A Phase 2, Multicenter, Randomized, Double-blind Study of the Safety, Tolerability, and Efficacy of Intravenous CD101 vs Intravenous Caspofungin Followed by Oral Fluconazole Step-down in the Treatment of Subjects With Candidemia and/or Invasive Candidiasis
Phase: PHASE2
Conditions: Candidemia, Mycoses, Fungal Infection, Fungemia, Invasive Candidiasis
Sponsor: Cidara Therapeutics Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Cidara Therapeutics, Inc. 
Protocol CD101.IV.2.03 A6 
Intravenous CD101
Protocol Amendment 6 
Confidential 
Page 1 of 128 
Title 
A Phase 2, Multicenter, Randomized, Double-blind Study of the Safety, 
Tolerability, and Efficacy of Intravenous CD101 vs Intravenous 
Caspofungin Followed by Oral Fluconazole Step-down in the Treatment 
of Subjects with Candidemia and/or Invasive Candidiasis 
Study Drug 
Intravenous CD101 
Original Protocol 
18FEB2016 
Amendment 1 
14MAY2016 
Amendment 1-IT (Italy only) 
02SEP2016 
Amendment 2 
14SEP2016 
Amendment 3 
23FEB2017 
Amendment 4 
05APR2017 
Amendment 5 
04AUG2017 
Amendment 6 
20APR2018 
Sponsor 
Cidara Therapeutics Inc. 
6310 Nancy Ridge Dr., Suite 101, San Diego CA 92121 
Telephone: 001-858.752.6170 
Facsimile: 001-858.408.3509 
Sponsor Medical Monitor 
Name: Taylor Sandison, MD MPH 
Company: Cidara Therapeutics Inc. 
Address: 6310 Nancy Ridge Dr., Suite 101, San Diego CA 92121 
Telephone: 001-858.249.7429 
Mobile: 001-858.249.9459 
Facsimile: 001-858.408.3509 
Sponsor Clinical Project 
Manager 
Name: Karen Mena 
Company: Cidara Therapeutics Inc. 
Address: 6310 Nancy Ridge Drive, Suite 101, San Diego, CA 92121 
Telephone: 001-858.249.7430 
Facsimile: 001-858.408.3509  
European Union Drug 
Regulating Authorities Clinical 
Trials (EudraCT) # 
2015-005599-51 
Confidentiality Statement: 
This document is a confidential communication from Cidara Therapeutics Inc. Acceptance of 
this document constitutes an agreement by the recipient(s) that no information contained herein 
will be published or disclosed without prior written approval from Cidara Therapeutics Inc., 
except that this document may be disclosed to appropriate Institutional Review Boards and/or 
Ethics Committees under the condition that they are also required to maintain confidentiality 

Cidara Therapeutics, Inc. 
Intravenous CD 10 I 
Protocol: CD101.IV.2.03 
PROTOCOL APPROVAL PAGE 
 
Protocol CDIOI.IV.2.03 A6 
A Phase 2, Multicenter, Randomized, Double-blind Study of the Safety, Tolerability, 
and Efficacy of Intravenous CD101 vs Intravenous Caspofungin Followed By Oral 
Fluconazole Step-down in the Treatment of Subjects with Candidemia and/or 
Invasive Candidiasis 
Signature 
Original Protocol: 18FEB2016 
Amendment 1: 14MAY2016 
Amendment 1-IT (Italy only): 02SEP2016 
Amendment 2: 14SEP2016 
Amendment 3: 23FEB2017 
Amendment 4: 05APR2017 
Amendment 5: 04AUG2017 
Amendment 6: 20APR2018 
Date 
Taylor Sa 
son, MD MPH 
Chief Medical Officer 
Cidara Therapeutics, Inc. 
Protocol Amendment 6 
Con+ntial 
Page 2 of201 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 3 of 128 
 
1.0 
PROTOCOL SYNOPSIS 
Sponsor: Cidara Therapeutics Inc., San Diego CA 
Product Name: Intravenous CD101  
Active Ingredients: CD101 acetate 
Protocol Title: A Phase 2, Multicenter, Randomized, Double-blind Study of the Safety, Tolerability, and 
Efficacy of Intravenous CD101 vs Intravenous Caspofungin Followed By Oral Fluconazole Step-down in the 
Treatment of Subjects with Candidemia and/or Invasive Candidiasis 
Planned Study Centers: Approximately 60 
Phase of Development: 2 
Objectives  
The primary objectives of this study are to: 
• 
Evaluate the safety and tolerability of intravenous CD101 (CD101 IV) in the Safety population 
• 
Evaluate overall success (mycological eradication and resolution of systemic signs attributable to 
candidemia and/or invasive candidiasis [IC]) of CD101 IV in subjects with candidemia and/or IC at Day 
14 (±1 day) in the Microbiological Intent-to-treat (mITT) population 
The secondary objectives of this study are to: 
• 
Evaluate overall success (mycological eradication and resolution of systemic signs attributable to 
candidemia and/or IC) of CD101 IV at Day 5, Day 28 (±2 days; only for subjects with IC), and Follow-up 
(FU, Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without 
candidemia) in the mITT population 
• 
Evaluate mycological success (eradication) of CD101 IV at Day 5, Day 14 (±1 day), Day 28 (±2 days; 
only for subjects with IC), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for 
subjects with IC, with or without candidemia) in the mITT population 
• 
Evaluate clinical cure as assessed by the Investigator for CD101 IV at Day 14 (±1 day), Day 28 (±2 days; 
only for subjects with IC), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for 
subjects with IC, with or without candidemia) in the mITT population 
• 
Evaluate the pharmacokinetics (PK) of CD101 IV 
Study Design: This is a Phase 2, multicenter, prospective, randomized, double-blind, study of CD101 IV or IV 
caspofungin followed by oral fluconazole step-down therapy for treatment of subjects with candidemia and/or 
IC. In Part A, subjects will be randomized in a 1:1:1 ratio to receive CD101 IV treatment Group 1, CD101 IV 
treatment Group 2, or IV caspofungin (Figure 1, Figure 2, Figure 3, Table 1). Oral step-down therapy is 
allowed in all 3 treatment groups in Part A; oral placebo in the CD101 IV groups and oral fluconazole in the 
caspofungin group. After approximately 90 subjects have been enrolled in the mITT population in Part A, 
enrollment into Part A of the study will close and Part B will begin. In Part B, subjects will be randomized in a 
2:1 ratio to receive CD101 IV treatment or IV caspofungin (Figure 1, Figure 2, Figure 3, Table 1) until ≥45 
additional subjects and no more than 120 subjects have been enrolled. (Note: Subjects enrolled under 
Amendment 5 and assigned to CD101 IV receive Group 1 treatment and subjects enrolled under Amendment 6 
and assigned to CD101 IV receive Group 2 treatment. Subjects enrolled to Amendment 5 continue study 
participation according to the same amendment regardless of subsequent approval of Amendment 6.) Total 
enrollment will depend on the enrollment rate for the 6- to 8-month period between the end of Part A and the 
staged start of the Phase 3 study, which is the trigger for the rolling close-out of Part B. Oral step-down therapy 
is allowed in both treatment groups in Part B; oral placebo in the CD101 IV group and oral fluconazole in the 
caspofungin group. 
Subjects with candidemia only may be treated with study drug for a maximum of 21 days. Subjects with IC 
(with or without candidemia) may be treated with study drug for a maximum of 28 days.  For this study, 
subjects will be presumed to have IC if there is a positive culture for Candida spp. from a normally sterile site 
other than blood or if there is a positive sponsor-approved rapid in vitro diagnostic (IVD) or blood culture for 
Candida spp. combined with radiographic evidence of IC. 
Subjects in the CD101 IV treatment Group 1 will receive CD101 IV 400 mg on Day 1 and Day 8, with an 
optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 4 of 128 
 
subjects with IC), if needed. Subjects in the CD101 IV treatment Group 2 will receive CD101 IV 400 mg on 
Day 1 and 200 mg on Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose 
of 200 mg on Day 22 (only for subjects with IC), if needed. Subjects in the caspofungin group will receive IV 
caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a 
maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC 
(with or without candidemia). The optional doses of CD101 IV on Day 15 and Day 22 may be administered 
according to the subject’s clinical response and the medical judgment of the Principal Investigator (PI).  
After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of 
fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day 
thereafter) if criteria are met. In order to maintain the blind, subjects in the CD101 IV groups who have 
switched to oral step-down therapy will receive oral placebo (4 capsules on the first day followed by 2 capsules 
/day thereafter) and subjects in the caspofungin treatment group will receive IV placebo on Day 8, and on Days 
15 and 22 if study drug is administered through these timepoints. The total IV plus oral treatment duration will 
be ≥14 days and up to a maximum of 28 days.  
The dose and duration of any prior antifungal treatment taken within 4 weeks from randomization will be 
recorded at Screening. A retinal examination for evidence of a Candida eye infection, including 
endophthalmitis or chorioretinitis, will be performed during Screening or by Day 7 only on subjects with 
candidemia by blood culture, and should be repeated in subjects who were negative at baseline if the subject 
develops visual signs or symptoms of a Candida eye infection during the course of the study. Subjects who 
were negative at baseline and diagnosed with a Candida eye infection after initiating study drug should have an 
urgent ophthalmologic consultation (if not already done), should stop study drug, and be initiated on 
appropriate therapy for Candida eye infection per the local guidelines. If possible, all subjects diagnosed with 
endophthalmitis or choriorentinitis should remain in the study and all subsequent antifungal drugs, 
interventions, and outcomes for endophthalmitis or chorioretinitis should be recorded. 
The Schedule of Assessments and Procedures is presented in Table 2. Study Day 1 is defined as the first day of 
study drug administration. Subsequent study days are defined by the number of consecutive calendar days 
thereafter. All subjects will be monitored for adverse events (AEs) and serious adverse events (SAEs) 
following signing of the Informed Consent Form at screening and throughout the study until the FU visit (Days 
45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia) for 
each treatment group. Vital signs (temperature, heart rate, blood pressure, respiratory rate) will be recorded 
daily while receiving IV study drug and at Day 4, Day 5, Day 14 (±1 day), Day 28 (±2 days; only for subjects 
with IC), End-of-Treatment (EOT) (+2 days allowed after last dose of study drug) and FU (Days 45-52 for 
subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia). Hematology 
and chemistry laboratory tests will be performed at Screening; Days 2 and 4; Day 8, Day 14 (±1 day), EOT (+2 
days allowed after last dose of study drug), and at the FU visits. Coagulation laboratory tests (prothrombin 
time/international normalized ratio [PT/INR] and either partial thromboplastin time [PTT] or activated partial 
thromboplastin time [aPTT]) will be performed at Screening. Electrocardiograms (ECGs) will be performed at 
Screening (before subject randomization) and EOT (+2 days allowed after the last dose of study drug). 
Mycological diagnosis of candidemia or IC sufficient for inclusion in the study will be established by a positive 
microbiological test for yeast or Candida within 96 hours from time of collection of the sample until 
randomization. Acceptable positive microbiological tests for yeast or Candida include ≥1 blood culture 
positive for yeast or Candida, a Sponsor-approved rapid IVD test positive for Candida spp, or a positive Gram 
stain for yeast or positive culture for Candida spp. from a specimen obtained from a normally sterile site. If the 
positive blood culture used to qualify the subject for the study is drawn >12 hours from randomization, then an 
additional set of blood cultures must be obtained ≤12 hours before randomization. Blood cultures should be 
performed daily (preferred) or every other day until 2 blood cultures drawn ≥12 hours apart are negative 
without an intervening positive culture. Generally, blood cultures should involve 2 separate draws with ≥1 
draw from a peripheral vein without an IV catheter. Two bottles should be filled from each draw site, totaling 4 
bottles for each set of blood cultures. If possible, use 3 aerobic and 1 anaerobic bottle (if available at the site) 
for each blood culture set.  
In Part A only, blood samples will be collected for PK analysis from the OPPOSITE arm of the infusion on 
Day 1 (within 10 minutes before the end of infusion, between 15 minutes and 1 hour after the end of infusion, 
and between 2 hours and 12 hours after the end of infusion), Day 2 (random draw, with safety labs if possible), 
Day 4 (random draw, with safety labs if possible), Day 8 (predose only), and Day 15 (predose only). If therapy 
is stopped on or before Day 14 and there is no Day 15 dose, then the Day 15 PK sample should be drawn with 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 5 of 128 
 
the safety laboratory samples for the Day 14 visit. For the purpose of maintaining the blind, blood samples will 
be collected from all subjects, when possible, in all 3 treatment groups in Part A, but only PK samples from the 
CD101 IV groups will be analyzed (using a validated assay) by an independent, central bioanalytical 
laboratory. In part B, PK samples will not be collected.  
Overall success and mycological eradication will be assessed at Day 5, Day 14 (±1 day), Day 28 (±2 days; only 
for subjects with IC), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with 
IC, with or without candidemia). Clinical response will be assessed at Day 14 (±1 day), Day 28 (±2 days; only 
for subjects with IC), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with 
IC, with or without candidemia).  
Number of Subjects  
In Part A, subjects will be randomized (1:1:1) until there are approximately 30 subjects in the CD101 IV 
treatment Group 1, 30 subjects in the CD101 IV treatment Group 2, and 30 subjects in the comparator group in 
the mITT population. It is expected that approximately 114 subjects will need to be randomized to achieve 90 
subjects in the mITT population (assuming 80% of randomized subjects will be included in mITT population).  
In Part B, subjects will be randomized (2:1) until there are ≥30 subjects in the CD101 IV treatment groups and 
≥15 subjects in the comparator group (≥45 additional subjects and no more than 120 subjects). Total enrollment 
will depend on the enrollment rate for the 6- to 8-month period between the end of Part A and the staged start 
of the Phase 3 study, which is the trigger for the rolling close-out of Part B.  
Figure 1:  
Study Randomization and Treatment Regimens 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 6 of 128 
 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 7 of 128 
 
Figure 2:  
Study Design Diagram for Subjects with Candidemia Only 
 
Figure 3:  
Study Design Diagram for Subjects with Invasive Candidiasis (with or without 
Candidemia) 
 
 
Applies to CD101 Group 1 (Part A only) and Group 2 (Parts A and B) 
Applies to CD101 Group 1 (Part A only) and Group 2 (Parts A and B) 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 8 of 128 
 
Inclusion Criteria 
Subjects must meet ALL of the following inclusion criteria to be enrolled: 
1. Males or females ≥18 years.  
2. Established mycological diagnosis of candidemia and/or IC from a sample taken ≤96 hours before 
randomization defined as: 
a. 
 ≥1 blood culture positive for yeast or Candida  
OR 
b. Positive test for Candida from a Sponsor-approved rapid IVD 
OR 
c. 
Positive Gram stain for yeast or positive culture for Candida spp. from a specimen obtained from a 
normally sterile site 
3. Willing to initiate or continue medical treatment to cure infections, including receipt of antibiotics and 
surgical procedures, if required. Subjects receiving only medications and measures for comfort and not 
cure should not be enrolled. 
4. Female subjects of child-bearing potential <2 years postmenopausal must agree to and comply with using 1 
barrier method (eg, female condom with spermicide) plus 1 other highly effective method of birth control 
(eg, oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual 
abstinence while participating in this study. Male subjects must be vasectomized, abstain from sexual 
intercourse, or agree to use barrier contraception (condom with spermicide), and also agree not to donate 
sperm from first dose of CD101 (Day 1) until 90 days following last administration of study drug. 
5. Willing and able to provide written informed consent. If the subject is unable to consent for 
himself/herself, a legally acceptable representative must provide informed consent on their behalf. 
6. Presence of 1 or more systemic signs attributable to candidemia and/or IC (eg, fever, hypothermia, 
hypotension, tachycardia, tachypnea) 
Exclusion Criteria 
Subjects must NOT meet any of the following exclusion criteria to be enrolled: 
1. Any of the following forms of IC: 
a. 
Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed) 
b. Osteomyelitis  
c. 
Endocarditis or myocarditis 
d. Meningitis, endophthalmitis, or any central nervous system infection 
2. Neutropenia (absolute neutrophil count ≤500/µL) at Screening or anticipated neutropenia during the study 
3. Alanine aminotransferase or aspartate aminotransferase levels >10-fold the upper limit of normal 
4. Severe hepatic impairment in subjects with a history of chronic cirrhosis (Child-Pugh score >9) 
5. Received systemic treatment with an antifungal agent at approved doses for treatment of candidemia or IC 
for >48 hours (for example, >2 doses of a once daily antifungal agent or >4 doses of a twice daily 
antifungal agent) in the last 96 hours before randomization 
a. 
Exception: Receipt of antifungal therapy to which any Candida spp. isolated at Screening in qualifying 
cultures is not susceptible 
6. Pregnant females  
7. Lactating females who are nursing  
8. Known hypersensitivity to CD101 IV, caspofungin, any echinocandin, or to any of their excipients 
9. Previous participation in this or any previous CD101 study.  
10. Recent use of an investigational medicinal product within 28 days of the first dose of study drug or 
presence of an investigational device at the time of Screening  
11. The PI considers that the subject should not participate in the study 
12. Presence of an indwelling vascular catheter or device that cannot be removed and is likely to be the source 
of candidemia 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 9 of 128 
 
Test Product, Dose, and Mode of Administration  
Rezafungin for injection is a sterile product of lyophilized powder in a single-use vial for reconstitution with 
sterile water for injection prior to dilution into normal saline infusion bags. 
Subjects randomized to the CD101 IV treatment Group 1 will receive 1 dose of CD101 IV (400 mg) on Day 1 
and Day 8 (Table 1). Subjects in Group 1 who require >14 days of IV therapy will receive an optional third 
dose of CD101 IV (400 mg) on Day 15. Subjects in Group 1 with IC (with or without candidemia) who require 
>21 days of IV therapy will receive an optional fourth dose of CD101 IV (400 mg) on Day 22. Subjects in 
Group 1 will receive IV placebo on other study days in order to maintain the blind. 
Subjects randomized to the CD101 IV treatment Group 2 will receive 1 dose of CD101 IV 400 mg on Day 1 
and 200 mg on Day 8 (Table 1). Subjects in Group 2 who require >14 days of IV therapy will receive an 
optional third dose of CD101 IV (200 mg) on Day 15. Subjects in Group 2 with IC (with or without 
candidemia) who require >21 days of IV therapy will receive an optional fourth dose of CD101 IV (200 mg) 
on Day 22. Subjects in Group 2 will receive IV placebo on other study days in order to maintain the blind. 
Intravenous infusion of CD101 IV is nominally over 60 (±10) minutes, but the time may be increased as 
needed up to 180 (±10) minutes to manage symptoms of infusion reaction consistent with management of 
echinocandin class infusion reactions, whereby decreasing the rate of infusion often alleviates symptoms. 
(Note: infusion must be completed within the 4-hour stability limit, which starts at the time of reconstitution of 
rezafungin for injection lyophilized powder in the single-use vial.) Intravenous study drug is administered 24 
(±2) hours after study drug was administered on the previous day. Dosage adjustments of CD101 IV are not 
allowed. 
Subjects may receive oral step-down therapy after ≥3 days of IV therapy. Step-down therapy in both CD101 IV 
treatment groups will be oral placebo, in order to maintain the blind. Subjects with creatinine clearance >50 
mL/min will receive oral placebo (4 capsules on the first day followed by 2 capsules/day thereafter) in the 
CD101 treatment group. Subjects with creatinine clearance ≤50 mL/min will receive oral placebo (2 capsules 
on the first day followed by 1 capsule /day thereafter) in the CD101 treatment group. Subjects receiving 
hemodialysis will receive oral placebo (4 capsules on the first day followed by 2 capsules after each 
hemodialysis) in the CD101 treatment group. Subjects who have already switched to oral step-down therapy 
will receive both oral placebo and IV CD101 on Day 8, and if required on Day 15 and Day 22 for subjects who 
are administered study drug through these timepoints.  
Comparator 
Subjects randomized to the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on 
Day 1 followed by 50 mg once daily) for ≥3 days and up to a maximum of 21 days for subjects with 
candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia) (Table 1). 
Intravenous infusion of caspofungin is nominally over 60 (±10) minutes, but the time may be increased as 
needed up to 180 (±10) minutes to manage symptoms of infusion reaction. Intravenous study drug is 
administered 24 (±2) hours after study drug was administered on the previous day. 
Use of concomitant cyclosporine should be limited to subjects for whom potential benefit outweighs potential 
risk of drug-drug interactions with caspofungin. 
Subjects in the caspofungin group with moderate hepatic impairment (Child-Pugh score of 7-9 with a history 
of chronic cirrhosis) will receive a loading dose of caspofungin of 70 mg on Day 1 and 35 mg/day thereafter. 
Subjects in the caspofungin group weighing >80 kg or on concomitant rifampin, nevirapine, efavirenz, 
phenytoin, dexamethasone, or carbamazepine may receive 70 mg caspofungin daily. Dose adjustment due to 
drug-drug interactions may be considered at the Investigator’s discretion.  
Subjects in Part A and Part B may receive oral step-down therapy after ≥3 days of IV therapy. Step-down 
therapy in the caspofungin treatment group will be oral fluconazole. Subjects with creatinine clearance >50 
mL/min will receive oral fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 
mg [2 capsules]/day thereafter). Subjects in the caspofungin group with renal impairment who are switched to 
oral stepdown therapy may receive reduced doses of fluconazole. For subjects with creatinine clearance ≤50 
mL/min, the loading dose of fluconazole should be 400 mg [2 capsules] and the daily dose of fluconazole 
should be 200 [1 capsule] mg/day. For subjects receiving hemodialysis, the loading dose of fluconazole should 
be 800 mg [4 capsules] followed by 400 mg [2 capsules] of fluconazole after each hemodialysis. In order to 
maintain the blind, subjects who have already switched to oral step-down therapy will receive both oral 
fluconazole and IV placebo on Day 8, and if required on Day 15 and Day 22 for subjects who are administered 
study drug through these timepoints.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 10 of 128 
 
