study Day 30 is defined as patient alive by study day 30. 


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The number of percentage of patients alive or dead by Study Day 30 will be summarized for the 
MITT and PP Population.  
Time to death is defined as the number of days from first dose date of study drug to the date of 
death from any cause plus 1. Patients without death or lost to follow-up will be censored on the 
last date the patient is known to be alive. The Kaplan-Meier estimate of the median time to death 
and the associated 95% confidence interval will be presented. 
7.4.2.5. 
DRC Assessments  
Reasons for treatment failure according to DRC classifications (i.e. blood cultures did not become 
negative, or additional antifungals given, or died, or withdrew from study but did not die) will be 
summarized descriptively at EOST and EOT visits for the MITT and PP populations. 
Reasons for relapse or other reasons for not having an outcome of sustained success at follow-up 
according to DRC classifications, will be summarized descriptively at 2 and 4 weeks after EOT 
for the MITT and PP populations. 
Reasons for death according to DRC classifications (i.e. candidemia probably contributory, 
candidemia probably not contributory, or not known) will be tabulated for the MITT and PP 
populations. 
7.4.3. 
Exploratory Efficacy Analysis 
Change in serum (1,3)-β-D-glucan levels from Baseline (pre-dose) to EOST will be summarized 
in total with descriptive statistics for the MITT Population. 
Correlation of blood culture and T2MR assay Candida spp. results from Baseline (pre-dose) 
through EOST will be explored. The number and percentage of patients with different Candida 
spp. isolated from blood culture and Candida spp. results from T2MR assay will be summarized 
by each visit from Baseline (pre-dose) through EOST for the MITT Population. 
7.4.4. 
Other Efficacy Data 
All other efficacy data will be listed by patient. 
7.5. 
Safety Analysis 
All safety analyses will be performed on the Safety Population. 
7.5.1. 
Adverse Events 
AEs will be captured from the date of informed consent through study completion.  All AEs will 
be coded to system organ class and preferred term using the MedDRA, Version 20.1. TEAEs are 
defined as AEs that start on or after the administration of study drug.   
An overview of AEs will be provided including counts and percentages of patients (and event 
counts) with the following: 
 Any AEs; 
 Any TEAEs (overall and by maximum severity); 


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 Any study drug-related TEAEs (overall and by maximum severity); 
 Any serious AEs (SAEs); 
 Any treatment-emergent SAEs (TESAEs); 
 Any study drug-related treatment-emergent SAEs (TESAEs); 
 Any TEAEs leading to discontinuation of study drug; 
 Any study drug-related TEAEs leading to discontinuation of study drug; 
 Any AEs leading to discontinuation of study; 
 Any study drug-related TEAEs leading to discontinuation of study; and 
 Any AEs leading to death. 
The number and percentage of patients who experienced at least one TEAE will be presented by 
system organ class and preferred term. Drug-related TEAEs, study drug withdrawals due to 
TEAEs, and all SAEs will be summarized in the same manner.  
Summaries will be provided by worst grade for the number and percentage of patients with TEAEs 
and for patients with drug-related TEAEs by system organ class and preferred term. 
Although a patient may have two or more TEAEs, the patient is counted only once within a System 
Organ Class and Preferred Term category. The same patient may contribute to two or more 
preferred terms in the same System Organ Class category or to two different System Organ Class 
categories. 
A list of patients who have serious adverse events (SAEs), a list of patients who discontinue from 
study drug due to TEAEs, and a list of death due to AEs will be provided. All adverse events will 
be listed.  
7.5.2. 
Clinical Laboratory Tests 
Central laboratory test results (chemistry, hematology, coagulation, and urinalysis) at each 
scheduled visit and change from baseline will be summarized with descriptive statistics. 
Shift tables from baseline to each scheduled post-baseline visit will be provided for selected 
chemistry parameters (ALT, AST, ALP, Total Bilirubin, Creatinine, and Creatinine Kinase) and 
hematology parameters (Hematocrit, Hemoglobin, Platelets, White blood cell count and 
differential). For chemistry parameters, the following categories will be used: < the lower limit of 
normal (LLN), normal, >ULN to ≤2×ULN, >2×ULN to ≤3×ULN, >3×ULN to ≤5×ULN, 
>5×ULN, and missing. For hematology parameters, the following categories will be used: low, 
normal, high, and missing. 
The number and percentage of patients with the following potentially clinically significant 
abnormal liver function tests at any post-baseline visit will be summarized:  
 ALT ≥3×ULN; 
 ALT ≥5×ULN; 


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 ALT ≥10×ULN; 
 AST ≥3×ULN; 
 AST ≥5×ULN; 
 AST ≥10×ULN; 
 ALT or AST ≥3×ULN; 
 Total Bilirubin >1.5×ULN; 
 Total Bilirubin >2×ULN; 
 ALP ≥1.5×ULN; 
 ALP ≥2×ULN; 
 ALT or AST ≥3×ULN and Total Bilirubin >1.5×ULN; 
 ALT or AST ≥3×ULN and Total Bilirubin >2×ULN; and 
 Potential Hy’s Law cases: ALT or AST ≥3×ULN and Total Bilirubin >2×ULN, and ALP 
≤ 2×ULN 
A listing of patients with any post-baseline clinically significant abnormal liver function tests will 
be presented. 
All clinical laboratory data will be listed. Values outside the normal ranges will be flagged. 
7.5.3. 
Vital Signs 
Descriptive statistics will be provided for vital sign data (systolic and diastolic blood pressure, 
heart rate, respiratory rate, body temperature, and oxygen saturation) presented as both actual 
values and changes from baseline over time. 
A listing of all vital signs will be provided by patient. 
7.5.4. 
Electrocardiograms 
Descriptive statistics will be provided for 12-lead ECG interval data (Heart rate, PR, QRS, QT, 
and RR) and changes from baseline for each scheduled visit. 
All 12-lead ECG findings will be listed by patient. 
7.5.5. 
Physical Examinations 
Physical examination findings will be listed by patient. 
7.5.6. 
Other Safety Assessments 
Other safety assessments will be listed by patient. 
7.6. 
Pharmacokinetic Analyses 
All pharmacokinetic analyses will be performed by another vendor and described in a standalone 
PK analysis plan. 


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A listing of the PK concentrations by patient will be provided. 
8. 
INTERIM ANALYSIS 
No interim analysis is planned for this study. 
9. 
CHANGES FROM PROTOCOL-SPECIFIED STATISTICAL ANALYSES 
No changes or plans to deviate from the analysis described in the protocol have been made.  
10. 
PROGRAMMING SPECIFICATIONS 
Analyses will be performed using SAS® version 9.3 or higher. All available data will be 
presented in patient data listings which will be sorted by patient as applicable. Detailed 
Programming Specifications will be provided in a separate document.