Oral Step Down Therapy 
An oral step-down therapy is allowed in all treatment groups, provided the following criteria are met:  
• 
Able to take oral medication 
• 
≥3 days of IV study drug 
• 
The Candida species isolated is susceptible to fluconazole.  
• 
The subject’s clinical status is considered stable based on Investigator assessment 
• 
If a blood culture is positive at Screening, 2 post-baseline blood cultures drawn ≥12 hours apart are 
negative for Candida spp. without an intervening positive culture, and the first of the 2 cultures was drawn 
≥48 hours prior to oral study drug initiation 
• 
No evidence of moderate or severe hepatic insufficiency (alanine aminotransferase or aspartate 
aminotransferase >3× the upper limit of normal) 
• 
No history of hypersensitivity or any other contraindications to the use of fluconazole and, in the 
Investigator’s opinion, the subject can tolerate oral fluconazole therapy (refer to current fluconazole 
Prescribing Information)  
Oral step-down therapy will be fluconazole in the caspofungin group and oral placebo in the CD101 treatment 
groups. 
The total IV plus oral treatment duration will be ≥14 days and up to 28 days. 
Table 1:  
Study Treatments 
Study 
Day 
CD101 IV  
Group 1  
Group 2 
Caspofungin Group 
1 
IV CD101 (400 mg) 
IV caspofungin (a single 70 mg loading dose) 
2-3 a 
IV placebo 
IV caspofungin (50 mg/day) 
4-7 
IV placebo if not stepped down 
OR 
oral step-down therapy (placebo) if already 
stepped down 
IV caspofungin (50 mg/day) if not stepped down 
OR 
oral step-down therapy (fluconazole, a loading 
dose of 800 mg [4 capsules] on the first day 
followed by 400 mg [2 capsules]/day thereafter) 
if already stepped down 
8 b 
IV CD101 (400 mg Group 1; 200 mg 
Group 2) if not stepped down  
OR 
IV CD101 (400 mg Group 1; 200 mg 
Group 2) PLUS oral step-down therapy 
(placebo) if already stepped down 
IV caspofungin (50 mg/day) if not stepped down  
OR  
IV placebo PLUS oral step-down therapy 
(fluconazole, a loading dose of 800 mg [4 
capsules] on the first day followed by 400 mg [2 
capsules]/day thereafter) if already stepped down 
9-14 c 
IV placebo if not stepped down 
OR 
oral step-down therapy (placebo) if already 
stepped down 
IV caspofungin (50 mg/day) if not stepped down 
OR 
oral step-down therapy (fluconazole, a loading 
dose of 800 mg [4 capsules] on the first day 
followed by 400 mg [2 capsules]/day thereafter) 
if already stepped down 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 11 of 128 
 
15 b  
(if 
needed) 
IV CD101 (400 mg Group 1; 200 mg 
Group 2) if not stepped down 
OR 
IV CD101 (optional) d (400 mg Group 1; 200 
mg Group 2) PLUS 
oral step-down therapy (placebo) if already 
stepped down 
OR  
No treatment 
IV caspofungin (50 mg/day) if not stepped down 
OR 
IV placebo (optional) d PLUS oral step-down 
therapy (fluconazole, a loading dose of 800 mg [4 
capsules] on the first day followed by 400 mg [2 
capsules]/day thereafter) if already stepped down 
OR  
No treatment 
16-21 e 
(if 
needed) 
IV placebo if not stepped down 
OR 
oral step-down therapy (placebo) if already 
stepped down 
OR  
No treatment 
IV caspofungin (50 mg/day) if not stepped down 
OR 
oral step-down therapy (fluconazole, a loading 
dose of 800 mg [4 capsules] on the first day 
followed by 400 mg [2 capsules]/day thereafter) 
if already stepped down 
OR  
No treatment 
22 b  
(if 
needed, 
only for 
subjects 
with IC) 
IV CD101 (400 mg Group 1; 200 mg 
Group 2) if not stepped down 
OR 
IV CD101 (optional) f (400 mg Group 1; 200 
mg Group 2) PLUS 
oral step-down therapy (placebo) if already 
stepped down 
OR  
No treatment 
IV caspofungin (50 mg/day) if not stepped down 
OR 
IV placebo (optional) f PLUS oral step-down 
therapy (fluconazole, a loading dose of 800 mg [4 
capsules] on the first day followed by 400 mg [2 
capsules]/day thereafter) if already stepped down 
OR  
No treatment 
23-28 g, h 
(if 
needed, 
only for 
subjects 
with IC) 
IV placebo if not stepped down 
OR 
oral step-down therapy (placebo) if already 
stepped down 
OR  
No treatment 
IV caspofungin (50 mg/day) if not stepped down 
OR 
oral step-down therapy (fluconazole, a loading 
dose of 800 mg [4 capsules] on the first day 
followed by 400 mg [2 capsules]/day thereafter) 
if already stepped down 
OR  
No treatment 
IC = invasive candidiasis; IV= intravenous 
a. 
Subjects must receive IV therapy for ≥3 days before switching to oral step-down therapy 
b. The Day 8, Day 14, Day 15, and Day 22 visits have a window of ±1 day if subject already stepped down to 
oral therapy and discharged from the study site 
c. 
Total IV plus oral treatment duration must be ≥14 days  
d. Subjects who require >14 days of therapy may receive an optional third dose of IV study drug on Day 15, 
if needed.  
e. 
Total IV plus oral treatment duration must be ≤21 days for subjects with candidemia only. 
f. 
Subjects with IC (with or without candidemia) who require >21 days of therapy may receive an optional 
fourth dose of IV study drug on Day 22, if needed 
g. The Day 28 visit has a window of ±2 days if subject already stepped down to oral therapy and discharged 
from the study site 
h. Total IV plus oral treatment duration must be ≤28 days for subjects with IC (with or without candidemia)  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 12 of 128 
 
Duration of Treatment  
Study participation will require from 45 to 52 days for subjects with candidemia only (or from 52-59 days for 
subjects with IC, with or without candidemia) after the first dose of study drug; study drug administration from 
Day 1 up to Day 21 (for subjects with candidemia) or up to Day 28 (±2 days; only for subjects with IC); safety, 
tolerability, and efficacy assessments up to Day 21 (for subjects with candidemia only) or up to Day 28 (±2 
days; only for subjects with IC); and a FU visit (Days 45 to 52 for subjects with candidemia only or Days 52-
59 days for subjects with IC, with or without candidemia).  
Criteria for Evaluation 
Efficacy 
Efficacy assessments will be recorded on Day 5, Day 14 (±1 day), Day 28 (±2 days; only for subjects with IC), 
and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without 
candidemia) 
The primary efficacy endpoint is overall success at Day 14 (±1 day), as defined below: 
• 
Mycological eradication defined as:  
o 
If positive blood culture at baseline: 2 negative blood cultures drawn ≥12 hours apart without 
intervening positive blood cultures  
 
OR 
o 
If positive culture from a normally sterile site (other than blood): 
― Documented mycological eradication: most recent culture on or prior to Day 14 (±1 day) from all 
normally sterile sites of baseline Candida infection (if accessible) is negative 
OR 
― Presumed mycological eradication: follow-up culture is not available (eg, normally sterile 
baseline site of Candida infection not accessible) in a subject with a successful clinical outcome 
(ie, did not receive rescue antifungal treatment and has resolution of systemic signs of IC that 
were present at baseline) and resolution or improvement of any baseline radiographic 
abnormalities due to IC 
AND 
• 
Resolution of attributable systemic signs of candidemia and/or IC that were present at baseline  
AND  
• 
No change of antifungal therapy for the treatment of candidemia and/or IC 
AND 
• 
The subject is not lost to follow up on the day of assessment  
 
Secondary efficacy outcome measures include: 
• 
Mycological eradication  
• 
Clinical cure as assessed by the Investigator  
Additional efficacy outcome measures include: 
• 
All-cause 30-day mortality 
• 
Time to first of 2 negative blood cultures drawn ≥12 hours apart, without an intervening positive culture 
 
Safety 
Safety will be assessed from the signing of the Informed Consent Form at Screening to the FU visit through the 
evaluation of AEs, vital signs (temperature, heart rate, blood pressure, and respiratory rate), ECGs, and clinical 
laboratory data (clinical chemistry panels, hematology evaluations, and urinalyses). 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 13 of 128 
 
Pharmacokinetics (Part A only) 
Blood samples will be obtained from subjects to evaluate the PK of CD101 IV. Blood samples will be collected 
for all 3 treatment groups for the purpose of maintaining the blind, but only PK samples from the CD101 IV 
groups will be analyzed by a central bioanalytical laboratory. When >1 assessment occurs at any time point, the 
PK blood sample will be given priority and taken at the correct protocol-specified time. Plasma samples will be 
analyzed for the concentration of CD101 by a validated liquid chromatography-tandem mass spectrometry 
method. 
Blood for PK analyses will be drawn from the OPPOSITE arm of the infusion at the following times: 
On Day 1 (within 10 minutes [ie, >0 to 10 minutes] before the end of infusion, between 15 minutes and 1 hour 
after the end of infusion, and between 2 hours and 12 hours after the end of infusion), Day 2 (random draw with 
date of sample same as Day 2 date of dose, with safety labs if possible), Day 4 (random draw with date of 
sample same as Day 4 date of dose, with safety labs if possible), Day 8 (predose only), and Day 15 (predose 
only). Day 8 and Day 15 PK draws should be performed within 30 minutes before the second and third dose of 
study drug, regardless of the exact day and time of these infusions. If therapy is stopped on or before Day 14 
and there is no Day 15 dose, then the Day 15 PK sample should be drawn with the safety laboratory samples 
for the Day 14 visit. Ideally, PK samples would be drawn with the safety laboratory samples for that day to 
prevent multiple needle sticks. 
Statistical Methods 
The study is not powered for inferential statistical analysis. A sufficient number of subjects are randomized to 
the CD101 IV and caspofungin groups in Part A to provide an initial, substantive analysis of safety and 
tolerability, and estimate efficacy. In Part A, assuming a 73% overall success rate, the sample size of 30 
subjects in each CD101 IV group will yield a 95% confidence interval (CI) of 53.8% to 87.5%. With the 
addition of Part B subjects and assuming a 73% overall success rate, a total approximate sample size of 60 
subjects in the CD101 treatment group  (consisting of Group 1 from Amendment 5 and Group 2 from 
Amendment 6) will yield a 95% CI of 60.0% to 83.7%, and a total approximate sample size of 110 subjects in 
the CD101 treatment group   (consisting of Group 1 from Amendment 5 and Group 2 from Amendment 6) will 
yield a 95% CI of 63.7% to 81.0%. 
Analysis populations are: 
• 
The Intent-to-treat (ITT) population: all randomized subjects  
• 
The Safety population: all subjects who received any amount of study drug 
• 
The Microbiological Intent-to-treat population (mITT): all subjects who had documented Candida infection 
based on Central Laboratory evaluation of a blood culture obtained within 96 hours of randomization, or 
from a specimen obtained from a normally sterile site, and received ≥1 dose of study drug 
To demonstrate preliminary efficacy and safety of CD101 and to confirm the correct CD101 dose regimen is 
utilized in Part B, an unblinded interim analysis will be performed after approximately 40 to 60 subjects in the 
mITT population have been enrolled and completed study drug therapy. This unblinded interim analysis of a 
few key efficacy and safety outcomes will be performed by an independent unblinded statistician. Interim 
efficacy and safety summary tables will be produced, but the identity of the group assignment for each 
individual subject will remain blinded until the completion of the study and the database for both Parts A and B 
are locked. Once Part A is completed, the database will be locked and a full unblinded analysis with all 
summary tables will be performed on Part A alone. As with the initial interim analysis and to help avoid bias, 
the full Part A analysis will be performed by an independent unblinded statistician, keeping the identity of the 
group assignment for each individual subject blinded until the completion of the study and the database for both 
Parts A and B are locked. (Note: An addendum to the Unblinding Plan for Part A allowed for unblinded safety 
review of adverse events of interest identified during blinded safety review; the addendum allowed for no more 
than 5% of subjects to be unblinded.) 
A Statistical Analysis Plan (SAP) will be prepared and finalized before the interim analysis. Any changes to the 
SAP from the time of the interim analysis to the final database lock of Part B will be documented in an 
addendum to the SAP. Any deviations from the final SAP/addendum will be described and justified in the 
study report. All statistical analyses will be performed using SAS®. All analyses will be completed for Part A. 
Selected analyses will be completed only for Part B and for Part A and B combined. 
The primary efficacy outcome is overall response and is determined programmatically from the mycological 
response and assessment of systemic signs of infection attributable to candidemia and/or IC at Day 14 (±1 day). 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 14 of 128 
 
The number and percentage of subjects with a success, failure, or indeterminate will be presented by treatment 
group. Two-sided 95% CIs for the point estimates of success in the mITT population will be determined. 
Analyses will be completed for Part A, Part B, and combined Part A and B. 
Safety will be evaluated by presenting summaries of AEs, clinical laboratory evaluations (hematology 
evaluation, chemistry panel, urinalysis), vital signs, and ECGs. Safety variables will be tabulated and presented 
for all subjects by study drug. Adverse events will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). A treatment-emergent adverse event (TEAE) is defined as an AE that occurs during or 
after study drug administration and up through the FU visit. The incidence of TEAEs will be presented by 
system organ class and preferred term, by relationship to study drug, by severity, and by whether or not they 
resulted in alteration of administration of or discontinuation of study drug (IV and IV/oral). In addition, the 
incidence of serious TEAEs and TEAEs leading to discontinuation of study drug (IV and IV/oral) will be 
presented by system organ class and preferred term. Descriptive statistics for clinical laboratory test results, 
vital signs, and ECG parameters, including changes from baseline, will be presented by time point. Incidences 
of potentially clinically significant clinical laboratory results, vital signs, and ECG parameters, as defined in the 
SAP, will also be summarized by time point. Analyses will be completed for Part A and for combined Part A 
and B. 
In Part A only, PK parameter assessment will be reported separately for the PK Analysis population and may 
include: maximum plasma concentration (Cmax), time to Cmax, and area under the curve, if applicable.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 15 of 128 
 
Table 2: 
Schedule of Assessments and Procedures 
Study Day  
(window) 
Screen 
 
Study Drug Administration, Days 
 
 
 
EOT 
+2 days 
after last 
dose of 
study 
drug (IV 
and oral) 
FU 
Visit 
Days 45-52 
for subjects 
with 
candidemia 
only (or 
Days 52-59 
for IC 
subjects with 
or without 
candidemia) 
1a 
 
2 
 
3 
 
4 
 
 
5 
 
 
6, 7 
 
8b 
(±1) 
9-13 
 
 
14b 
(±1) 
15 b 
(±1) 
16-
21 
 
22b,c  
(±1) 
23- 
27c 
 
 
 
 
 
28b,d 
(±2) 
Informed consent e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history f 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
including height and 
weight g 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
Calculate Child-Pugh 
score h 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Modified APACHE II 
score) with Glasgow 
coma scorei 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs j 
X 
X 
X 
X 
X 
X 
Xk 
X 
Xk 
X 
Xk 
Xk 
X 
Xk 
X 
X 
X 
12-lead ECG l  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Radiologic test  
results m 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for hematology 
and chemistry tests n 
 X 
 
X 
 
X 
 
 
X 
 
X 
 
 
 
 
 
X 
X 
Blood for coagulation 
panel 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 16 of 128 
Table 2: 
Schedule of Assessments and Procedures 
Study Day  
(window) 
Screen 
 
Study Drug Administration, Days 
 
 
 
EOT 
+2 days 
after last 
dose of 
study 
drug (IV 
and oral) 
FU 
Visit 
Days 45-52 
for subjects 
with 
candidemia 
only (or 
Days 52-59 
for IC 
subjects with 
or without 
candidemia) 
1a 
 
2 
 
3 
 
4 
 
 
5 
 
 
6, 7 
 
8b 
(±1) 
9-13 
 
 
14b 
(±1) 
15 b 
(±1) 
16-
21 
 
22b,c  
(±1) 
23- 
27c 
 
 
 
 
 
28b,d 
(±2) 
Urine for urinalyses, 
microscopy 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Urine pregnancy test o 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Retinal examination 
for Candida eye 
infectionp 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study randomization q 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer IV CD101 
or IV placebo 
 
Xr 
Xs 
Xs 
Xt 
Xt 
Xt 
Xu 
Xt 
Xt 
Xv 
Xw 
Xx 
Xy 
Xy 
 
 
Administer IV 
caspofungin or IV 
placebo  
 
Xr 
Xs 
Xs 
Xt 
Xt 
Xt 
Xu 
Xt 
Xt 
Xv 
Xw 
Xx 
Xy 
Xy 
 
 
Administer oral 
fluconazole or oral 
placebo step-down 
therapy if switched z 
 
 
 
 
Xt 
Xt 
Xt 
Xu 
Xt 
Xt 
Xv 
Xw 
Xx 
Xy 
Xy 
 
 
Record prior and/or 
concomitant 
medications aa 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 17 of 128 
Table 2: 
Schedule of Assessments and Procedures 
Study Day  
(window) 
Screen 
 
Study Drug Administration, Days 
 
 
 
EOT 
+2 days 
after last 
dose of 
study 
drug (IV 
and oral) 
FU 
Visit 
Days 45-52 
for subjects 
with 
candidemia 
only (or 
Days 52-59 
for IC 
subjects with 
or without 
candidemia) 
1a 
 
2 
 
3 
 
4 
 
 
5 
 
 
6, 7 
 
8b 
(±1) 
9-13 
 
 
14b 
(±1) 
15 b 
(±1) 
16-
21 
 
22b,c  
(±1) 
23- 
27c 
 
 
 
 
 
28b,d 
(±2) 
Record adverse events 
bb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Blood or normally 
sterile tissue/fluid for 
culture cc  
Xdd 
Xee 
Xee 
Xee 
Xee 
Xee 
Xee 
Xee 
Xee 
Xee 
Xee 
Xee 
Xee 
Xee 
Xee 
Xee 
Xff 
Rapid In Vitro 
Diagnostic 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Determine overall 
response 
programmatically gg 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
X 
Assess presence or 
absence of systemic 
signs and symptoms 
attributable to 
candidemia and/or IC 
Xhh 
 
 
 
 
Xii 
 
 
 
X 
 
 
 
 
X 
 
X 
Assess for clinical 
response jj 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
Blood for PK testing 
(Part A only) kk 
 
X 
X 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 18 of 128 
APACHE = Acute Physiology and Chronic Health Evaluation; ECG = electrocardiogram; EOT = End-of-Therapy; ESCMID = European Society Clinical 
Microbiology and Infectious Disease; FU = follow-up; IC = invasive candidiasis; IDSA = Infectious Diseases Society of America; IV = Intravenous; IVD = in 
vitro diagnostic; PK = pharmacokinetic. 
a. 
Study Day 1 is the first day of study drug administration; subsequent study days are consecutive calendar days. 
b. The time windows on Study Day 8, 14, 15, 22, and 28 visits apply only to subjects already stepped down to oral therapy and discharged from the study site. 
c. 
Continue study drug therapy and assessments if further therapy is clinically indicated; only for subjects with IC (with or without candidemia). Subjects will 
be presumed to have IC if there is a positive culture for Candida spp. from a normally sterile site other than blood or if there is a positive sponsor-approved 
rapid IVD or blood culture for Candida spp. combined with radiographic evidence of IC. 
d. The Day 28 visit is only for subjects with IC (with or without candidemia). Note that the Day 28 (±2 days) visit could be the same visit as the EOT visit if 
the subject receives ≥26 days of therapy. 
e. 
Written informed consent must be obtained prior to initiating any study related assessments or procedures. 
f. 
Medical history for the last 5 years and Candida risk factors for the last 3 months (eg, central line, active malignancy, broad-spectrum antibiotic therapy, 
diabetes mellitus, immunosuppression, major surgery, total parenteral nutrition, transplant recipient, trauma, dialysis, burns, pancreatitis) and Intensive Care 
Unit admission and discharge (if applicable). Short-term central venous catheters (eg, peripherally-inserted central catheters, internal jugular or subclavian 
central venous catheters) and long-term central venous catheters (eg, tunneled catheters) are recommended to be removed within 48 hours after diagnosis 
with candidemia, consistent with IDSA and ESCMID guidelines 
g. Physical exams are required at Screening, on Day 14, Day 28 (±2 days; only for subjects with IC), and at the FU visit. Height is recorded at Screening. 
Weight is recorded at Screening, on Day 14, and at the FU visit. If a physical exam is performed at any other visit, abnormal findings that represent a new or 
worsening condition as compared to baseline should be recorded as an adverse event.  
h. Calculate Child-Pugh score only if the subject has a history of chronic cirrhosis 
i. 
APACHE II score can be calculated after enrollment, but should use the vital signs and laboratory results from the Screening visit. 
j. 
If hospitalized, record the range of vital signs; highest and lowest daily temperature and the method used (oral, rectal, temporal, tympanic, or core), highest 
and lowest heart rate, highest and lowest respiratory rate, and highest and lowest blood pressure measured. If not hospitalized, record single measurements 
for daily temperature and the method used (oral, rectal, temporal, tympanic, or core), heart rate, respiratory rate, and blood pressure. 
k. For subjects discharged from the hospital and in the community, vital signs (temperature, heart rate, blood pressure, respiratory rate) are only performed on 
Days 6-28 if the subject is seen for clinical assessment or IV study drug infusion 
l. 
ECG must be conducted before subject randomization. 
m. If radiologic test performed, record radiologic test type with Findings and Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs. 
n. In general, the laboratory values to be entered into the electronic case report form will be from the first laboratory samples drawn each day with routine 
morning laboratory samples. 
o. Perform urine pregnancy test only for women of childbearing potential. Do not perform for women who are ≥2 years postmenopausal or surgically sterile.  
p. Perform a retinal examination for evidence of a Candida eye infection, including endophthalmitis or chorioretinitis, by Day 7 only on subjects with 
candidemia by blood culture, and repeat in subjects who were negative at baseline if the subject develops visual signs or symptoms of a Candida eye 
infection during the course of the study. 
q. Verify that the subject meets all study inclusion and exclusion criteria before randomization. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 19 of 128 
r. 
On Day 1, subjects will receive IV CD101 or IV caspofungin 
s. 
On Days 2-3, subjects will receive IV caspofungin or IV placebo.  
t. 
On Days 4-7, and 9-14, subjects will receive either IV caspofungin; IV placebo (if in a CD101 group); oral fluconazole (caspofungin group) if already 
switched; or oral placebo (CD101 groups) if already switched. 
u. On Day 8, subjects will receive either IV CD101 (if in a CD101 group and not switched to oral therapy); IV caspofungin (if in caspofungin group and not 
switched to oral therapy), IV CD101 plus oral placebo (if in a CD101 group and already switched to oral therapy); or IV placebo plus oral fluconazole (if in 
caspofungin group and already switched to oral therapy).  
v. On Day 15, subjects may receive either IV CD101 (if in a CD101 group and not switched to oral therapy), if needed; IV caspofungin (if in caspofungin 
group and not switched to oral therapy), if needed; IV CD101 plus oral placebo (if in a CD101 group and already switched to oral therapy), if needed; IV 
placebo plus oral fluconazole (if in caspofungin group and already switched to oral therapy), if needed; or no treatment.  
w. On Days 16-21, subjects may receive either IV caspofungin (if in caspofungin group), if needed; IV placebo (if in a CD101 group), if needed; oral 
fluconazole (caspofungin group) if already switched and needed; oral placebo (CD101 groups) if already switched and needed; or no treatment 
x. On Day 22, subjects with IC (with or without candidemia) may receive either IV CD101 (if in a CD101 group and not switched to oral therapy), if needed; 
IV caspofungin (if in caspofungin group and not switched to oral therapy), if needed; IV CD101 plus oral placebo (if in a CD101 group and already switched 
to oral therapy), if needed; IV placebo plus oral fluconazole (if in caspofungin group and already switched to oral therapy), if needed; or no treatment.  
y. On Days 23-28, subjects may receive either IV caspofungin (if in caspofungin group), if needed; IV placebo (if in a CD101 group), if needed; oral 
fluconazole (caspofungin group) if already switched and needed; oral placebo (CD101 groups) if already switched and needed; or no treatment 
z. 
Oral step-down therapy will be fluconazole (a loading dose of 800 mg [4 capsules ] on the first day followed by 400 mg [2 capsules ]/day thereafter) in the 
caspofungin group and oral placebo (4 capsules on the first day followed by 2 capsules/day thereafter) in the CD101 groups. 
aa. Record all systemic antifungal therapy administered within 4 weeks and all non-antifungal therapy administered within 1 week prior to randomization 
Record concomitant antimicrobial agents, including all antifungal agents at each study visit.  
bb. Adverse events are collected following signing of the Informed Consent Form at Screening through the last study visit (FU) 
cc. Perform identification and susceptibility testing at local laboratory for Candida for any positive blood culture or positive culture from a specimen obtained 
from a normally sterile site at Screening and for any positive culture requiring a change of antifungal therapy (ie, identification and susceptibility testing not 
required for Candida isolates cultured from specimens obtained on other study days without a required change in antifungal therapy). 
dd. Blood for culture must be obtained as part of the standard of care for inclusion in the study. Established mycological diagnosis of candidemia and/or IC 
sufficient for inclusion in the study is defined as ≥1 blood culture positive for yeast or Candida, a Sponsor-approved rapid IVD test positive for Candida spp, 
or a positive Gram stain for yeast or positive culture for Candida spp. from a specimen obtained from a normally sterile site ≤96 hours before randomization. 
Record species and susceptibilities for all bacteria isolated within 1 week prior to randomization from blood or any other normally sterile site. If the positive 
blood culture used to qualify the subject for the study is drawn >12 hours from randomization, then an additional set of blood cultures must be obtained ≤12 
hours before randomization.  
ee. Obtain blood and/or normally sterile tissue/fluid for culture if demonstrating mycological eradication or if clinically indicated. Blood cultures should be 
repeated daily (preferred) or every other day until 2 negative blood cultures are obtained ≥12 hours apart, without an intervening positive culture. All fungal 
isolates cultured from blood and normally sterile tissue/fluid from Screening through the last study visit must be sent to the Central Laboratory. Record the 
species and susceptibilities for any new bacteria isolated from blood or any other normally sterile site.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 20 of 128 
ff. Obtain blood for culture at FU. If feasible, and if there was a previous culture from a site positive for Candida spp., obtain culture from normally sterile 
tissue/fluid from the same site. All fungal isolates cultured from blood and normally sterile tissue/fluid from Screening through the last study visit must be 
sent to the Central Laboratory. Record the species and susceptibilities for any new bacteria isolated from blood or any other normally sterile site.  
gg. Overall success for subjects with candidemia occurs if 2 blood cultures are negative and ≥12 hours apart without intervening positive blood cultures, there 
was no change of antifungal therapy for the treatment of candidemia, and signs attributable to candidemia at baseline have resolved; blood cultures are 
drawn daily until the subject qualifies as a success. Success for subjects with IC (with or without candidemia) occurs if negative culture from a normally 
sterile site is either documented or presumed, there was no change of antifungal therapy for the treatment of IC, and signs attributable to IC at baseline have 
resolved: documented mycological eradication occurs if most recent culture on or prior to the day of assessment from all normally sterile sites of baseline 
Candida infection (if accessible) is negative; presumed mycological eradication occurs if follow-up culture is not available (eg, normally sterile baseline site 
of Candida infection not accessible) in a subject with a successful clinical outcome (ie, did not receive rescue antifungal treatment and has resolution of 
systemic signs of IC) and resolution or improvement of any baseline radiographic abnormalities due to IC. 
hh. The Screening period for assessing systemic signs for inclusion in the study may include the 4 hours prior to the drawing of the qualifying positive blood 
culture (when systemic signs of infection resulted in obtaining blood cultures), qualifying positive culture from a sterile site, or qualifying rapid in vitro 
diagnostic, through enrollment. 
ii. On Day 5, assess presence or absence of systemic signs only (ie, not symptoms) and determine which are attributable to candidemia and/or IC 
jj. Principal Investigator to assess if the subject is a cure, indeterminate, or failure based on the criteria in Table 11; there is a specific electronic case report 
form page for completion of this assessment.  
kk. In Part A only, obtain blood for PK sampling from the OPPOSITE arm of the infusion on Day 1 (within 10 minutes [ie, >0 to 10 minutes] before the end of 
infusion, between 15 minutes and 1 hour after the end of infusion, and between 2 hours and 12 hours after the end of infusion), Day 2 (random draw with 
date of sample same as Day 2 date of dose, with safety labs if possible), Day 4 (random draw with date of sample same as Day 4 date of dose, with safety 
labs if possible), Day 8 (predose only), and Day 15 (predose only). Day 8 and Day 15 PK draws should be performed within 30 minutes before the second 
and third dose of study drug, regardless of the exact day and time of these infusions. If therapy is stopped on or before Day 14 and there is no Day 15 dose, 
then the Day 15 PK sample should be drawn with the safety laboratory samples for the Day 14 visit. Ideally, PK samples would be drawn with the safety 
laboratory samples for that day to prevent multiple needle sticks.  
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 21 of 128 
 
2.0 
TABLE OF CONTENTS 
1.0 
PROTOCOL SYNOPSIS .................................................................................................................. 3 
2.0 
TABLE OF CONTENTS ................................................................................................................ 21 
3.0 
LIST OF ACRONYMS, ABBREVIATIONS AND DEFINITIONS OF TERMS ......................... 25 
4.0 
BACKGROUND AND RATIONALE ........................................................................................... 28 
4.1 
Candidemia and invasive candidiasis ............................................................................... 28 
4.2 
CD101 ............................................................................................................................... 30 
4.3 
Nonclinical Pharmacology and Toxicology ...................................................................... 30 
4.4 
Clinical Experience ........................................................................................................... 33 
4.5 
Clinical Pharmacology ...................................................................................................... 35 
4.5.1 
Single Ascending Dose Pharmacokinetics (CD101.IV.1.01) ............................. 35 
4.5.2 
Multiple Ascending Dose Pharmacokinetics (CD101.IV.1.02) .......................... 36 
4.6 
Summary of Known Benefits and Potential Risks ............................................................ 37 
4.6.1 
Potential Benefits ................................................................................................ 37 
4.6.2 
Known Risks ...................................................................................................... 37 
4.6.3 
Potential Risks .................................................................................................... 38 
4.6.4 
Risk-Benefit Summary ....................................................................................... 38 
4.7 
Justification for Dosing Regimen ..................................................................................... 39 
4.8 
Population to be Studied ................................................................................................... 45 
4.9 
Statement of Compliance .................................................................................................. 45 
4.10 
Justification for Use of CD101 in Candidemia and Invasive Candidiasis ........................ 45 
4.11 
Justification of the Part B Study ....................................................................................... 46 
5.0 
STUDY PURPOSE AND OBJECTIVES ....................................................................................... 47 
6.0 
STUDY DESIGN ............................................................................................................................ 48 
6.1 
Description of the Study ................................................................................................... 48 
6.2 
Number of Subjects .......................................................................................................... 55 
6.3 
Measures Taken to Minimize Bias .................................................................................... 55 
6.4 
Expected Duration of Subject Participation ...................................................................... 55 
6.5 
Method of Treatment Assignment and Blinding ............................................................... 56 
7.0 
SELECTION, DISCONTINUATION, AND WITHDRAWAL OF SUBJECTS ........................... 57 
7.1 
Subject Inclusion Criteria ................................................................................................. 57 
7.1.1 
Rapid In Vitro Diagnostics for Candidemia and Invasive Candidiasis ............... 58 
7.1.2 
Systemic Signs of Candidemia and Invasive Candidiasis .................................. 58 
7.2 
Subject Exclusion Criteria ................................................................................................ 59 
7.3 
Requalification for Entry .................................................................................................. 60 
7.4 
Subject Withdrawal Criteria ............................................................................................. 60 
7.4.1 
Withdrawal from Study Protocol ........................................................................ 60 
7.4.2 
Early Discontinuation from Study Drug Administration .................................... 61 
7.5 
Replacement of Subjects ................................................................................................... 63 
7.6 
Study Termination by Sponsor and Termination Criteria ................................................. 63 
8.0 
STUDY DRUGS ............................................................................................................................. 63 
8.1 
CD101 for Injection .......................................................................................................... 67 
8.1.1 
Directions for Use ............................................................................................... 67 
8.1.2 
Drug Storage ....................................................................................................... 68 
8.2 
Caspofungin ...................................................................................................................... 68 
8.3 
Oral Step-Down Therapy .................................................................................................. 68 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 22 of 128 
 
8.4 
Dose Adjustment ............................................................................................................... 69 
8.4.1 
CD101 IV ........................................................................................................... 69 
8.4.2 
Caspofungin ........................................................................................................ 69 
8.4.3 
Fluconazole ......................................................................................................... 69 
8.5 
Compliance ....................................................................................................................... 69 
8.6 
Breaking the Blind ............................................................................................................ 70 
8.7 
Previous and Concomitant Medications and Substances .................................................. 70 
8.8 
Accountability Procedures ................................................................................................ 71 
8.9 
Study Drug Handling And Disposal ................................................................................. 71 
9.0 
STUDY PROCEDURES................................................................................................................. 71 
9.1 
Screening .......................................................................................................................... 72 
9.2 
Days 1, 2, and 3 ................................................................................................................ 74 
9.3 
Days 4 to 7 ........................................................................................................................ 75 
9.4 
Day 8 (±1 day if already switched to oral step-down therapy and discharged from the 
study site) .......................................................................................................................... 77 
9.5 
Days 9 to 13 ...................................................................................................................... 79 
9.6 
Day 14 (±1 day if already switched to oral step-down therapy and discharged from 
the study site) .................................................................................................................... 80 
9.7 
Day 15 (±1 day if already switched to oral step-down therapy and discharged from 
the study site) .................................................................................................................... 82 
9.8 
Days 16 to 21 .................................................................................................................... 83 
9.9 
Day 22 (±1 day if already switched to oral step-down therapy and discharged from 
the study site) - Only Subjects With Invasive Candidiasis ............................................... 85 
9.10 
Days 23 to 27 - Only Subjects with Invasive Candidiasis ................................................ 86 
9.11 
Day 28 (±2 days if already switched to oral step-down therapy and discharged from 
the study site) - Only Subjects with Invasive Candidiasis ................................................ 88 
9.12 
End of Therapy (+2 days allowed after last dose of study drug) ...................................... 89 
9.13 
Follow-Up Visit (Days 45-52 for Subjects with Candidemia Only or Days 52-59 for 
Subjects with Invasive Candidiasis, With or Without Candidemia) ................................. 91 
10.0 
ASSESSMENT OF SAFETY ......................................................................................................... 92 
10.1 
Safety Parameters ............................................................................................................. 92 
10.2 
Adverse Events ................................................................................................................. 92 
10.3 
Adverse Event Reporting .................................................................................................. 92 
10.4 
Definitions ........................................................................................................................ 93 
10.4.1 
Adverse Event .................................................................................................... 93 
10.4.2 
Suspected Adverse Reaction ............................................................................... 94 
10.4.3 
Life-Threatening Adverse Event or Life-Threatening Suspected Adverse 
Reaction .............................................................................................................. 94 
10.4.4 
Serious Adverse Event or Serious Suspected Adverse Reaction ........................ 94 
10.4.5 
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction .......... 95 
10.5 
Adverse Event Classification ............................................................................................ 95 
10.5.1 
Relationship to Investigational Drug .................................................................. 95 
10.5.2 
Severity ............................................................................................................... 96 
10.5.3 
Serious Adverse Event ........................................................................................ 96 
10.6 
Adverse Event Follow-up ................................................................................................. 97 
10.7 
Adverse Events of Special Interest ................................................................................... 98 
10.7.1 
CD101 IV Intolerability ...................................................................................... 98 
10.7.2 
Phototoxicity ....................................................................................................... 98 
10.7.3 
Neuropathy and Tremors .................................................................................... 98 
10.8 
Toxicity Management ....................................................................................................... 98 
10.9 
Risks for Women of Child-Bearing Potential or During Pregnancy ................................. 98 
10.10 
Risks for Males of ChildBearing Potential ....................................................................... 99 
11.0 
ASSESSMENT OF EFFICACY PARAMETERS .......................................................................... 99 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 23 of 128 
 
12.0 
ASSESSMENT OF PHARMACOKINETIC PARAMETERS (Part A only) ............................... 102 
13.0 
STATISTICAL METHODS ......................................................................................................... 103 
13.1 
Analysis Populations ....................................................................................................... 104 
13.2 
Analysis of Study Population and Subject Characteristics ............................................. 104 
13.3 
Safety Analyses ............................................................................................................... 104 
13.4 
Efficacy Analyses ........................................................................................................... 105 
13.5 
Pharmacokinetic Analyses (Part A only) ........................................................................ 106 
13.6 
Determination of Study Sample Size .............................................................................. 107 
13.7 
Handling of Dropouts and Missing, Unused, and Spurious Data.................................... 107 
13.8 
Termination Criteria........................................................................................................ 107 
13.9 
Deviation Reporting ........................................................................................................ 107 
14.0 
INVESTIGATOR REQUIREMENTS .......................................................................................... 108 
14.1 
Protocol Adherence ......................................................................................................... 108 
14.2 
Electronic Case Report Forms ........................................................................................ 108 
14.3 
Source Document Maintenance ...................................................................................... 108 
14.4 
Study Monitoring Requirements ..................................................................................... 108 
14.5 
Study Completion ........................................................................................................... 108 
15.0 
QUALITY CONTROL AND QUALITY ASSURANCE ............................................................ 109 
16.0 
PROTECTION OF HUMAN SUBJECTS .................................................................................... 110 
16.1 
Informed Consent ........................................................................................................... 110 
16.2 
IRB/IEC Approval .......................................................................................................... 110 
17.0 
DATA HANDLING AND RECORD KEEPING ......................................................................... 110 
17.1 
Direct Access to Source Data/Documentation ................................................................ 111 
17.2 
Study Drug Accountability ............................................................................................. 111 
17.3 
Retention of Records....................................................................................................... 111 
18.0 
FINANCING AND INSURANCE ............................................................................................... 111 
19.0 
PUBLICATION POLICY ............................................................................................................. 111 
20.0 
REFERENCES .............................................................................................................................. 112 
21.0 
APPENDICES .............................................................................................................................. 118 
APPENDIX 1: CLINICAL and LABORATORY STANDARDS INSTITUTE (CLSI) and 
EUROPEAN COMMITTEE on ANTIMICROBIAL SUSCEPTIBILITY TESTING 
(EUCAST) BREAKPOINTS for CANDIDA spp: .......................................................... 118 
APPENDIX 2: Creatinine clearance ............................................................................................. 120 
Appendix 3: Safety Laboratory Tests ............................................................................................ 121 
Appendix 4: Child-Pugh Score ..................................................................................................... 122 
Appendix 5: MODIFIED ACUTE PHYSIOLOGY AND CHRONIC HEALTH  
       EVALUATION (APACHE) II SCORE ................................................................... 123 
Appendix 6: Glasgow Coma Score ............................................................................................... 125 
Appendix 7: Pharmacokinetic Sample Processing and Shipment (Part A only) ........................... 126 
Appendix 8: Investigator Signature ............................................................................................... 128 
 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 24 of 128 
 
List of Tables 
 
Table 1:  
Study Treatments ..............................................................................................................10 
Table 2: 
Schedule of Assessments and Procedures .........................................................................15 
Table 3: 
Summary of Plasma CD101 Exposures Following Administration of 50, 100, 200,  
 
and 400 mg 1-hour Intravenous Infusion of CD101 .........................................................36 
Table 4: 
Summary of Plasma CD101 Exposures Following Administration of 100 mg  
 
(Day 1/Day8), 200 mg (Day 1/Day8), and 400 mg (Day 1/Day15) Weekly 1-hour  
 
Intravenous Infusion of CD101.........................................................................................37 
Table 5: 
Predicted Pharmacokinetic-Pharmacodynamic Target Attainment for Rezafungin  
 
Regimens, Stratified by Week and Minimal Inhibitory Concentration, against  
 
C. albicans ........................................................................................................................40 
Table 6: 
Predicted Pharmacokinetic-Pharmacodynamic Target Attainment for Rezafungin  
 
Regimens, Stratified by Week and Minimal Inhibitory Concentration, against  
 
C. glabrata ........................................................................................................................42 
Table 7: 
Percent Probabilities of Pharmacokinetic-Pharmacodynamic Target Attainment  
 
by Anidulafungin, Caspofungin, and Micafungin against Candida spp. ..........................44 
Table 6:  
Study Treatments ..............................................................................................................66 
Table 7:  
Guidelines for Assessing Relationship of Event to Study Drug .......................................96 
Table 8: 
Guidelines for Severity Assessments ................................................................................96 
Table 9:  
Mycological Outcome Categories at Day 5, Day 14 (±1 day), Day 28 (±2 days; only  
 
for subjects with invasive candidiasis), and Follow-up Visit ............................................99 
Table 10:  
Overall Response Categories at Day 5, Day 14 (±1 day), Day 28 (±2 days; only  
 
for subjects with invasive candidiasis), and Follow-up Visit ..........................................101 
Table 11: 
Investigator’s Assessment of Clinical Response at Day 14 (±1 day),  
 
Day 28 (±2 days; only for subjects with invasive candidiasis), and Follow-up Visit .....102 
 
List of Figures 
 
Figure 1:  
Study Randomization and Treatment Regimens .......................................................... 5 
Figure 2:  
Study Design Diagram for Subjects with Candidemia Only .............................................. 7 
Figure 3:  
Study Design Diagram for Subjects with Invasive Candidiasis  
 
(with or without Candidemia) ............................................................................................ 7 
Figure 4: 
Predicted Pharmacokinetic-Pharmacodynamic Target Attainment for  
 
Rezafungin Regimens, against C. albicans relative to MIC Distribution .........................41 
Figure 5: 
Predicted Pharmacokinetic-Pharmacodynamic Target Attainment for  
 
Rezafungin Regimens, against C. glabrata relative to MIC Distribution .........................43 
Figure 5: 
Study Randomization and Treatment Regimens ...............................................................48 
Figure 6:  
Study Design Diagram for Subjects with Candidemia Only .............................................53 
Figure 7:  
Study Design Diagram for Subjects with Invasive Candidiasis  
 
(with or without Candidemia) ...........................................................................................54 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 25 of 128 
 
3.0 
LIST OF ACRONYMS, ABBREVIATIONS AND DEFINITIONS OF 
TERMS 
AE 
adverse event 
APACHE 
Acute Physiology and Chronic Health Evaluation 
aPTT 
activated partial thromboplastin time 
AUC 
area under the concentration time curve 
AUC0-168 
area under the concentration time curve from time 0 to 168 hours 
AUC0-∞ 
area under the curve from time 0 to infinity 
AUC0-t 
area under the curve from time 0 to the final sample  
BMI 
body mass index 
C144 
plasma concentration at 144 hours post start of infusion 
CD101 for Injection 
product name for the lyophilized form 
CD101 Injection 
product name for the liquid dosage form 
CD101 IV 
Intravenous CD101: CD101 Injection or CD101 for Injection 
CDC 
Centers for Disease Control and Prevention 
CLSI 
Clinical and Laboratory Standards Institute  
Cmax 
maximum plasma concentration 
eCRF 
electronic case report form 
ECG 
electrocardiogram 
EOT 
End-of-Treatment 
ESCMID 
European Society Clinical Microbiology and Infectious Diseases 
EUCAST 
European Committee on Antimicrobial Susceptibility Testing 
fAUC0-168 
free-drug area under the concentration time curve from time 0 to 168 hours 
FDA 
Food and Drug Administration 
FU 
Follow-up 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
IC 
invasive candidiasis 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IDSA 
Infectious Diseases Society of America 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 26 of 128 
 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IV 
intravenous 
IVD 
in vitro diagnostic 
IWRS 
Interactive Web Response System 
K2EDTA 
potassium ethylenediaminetetraacetic acid 
LC-MS/MS 
liquid chromatography- tandem mass spectrometry 
MAD 
multiple-ascending dose 
MALDI 
matrix-assisted laser desorption ionization 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
minimal inhibitory concentration 
MIC90 
minimal inhibitory concentration required to inhibit the growth of 90% of the isolates 
tested 
mITT 
Microbiological Intent-to-Treat 
NDA 
New Drug Application 
NOAEL 
no-observed-adverse-effect level 
OTC 
over the counter 
PD 
pharmacodynamic 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 
PT/INR 
prothrombin time/international normalized ratio 
PTT 
partial thromboplastin time 
R 
resistant 
S 
sensitive 
SAD 
single-ascending dose 
SAE 
serious adverse event 
SAER 
serious adverse event report 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
SOP 
standard operating procedure 
t1/2 
terminal half-life 
TEAE 
treatment-emergent adverse event 
Tmax 
time to Cmax 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 27 of 128 
 
UA 
urinalysis 
US 
United States 
Vss 
volume of distribution at steady state 
Vz 
volume of distribution 
WFI 
water for injection 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 28 of 128 
 
4.0 
BACKGROUND AND RATIONALE 
4.1 
CANDIDEMIA AND INVASIVE CANDIDIASIS 
Intravenous CD101 (CD101 IV), a new echinocandin antifungal agent, is being 
developed specifically to treat patients with systemic infections caused by Candida. 
These serious and life-threatening infections represent a significant public health issue, 
particularly in highly vulnerable patient populations such as the elderly, postsurgical, 
critically ill, and other hospitalized patients with serious medical conditions (Magill et al., 
2014; Andes et al., 2012; Wisplinghoff et al., 2004). In addition, because of increasing 
resistance to existing antifungal drugs, there is an urgent need to develop new and more 
effective antifungal agents to treat these serious infections (Alexander et al., 2013; 
Arendrup et al., 2013; Ostrosky-Zeichner 2013; Pfaller, 2012). The Centers for Disease 
Control and Prevention (CDC) recently warned that fluconazole-resistant Candida have 
the potential to pose a serious threat to public health (CDC, 2013; CDC, 2016). However, 
since 2007, no new antifungal agents have been approved for treatment of candidemia 
(The White House, 2014; Executive Office of the President, 2014; CDC, 2013). 
Candidemia and other forms of invasive candidiasis (IC) (eg, disseminated candidiasis, 
peritonitis, intra-abdominal abscess, hepatic candidiasis, endocarditis, and meningitis) are 
considered to be among the most critical invasive fungal infections in the United States 
(US) in terms of incidence and impact (Brown et al., 2012; Pfaller and Diekema, 2010; 
Arendrup et al. 2013; Azie et al., 2012; Menzin et al., 2009; Vincent et al., 2009). In a 
recent analysis of a large US patient database, Candida infections accounted for 40% of 
all invasive fungal infections and were associated with the highest excess length of stay, 
excess cost, and attributable mortality (Menzin et al., 2009). In fact, the mortality rate in 
patients with candidemia has been reported to be >40%, which is higher than that for 
some populations with invasive aspergillosis (Andes, et al. 2012; Wisplinghoff et al., 
2004; Mikulska et al., 2012; Falagas et al., 2006; Labelle et al., 2008; Pfaller and 
Diekema, 2010; Slavin et al., 2010; Mylonakis et al., 2015; Pfaller and Diekema, 2007).  
The US National Center for Health Statistics reported that the incidence of Candida 
infection is 8/100,000 population per year, but estimates range up to 26/100,000 in 
certain regions of the US, and the incidence continues to increase (Brown et al., 2012; 
Pfaller and Diekema, 2010; Menzin et al., 2009; Vincent et al., 2009; Cleveland et al., 
2012; Zilberberg et al., 2008a; Zilberberg et al., 2008b). In 2004, Candida was the fourth 
leading cause of healthcare-associated bloodstream infections overall (Wisplinghoff et 
al., 2004). In 2008, the National Healthcare Safety Network reported that Candida was 
the third most common cause of central line–associated bloodstream infections in US 
intensive care units (Hidron et al., 2008). However, the most recent survey reported that 
Candida was now the most common cause of hospital-acquired bloodstream infections in 
the US (Magill et al., 2014). Even more disturbing is that some of the highest rates of 
Candida infection have been observed among elderly hospitalized patients (Zaoutis et al., 
2005; Zilberberg et al., 2008b).  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 29 of 128 
 
More than 50% of all Candida infections are caused by non-albicans Candida species, 
including Candida glabrata, which is the most common non-albicans Candida species in 
North America and Europe. The incidence of infections caused by C. glabrata in the US 
has increased by >4 fold over the past 20 years (Cleveland et al., 2012). In the US-based 
SENTRY Antifungal Surveillance Program, the frequency of C. glabrata as a cause of 
bloodstream infections recently increased from 18% in 2008/2009 to 25% in 2010/2011 
(Pfaller et al., 2014). Azole-resistant C. glabrata has recently been identified as a serious 
threat to public health (The White House, 2014; Executive Office of the President, 2014; 
CDC, 2013). In the US-based SENTRY Antifungal Surveillance Program, the rate of 
azole-resistant C. glabrata has recently increased from 9% in the 1992-2001 time period 
to 14% in the 2001-2007 time period (Pfaller et al., 2014; 2013; 2012; 2010a, 2010b, 
2009), but it has been reported to be as high as 30% in some centers (Alexander et al., 
2013).  
The increasing incidence of non-albicans Candida and the greater efficacy of 
echinocandins compared to azoles in Candida infections provided support for the 
recommendation in Infectious Diseases Society of America (IDSA) and European 
Society Clinical Microbiology and Infectious Diseases (ESCMID) guidelines that an 
echinocandin be used for initial treatment of candidemia (Pappas et al., 2016; Ullmann et 
al., 2012; Cornely et al., 2012). These guidelines allow for a subsequent “step-down” to 
an azole for treatment, if the Candida species has been identified and has been 
demonstrated to be susceptible to the azole. However, not all US hospitals are currently 
able to perform antifungal susceptibility testing, making it difficult for many hospitals to 
follow this recommendation. In the context of increasing rates of azole-resistant C. 
glabrata, the current treatment regimen would be ≥2 weeks of a daily echinocandin.  
Moreover, because of its haploid genome, C. glabrata has the potential to more rapidly 
develop resistance to antifungal agents than other Candida spp. in multiple drug classes, 
including echinocandins (Ostrosky-Zeichner, 2013; Pfaller et al., 2012, 2008). 
Echinocandins inhibit the 1,3-β-D-glucan synthase (encoded by FKS1, FKS2, and FKS3 
genes), which synthesizes a major component of the fungal cell wall. Mutations in “hot 
spot” regions of FKS1 and/or FKS2 are associated with elevated echinocandin minimal 
inhibitory concentration (MIC) values, reduced glucan synthase enzyme sensitivity, and 
unfavorable outcomes in animal models (Beyda et al., 2014; Alexander et al., 2013). FKS 
mutations have been identified in 8% to 32% of patients with C. glabrata candidemia, 
particularly in patients with prior echinocandin exposure. FKS mutations have been 
associated with higher clinical failure rates compared to non-FKS mutants (60% vs 23%) 
(Beyda et al., 2014; Shields et al., 2013). In fact, in a recently reported case series, the 
clinical failure rate among patients with echinocandin-resistant C. glabrata was reported 
to be 91% (Shields et al., 2013).  
The emergence of multidrug resistance in C. glabrata can be considered a major public 
health issue because neither the azoles nor the currently available echinocandins would 
be appropriate for treatment, and high dose amphotericin is the only alternative and is 
associated with renal toxicity, particularly in older, critically-ill patients with sepsis 
(Alexander and Wingard, 2005; Chapeland-Leclerc et al., 2010; Krogh-Madsen et al., 
2006; Pappas et al., 2016).  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 30 of 128 
 
4.2 
CD101  
CD101 is a semi-synthetic echinocandin that inhibits the synthesis of 1,3-β-D-glucan, an 
essential component of the fungal cell wall of yeast forms of Candida species and regions 
of active cell growth of Aspergillus hyphae. The synthesis of 1,3-β-D-glucan is dependent 
upon the activity of 1,3-β-D-glucan synthase, an enzyme complex in which the catalytic 
subunit is encoded by FKS1, FKS2, and FKS3 genes. Inhibition of this enzyme results in 
rapid, concentration-dependent, fungicidal activity for Candida spp.  
CD101 is a broad-spectrum antifungal agent with excellent activity against wild-type and 
azole- and echinocandin-resistant strains of Candida spp. (Castanheira et al., 2014). 
CD101 demonstrated potent activity against representative strains of numerous fungal 
species, including Candida spp., Aspergillus spp., Trichophyton mentagrophytes, 
Trichophyton rubrum, and Microsporum gypseum, similar to that of anidulafungin. Poor 
activity was observed for single strains of Cryptococcus neoformans and Rhizopus 
oryzae, characteristic of echinocandins. When tested against multiple clinical isolates of 
wild-type and echinocandin-resistant and/or –azole resistant Candida spp., CD101 
activity was similar to that of anidulafungin versus all strains tested with MIC required to 
inhibit the growth of 90% of the isolates tested (MIC90) values ≤1 µg/mL for all species 
except Candida parapsilosis, which was 2 µg/mL. The potency of CD101 against strains 
with documented fks mutations was 2- to 8-fold greater than that of caspofungin and 
similar to that of anidulafungin. 
4.3 
NONCLINICAL PHARMACOLOGY AND TOXICOLOGY 
CD101 was found to be stable in liver microsomes from all species tested. A cross-
species stability study also determined that CD101 is stable in intestinal microsomes 
and no metabolic products were identified during incubations of CD101 with mouse, 
rat, monkey, or human liver microsomes, indicating a lack of biotransformation. In 
vivo, metabolite profiling of rat plasma and excreta samples is consistent with in vitro 
results confirming the lack of biotransformation.  
The pharmacokinetic (PK) profile of CD101 was investigated in mice, rats, dogs, 
cynomolgus monkeys, and chimpanzees following IV delivery, the intended clinical 
route of administration, and also after intraperitoneal administration to mice, 
intramuscular to rats, subcutaneous to rats and cynomolgus monkeys, and orally to 
dogs, monkeys, and chimpanzees. CD101 consistently exhibited very low clearance, 
modest volume of distribution (Vz) or volume of distribution at steady state (Vss), 
and long half-life (t1/2). Across all species tested, CD101 exhibited a favorable PK 
profile, mainly attributable to lower clearance (resulting in a longer t1/2). Additionally, 
there was low to no drug accumulation or gender differences found with CD101 
across all species tested after multiple doses and routes of administration.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 31 of 128 
 
Tissue distribution of CD101 was evaluated in rats and mean area under the 
concentration time curve (AUC) from time 0 to the final sample (AUC0-t) was lowest in 
brain tissue and highest in kidney tissue. Calculation of tissue/plasma AUC ratios 
indicated exposure relative to plasma was comparable between major organs (4- to 5-fold 
higher in kidney, lung, liver, and spleen) with the exception of much lower ratios in tissue 
from heart and brain (≤1). More importantly, CD101 appears to concentrate within fungal 
lesions even after the majority of drug has been cleared from an infected organ, as shown 
in a separate study by David Perlin and colleagues from Rutgers (Zhao, 2017). In the 
study, the authors utilized matrix-assisted laser desorption ionization (MALDI) imaging 
mass spectrometry technology to image kidney and liver cross-sections of mice with IC. 
MALDI imaging allowed for multiplexed analysis of different molecules simultaneously 
in the same tissue section, providing semi-quantitative information of fungal lesions and 
drug localization. From cross-sections of liver and kidney, across different timepoints 
from 1 to 48 hours, Perlin and colleagues noted that CD101 tissue levels begin to decline 
after reaching the maximum plasma concentration (Cmax) at 6 hours postdose, but 
increase and concentrate within fungal lesions at later timepoints (24 and 48 hours).  
CD101 has been evaluated in a full battery of Investigational New Drug (IND)-enabling 
toxicology studies up to 4 weeks in duration in rats and cynomolgus monkeys, and in 
bacterial and mammalian cell in vitro genetic toxicology studies. The pivotal nonclinical 
safety studies were conducted according to Good Laboratory Practices (GLP) guidances. 
CD101was evaluated in single dose and exploratory IV studies, in 2-week IV pilot 
toxicity studies, and in 4-week IV GLP toxicity studies. In addition, 3 Screening and 
investigative studies were conducted: one study compared the toxicity of CD101 to the 
marketed echinocandin, anidulafungin, with focus on assessing hepatotoxicity; a second 
study investigated different modes of IV tail vein administration in rats; and the third 
study measured plasma levels of histamine in rats. 
The main toxicology finding was a rat-specific histamine-release response that occurred 
primarily after the first dose. This histamine response was not seen in cynomolgus 
monkeys at Cmax levels that exceeded those where these effects were seen in rats. 
Echinocandins as a class are known to cause histamine release during infusions in rats, 
but not during infusions in monkeys when assessed during toxicity testing (Eraxis 
[anidulafungin] New Drug Application [NDA], Cancidas [caspofungin acetate] NDA). 
Rats appear to be much more sensitive to histamine-release responses of echinocandins 
versus primates, including humans where histamine-mediated infusion reactions appear 
to be uncommon (Eraxis [anidulafungin] Prescribing Information, 2013; Mycamine 
[micafungin sodium] Prescribing Information, 2013; Cancidas [caspofungin acetate] 
Prescribing Information, 2014). 
Hematological signs suggestive of red blood cell regeneration occurred in rats primarily 
at the high dose, were not considered adverse, and were not seen in monkeys.  
Local vascular injury was observed in rats, but adverse effects were confined to high dose 
males during the 4-week toxicity study; the no-observed-adverse-effect level (NOAEL) 
concentration for local injury is 6 mg/mL.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 32 of 128 
 
The safety margins appear to be large in rats and monkeys administered CD101 for up to 
4 weeks. The NOAEL for human relevant toxicities is 45 mg/kg in rats and 30 mg/kg in 
monkeys. These doses generate AUC plasma exposures 20-fold (rat) and 28-fold 
(monkey) over the efficacious plasma exposure determined in the neutropenic mouse 
systemic candidiasis model.  
No adverse CD101-related target organ toxicity was observed in either rats or monkeys 
over the 4-week dosing period.  
A CD101-related microscopic finding was seen in macrophages located in the lung of 
rats at ≥15 mg/kg that was characterized as a minimal alveolar histiocytosis. This change 
was not considered adverse since it was minimal, not associated with tissue injury, and 
reversible. This change was not observed in monkeys. 
Of importance is the lack of microscopic evidence for target organ toxicity previously 
identified in animals with marketed echinocandins dosed over a 4- or 5-week period 
(Eraxis [anidulafungin] NDA, Cancidas [caspofungin acetate] NDA, Mycamine 
[micafungin sodium] NDA). Target organs have included hepatotoxicity (anidulafungin, 
caspofungin and micafungin), renal toxicity (anidulafungin and micafungin), and skeletal 
muscle changes (anidulafungin). In addition, no CD101-related histopathological changes 
were seen in the spleen and bone marrow, whereas regenerative changes in these organs 
have been reported for anidulafungin and micafungin 
CD101 was negative for mutagenicity (bacteria) and clastogenicity (mammalian cells) 
during in vitro genetic toxicology studies and negative for clastogenicity in the in vivo 
bone marrow micronucleus assay in rats at doses up to 45 mg/kg IV. 
The results from the female fertility study in rats indicate no effects on reproductive 
performance and intrauterine survival up to the highest dose tested (45 mg/kg). Embryo-
fetal development studies in female rats (up to 45 mg/kg) and rabbits (up to 35 mg/kg) 
have been conducted and demonstrated no effects on fetal growth, survival, or fetal 
morphology. 
In a fertility study in male rats, no rezafungin-related effects were seen on reproductive 
performance up to the highest dose tested (45 mg/kg), dose-related lower mean sperm 
motility, concentration, and/or increased incidence of abnormal sperm morphology, along 
with microscopic findings of testicular seminiferous tubular epithelial degeneration 
associated with an effect on spermiation were noted at ≥ 30 mg/kg. Based on these data, 
the NOAEL for male reproductive toxicity was 15 mg/kg, which is approximately 2-5 
fold over steady state following IV 200 mg weekly preceded by an IV loading dose of 
400 mg.  Based on the lack of any effects on intrauterine survival in females at any 
dosage level, the NOAEL for early embryonic toxicity was 45 mg/kg, the highest dose 
evaluated. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 33 of 128 
 
In a 3-month study in monkeys, during the sixth week of dosing, unexpected intention 
tremors were observed. Throughout the 3-month dosing period, dose-related incidence of 
sporadic slight to moderate tremors/intention tremors were seen at ≥ 30 mg/kg (30 mg/kg 
is 11-fold versus the Group 2 dose regimen). Tremors were typically seen during dosing 
days at or around the time of infusion and intention tremors were observed periodically 
on both dosing and nondosing days. The incidence of tremors and intention tremors 
reversed for most animals, but intention tremors were seen in one male at the high dose 
(60 mg/kg) near the end of the recovery period. Due to the observed neurobehavioral 
effects, a detailed neuropathology assessment was performed which identified 
axonal/nerve fiber degeneration of peripheral nerves and sensory ganglia, along with 
prominent Schwann cell hyperplasia/hypertrophy primarily within the sensory ganglia, at 
≥ 30 mg/kg. Schwann cell changes reversed, but axonal/nerve fiber degeneration was still 
present at the end of the 4-week recovery period. No other test article-related microscopic 
changes were observed, including no test article-related effects in neurons of the sensory 
ganglia and in structures within the spinal cord or brain, including cerebellum. Although 
slight increases in serum calcium were observed at ≥ 30 mg/kg, an extensive evaluation 
of calcium homeostasis (i.e., ionized calcium, calcitonin, parathyroid hormone) failed to 
associate the minor increase in serum calcium to the observed neuropathological changes. 
Given the prominent Schwann hyperplasia/hypertrophy, it is not clear whether the 
axonal/nerve fiber degenerative changes are primary or secondary to an effect on the 
Schwann cells. The NOAEL level for neuropathology in monkeys is 10 mg/kg, which is 
approximately 4-fold over the estimated steady state plasma level in humans at 200 mg. 
Results from a phototoxicity study in rats indicate evidence of phototoxicity at elevated 
CD101 exposures. Relative to the repeat-dose human plasma Cmax level at 400 mg, the 
NOAEL for phototoxicity was 1.7-fold higher and the lowest-observed-adverse-effect 
level, where minimal changes were seen, was 3.6-fold higher. Review of the human 
safety data for CD101 and the medical literature for echinocandins indicate no evidence 
of phototoxicity. Results of a Phase 1 phototoxicity study in healthy human volunteers to 
elucidate the true risk of phototoxicity in subjects are pending. 
 
Additional nonclinical data is available in the Investigator Brochure. 
4.4 
CLINICAL EXPERIENCE 
CD101 Injection was safe and well tolerated as a single dose up to 400 mg and multiple 
doses up to 400 mg. The overall safety, tolerability, and PK profile of CD101 support 
continued development as a once-weekly therapy for invasive fungal infections. 
A Phase 1, single-center, randomized, double-blind, single-ascending dose (SAD) study 
of CD101 administered by IV injection to healthy adult subjects (CD101.IV.1.01) has 
completed. The primary objective was to determine the safety, tolerability, and PK 
profile of CD101. In this study, subjects in 4 cohorts of 8 subjects (6 active, 2 placebo) 
each were randomized to receive single IV doses of CD101 Injection or placebo (normal 
saline) infused over 60 (±10) minutes. Dose levels of CD101 assessed follow an 
ascending single-dose regimen (50, 100, 200, or 400 mg).  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 34 of 128 
 
A total of 32 subjects were randomized with 31 subjects completing all study 
assessments. One subject prematurely withdrew for personal reasons unrelated to safety 
or tolerability. Subjects were primarily White (97%), Hispanic (94%), and males and 
females were approximately equally represented (53% and 47%, respectively). There 
were no serious adverse events (SAEs), severe adverse events (AEs), or dose-response 
relationships for overall AEs. The majority of AEs were mild, and all AEs completely 
resolved by the end of the study. There were no drug-related AEs resulting from 
clinically significant hematology or clinical chemistry laboratory abnormalities at any 
dose. In addition, there were no safety issues related to electrocardiograms (ECGs), vital 
signs, or physical exam findings.  
A Phase 1, single-center, randomized, double-blind, multiple-ascending dose (MAD) 
study of CD101 administered by IV injection to healthy adult subjects (CD101.IV.1.02) 
has completed. The primary objective was to determine the safety, tolerability, and PK 
profile of CD101 when administered IV as multiple doses to healthy adult subjects. In 
this study, subjects in 3 cohorts of 8 subjects (6 active, 2 placebo) each were randomized 
to receive multiple IV doses of CD101 Injection or placebo (normal saline) infused over 
60 (±10) minutes. Dose levels of CD101 assessed follow an ascending multiple-dose 
regimen (100 mg ×2 doses, 200 mg ×2 doses, or 400 mg ×3 doses).  
A total of 24 subjects were randomized and all subjects completed the study. Subjects 
were primarily White (88%), Hispanic or Latino (88%), and had a mean body mass index 
(BMI) of 27.208 kg/m2 and a mean age of 42.8 years. Males and females were equally 
represented (50% each). There were no SAEs or severe AEs. The majority of AEs were 
mild, and all related AEs completely resolved by the end of the study. Four subjects in 
the CD101 group experienced mild, transient infusion reactions, characterized by 
flushing, sensation of warmth, nausea, and chest tightness. These infusion reactions were 
associated primarily with the 400 mg dose cohort and were most common with the third 
dose. These reactions occurred within minutes of infusion initiation and disappeared 
within minutes without interruption or discontinuation of the study drug infusion. There 
were no drug-related AEs resulting from clinically significant hematology or clinical 
chemistry laboratory abnormalities at any dose. In addition, there were no safety issues 
related to ECGs, vital signs, or physical exam findings. 
The safety and efficacy of rezafungin for injection is being evaluated in this Phase 2, 
multicenter, prospective, randomized, double-blind, comparator study (IV caspofungin 
with option for oral fluconazole step-down therapy) for the treatment of subjects with 
candidemia and/or invasive candidiasis. Subjects were randomly assigned to receive 1 of 
2 rezafungin for injection once weekly regimens or a daily IV caspofungin regimen with 
the option for oral fluconazole step-down therapy. Two rezafungin for injection dosing 
regimens were evaluated as follows: Group 1 was administered 400 mg ×2 weekly doses 
with a third optional weekly dose of 400 mg for all subjects and a fourth optional weekly 
dose 400 mg dose for subjects with invasive candidiasis; Group 1 was administered 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 35 of 128 
 
400 mg ×1 weekly dose followed by 200 mg ×1 weekly dose with a third optional weekly 
dose of 200 mg for all subjects and a fourth optional weekly dose of 200 mg for subjects 
with invasive candidiasis. The reference therapy caspofungin regimen was as follows: 
70 mg ×1 day and 50 mg/day for 13 days with additional optional dosing 50 mg/day up to 
21 days for all subjects and additional optional dosing 50 mg/day up to 28 days for 
patients with invasive candidiasis. 
In Part A of this Phase 2 study, there were 107 subjects enrolled; 56.1% were male, most 
subjects were White (83%) with other identified races of Black or African American 
(11.2%) and Asian (3.7%). Ethnicity was primarily Not Hispanic/Latino (87.9%). Mean 
age was approximately 52 years. Diagnosis at study entry was 89.7% candidemia and 
10.3% invasive candidiasis with reasonable balance across the treatment groups. The 
study demonstrated efficacy for rezafungin for injection comparable to standard of care at 
Day 14 for all endpoints. There are no notable imbalances in TEAEs across the study 
groups. Most adverse events were mild or moderate in severity. There were no notable 
imbalances in SAEs across the treatment groups and SAEs observed were not unexpected 
for the patient population. AEs of interest included those potentially representative of 
photosensitivity (results of Phase 1 photosensitivity study is pending) and neuropathy. 
One subject in a rezafungin for injection group had an AE of sunburn (Group 1) 
following substantial sun exposure. AEs in the rezafungin for injection groups potentially 
representing neuropathy were intensive care unit acquired weakness (Group 2, 1 subject, 
moderate severity), and tremor (Group 2, 1 subject, mild). An AE of intensive care unit 
acquired weakness also occurred in 1 subject receiving caspofungin (severe) and an AE 
of polyneuropathy (severe) occurred in 1 subject receiving caspofungin. These AEs of 
interest potentially representing study drug-related tremor/ataxia/neuropathy were 
followed until resolution; all resolved. The Investigator Brochure should be referenced 
for additional information. 
4.5 
CLINICAL PHARMACOLOGY 
The PK of CD101 has been well-characterized in healthy subjects for doses up to 400 mg 
for 3 weeks in the 2 Phase 1 studies: CD101.IV.1.01 (SAD study) and CD101.IV.1.02 
(MAD study). 
4.5.1 
Single Ascending Dose Pharmacokinetics (CD101.IV.1.01)  
Pharmacokinetics was determined by analyzing plasma and urine samples for 
concentration of CD101 obtained from subjects who received CD101 Injection in each 
cohort at various time points after administration of the single dose of the study drug. 
The plasma PK of CD101 was generally well-characterized following the 50, 100, 200, 
and 400 mg CD101 doses. Exposure to CD101 increased with increasing CD101 doses 
(Table 3). Time to reach Cmax (ie, Tmax) was observed at the end of infusion, as expected, 
at approximately 1 hour after the start of infusion for all doses. Elimination of CD101 
appears multiphasic. AUC and Cmax increased in a dose proportional manner and total 
body clearance was similar throughout the dose levels with t1/2 values of >80 hours 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 36 of 128 
 
through the first week of plasma collection (a longer terminal t1/2 of 127-146 hours is 
calculated when incorporating data from later collection times). Total body clearance was 
approximately 4 mL/min across the CD101 doses, indicating linear kinetics for CD101 
across the doses investigated. Volume of distribution (Vz and Vss) ranged from 33 to 
48 L. The fraction of dose excreted in urine was <1% at all dose levels, indicating minor 
contribution of renal clearance in CD101 excretion. 
Table 3: 
Summary of Plasma CD101 Exposures Following Administration of 
50, 100, 200, and 400 mg 1-hour Intravenous Infusion of CD101 
Dose 
(mg) 
Cmax 
(µg/mL) 
C144 
(µg/mL) 
AUC0-168 
(µg⋅h/mL) 
t1/2 
(hours) 
50 
2.76 
0.481 
145 
86 
100 
4.84 
0.854 
254 
92 
200 
10.9 
2.01 
592 
91 
400 
22.7 
3.83 
1160 
84 
AUC0-168 = area under the curve from time 0 to 168 hours; C144 = plasma 
concentration at 144 hours post start of infusion; Cmax = maximum plasma 
concentration; t1/2 = half-life. 
4.5.2 
Multiple Ascending Dose Pharmacokinetics (CD101.IV.1.02)  
Pharmacokinetics was determined by analyzing plasma and urine samples for 
concentration of CD101 obtained from subjects who received CD101 Injection in each 
cohort at various time points after administration of study drug. 
The plasma PK of CD101 was also well characterized following 2 or 3 weekly doses of 
CD101: 100 mg (Day 1/ Day 8), 200 mg (Day 1/ Day 8), and 400 mg (Day 1/ Day 8/ Day 
15). Exposures following the first dose were very comparable to that observed in the 
SAD study, with AUC and Cmax generally increasing in a dose proportional manner 
(Table 4). Accumulation was minor, ranging from 14% to 34% (or 1.14 to 1.34) as 
measured by Cmax ratio of last/first dose and 30% to 55% (or 1.30 to 1.55), as measured 
by the area under the curve from time 0 to 168 hours (AUC0-168) ratio of last/first dose. 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 37 of 128 
 
Table 4: 
Summary of Plasma CD101 Exposures Following Administration of 
100 mg (Day 1/Day8), 200 mg (Day 1/Day8), and 400 mg (Day 
1/Day15) Weekly 1-hour Intravenous Infusion of CD101 
Dose 
(mg) 
Day 
Cmax 
(µg/mL) 
AUC0-168 
(µg⋅h/mL) 
Accumulation Ratio 
Cmax 
AUC0-168 
100 
1 
5.67 
299 
1.14 
1.30 
8 
6.49 
390 
200 
1 
10.6 
570 
1.17 
1.43 
8 
12.4 
813 
400 
1 
22.7 
1190 
1.34 
1.55 
15 
30.5 
1840 
AUC0-168 = area under the curve from time 0 to 168 hours; Cmax = maximum plasma 
concentration. 
4.6 
SUMMARY OF KNOWN BENEFITS AND POTENTIAL RISKS 
4.6.1 
Potential Benefits 
It is anticipated that subjects participating in this study who are randomized to the CD101 
IV groups will experience at least similar therapeutic benefits as subjects randomized to 
the caspofungin group. Approximately two-thirds of the subjects enrolled in this study 
will be randomized to receive CD101 IV. 
The therapeutic benefits of caspofungin and fluconazole for the treatment of fungal 
infections are documented in the prescribing information and published literature. 
Approximately one-third of the subjects enrolled in this study will be randomized to 
receive IV caspofungin with the option of oral fluconazole step down therapy. 
4.6.2 
 Known Risks 
Safety and PK data from Study CD101.IV.1.01 and Study CD101.IV.1.02 are presented 
in Section 4.4.  
Nonclinical toxicology of CD101 is presented in Section 4.3 and described in the 
Investigator Brochure.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 38 of 128 
 
4.6.3 
Potential Risks  
Echinocandins are typically well tolerated (Eraxis [anidulafungin] Prescribing 
Information, 2013; Mycamine [micafungin sodium] Prescribing Information, 2013; 
Cancidas [caspofungin acetate] Prescribing Information, 2014). Potential drug class 
effects include risk of abnormal liver function tests, hepatitis, and hepatic failure. General 
and administration site events (infusion related reactions, peripheral edema, rigors, 
infusion site inflammation, and pyrexia) have been reported for echinocandins (Eraxis 
[anidulafungin] Prescribing Information, 2013; Mycamine [micafungin sodium] 
Prescribing Information, 2013; Cancidas [caspofungin acetate] Prescribing Information, 
2014). Possible histamine-mediated symptoms have been reported in patients who 
received rapid infusions of echinocandins, including rash, urticaria, flushing, pruritus, 
dyspnea, hypotension, facial swelling, and vasodilation. Anaphylactic-like reactions have 
been reported with micafungin (Mycamine [micafungin sodium] Prescribing Information 
2013). 
Results from a phototoxicity study in rats indicate evidence of phototoxicity at elevated 
CD101 exposures (Section 4.3). Because of the safety margin to the human-equivalent 
exposure of subjects in this study, the possibility of the rat-specific histamine release 
affecting the results, and the mild reaction seen in rats at 3.6-fold above the human 
equivalent plasma level, Cidara believes that the risk to humans is low. Nevertheless, 
pending resolution of this issue through a Phase 1 human clinical study, Cidara has 
notified investigators of the findings and added wording to the Informed Consent Form 
(ICF) for subjects to use measures to reduce sun exposure while on study drug. 
Based on a fertility study in male rats, there is the potential risk for decreased sperm 
motility, increased incidences of abnormal sperm morphology, and testicular 
seminiferous tubular epithelial degeneration. These findings were noted at 2.5-fold the 
exposure for Group 2. The risk to humans is unknown, thus the male contraception 
requirements in inclusion criterion 4 have been extended from first dose to 90 days with 
the inclusion of prohibited sperm donation within the period. This risk will be included in 
the ICF. 
In a 3-month study in monkeys, there were observations of tremors, intention tremors, 
and histology consistent with axonal degeneration (potentially consistent with clinical 
presentation of neuropathy) first appearing at week 6 of dosing. These observations 
occurred at 11-fold the exposure for Group 2. Given the late timing and high exposure 
relative to the Group 2 dosing regimen, the risk to study subjects is assessed as low. 
Because there may be unknown and potential risks with administration of CD101 IV, all 
subjects will be closely monitored for safety and tolerability by repeated assessment of 
clinical, vital signs, and clinical laboratory safety parameters and reporting of AEs. 
4.6.4 
Risk-Benefit Summary 
Overall, based on risk/benefit analysis, the current study appears to be fully justified in 
the planned population. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 39 of 128 
 
4.7 
JUSTIFICATION FOR DOSING REGIMEN 
A population PK model has been developed for rezafungin (Bader 2018). Data from a 
subset of Phase 2 Part A data as well as data from a Phase 1 study was added to update 
the structural model and evaluate covariate effects. Preliminary data from the modeling is 
used to set doses for upcoming Phase 3 studies. 
In brief, these data were best described using a 4-compartment model with 0-order drug 
input via the IV infusion and first-order, linear elimination. This model fit the observed 
data with very little bias and excellent precision. 
Monte Carlo simulations for 2000 hypothetical patients were conducted to assess the 
probability of PK/PD target attainment using the weekly free-drug area under the 
rezafungin concentration-time curve from time 0 to 168 hours (fAUC0-168) after each dose 
for the two dosing regimens tested in Part A; albumin, weight, and sex were bootstrapped 
(using random sampling and replacement) from the dataset of subjects and plasma protein 
binding of 97.4% was used. 
Nonclinical studies of C. albicans infection models in mice have shown that a rezafungin 
free-drug fAUC:MIC is the PK/PD parameter most predictive of efficacy, and fAUC0-
168:MIC targets have been established in the mouse model for important pathogenic 
Candida spp. (refer to Investigator Brochure). 
The PK/PD target attainment for the 2 regimens used in Part A (400 mg once weekly for 
2 to 4 weeks and a 400 mg loading dose on Week 1 followed by 200 mg once weekly for 
a total of 2 to 4 weeks) relative to the reported MIC distribution (Pfaller 2017) is shown 
in Table 5 and Figure 4 for C. albicans and in Table 6 and Figure 5 for C. glabrata. Both 
regimens provided adequate PK/PD target attainment throughout 4 weeks of dosing, up 
to a MIC of 0.5 µg/mL for C. albicans, and up to an MIC of 16 µg/mL for C. glabrata. 
The 400 mg once weekly dosing regimen seems to provide some additional benefit in 
terms of target attainment, improving by 40 to 70% for an MIC=1, but not until Week 2 
or beyond. However, most of the benefits of antifungal treatment occur in the first week 
of therapy, and the incremental improvement for the 400 mg once weekly dose regimen 
for Weeks 2 and 3 will likely be of little real clinical benefit in the treatment of 
candidemia or invasive candidiasis. In fact, in comparison to other echinocandins, the 
400 mg loading dose on Week 1, followed by 200 mg once weekly dose regimen 
provides a significant advantage in terms of potential to cover pathogens with higher 
MICs (Table 7). 
The data from Part A indicate that both rezafungin regimens were comparable to each 
other and to caspofungin for efficacy and safety. There were no adverse events that 
seemed to cluster in the 400 mg once weekly group to indicate any concern for increased 
toxicity with the higher dose. However, the Phase 1 results do indicate that there are 
infusion reactions that can occur in the higher dose rezafungin regimen that are an 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 40 of 128 
 
echinocandin class effect and are related to the rate of infusion (mg/min). Thus, given 
there is no apparent clinical benefit to the 400 mg once weekly dose regimen over the 
regimen with a 400 mg loading dose on Week 1, followed by 200 mg once weekly, and 
that both options provide at least a three dilution MIC improvement in target attainment 
over the best of the currently approved echinocandins (Table 7), the regimen of a 400 mg 
loading dose on Week 1, followed by 200 mg once weekly for a total of 2 to 4 doses can 
be selected for safety and efficacy in the treatment of candidemia and/or invasive 
candidiasis. 
Table 5: 
Predicted Pharmacokinetic-Pharmacodynamic Target Attainment for 
Rezafungin Regimens, Stratified by Week and Minimal Inhibitory 
Concentration, against C. albicans 
Regimena 
Week 
MIC (mg/L) b 
0.06 
0.12 
0.25 
0.5 
1 
2 
400/400 
1 
100 
100 
100 
98.8 
35.1 
0.05 
2 
100 
100 
100 
99.95 
73.4 
2.45 
3 
100 
100 
100 
100 
84.3 
7.1 
4 
100 
100 
100 
100 
88.3 
10.75 
400/200 
1 
100 
100 
100 
98.8 
35.1 
0.05 
2 
100 
100 
100 
92.55 
14.95 
0 
3 
100 
100 
100 
91.05 
14.45 
0 
4 
100 
100 
100 
90.55 
15 
 
MIC = minimal inhibitory concentration. 
a. 
Regimens defined by the weekly dose (eg, 400/200 represents 400 mg for the first dose, followed by 
200 mg IV once weekly). 
b. Shaded cells indicate PK-PD target attainment above 90%. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 41 of 128 
 
Figure 4: 
Predicted Pharmacokinetic-Pharmacodynamic Target Attainment for 
Rezafungin Regimens, against C. albicans relative to MIC 
Distribution 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 42 of 128 
 
Table 6: 
Predicted Pharmacokinetic-Pharmacodynamic Target Attainment for 
Rezafungin Regimens, Stratified by Week and Minimal Inhibitory 
Concentration, against C. glabrata 
Regimena 
Week 
MIC (mg/L) b 
0.12 
0.5 
2 
4 
8 
16 
400/400 
1 
100 
100 
100 
100 
100 
100 
2 
100 
100 
100 
100 
100 
100 
3 
100 
100 
100 
100 
100 
100 
4 
100 
100 
100 
100 
100 
100 
400/200 
1 
100 
100 
100 
100 
100 
100 
2 
100 
100 
100 
100 
100 
100 
3 
100 
100 
100 
100 
100 
100 
4 
100 
100 
100 
100 
100 
98.65 
MIC = minimal inhibitory concentration. 
a. 
Regimens defined by the weekly dose (eg, 400/200 represents 400 mg for the first dose, followed by 
200 mg once weekly). 
b. Shaded cells indicate PK-PD target attainment above 90%. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 43 of 128 
 
Figure 5: 
Predicted Pharmacokinetic-Pharmacodynamic Target Attainment for 
Rezafungin Regimens, against C. glabrata relative to MIC 
Distribution 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 44 of 128 
 
Table 7: 
Percent Probabilities of Pharmacokinetic-Pharmacodynamic Target 
Attainment by Anidulafungin, Caspofungin, and Micafungin against 
Candida spp. 
MIC 
(mg/L) 
Anidulafungin 
Caspofungin 
Micafungin 
Rezafungin* 
Candida 
albicans 
Candida 
glabrata 
Candida 
albicans 
Candida 
glabrata 
Candida 
albicans 
Candida 
glabrata 
Candida 
albicans 
Candida 
glabrata 
0.008 
100a,b 
100 
100 
100 
99.4 
100 
100 
100 
0.015 
99.1 
100 
100 
100 
71.2 
100 
100 
100 
0.03 
100 
99.2 
100 
100 
10.1 
97.5 
100 
100 
0.06 
39.8 
54.3 
97.9 
100 
0.10 
49.9 
100 
100 
0.12 
0 
0.95 
76.7 
100 
0 
3.4 
100 
100 
0.25 
0 
0 
35.7 
100 
0 
40.1 
100 
100 
0.5 
0 
0 
12.1 
97.0 
0 
0.15 
90.55 
100 
1 
0 
0 
4.4 
73.2 
0 
0 
15 
100 
2 
0 
0 
1.35 
33.9 
0 
0 
0 
100 
4 
0 
0 
0.25 
11.3 
0 
0 
0 
100 
8 
0 
0 
0.05 
4.35 
0 
0 
0 
100 
Note:  Data for other echinocandins (Bader 2017) 
Abbreviations: MIC, minimal inhibitory concentration; MIC90, minimal inhibitory concentration required 
to inhibit 90% of isolates. 
a 
Shaded cells indicate PK-PD target attainment values ≥90%.  
b 
Cells with dotted outlines represent the MIC90 values for each agent against the respective Candida 
spp. 
* 400/200/200/200 at wk 4 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 45 of 128 
 
4.8 
POPULATION TO BE STUDIED 
In this study, adult subjects with candidemia and/or IC will be included.  
4.9 
STATEMENT OF COMPLIANCE 
This study will be conducted in compliance with the protocol, Good Clinical Practice 
(GCP), the ethical principles of the Declaration of Helsinki, and applicable regulatory and 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) requirements. 
4.10 
JUSTIFICATION FOR USE OF CD101 IN CANDIDEMIA AND 
INVASIVE CANDIDIASIS 
Candidemia is a fungal bloodstream infection usually affecting patients who are already 
ill with other comorbidities. Invasive candidiasis defines a number of different organ-
specific infections with Candida spp. Candidemia and IC may present without the other 
syndrome or may exist together as part of the same pathophysiology of disseminated 
candidiasis. Risk factors for candidemia and IC include recent surgery, organ and bone 
marrow transplants, broad-spectrum antibiotic use, receipt of total parenteral nutrition, 
end stage renal disease, indwelling vascular catheters or other devices, etc. While 
candidemia is often associated with other forms of IC, including intra-abdominal abscess, 
peritonitis, or pleuritic involvement, candidemia without other overt organ involvement is 
the most common form of IC diagnosed. A recent study by the ESCMID Fungal Infection 
Study Group reported the incidence of candidemia as 6.9 per 1000 intensive care unit 
patients with mortality rates between 20% and 49% (Kett et al., 2011; Gudlaugsson et al., 
2003; Arendrup et al., 2011). Candidemia and IC are serious and potentially life-
threatening infectious complications that require aggressive and timely antifungal 
management. 
The current IDSA and ESCMID guidelines recommend echinocandins as first-line 
therapy for candidemia and most forms of IC (Pappas et al., 2016; Cornely et al., 2012). 
There are currently 3 commercially authorized echinocandins in the US and the European 
Union: caspofungin, micafungin, and anidulafungin. These echinocandins are 
administered once daily via IV infusion and share similar PK parameters and safety 
profiles. CD101 is a novel echinocandin derived from another echinocandin 
(anidulafungin). CD101 has a more stable molecular structure compared to the other 
echinocandins, which results in a reduction in the formation of toxic metabolites and an 
improvement in the duration of exposure to active drug. This stability further translates 
into a better safety profile as demonstrated in both nonclinical and clinical studies, as 
well as a unique PK profile that allows for high dose, front-loaded exposures for 
improved fungal killing and once weekly IV dosing. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 46 of 128 
 
Both in vitro and in vivo data have demonstrated the potency and efficacy of CD101 
against Candida and disseminated candidiasis (Section 4.2, Section 4.3, and Investigator 
Brochure). In all nonclinical efficacy studies performed for CD101 in neutropenic 
disseminated candidiasis, CD101 has performed as well as, or better than, currently 
approved echinocandin comparators. This Phase 2 double-blind, randomized, controlled 
trial comparing 2 dose regimens of CD101 against caspofungin is the first efficacy study 
in humans for CD101. The duration of antifungal therapy in standard practice depends on 
the time it takes to clear the Candida from infected blood or tissues, and thus patients 
with IC often require a longer duration of therapy than patients with candidemia alone. 
To that end, all subjects in this study must be administered study drug for at least 14 days 
followed by an optional third week (for subjects with either candidemia or IC) or fourth 
week (for subjects with IC only) of treatment if clinically indicated. 
In PK and PD models, both of the CD101 dosing regimens proposed for the Phase 2 
study demonstrate 100% target attainment of wild-type C. albicans and C. glabrata (C. 
albicans data is presented in Section 4.7). The 400-mg, once-weekly dosing regimen may 
have improved coverage of isolates with MICs >0.5 µg/mL, which is now of increasing 
prevalence in some institutions. Therefore, in this nonpowered study, both CD101 groups 
are expected to have equal efficacy with each other, as well as with the comparator. Since 
mild infusion reactions were observed in the Phase 1 studies, occurring most frequently 
in the third dose of the 400-mg dose group, it is possible that the lower dose regimen of 
CD101 may be better tolerated than the higher dose. This Phase 2 study is intended to 
assess, but not directly compare, the efficacy of both CD101 and the approved first-line 
comparator in the same patient population and to build confidence in the efficacy of 
CD101 for a larger powered Phase 3 study. Results from this study should help to discern 
any differences in safety and tolerability between the 2 CD101 dose groups and help to 
select the best CD101 dose and regimen for the Phase 3 study. 
4.11 
JUSTIFICATION OF THE PART B STUDY  
The addition of Part B in Amendment 5 of the protocol increased the study sample size 
by approximately 50% to 130% (depending on the rate of enrollment over the additional 
months to the staged start of the Phase 3 study, and the rolling close-out of Part B) with 
an interim analysis performed after approximately 40 to 60 subjects in the 
Microbiological Intent-to-Treat (mITT) population were enrolled and completed study 
drug therapy. The timing of this interim analysis enabled a smooth transition from the 
end of enrollment for Part A to the initiation of enrollment in Part B, and helped protect 
Part B subjects from unknown risks of low efficacy or safety findings prior to the start of 
the study extension.  
As detailed in Section 4.10, efficacy is expected to be equal between the 2 regimens in 
this study. There may be some advantages for the Group 1 subjects due to higher 
exposures, especially for Candida strains with higher MICs, but due to the low 
prevalence of these organisms, the effect of the higher exposure of Group 1 on the overall 
efficacy estimates is expected to be minimal.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 47 of 128 
 
The purpose of Part B is to further assess the safety and efficacy of CD101. Assessment 
of blinded safety data and data unblinded for safety purposes in Part A indicated that 
there were no known episodes of flushing, infusion reactions, or any evidence of target 
organ toxicity in Part A, and thus the focus of continued CD101 assessment in Part B was 
Group 1. Part B was initiated directly after the close of enrollment for Part A and 
continued during the analysis of Part A data. Following evaluation of the unblinded 
results from Part A, it was determined that the best CD101 dose regimen for Phase 3 was 
the 400 mg loading dose on Week 1 followed by 200 mg once weekly for a total of 
2 to 4 weeks (Group 2). Thus, with this amendment, enrollment in Group 1 will stop and 
Part B will continue enrollment of rezafungin for injection Group 2 and caspofungin 
enrolled in a 2:1 ratio. This extension is expected to at least double the size of the 
rezafungin for injection safety database. 
5.0 
STUDY PURPOSE AND OBJECTIVES 
The primary objectives of this study are to: 
• Evaluate the safety and tolerability of CD101 IV in the Safety population 
• Evaluate overall success (mycological eradication and resolution of systemic 
signs attributable to candidemia and/or IC) of CD101 IV in subjects with 
candidemia and/or IC at Day 14 (±1 day) in the Microbiological Intent-to-treat 
(mITT) population 
The secondary objectives of this study are to: 
• Evaluate overall success (mycological eradication and resolution of systemic 
signs attributable to candidemia and/or IC) of CD101 IV at Day 5, Day 28 (±2 
days; only for subjects with IC), and Follow-up (FU, Days 45-52 for subjects with 
candidemia only or Days 52-59 for subjects with IC, with or without candidemia) 
in the mITT population 
• Evaluate mycological success (eradication) of CD101 IV at Day 5, Day 14 (±1 
day), Day 28 (±2 days; only for subjects with IC), and FU (Days 45-52 for 
subjects with candidemia only or Days 52-59 for subjects with IC, with or without 
candidemia) in the mITT population 
• Evaluate clinical cure as assessed by the Investigator for CD101 IV at Day 14 (±1 
day), Day 28 (±2 days; only for subjects with IC), and FU (Days 45-52 for 
subjects with candidemia only or Days 52-59 for subjects with IC, with or without 
candidemia) in the mITT population 
• Evaluate the PK of CD101 IV 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 48 of 128 
 
6.0 
STUDY DESIGN 
6.1 
DESCRIPTION OF THE STUDY 
This is a Phase 2, multicenter, prospective, randomized, double-blind study of CD101 IV 
or IV caspofungin followed by oral fluconazole step-down therapy for treatment of 
subjects with candidemia and/or IC. In Part A, subjects will be randomized in a 1:1:1 
ratio to receive CD101 IV treatment Group 1; CD101 IV treatment Group 2, or IV 
caspofungin (Figure 5, Figure 6, Figure 7, Table 6). Oral step-down therapy is allowed in 
all 3 treatment groups in Part A; oral placebo in the CD101 IV groups and oral 
fluconazole in the caspofungin group. After approximately 90 subjects have been 
enrolled in the mITT population in Part A, enrollment into Part A of the study will close 
and Part B will begin. In Part B, subjects will be randomized in a 2:1 ratio to receive 
CD101 IV treatment Group 1 or IV caspofungin (Figure 5, Figure 6, Figure 7, Table 6) 
until ≥45 additional subjects and no more than 120 subjects have been enrolled. (Note: 
Subjects enrolled under Amendment 5 and assigned to CD101 IV receive Group 1 
treatment and subjects enrolled under Amendment 6 and assigned to CD101 IV treatment 
receive Group 2 treatment. Subjects enroll under the current, approved amendment at the 
site at the time of randomization; subjects enrolled to Amendment 5 continue study 
participation according to the same amendment regardless of subsequent approval of 
Amendment 6.) Total enrollment will depend on the enrollment rate for the 6- to 8-month 
period between the end of Part A and the staged start of the Phase 3 study, which is the 
trigger for the rolling close-out of Part B. Oral step-down therapy is allowed in both 
treatment groups in Part B; oral placebo in the CD101 IV group and oral fluconazole in 
the caspofungin group. 
Figure 6: 
Study Randomization and Treatment Regimens 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 49 of 128 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 50 of 128 
 
Subjects with candidemia only may be treated with study drug for a maximum of 
21 days. Subjects with IC (with or without candidemia) may be treated with study drug 
for a maximum of 28 days. Subjects will be presumed to have IC if there is a positive 
culture for Candida spp. from a normally sterile site other than blood or if there is a 
positive sponsor-approved rapid in vitro diagnostic (IVD) or blood culture for Candida 
spp. combined with radiographic evidence of IC. 
Subjects in the CD101 IV treatment Group 1 will receive CD101 IV 400 mg on Day 1 
and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional 
dose of 400 mg on Day 22 (only for subjects with IC), if needed.Subjects in the CD101 
IV treatment Group 2 will receive CD101 IV 400 mg on Day 1 and 200 mg on Day 8, 
with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 
200 mg on Day 22 (only for subjects with IC), if needed. Subjects in the caspofungin 
group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 
50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia 
only and up to a maximum of 28 days for subjects with IC (with or without candidemia). 
The optional doses of CD101 IV on Day 15 and Day 22 may be administered according 
to the subject’s clinical response and the medical judgment of the Principal Investigator 
(PI).  
After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral 
step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day 
followed by 400 mg [2 capsules]/day thereafter) if criteria are met. In order to maintain 
the blind, subjects in the CD101 IV groups who have switched to oral step-down therapy 
will receive oral placebo (4 capsules on the first day followed by 2 capsules/day 
thereafter) and subjects in the caspofungin treatment group will receive IV placebo on 
Day 8, and on Days 15 and 22 if study drug is administered through these timepoints. The 
total IV plus oral treatment duration will be ≥14 days and up to a maximum of 28 days.  
The dose and duration of any prior antifungal treatment taken within 4 weeks of 
randomization will be recorded at Screening. A retinal examination for evidence of a 
Candida eye infection, including endophthalmitis or chorioretinitis, will be performed 
during Screening or by Day 7 only on subjects with candidemia by blood culture, and 
should be repeated in subjects who were negative at baseline if the subject develops 
visual signs or symptoms of a Candida eye infection during the course of the study. 
Subjects who were negative at baseline and diagnosed with a Candida eye infection after 
initiating study drug should have an urgent ophthalmologic consultation (if not already 
done), should stop study drug, and be initiated on appropriate therapy for Candida eye 
infection per the local guidelines (Pappas et al., 2016; Cornely et al., 2012). If possible, 
all subjects diagnosed with endophthalmitis or chorioretinitis should remain in the study 
and all subsequent antifungal drugs, interventions, and outcomes for endophthalmitis or 
chorioretinitis should be recorded.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 51 of 128 
 
The Schedule of Assessments and Procedures is presented in Table 2. Study Day 1 is 
defined as the first day of study drug administration. Subsequent study days are defined 
by the number of consecutive calendar days thereafter. All subjects will be monitored for 
AEs and SAEs following signing of the ICF at Screening and throughout the study until 
the FU visit (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects 
with IC, with or without candidemia) for each treatment group. Vital signs (temperature, 
heart rate, blood pressure, respiratory rate) will be recorded daily while receiving IV 
study drug and at Day 14 (±1 day), Day 28 (±2 days; only for subjects with IC), End-of-
Treatment (EOT) (+2 days allowed after last dose of study drug), and FU (Days 45-52 for 
subjects with candidemia only or Days 52-59 for subjects with IC, with or without 
candidemia). Hematology and chemistry laboratory tests will be performed at Screening; 
Days 2 and 4; Day 8, Day 14 (±1 day), EOT (+2 days allowed after last dose of study 
drug) and at the FU visit. Coagulation laboratory tests (prothrombin time/international 
normalized ratio [PT/INR] and either partial thromboplastin time [PTT] or activated 
partial thromboplastin time [aPTT]) will be performed at Screening. ECGs will be 
performed at Screening (before subject randomization) and EOT (+2 days allowed after 
the last dose of study drug). 
Mycological diagnosis of candidemia or IC sufficient for inclusion in the study will be 
established by a positive microbiological test for yeast or Candida within 96 hours from 
time of collection of the sample until randomization. Acceptable positive microbiological 
tests for yeast or Candida include ≥1 blood culture positive for yeast or Candida, a 
Sponsor-approved rapid IVD test positive for Candida spp, or a positive Gram stain for 
yeast or positive culture for Candida spp. from a specimen obtained from a normally 
sterile site. If the positive blood culture used to qualify the subject for the study is drawn 
>12 hours from randomization, then an additional set of blood cultures must be obtained 
≤12 hours before randomization. Blood cultures should be performed daily (preferred) or 
every other day until 2 blood cultures drawn ≥12 hours apart are negative, without an 
intervening positive culture. Generally, blood cultures should involve 2 separate draws 
with ≥1 draw from a peripheral vein without an IV catheter. Two bottles should be filled 
from each draw site, totaling 4 bottles for each set of blood cultures. If possible, use 3 
aerobic and 1 anaerobic bottle (if available at the site) for each blood culture set, although 
2 aerobic and 2 anaerobic (if available) is also acceptable. 
In Part A only, blood samples will be collected for PK analysis from the OPPOSITE arm 
of the infusion on Day 1 (within 10 minutes before the end of infusion, between 15 
minutes and 1 hour after the end of infusion, and between 2 hours and 12 hours after the 
end of infusion), Day 2 (random draw, with safety labs if possible), Day 4 (random draw, 
with safety labs if possible), Day 8 (predose only), and Day 15 (predose only). If therapy 
is stopped on or before Day 14 and there is no Day 15 dose, then the Day 15 PK sample 
should be drawn with the safety laboratory samples for the Day 14 visit. For the purpose 
of maintaining the blind, blood samples will be collected from all subjects, when 
possible, in all 3 treatment groups in Part A, but only PK samples from the CD101 IV 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 52 of 128 
 
groups will be analyzed (using a validated assay) by an independent, central bioanalytical 
laboratory. In Part B, PK samples will not be collected. 
Overall success and mycological eradication will be assessed at Day 5, Day 14, Day 28 
(±2 days; only for subjects with IC), and FU (Days 45-52 for subjects with candidemia 
only or Days 52-59 for subjects with IC, with or without candidemia). Clinical response 
will be assessed at Day 14 (±1 day), Day 28 (±2 days; only for subjects with IC), and FU 
(Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with 
or without candidemia).

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 53 of 128 
Figure 7:  
Study Design Diagram for Subjects with Candidemia Only  
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 54 of 128 
Figure 8:  
Study Design Diagram for Subjects with Invasive Candidiasis (with or without Candidemia) 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 55 of 128 
 
6.2 
NUMBER OF SUBJECTS 
In Part A, subjects will be randomized (1:1:1) until there are approximately 30 subjects in 
the CD101 IV treatment Group 1, 30 subjects in the CD101 IV treatment Group 2, and 30 
subjects in the comparator group in the mITT population. It is expected that 
approximately 114 subjects will need to be randomized to achieve 90 subjects in the 
mITT population (assuming 80% of randomized subjects will be included in mITT 
population).  
In Part B, subjects will be randomized (2:1) until there are ≥30 subjects in the CD101 IV 
treatment and ≥15 subjects in the comparator group (≥45 additional subjects and no more 
than 120 subjects). (Note: Subjects enrolled under Amendment 5 and assigned to CD101 
IV receive Group 1 treatment and subjects enrolled under Amendment 6 and assigned to 
CD101 IV treatment receive Group 2 treatment. Subjects enroll under the current, 
approved amendment at the site at the time of randomization; subjects enrolled to 
Amendment 5 continue study participation on the same amendment regardless of 
subsequent approval of Amendment 6.) Total enrollment will depend on the enrollment 
rate for the 6- to 8-month period between the end of Part A and the staged start of the 
Phase 3 study, which is the trigger for the rolling close-out of Part B.  
6.3 
MEASURES TAKEN TO MINIMIZE BIAS 
Bias is minimized by subject randomization and blinding in both Part A and Part B 
(Section 6.5).  
For the interim analysis, a few (≤5) efficacy and safety tables will be provided by an 
independent unblinded statistician without individual subject data to allow for 
continuation to Part B of the study. After the database for Part A is locked, summary 
tables of unblinded efficacy and safety data will be provided. Individual subjects will not 
be unblinded for either the interim analysis or the Part A analysis. (Note: An addendum 
to the Unblinding Plan for Part A allowed for unblinded safety review of adverse events 
of interest identified during blinded safety review; the addendum allowed for no more 
than 5% of subjects to be unblinded.) The data from Part B will only be unblinded and 
analyzed after database lock for Part B at completion of the study. 
6.4 
EXPECTED DURATION OF SUBJECT PARTICIPATION 
Study participation will require from 45 to 52 days for subjects with candidemia only (or 
from 52-59 days for subjects with IC, with or without candidemia) after the first dose of 
study drug: study drug administration from Day 1 up to Day 21 (for subjects with 
candidemia) or up to Day 28 (±2 days; only for subjects with IC); safety, tolerability, and 
efficacy assessments up to Day 21 (for subjects with candidemia) or up to Day 28 (±2 
days; only for subjects with IC); and a FU visit (Days 45 to 52 for subjects with 
candidemia only or Days 52-59 for subjects with IC, with or without candidemia).  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 56 of 128 
 
6.5 
METHOD OF TREATMENT ASSIGNMENT AND BLINDING 
After informed consent has been obtained, subjects will be screened for study eligibility 
before randomization. Subjects in Part A will be assigned a subject number and 
randomized (1:1:1) to receive CD101 IV treatment Group 1, CD101 IV treatment Group 
2, or caspofungin on Day 1 just prior to dosing. Subjects in Part B will be assigned a 
subject number and randomized (2:1) to receive CD101 IV treatment or caspofungin on 
Day 1 just prior to dosing. Randomization will be stratified based on the method used at 
Screening to establish the diagnosis (blood culture/rapid IVD and positive Gram 
stain/culture from a specimen obtained from a normally sterile site). If a subject has both 
a positive blood culture/rapid IVD and Gram stain/culture from a specimen obtained from 
a normally sterile site, the subject will be randomized within the positive Gram 
stain/culture from a specimen obtained from a normally sterile site stratum. The study 
site’s pharmacist (or pharmacist designee) will obtain the study drug assignment from a 
computer-generated randomization schedule. A subject is considered randomized when 
the randomization transaction is recorded in the Interactive Web Response System 
(IWRS). 
The data for the 40 to 60 subjects in the mITT population involved in the interim analysis 
will be locked prior to the unblinded interim analysis, and the database for Part A will be 
locked prior to the Part A analysis. The data from Part A will be unblinded after the 
database is locked for Part A, but likely prior to completion of Part B, and interim 
summary results and full Part A summary results will be reported when available.  
All study personnel, including the Sponsor, PI, and site personnel involved in study 
conduct, and subjects will remain blinded to by-subject study medication assignment for 
both Part A and Part B until the study is completed, with the exception of the pharmacy 
monitor, unblinded program manager, clinical supplies, document manager, and quality 
(per the Sponsor Blinding Plan). Additionally, in Part A only, some personnel from 
vendors, including the PK analyst and an independent unblinded statistician, will be 
unblinded, but will not be involved in study conduct or the final analysis. An independent 
unblinded statistician will perform the analysis on the interim and final unblinded Part A 
data. (Note: An addendum to the Unblinding Plan for Part A allowed for unblinded safety 
review of adverse events of interest identified during blinded safety review; the 
addendum allowed for no more than 5% of subjects to be unblinded.) The Pharmacy 
Monitor will monitor drug preparation and drug accountability during the study and cases 
in which unblinding is required due to a safety or tolerability issue. To maintain study 
blinding, study drug preparation will be performed by an unblinded site pharmacist (or 
qualified unblinded personnel at the study site not involved with study procedures or 
evaluations).  
Instructions for study drug preparation and dosing are outlined in the Pharmacy Manual 
provided separately to the site. To maintain the blind, oral study drug pills must never be 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 57 of 128 
 
crushed. In the case of a medical emergency requiring the PI to know the identity of the 
study drug, the PI will follow the procedures outlined in Section 8.6.  
7.0 
SELECTION, DISCONTINUATION, AND WITHDRAWAL OF 
SUBJECTS 
To be enrolled in this study, all subjects must meet all of the following inclusion criteria 
and none of the exclusion criteria.  
7.1 
SUBJECT INCLUSION CRITERIA 
Subjects in must meet ALL of the following inclusion criteria to be enrolled: 
1. Males or females ≥18 years.  
2. Established mycological diagnosis of candidemia and/or IC from a sample taken 
≤96 hours before randomization defined as: 
a.  ≥1 blood culture positive for yeast or Candida  
OR 
b. Positive test for Candida from a Sponsor-approved rapid IVD 
OR 
c. Positive Gram stain for yeast or positive culture for Candida spp. from a 
specimen obtained from a normally sterile site 
3. Willing to initiate or continue medical treatment to cure infections, including receipt 
of antibiotics and surgical procedures, if required. Subjects receiving only 
medications and measures for comfort, and not cure, should not be enrolled. 
4. Female subjects of child-bearing potential <2 years postmenopausal must agree to 
and comply with using 1 barrier method (eg, female condom with spermicide) plus 1 
other highly effective method of birth control (eg, oral contraceptive, implant, 
injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence 
while participating in this study. Male subjects must be vasectomized, abstain from 
sexual intercourse, or agree to use barrier contraception (condom with spermicide), 
and also agree not to donate sperm from first dose of CD101 (Day 1) until 90 days 
following last administration of study drug. 
5. Willing and able to provide written informed consent. If the subject is unable to 
consent for himself/herself, a legally acceptable representative must provide informed 
consent on their behalf. 
6. Presence of 1 or more systemic signs attributable to candidemia and/or IC (eg, fever, 
hypothermia, hypotension, tachycardia. tachypnea) (Section 7.1.2) 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 58 of 128 
 
7.1.1 
Rapid In Vitro Diagnostics for Candidemia and Invasive Candidiasis 
The addition of rapid IVD for the identification of subjects with candidemia and/or IC is 
being employed to reduce the amount of prior empiric antifungal therapy being 
administered to potential study subjects. Rapid IVDs for Candida spp. used for inclusion 
in this study must be approved by the Sponsor prior to use in the study. Subjects may be 
enrolled based on a positive result at Screening from a Sponsor-approved rapid IVD, but 
a culture from blood or normally sterile tissue or fluid that is positive for Candida spp. 
will still be the required objective measure for candidemia or IC in the study analyses for 
efficacy. Subjects who are enrolled based on a positive rapid IVD test and have negative 
or missing blood culture at Screening and remain culture negative, may or may not have 
study therapy discontinued, but should continue to be followed in the study for safety 
assessments. 
Potential subjects with 1 or more risk factors for candidemia and IC should have a 
Sponsor-approved rapid IVD for Candida spp. performed only if the site is drawing a 
blood sample for blood culture and if empiric antifungal therapy for candidiasis has been 
administered or will be administered within the subsequent day. Risk factors for 
candidemia and IC include (but are not limited to): 
• Immunosuppression without frank neutropenia 
• Central venous catheter 
• Recent abdominal surgery 
• Pancreatitis 
• End stage renal disease 
• Current daily administration of total parenteral nutrition 
• Systemic inflammatory response syndrome while on broad spectrum antibiotics 
Sites may choose to perform a sponsor-approved rapid IVD in potential subjects without 
the listed risk factors for candidemia and IC, but the potential subject still must have a 
blood culture drawn and empiric antifungal therapy administered. A call to the Medical 
Monitor is recommended for any questions about risk factors for candidemia and the 
appropriate subjects on which to perform a rapid IVD for Candida spp. 
7.1.2 
Systemic Signs of Candidemia and Invasive Candidiasis 
It is a requirement that at least 1 systemic sign attributable to candidemia and/or IC be 
present at Screening for the subject to be eligible for enrollment. The Screening period 
for assessing systemic signs for inclusion in the study may include the 4 hours prior to the 
drawing of the qualifying positive blood culture (when systemic signs of infection 
resulted in obtaining blood cultures), qualifying positive culture from a sterile site, or 
qualifying rapid IVD, through enrollment. The possible signs of infection that might be 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 59 of 128 
 
attributable to candidemia and/or IC at baseline include fever, hypothermia, hypotension, 
tachycardia, and tachypnea. 
 
For the listed systemic signs of candidemia, the qualifying parameters are listed below: 
 
Fever: Oral temperature ≥38°C [100.4°F] or a tympanic, temporal, rectal, or core body 
temperature ≥38.3°C [101°F])  
 
Hypothermia: Tympanic, temporal, rectal, or core body temperature ≤35°C [95.2°F]  
 
Hypotension: Systolic blood pressure <90 mm Hg or mean arterial pressure <70 mm Hg 
with a normovolemic or hypervolemic status 
 
Tachycardia: Heart rate >100 beats per minute with a normovolemic or hypervolemic 
status 
 
Tachypnea: Respiratory rate >20 breaths per minute 
7.2 
SUBJECT EXCLUSION CRITERIA 
Subjects must NOT meet any of the following exclusion criteria to be enrolled: 
1. Any of the following forms of IC: 
a. Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed) 
b. Osteomyelitis  
c. Endocarditis or myocarditis 
d. Meningitis, endophthalmitis, or any central nervous system infection 
2. Neutropenia (absolute neutrophil count ≤500/µL) at Screening or anticipated 
neutropenia during the study 
3. Alanine aminotransferase or aspartate aminotransferase levels >10-fold the upper 
limit of normal 
4. Severe hepatic impairment in subjects with a history of chronic cirrhosis (Child-Pugh 
score >9) 
5. Received systemic treatment with an antifungal agent at approved doses for treatment 
of candidemia or IC for >48 hours (for example, >2 doses of a once daily antifungal 
agent or >4 doses of a twice daily antifungal agent) in the last 96 hours before 
randomization 
a. Exception: Receipt of antifungal therapy to which any Candida spp. isolated at 
Screening in qualifying cultures is not susceptible (Appendix 1) 
6. Pregnant females  
7. Lactating females who are nursing  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 60 of 128 
 
8. Known hypersensitivity to CD101 IV, caspofungin, any echinocandin, or to any of 
their excipients 
9. Previous participation in this or any previous CD101 study  
10. Recent use of an investigational medicinal product within 28 days of the first dose of 
study drug or presence of an investigational device at the time of Screening  
11. The PI considers that the subject should not participate in the study 
12. Presence of an indwelling vascular catheter or device that cannot be removed and is 
likely to be the source of candidemia 
7.3 
REQUALIFICATION FOR ENTRY 
Subjects not fulfilling the entry criteria and not randomized may be rescreened for 
participation if their eligibility characteristics have changed.  
7.4 
SUBJECT WITHDRAWAL CRITERIA 
7.4.1 
Withdrawal from Study Protocol 
Subjects on study drug who wish to withdraw completely from this clinical study should 
be encouraged to complete the assessments at EOT. However, subjects may withdraw 
consent to participate in this study at any time without penalty or loss of benefits to which 
the subject is otherwise entitled. Every reasonable effort should be made to determine the 
reason a subject withdraws prematurely and this information should be recorded on the 
appropriate page(s) of the electronic case report form (eCRF). Subjects may be 
withdrawn from the study for any of the following reasons: 
• Subject unable or unwilling to continue 
• Subject elects to withdraw informed consent 
• AE (whether or not related to study drug) that precludes further participation in the 
study in the judgment of the PI and/or Sponsor 
• Protocol non-compliance 
• Subject lost to follow up 
• The PI considers that it is in the subject’s best interest not to continue participation in 
the study 
Subjects withdrawn from the study need not participate in the FU visit. 
Following enrollment, subjects diagnosed with IC involving 1 or more organ systems and 
normally excluded from study participation (Exclusion Criterion #1, Section 7.2) do not 
need to exit the study. Documentation of the disease should be placed in the eCRF along 
with any further interventions related to the disease. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 61 of 128 
 
7.4.2 
Early Discontinuation from Study Drug Administration  
For subjects who prematurely discontinue study drug (ie, before the anticipated full 
course of study drug therapy required for effective treatment of candidemia and/or IC), 
EOT assessments should be performed on the day of discontinuation. The reason for 
premature discontinuation of study drug administration should be recorded on the 
appropriate page(s) of the eCRF. Reasons for withdrawal from study drug may include, 
but are not limited to: 
• Cultures negative for Candida spp. 
o Blood culture is positive for yeast at enrollment, but the final local blood culture 
results conclude the yeast is not Candida spp. 
o Subject is enrolled based on a rapid IVD test positive for Candida spp., but final 
local blood culture results from Screening or tissue/fluid culture results from a 
normally sterile site are negative for Candida spp. 
• Safety  
o Subject unable or unwilling to continue or informed consent withdrawn  
○ Occurrence of an AE that, in the opinion of the Investigator, warrants the 
subject’s permanent discontinuation from study drug therapy. This includes 
development of a clinically significant laboratory abnormality that requires 
discontinuation from study drug (IV and IV/oral) therapy. In the event of 
discontinuation from study drug therapy due to the occurrence of an AE, the study 
site should notify the Medical Monitor as soon as possible 
○ Suspected or confirmed pregnancy or nursing during the study drug 
administration period.  
• Invasive Candidiasis 
Echinocandins are not appropriate therapy for Candida infections of the eye or central 
nervous system due to low drug distribution to these sites. In the event that a subject 
is diagnosed with endophthalmitis or chorioretinitis or a central nervous system 
infection with Candida species, study drug should be stopped and appropriate therapy 
should be started based on local guidelines (Pappas et al., 2016; Cornely et al., 2012). 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 62 of 128 
 
Study drug may be continued in the event of diagnosis of other forms of IC listed in 
the exclusion criteria if the involvement of other organ systems was thought to be 
present at the time of enrollment and the diagnosis was delayed. If, on the other hand, 
the spread of Candida infection to other organ systems was thought to have occurred 
following enrollment and initiation of study drug, then the investigator should 
consider a change of therapy due to insufficient therapeutic effect of study drug. In all 
cases of other forms of IC, the investigator should consult local guidelines for the 
most appropriate management of disease and whether or not additional antifungal 
therapy may be warranted either during study drug administration or following 
completion of study drug therapy. 
• Insufficient therapeutic effect 
An insufficient therapeutic effect may be determined prior to the planned EOT visit. 
This determination will require an assessment of clinical status including the 
synthesis of symptoms and signs data (both local and systemic) and available 
laboratory data. Subjects who are deemed to have an insufficient therapeutic effect 
should be discontinued from study drug therapy.  
If a subject has daily blood cultures positive for Candida spp. through Day 7 despite 
appropriate study drug administration then this should be considered an insufficient 
therapeutic effect and study drug should be discontinued and salvage therapy 
initiated. The subject should remain in the study through the FU visit to complete 
safety assessments and assess for mortality.  
Seven days is the maximum number of daily positive blood cultures allowed prior to 
a change in antifungal therapy. The investigator may determine that there is an 
insufficient therapeutic response prior to Day 7. 
• Investigator discretion 
○ Resistant Pathogen(s): In the event that an organism resistant to ≥1 of the 
potential study drugs is isolated, the Investigator will determine whether the 
subject remains on study drug therapy. The Investigator may decide to continue 
study drug therapy if, in the Investigator’s opinion, there is clear and continuing 
clinical improvement while on therapy.  
○ The Investigator may decide to prematurely discontinue study drug therapy and to 
initiate an alternative and appropriate therapy if, in the Investigator’s opinion, the 
subject is not benefiting from study drug.  
NOTE: The Medical Monitor should be contacted to discuss whether to continue or 
prematurely discontinue a subject on the study drug in the event that the subject requires 
systemic concomitant antifungal therapy.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 63 of 128 
 
In the event that salvage therapy is required due to either insufficient therapeutic effect or 
Investigator discretion, the Investigator should note that since the subject has failed 
echinocandin therapy, other echinocandins may not be the best choice for salvage 
therapy. If the subject is switched to oral stepdown therapy prior to study drug failure, 
then the Investigator should consider that subjects in the caspofungin arm will also have 
been taking fluconazole. In both circumstances, the Investigator should refer to the IDSA 
(Pappas et al., 2016) or ESCMID (Ullmann et al., 2012; Cornely et al., 2012) guidelines 
for treatment failure in candidemia, and will need to determine whether or not breaking 
the blind is necessary to make an informed choice of future antifungal therapies. 
7.5 
REPLACEMENT OF SUBJECTS 
Randomized subjects who are withdrawn will not be replaced.  
7.6 
STUDY TERMINATION BY SPONSOR AND TERMINATION 
CRITERIA 
The Sponsor reserves the right to terminate an investigational site or this clinical study at 
any time. Reasons for termination may include, but are not limited to, the following: 
• The incidence or severity of AEs in this or other studies of CD101 IV indicate a 
potential health hazard to subjects 
• Serious or persistent noncompliance by the Investigator with the protocol, clinical 
research agreement, or applicable regulatory guidelines in conducting the study 
• IRB/IEC decision to terminate or suspend approval for the investigation or the 
Investigator 
• Investigator request to withdraw from participation 
• Subject enrollment is unsatisfactory 
8.0 
STUDY DRUGS 
In Part A, subjects were randomized in a 1:1:1 ratio to receive CD101 IV treatment 
Group 1, CD101 IV treatment Group 2, or IV caspofungin. In Part B, subjects will be 
randomized in a 2:1 ratio to receive CD101 IV treatment Group 2 or IV caspofungin. 
(Note: Subjects enrolled under Amendment 5 and assigned to CD101 IV receive Group 1 
treatment and subjects enrolled under Amendment 6 and assigned to CD101 IV treatment 
receive Group 2 treatment. Subjects enroll under the current, approved amendment at the 
site at the time of randomization; subjects enrolled to Amendment 5 continue study 
participation on the same amendment regardless of subsequent approval of 
Amendment 6.) Oral step-down therapy is allowed in all treatment groups in Part A and 
Part B; oral placebo in the CD101 IV groups and oral fluconazole in the caspofungin 
group. The total IV plus oral treatment duration will be ≥14 days and up to a maximum of 
28 days (Table 6). 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 64 of 128 
 
In order to stop study drug for successful completion of therapy prior to 21 days, the 
following criteria must be met: 
• ≥14 days of study drug 
• The subject’s clinical status is considered stable based on Investigator assessment 
• All systemic signs attributable to candidemia and/or IC that were present at baseline 
have resolved 
• For subjects with IC, there is documented or presumed eradication of IC 
• If a blood culture is positive at Screening, 2 post-baseline blood cultures collected 
≥12 hours apart are negative for Candida spp. without an intervening positive culture, 
and there are no subsequent blood cultures following the first qualifying negative 
culture that are positive for Candida spp. 
Once these criteria are met, the total duration of study drug is at the discretion of the PI. 
Subjects randomized to the CD101 IV treatment Group 1 will receive 1 dose of CD101 
IV (400 mg) nominally over 60 (±10) minutes on Day 1 and Day 8 (Table 6). Subjects in 
Group 1 who require >14 days of IV therapy will receive an optional third dose of CD101 
IV (400 mg) on Day 15. Subjects in Group 1 with IC (with or without candidemia) who 
require >21 days of IV therapy will receive an optional fourth dose of CD101 IV (400 
mg) on Day 22. Subjects in Group 1 will receive IV placebo on other study days in order 
to maintain the blind. 
Subjects randomized to the CD101 IV treatment Group 2 will receive 1 dose of CD101 
IV (400 mg) nominally over 60 (±10) minutes on Day 1 and 200 mg on Day 8 (Table 6). 
Subjects in Group 2 who require >14 days of IV therapy will receive an optional third 
dose of CD101 IV (200 mg) on Day 15. Subjects in Group 2 with IC (with or without 
candidemia) who require >21 days of IV therapy will receive an optional fourth dose of 
CD101 IV (200 mg) on Day 22. Subjects in Group 1 will receive IV placebo on other 
study days in order to maintain the blind. 
For both CD101 IV groups, the time may be increased as needed up to 180 (±10) minutes 
to manage symptoms of infusion reaction consistent with management of echinocandin 
class infusion reactions, whereby decreasing the rate of infusion often alleviates 
symptoms. (Note: infusion must be completed within the 4-hour stability limit, which 
starts at the time of reconstitution of rezafungin for injection lyophilized powder in the 
single-use vial.) 
Intravenous study drug is administered 24 (±2) hours after study drug was administered 
on the previous day. 
Subjects may receive oral step-down therapy after ≥3 days of IV therapy. Step-down 
therapy in both CD101 IV treatment groups will be oral placebo, in order to maintain the 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 65 of 128 
 
blind. Subjects who have already switched to oral step-down therapy will receive both 
oral placebo and CD101 IV on Day 8 (±1 day), Day 15 (±1 day) for subjects who require 
>14 days of therapy, and Day 22 (±1 day) for subjects with IC (with or without 
candidemia) who require >21 days of therapy.  
Subjects randomized to the caspofungin group will receive IV caspofungin (a single 70 
mg loading dose on Day 1 followed by 50 mg once daily over 60 (±10) minutes) for ≥3 
days and up to a maximum of 21 days for subjects with candidemia only and up to a 
maximum of 28 days for subjects with IC (with or without candidemia) (Table 6). 
Intravenous study drug is administered 24 (±2) hours after study drug was administered 
on the previous day. 
Step-down therapy in the caspofungin treatment group will be oral fluconazole (a loading 
dose of 800 mg [4 capsules] the first day followed by 400 mg [2 capsules]/day 
thereafter). In order to maintain the blind, subjects who have already switched to oral 
step-down therapy will receive both oral fluconazole and IV placebo on Day 8 (±1 day), 
Day 15 (±1 day) for subjects who require >14 days of therapy, and Day 22 (±1 day) for 
subjects with IC (with or without candidemia) who require >21 days of therapy.  
The total IV plus oral treatment duration will be ≥14 days and up to 28 days. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 66 of 128 
 
Table 8:  
Study Treatments 
Study Day 
CD101 IV  
Group 1  
Group 2 
Caspofungin Group  
1 
IV CD101 (400 mg) 
IV caspofungin (a single 70 mg loading dose) 
2-3 a 
IV placebo 
IV caspofungin (50 mg/day) 
4-7 
IV placebo if not stepped down 
OR 
oral step-down therapy (placebo) if 
already stepped down 
IV caspofungin (50 mg/day) if not stepped down 
OR 
oral step-down therapy (fluconazole, a loading 
dose of 800 mg [4 capsules] on the first day 
followed by 400 mg [2 capsules]/day thereafter) 
if already stepped down 
8 b 
IV CD101 (400 mg Group 1, 200 mg 
Group 2) if not stepped down  
OR 
IV CD101 (400 mg Group 1, 200 mg 
Group 2) PLUS oral step-down therapy 
(placebo) if already stepped down 
IV caspofungin (50 mg/day) if not stepped down  
OR  
IV placebo PLUS oral step-down therapy 
(fluconazole, a loading dose of 800 mg [4 
capsules] on the first day followed by 400 mg [2 
capsules]/day thereafter) if already stepped 
down 
9-14 c 
IV placebo if not stepped down 
OR 
oral step-down therapy (placebo) if 
already stepped down 
IV caspofungin (50 mg/day) if not stepped down 
OR 
oral step-down therapy (fluconazole, a loading 
dose of 800 mg [4 capsules] on the first day 
followed by 400 mg [2 capsules]/day thereafter) 
if already stepped down 
15 b 
(if needed) 
IV CD101 (400 mg Group 1, 200 mg 
Group 2) if not stepped down 
OR 
IV CD101 (optional) d (400 mg Group 1, 
200 mg Group 2) PLUS 
oral step-down therapy (placebo) if 
already stepped down 
OR  
No treatment 
IV caspofungin (50 mg/day) if not stepped down 
OR 
IV placebo (optional) d PLUS oral step-down 
therapy (fluconazole, a loading dose of 800 mg 
[4 capsules] on the first day followed by 400 mg 
[2 capsules]/day thereafter) if already stepped 
down 
OR  
No treatment 
16-21 e 
(if needed) 
IV placebo if not stepped down 
OR 
oral step-down therapy (placebo) if 
already stepped down 
OR  
No treatment 
IV caspofungin (50 mg/day) if not stepped down 
OR 
oral step-down therapy (fluconazole, a loading 
dose of 800 mg [4 capsules] on the first day 
followed by 400 mg [2 capsules]/day thereafter) 
if already stepped down 
OR  
No treatment 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 67 of 128 
 
Table 8:  
Study Treatments 
Study Day 
CD101 IV  
Group 1  
Group 2 
Caspofungin Group  
22 b  
(if needed, 
only for 
subjects 
with IC) 
IV CD101 (400 mg Group 1; 200 mg 
Group 2) if not stepped down 
OR 
IV CD101 (optional) f (400 mg Group 1; 
200 mg Group 2) PLUS 
oral step-down therapy (placebo) if 
already stepped down 
OR  
No treatment 
IV caspofungin (50 mg/day) if not stepped down 
OR 
IV placebo (optional) f PLUS oral step-down 
therapy (fluconazole, a loading dose of 800 mg 
[4 capsules] on the first day followed by 400 mg 
[2 capsules]/day thereafter) if already stepped 
down 
OR  
No treatment 
23-28 g,h 
(if needed, 
only for 
subjects 
with IC) 
IV placebo if not stepped down 
OR 
oral step-down therapy (placebo) if 
already stepped down 
OR  
No treatment 
IV caspofungin (50 mg/day) if not stepped down 
OR 
oral step-down therapy (fluconazole, a loading 
dose of 800 mg [4 capsules] on the first day 
followed by 400 mg [2 capsules]/day thereafter) 
if already stepped down 
OR  
No treatment 
IC = invasive candidiasis; IV= intravenous 
a. 
Subjects must receive IV therapy for ≥3 days before switching to oral step-down therapy. 
b. The Day 8, Day 14, Day 15, and Day 22 visits have a window of ±1 day if subject already stepped down 
to oral therapy and discharged from the study site. 
c. 
Total IV plus oral treatment duration must be ≥14 days.  
d. Subjects who require >14 days of therapy may receive an optional third dose of IV study drug on Day 
15, if needed. 
e. 
Total IV plus oral treatment duration must be ≤21 days for subjects with candidemia only. 
f. 
Subjects with IC (with or without candidemia) who require >21 days of therapy may receive a fourth 
dose of IV study drug on Day 22, if needed 
g. The Day 28 visit has a window of ±2 days if subject already stepped down to oral therapy and 
discharged from the study site 
h. Total IV plus oral treatment duration must be ≤28 days for subjects with IC (with or without 
candidemia). 
8.1 
CD101 FOR INJECTION 
CD101 for Injection (100 mg) is supplied as a sterile lyophilized powder for 
reconstitution prior to dilution into infusion bags. The product is limited to 
investigational use only. Please refer to the current Investigator Brochure for additional 
information.  
8.1.1 
Directions for Use 
One vial of CD101 for Injection will be reconstituted with 8 mL sterile water for 
injection (WFI) prior to diluting into infusion bags. Subject infusions must be completed 
within 4 hours of reconstitution of the lyophilized powder in the vial. Please refer to the 
Pharmacy Manual for detailed information on study drug preparation. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 68 of 128 
 
8.1.2 
Drug Storage 
Vials of CD101 for Injection and diluted infusion bags should be stored and used per the 
directions presented in the Pharmacy Manual. 
8.2 
CASPOFUNGIN 
Please refer to the prescribing information provided in the Pharmacy Manual for 
additional information. 
8.3 
ORAL STEP-DOWN THERAPY 
An oral step-down therapy is allowed in all treatment groups provided the following 
criteria are met:  
• Able to take oral medication 
• ≥3 days of IV study drug 
• The Candida species isolated is susceptible to fluconazole  
• The subject’s clinical status is considered stable based on Investigator assessment 
• If a blood culture is positive at Screening, 2 post-baseline blood cultures drawn ≥12 
hours apart are negative for Candida spp., without an intervening positive culture, 
and the first of the 2 cultures was drawn ≥48 hours prior to oral study drug initiation 
• No evidence of moderate or severe hepatic insufficiency (alanine aminotransferase or 
aspartate aminotransferase >3× the upper limit of normal) 
• No history of hypersensitivity or any other contraindications to the use of fluconazole 
and in the Investigator’s opinion, the subject can tolerate oral fluconazole therapy 
(refer to current fluconazole Prescribing Information)  
The principal contraindications to fluconazole use are hepatic injury, anaphylaxis 
(hypersensitivity), drug-induced exfoliative skin disorders, and pregnancy. Medical staff 
should also beware of the potential of QT prolongation, especially when administered to 
subjects with known heart disease or with other drugs that cause this same side effect. 
Fluconazole should be administered with caution to subjects with potentially 
proarrhythmic conditions. The potential for drug-drug interactions with fluconazole is 
summarized in Section 8.7. 
It is the responsibility of the PI to carefully read the list of requirements for the switch to 
oral fluconazole listed above, as well as the list of contraindications, warning and 
precautions, and drug-drug interactions in the US Package Insert or European Union 
Summary of Product Characteristics that are summarized here and in Section 8.3, in order 
to determine whether or not the subject may be eligible and safely started on oral 
fluconazole stepdown therapy. 
For subjects with creatinine clearance >50 mL/min (Appendix 2), oral step-down therapy 
will be fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 
400 mg [2 capsules]/day thereafter) in the caspofungin treatment group and oral placebo 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 69 of 128 
 
(4 capsules on the first day followed by 2 capsules/day thereafter) in the CD101 treatment 
groups.  
To maintain the blind, oral study drug pills must never be crushed. 
The total IV plus oral treatment duration will be ≥14 days and up to 28 days. 
8.4 
DOSE ADJUSTMENT 
8.4.1 
CD101 IV 
Dosage adjustments are not allowed in the CD101 IV groups. 
8.4.2 
Caspofungin 
Subjects in the caspofungin group with moderate hepatic impairment (Child-Pugh score 
of 7-9 with a history of chronic cirrhosis) will receive a loading dose of caspofungin of 
70 mg on Day 1 and 35 mg/day thereafter.  
Subjects in the caspofungin group weighing >80 kg or on concomitant rifampin, 
nevirapine, efavirenz, phenytoin, dexamethasone, or carbamazepine may receive 70 mg 
caspofungin daily. Dose adjustment based on potential drug-drug interactions may be 
considered at the Investigator’s discretion. 
8.4.3 
Fluconazole 
Subjects in the caspofungin group with renal impairment who are switched to oral 
stepdown therapy may receive reduced doses of fluconazole.  
For subjects with creatinine clearance ≤50 mL/min (Appendix 2), oral step-down therapy 
should be fluconazole (a loading dose of 400 mg [2 capsules] on the first day followed by 
200 mg [1 capsule]/day thereafter) in the caspofungin treatment group and oral placebo 
(2 capsules on the first day followed by 1 capsule/day thereafter) in the CD101 treatment 
groups.  
For subjects receiving hemodialysis, oral step-down therapy should be fluconazole (a full 
loading dose of 800 mg [4 capsules] followed by 400 mg [2 capsules] only after each 
episode of hemodialysis) in the caspofungin treatment group and oral placebo (4 capsules 
on the first day followed by 2 capsules after each hemodialysis) in the CD101 treatment 
groups. 
8.5 
COMPLIANCE 
Treatment compliance for IV study drugs will be documented in the eCRF by recording 
the date, start time, stop time, and whether the dose of study drug was completely 
infused. For oral fluconazole (caspofungin group) or oral placebo (CD101 groups), 
treatment compliance will be documented by recording start date, end date, and pill 
counts.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 70 of 128 
 
8.6 
BREAKING THE BLIND 
This study is a double-blind design. The PI, study personnel, and subjects will not make 
any effort to determine which study drug therapy is being received. Unblinded pharmacy 
personnel or unblinded study personnel (ie, PK analyst in Part A only and statistician in 
Part A and Part B) may be utilized in this study.  
The data for the 40 to 60 subjects in the mITT population involved in the interim analysis 
will be locked prior to the unblinded interim analysis, and the database for Part A will be 
locked prior to the Part A analysis. The data from Part A will be unblinded after the 
database is locked for Part A, but likely prior to completion of Part B, and interim 
summary results and full Part A summary results will be reported when available. 
Individual subjects will not be unblinded for either the interim analysis or the Part A 
analysis. Thus, no by-subject data will be made available to the Sponsor until after 
database lock for Part B. (Note: An addendum to the Unblinding Plan for Part A allowed 
for unblinded safety review of adverse events of interest identified during blinded safety 
review; the addendum allowed for no more than 5% of subjects to be unblinded.) The 
data from Part B will only be unblinded and analyzed after database lock for Part B at 
completion of the study.  
Only in the case of an emergency, when knowledge of the study drug is essential for the 
clinical management or welfare of a specific subject, may the PI unblind a subject’s 
treatment assignment. Prior to any unblinding, the PI is strongly advised to discuss 
options with the Medical Monitor or appropriate Sponsor study personnel. As soon as 
possible and without revealing the subject’s study treatment assignment (unless important 
to the safety of subjects remaining in the study), the PI must notify the Sponsor if the 
blind is broken for any reason and the PI was unable to contact the Sponsor prior to 
unblinding. The PI will record in source documentation the date and reason for revealing 
the blinded treatment assignment for that subject. 
8.7 
PREVIOUS AND CONCOMITANT MEDICATIONS AND 
SUBSTANCES 
All systemic antifungal therapy administered within 4 weeks and all non-antifungal 
therapy administered within 1 week prior to randomization in will be documented in the 
CRF. Subjects who received systemic treatment with an antifungal agent at approved 
doses for treatment of candidemia for >48 hours before randomization will be excluded 
from the study.  
Concomitant systemic antifungal agents, other than those listed as part of study drug 
therapy, are not permitted and their use, for any reason other than the subject being 
considered a treatment failure, must be discussed with the Medical Monitor before 
administration.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 71 of 128 
 
Use of concomitant cyclosporine should be limited to subjects for whom potential benefit 
outweighs potential risk of drug-drug interactions with caspofungin. All other 
concomitant medications necessary for the health and wellbeing of the subject are 
permitted. 
Fluconazole is contraindicated in subjects with hypersensitivity to fluconazole and should 
be used with caution in subjects with hypersensitivity to other azoles. Fluconazole should 
not be co-administered with terfenadine, cisapride, astemizole, erythromycin, pimozide, 
quinidine, or any other drug metabolized via the cytochrome P450 (CYP)3A4 enzymatic 
pathway and may cause prolongation of the QT interval. Fluconazole should be 
administered with caution in patients with evidence of hepatic toxicity or liver dysfunction. 
Patients who have or develop abnormal liver function tests during fluconazole therapy 
should be monitored for the development of more severe hepatic injury. Hepatic toxicity 
secondary to fluconazole is usually reversible. 
Fluconazole is a potent CYP2C9 inhibitor and a moderate CYP3A4 inhibitor and thus all 
subjects on fluconazole who are concomitantly taking drugs that are also metabolized 
through these pathways should be monitored closely. Please refer to the US Package 
Insert or the European Union Summary of Product Characteristics for fluconazole for 
more information about the contraindications, warnings and precautions, and likely drug-
drug interactions. 
8.8 
ACCOUNTABILITY PROCEDURES 
The pharmacy or study personnel are responsible for ensuring that a current record of 
CD101 IV, caspofungin, fluconazole, and over encapsulated placebo inventory and 
accountability is maintained.  
A Pharmacy Monitor will be responsible for checking drug accountability at the site. 
Inventory records must be readily available for inspection by regulatory authorities at any 
time. Each shipment of study drug will contain an acknowledgment of receipt section for 
site signature. Upon receipt of study drug, the pharmacy or study personnel will visually 
inspect the shipment and verify the number and condition of vials or capsules received. 
Refer to the Pharmacy Manual for additional information.  
8.9 
STUDY DRUG HANDLING AND DISPOSAL 
Unless expressly disallowed by institution rules, used and unused vials of study drug 
(including CD101 and caspofungin) will be retained at the study site until study drug 
accountability has been performed by the Pharmacy Monitor. Upon completion of the 
study, termination of the study, or upon written authorization from the Sponsor, all 
retained unused and partially used study drug will be centrally destroyed. All records of 
disposal by a centralized destruction site will be maintained by the Sponsor. 
9.0 
STUDY PROCEDURES 
Study procedures should be completed within the windows provided in the Schedule of 
Assessments and Procedures located in Table 2. However, if a subject is unable to attend 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 72 of 128 
 
a visit within the specified windows, the PI (or qualified designee) should discuss 
appropriate scheduling with the Medical Monitor (or appropriate designee). 
For Part A of this study, the blood sample for CD101 PK is a critical parameter and any 
postdose time point for blood sample needs to be collected within the specified window. 
All other procedures should be completed as close to the prescribed/scheduled time as 
possible. Any nonscheduled procedures required for urgent evaluation of safety concerns 
take precedence over all routine scheduled procedures.  
9.1 
SCREENING 
Unless otherwise indicated, Screening assessments should be performed within 48 hours 
of randomization.  
• Obtain signed informed consent prior to initiating any study-related assessments or 
procedures. Consent from a legally acceptable representative may be obtained if the 
subject is unable to consent for themselves 
• Obtain a complete medical history for the last 5 years and Candida risk factors for the 
last 3 months (eg, central line, active malignancy, broad-spectrum antibiotic therapy, 
diabetes mellitus, immunosuppression, major surgery, total parenteral nutrition, 
transplant recipient, trauma, dialysis, burns, pancreatitis) and Intensive Care Unit 
admission and discharge (if applicable) 
• Short-term central venous catheters (eg, peripherally-inserted central catheters, 
internal jugular or subclavian central venous catheters) and long-term central venous 
catheters (eg, tunneled catheters) are recommended to be removed within 48 hours 
after diagnosis with candidemia, consistent with IDSA (Pappas et al., 2016) and 
ESCMID (Ullmann et al., 2012; Cornely et al., 2012) guidelines. 
• Record all systemic antifungal therapy administered within 4 weeks and all non-
antifungal therapy (including other anti-infective therapy) administered within 1 week 
prior to randomization 
• Clinical assessments 
o Conduct complete physical examination, including height and weight 
o Measure vital signs (temperature and the method used [oral, rectal, temporal, 
tympanic, or core], heart rate, blood pressure, and respiratory rate) 
− Record the highest and lowest daily temperature and the method used (oral, 
rectal, temporal, tympanic, or core), highest and lowest heart rate, highest and 
lowest respiratory rate, and highest and lowest blood pressure measured 
o Perform 12-lead ECG before subject randomization 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 73 of 128 
 
o Perform retinal examination for Candida eye infection by Day 7 only on subjects 
with candidemia by blood culture. This assessment is the standard of care for 
subjects with candidemia, and ideally would be performed by an ophthalmologist, 
if available. 
o Assess presence or absence of systemic signs and symptoms and determine which 
are attributable to candidemia and/or IC. The Screening period for assessing 
systemic signs for inclusion in the study may include the 4 hours prior to the 
drawing of the qualifying positive blood culture (when systemic signs of infection 
resulted in obtaining blood cultures), qualifying positive culture from a sterile 
site, or sponsor-approved IVD, through enrollment. 
• Laboratory assessments 
○ Prior to the start of the Screening period, consider use of a Sponsor-approved 
rapid IVD for Candida spp. while drawing blood culture if the potential subject 
has known risk factors for candidemia and will be administered empiric 
antifungal therapy (Section 7.1.1) 
− All sites using rapid IVDs must label samples with subject identification 
number and date/time of blood draw and follow all necessary timing and 
procedures required for proper testing and interpretation of results  
− For commercial IVDs, sample handling and storage procedures should follow 
the package insert 
○ A culture must be obtained as part of the standard of care for inclusion in the 
study. Established mycological diagnosis of candidemia sufficient for inclusion in 
the study will be established by either ≥1 blood culture positive for yeast or 
Candida OR a Sponsor-approved rapid IVD test positive for Candida spp. OR a 
positive Gram stain for yeast or positive culture for Candida spp. from a specimen 
obtained from a normally sterile site from a sample taken ≤96 hours before 
randomization.  
− If the positive blood culture used to qualify the subject for the study is drawn 
>12 hours from randomization, then an additional set of blood cultures must 
be obtained ≤12 hours before randomization. 
− If the subject is suspected of having IC, then all reasonable attempts to obtain 
a culture from the suspected site of infection should be made as early as 
possible before empiric therapy. 
− Perform identification and susceptibility testing at local laboratory for 
Candida for any positive blood culture or any positive culture from normally 
sterile site 
− Record the species and susceptibilities for all bacteria isolated within 1 week 
prior to randomization from blood or any other normally sterile site  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 74 of 128 
 
− Send all fungal isolates cultured from blood or normally sterile tissue/fluid to 
the Central Laboratory  
○ Perform urine pregnancy test on female subjects of childbearing potential. Do not 
perform on women who are ≥2 years postmenopausal or surgically sterile.  
○ Obtain blood samples for hematology tests, coagulation laboratory tests (PT/INR 
and either PTT or aPTT), and serum chemistry tests (Appendix 3) 
○ Obtain a urine sample for urinalysis (UA) and microscopy (Appendix 3) 
• Calculate Child-Pugh score only if the subject has a history of chronic cirrhosis 
(Appendix 4) 
• Record modified Acute Physiology and Chronic Health Evaluation (APACHE) II 
parameters (Appendix 5) with Glasgow Coma Score (Appendix 6); note that the 
APACHE II score can be calculated after enrollment, but should use the vital signs 
and laboratory results from the Screening visit. 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC 
• Assess, identify, and record any AEs following signing of the ICF 
• Confirm subject qualification by inclusion/exclusion criteria 
9.2 
DAYS 1, 2, and 3 
• Randomize subject just prior to dosing (Day 1 only) 
• Administer study drug (Section 8.0 and Study Pharmacy Manual) 
o IV infusion of study drug over 60 (±10) minutes on Days 1, 2, and 3; 24 (±2) 
hours after study drug was administered on the previous day (for Days 2 and 3 
only) 
• Clinical assessments 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
− Record the highest and lowest daily temperature and the method used (oral, 
rectal, temporal, tympanic, or core), highest and lowest heart rate, highest and 
lowest respiratory rate, and highest and lowest blood pressure measured each 
day 
○ Perform retinal examination for Candida eye infection once by Day 7 only on 
subjects with candidemia by blood culture. This assessment is the standard of care 
for subjects with candidemia, and ideally would be performed by an 
ophthalmologist, if available. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 75 of 128 
 
• Laboratory assessments 
○ Obtain blood samples for hematology and serum chemistry tests (Day 2 only) 
(Appendix 3); in general, the laboratory values to be entered into the eCRF will 
be from the first laboratory samples drawn each day with routine morning 
laboratory samples 
○ Obtain culture from blood and/or normally sterile tissue/fluid if demonstrating 
mycological eradication or if clinically indicated 
− Obtain blood for culture daily (preferred) or every other day until 2 blood 
cultures drawn ≥12 hours apart are negative, without an intervening positive 
culture 
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site 
− Perform identification and susceptibility testing for Candida for any positive 
culture requiring a change of antifungal therapy (ie, identification and 
susceptibility testing not required for Candida isolates cultured from 
specimens obtained without a required change in antifungal therapy) 
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
○ In Part A only, obtain blood samples for PK analysis from the OPPOSITE arm of 
the infusion on Day 1 (within 10 minutes [ie, >0 to 10 minutes] before the end of 
infusion, between 15 minutes and 1 hour after the end of infusion, and between 2 
hours and 12 hours after the end of infusion) and Day 2 (random draw with date 
of sample same as Day 2 date of dose, with safety labs if possible) 
• Record all concomitant medications including prescription, over the counter (OTC), 
and herbal medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 
• Assess, identify, and record any AEs 
9.3 
DAYS 4 to 7 
• Administer study drug (Section 8.0 and Study Pharmacy Manual) 
o IV infusion of study drug over 60 (±10) minutes, 24 (±2) hours after study drug 
was administered on the previous day  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 76 of 128 
 
OR  
 
o Oral step-down therapy if stepped down (Days 5, 6, and 7) 
― If on oral step-down therapy and discharged from study site, subject must 
mark date/time and number of capsules taken each day in Daily Subject Diary 
• Clinical assessments 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
only if receiving IV study drug 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured. 
− Vital signs are required on Days 4 and 5 (temperature, heart rate, blood 
pressure, respiratory rate) 
− For subjects discharged from the hospital and in the community, vital signs 
(temperature, heart rate, blood pressure, respiratory rate) are only performed 
on Days 6 to 7 if the subject is seen for clinical assessment or IV study drug 
infusion 
○ Perform retinal examination for Candida eye infection once by Day 7 only on 
subjects with candidemia by blood culture. This assessment is the standard of care 
for subjects with candidemia, and ideally would be performed by an 
ophthalmologist, if available. 
○ Assess presence or absence of systemic signs and determine which are 
attributable to candidemia and/or IC (Day 5 only)  
• Laboratory assessments 
○ Obtain blood samples for hematology and serum chemistry tests (Day 4 only) 
(Appendix 3); in general, the laboratory values to be entered into the eCRF will 
be from the first laboratory samples drawn each day with routine morning 
laboratory samples 
○ Obtain culture from blood and/or normally sterile tissue/fluid if demonstrating 
mycological eradication or if clinically indicated 
− Obtain blood for culture daily (preferred) or every other day until 2 blood 
cultures drawn ≥12 hours apart are negative, without an intervening positive 
culture 
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 77 of 128 
 
− Perform identification and susceptibility testing for Candida for any positive 
culture requiring a change of antifungal therapy (ie, identification and 
susceptibility testing not required for Candida isolates cultured from 
specimens obtained without a required change in antifungal therapy) 
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
• In Part A only, obtain blood samples for PK analysis on Day 4 (random draw with 
date of sample same as Day 4 date of dose, with safety labs if possible) 
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 
• Assess, identify, and record any AEs 
9.4 
DAY 8 (±1 day if already switched to oral step-down therapy and 
discharged from the study site) 
• Administer study drug (Section 8.0 and Study Pharmacy Manual) 
o IV infusion of study drug over 60 (±10) minutes, 24 (±2) hours after study drug 
was administered on the previous day, if not stepped down 
OR  
o IV infusion of study drug over 60 (±10) minutes, PLUS oral step-down therapy if 
already stepped down  
― Note that oral study drug must be taken every day if the subject has stepped 
down to oral therapy. 
― If on oral step-down therapy and discharged from study site, subject must 
mark date/time and number of capsules taken each day in Daily Subject Diary  
• Clinical assessments 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate)  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 78 of 128 
 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured. 
− If not hospitalized, record single measurements for daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), heart rate, respiratory 
rate, and blood pressure 
○ Repeat retinal examination for Candida eye infection only on subjects with 
candidemia by blood culture and only if the subject develops visual signs or 
symptoms of Candida eye infection during the course of the study  
• Laboratory assessments 
○ Obtain culture from blood and/or normally sterile tissue/fluid if demonstrating 
mycological eradication or if clinically indicated 
− Obtain blood for culture if demonstrating mycological eradication (if not 
already done) or if clinically indicated 
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site 
− Perform identification and susceptibility testing for Candida for any positive 
culture requiring a change of antifungal therapy (ie, identification and 
susceptibility testing not required for Candida isolates cultured from 
specimens obtained without a required change in antifungal therapy)  
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
○ Obtain blood samples for hematology/serum chemistry tests (Appendix 3); in 
general, the laboratory values to be entered into the eCRF will be from the first 
laboratory samples drawn each day with routine morning laboratory samples 
○ Obtain blood samples for PK analysis (predose only; Part A only) 
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 79 of 128 
 
• Assess, identify, and record any AEs 
9.5 
DAYS 9 to 13 
• Administer study drug (Section 8.0 and Study Pharmacy Manual) 
o IV infusion of study drug over 60 (±10) minutes, 24 (±2) hours after study drug 
was administered on the previous day, if not stepped down 
OR  
o Oral step-down therapy if already stepped down 
― If on oral step-down therapy and discharged from study site, subject must 
mark date/time and number of capsules taken each day in Daily Subject Diary 
• Clinical assessments 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
only if receiving IV study drug 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured. 
− If not hospitalized, record single measurements for daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), heart rate, respiratory 
rate, and blood pressure 
− For subjects discharged from the hospital and in the community, vital signs 
(temperature, heart rate, blood pressure, respiratory rate) are only performed 
on Days 9 to 13 if the subject is seen for clinical assessment or IV study drug 
infusion 
• Repeat retinal examination for Candida eye infection only on subjects with 
candidemia by blood culture and only if the subject develops visual signs or 
symptoms of Candida eye infection during the course of the study 
•  Laboratory assessments 
○ Obtain culture from blood and/or normally sterile tissue/fluid if demonstrating 
mycological eradication or if clinically indicated 
− Obtain blood for culture if demonstrating mycological eradication (if not 
already done) or if clinically indicated 
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 80 of 128 
 
− Perform identification and susceptibility testing for Candida for any positive 
culture requiring a change of antifungal therapy (ie, identification and 
susceptibility testing not required for Candida isolates cultured from 
specimens obtained without a required change in antifungal therapy) 
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 
• Assess, identify, and record any AEs if subject has a study visit 
9.6 
DAY 14 (±1 day if already switched to oral step-down therapy and 
discharged from the study site) 
• Administer study drug (Section 8.0 and Study Pharmacy Manual) 
o IV infusion of study drug over 60 (±10) minutes, 24 (±2) hours after study drug 
was administered on the previous day, if not stepped down 
OR  
o Oral step-down therapy if already stepped down 
― If on oral step-down therapy and discharged from study site, subject must 
mark date/time and number of capsules taken each day in Daily Subject Diary 
• Clinical assessments 
o Conduct complete physical examination, including weight 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured.  
− If not hospitalized, record single measurements for daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), heart rate, respiratory 
rate, and blood pressure 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 81 of 128 
 
○ Repeat retinal examination for Candida eye infection only on subjects with 
candidemia by blood culture and only if the subject develops visual signs or 
symptoms of Candida eye infection during the course of the study 
○ Assess presence or absence of systemic signs and symptoms and determine which 
are attributable to candidemia and/or IC 
• Laboratory assessments 
○ Obtain culture from blood and/or normally sterile tissue/fluid if demonstrating 
mycological eradication or if clinically indicated 
− Review previous blood cultures drawn and obtain blood for culture if there is 
no evidence of mycological eradication (ie, 2 negative blood cultures drawn 
≥12 hours apart without intervening positive blood cultures) 
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site 
− Perform identification and susceptibility testing for Candida for any positive 
blood culture requiring a change in antifungal therapy (ie, identification and 
susceptibility testing not required for Candida isolates cultured from 
specimens obtained without a required change in antifungal therapy) 
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
○ Obtain blood samples for hematology/serum chemistry tests (Appendix 3); in 
general, the laboratory values to be entered into the eCRF will be from the first 
laboratory samples drawn each day with routine morning laboratory samples 
− In Part A only, if therapy is stopped on or before Day 14 and there is no Day 15 
dose, then the Day 15 PK sample should be drawn with the safety laboratory 
samples for the Day 14 visit 
• PI to assess clinical response. Refer to Table 11 for definitions of clinical cure and 
failure  
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 82 of 128 
 
• Assess, identify, and record any AEs 
9.7 
DAY 15 (±1 day if already switched to oral step-down therapy and 
discharged from the study site) 
• Administer study drug (Section 8.0 and Study Pharmacy Manual) if further therapy is 
clinically indicated 
o IV infusion of study drug over 60 (±10) minutes, 24 (±2) hours after study drug 
was administered on the previous day, if not stepped down and if needed 
OR  
o IV infusion of study drug over 60 (±10) minutes, PLUS oral step-down therapy, if 
already stepped down and if needed 
― Note that oral study drug must be taken every day if the subject has stepped 
down to oral therapy.  
― If on oral step-down therapy and discharged from study site, subject must 
mark date/time and number of capsules taken each day in Daily Subject Diary 
OR 
o No treatment 
• Clinical assessments 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
only if receiving IV study drug 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured. 
− For subjects discharged from the hospital and in the community, vital signs 
(temperature, heart rate, blood pressure, respiratory rate) are only performed 
on Day 15 if the subject is seen for clinical assessment or IV study drug 
infusion 
• Repeat retinal examination for Candida eye infection only on subjects with 
candidemia by blood culture and only if the subject develops visual signs or 
symptoms of Candida eye infection during the course of the study 
• Laboratory assessments 
○ Obtain culture from blood and/or normally sterile tissue/fluid if demonstrating 
mycological eradication or if clinically indicated 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 83 of 128 
 
− Obtain blood for culture if demonstrating mycological eradication (if not 
already done) or if clinically indicated  
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site  
− Perform identification and susceptibility testing for Candida for any positive 
culture requiring a change in antifungal therapy (ie, identification and 
susceptibility testing not required for Candida isolates cultured from 
specimens obtained without a required change in antifungal therapy) 
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
○ In Part A only, obtain blood samples for PK analysis (predose only); if therapy is 
stopped on or before Day 14 and there is no Day 15 dose, then the Day 15 PK 
sample should be drawn with the safety laboratory samples for the Day 14 visit  
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 
• Assess, identify, and record any AEs 
 
9.8 
DAYS 16 to 21 
• Administer study drug (Section 8.0 and Study Pharmacy Manual) 
o IV infusion of study drug over 60 (±10) minutes, 24 (±2) hours after study drug 
was administered on the previous day, if not stepped down and if needed 
OR  
o Oral step-down therapy, if already stepped down and if needed 
― If on oral step-down therapy and discharged from study site, subject must 
mark date/time and number of capsules taken each day in Daily Subject Diary 
OR  
o No treatment 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 84 of 128 
 
• Clinical assessments 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
only if receiving IV study drug 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured.  
− For subjects discharged from the hospital and in the community, vital signs 
(temperature, heart rate, blood pressure, respiratory rate) are only performed 
on Days 16 to 21 if the subject is seen for clinical assessment or IV study drug 
infusion  
○ Repeat retinal examination for Candida eye infection only on subjects with 
candidemia by blood culture and only if the subject develops visual signs or 
symptoms of Candida eye infection during the course of the study 
• Laboratory assessments 
○ Obtain culture from blood and/or normally sterile tissue/fluid if demonstrating 
mycological eradication or if clinically indicated 
− Obtain blood for culture if demonstrating mycological eradication (if not 
already done) or if clinically indicated  
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site  
− Perform identification and susceptibility testing for Candida for any positive 
culture requiring a change in antifungal therapy (ie, identification and 
susceptibility testing not required for Candida isolates cultured from 
specimens obtained without a required change in antifungal therapy) 
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 
• Assess, identify, and record any AEs 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 85 of 128 
 
9.9 
DAY 22 (±1 day if already switched to oral step-down therapy and 
discharged from the study site) - Only Subjects With Invasive 
Candidiasis 
• Administer study drug (Section 8.0 and Study Pharmacy Manual) if further therapy is 
clinically indicated only for subjects with IC (with or without candidemia) 
o IV infusion of study drug over 60 (±10) minutes, 24 (±2) hours after study drug 
was administered on the previous day, if not stepped down and if needed 
OR  
o IV infusion of study drug over 60 (±10) minutes, PLUS oral step-down therapy, if 
already stepped down and if needed 
― Note that oral study drug must be taken every day if the subject has stepped 
down to oral therapy.  
― If on oral step-down therapy and discharged from study site, subject must 
mark date/time and number of capsules taken each day in Daily Subject Diary 
OR 
o No treatment 
• Clinical assessments 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
only if receiving IV study drug 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured. 
− For subjects discharged from the hospital and in the community, vital signs 
(temperature, heart rate, blood pressure, respiratory rate) are only performed 
on Day 22 if the subject is seen for clinical assessment or IV study drug 
infusion 
o Repeat retinal examination for Candida eye infection only on subjects with 
candidemia by blood culture and only if the subject develops visual signs or 
symptoms of Candida eye infection during the course of the study 
• Laboratory assessments 
○ Obtain culture from blood and/or normally sterile tissue/fluid if demonstrating 
mycological eradication or if clinically indicated 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 86 of 128 
 
− Obtain blood for culture if demonstrating mycological eradication (if not 
already done) or if clinically indicated  
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site  
− Perform identification and susceptibility testing for Candida for any positive 
culture requiring a change in antifungal therapy (ie, identification and 
susceptibility testing not required for Candida isolates cultured from 
specimens obtained without a required change in antifungal therapy) 
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 
• Assess, identify, and record any AEs 
9.10 
DAYS 23 to 27 - Only Subjects with Invasive Candidiasis 
• Administer study drug (Section 8.0 and Study Pharmacy Manual) only for subjects 
with IC (with or without candidemia) 
o IV infusion of study drug over 60 (±10) minutes, 24 (±2) hours after study drug 
was administered on the previous day, if not stepped down and if needed 
OR  
o Oral step-down therapy, if already stepped down and if needed 
― If on oral step-down therapy and discharged from study site, subject must 
mark date/time and number of capsules taken each day in Daily Subject Diary 
OR  
o No treatment 
• Clinical assessments 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
only if receiving IV study drug 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 87 of 128 
 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured. 
− For subjects discharged from the hospital and in the community, vital signs 
(temperature, heart rate, blood pressure, respiratory rate) are only performed if 
the subject is seen for clinical assessment or IV study drug infusion 
○ Repeat retinal examination for Candida eye infection only on subjects with 
candidemia by blood culture and only if the subject develops visual signs or 
symptoms of Candida eye infection during the course of the study 
• Laboratory assessments 
○ Obtain culture from blood and/or normally sterile tissue/fluid if demonstrating 
mycological eradication or if clinically indicated 
− Obtain blood for culture if demonstrating mycological eradication (if not 
already done) or if clinically indicated  
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site  
− Perform identification and susceptibility testing for Candida for any positive 
culture requiring a change in antifungal therapy (ie, identification and 
susceptibility testing not required for Candida isolates cultured from 
specimens obtained without a required change in antifungal therapy) 
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 
• Assess, identify, and record any AEs 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 88 of 128 
 
9.11 
DAY 28 (±2 days if already switched to oral step-down therapy 
and discharged from the study site) - Only Subjects with Invasive 
Candidiasis 
Perform Day 28 (±2 days) assessments and procedures only for subjects with IC (with or 
without candidemia). Note that the Day 28 (±2 days) visit could be the same visit as the 
EOT visit if the subject receives ≥26 days of therapy. 
• Administer study drug (Section 8.0 and Study Pharmacy Manual) only to subjects 
with IC (with or without candidemia) 
o IV infusion of study drug over 60 (±10) minutes, 24 (±2) hours after study drug 
was administered on the previous day, if not stepped down and if needed 
OR  
o Oral step-down therapy, if already stepped down and if needed 
― If on oral step-down therapy and discharged from study site, subject must 
mark date/time and number of capsules taken each day in Daily Subject Diary 
OR  
o No treatment 
• Clinical assessments 
o Conduct complete physical examination, including weight 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured.  
− If not hospitalized, record single measurements for daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), heart rate, respiratory 
rate, and blood pressure 
○ Repeat retinal examination for Candida eye infection only on subjects with 
candidemia by blood culture and only if the subject develops visual signs or 
symptoms of Candida eye infection during the course of the study 
○ Assess presence or absence of systemic signs and symptoms and determine which 
are attributable to candidemia and/or IC 
• Laboratory assessments 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 89 of 128 
 
○ Obtain culture from blood and/or normally sterile tissue/fluid if demonstrating 
mycological eradication or if clinically indicated 
− Review previous blood cultures drawn and obtain blood for culture if there is 
no evidence of mycological eradication (ie, 2 negative blood cultures drawn 
≥12 hours apart without intervening positive blood cultures) 
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site 
− Perform identification and susceptibility testing for Candida for any positive 
culture requiring a change in antifungal therapy (ie, identification and 
susceptibility testing not required for Candida isolates cultured from 
specimens obtained without a required change in antifungal therapy) 
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
• PI to assess clinical response. Refer to Table 11 for definitions of clinical cure and 
failure  
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 
• Assess, identify, and record any AEs 
9.12 
END OF THERAPY (+2 days allowed after last dose of study 
drug) 
Criteria for Completion of Study Drug Therapy (Section 8.0): 
In order to stop study drug for successful completion of therapy prior to 21 days (or prior 
to 28 days for subjects with IC), the following criteria must be met: 
• ≥14 days of study drug 
• The subject’s clinical status is considered stable based on Investigator assessment 
• All systemic signs attributable to candidemia and/or IC that were present at baseline 
have resolved 
• For subjects with IC, there is documented or presumed eradication of IC 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 90 of 128 
 
• If a blood culture is positive at Screening, 2 post-baseline blood cultures collected 
≥12 hours apart are negative for Candida spp. without an intervening positive culture, 
and there are no subsequent blood cultures following the first qualifying negative 
culture that are positive for Candida spp. 
Once these criteria are met, the total duration of study drug is at the discretion of the PI. 
• Clinical assessments 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured. 
− If not hospitalized, record single measurements for daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), heart rate, respiratory 
rate, and blood pressure 
○ Perform 12-lead ECG 
○ Repeat retinal examination for Candida eye infection only on subjects with 
candidemia by blood culture and only if the subject develops visual signs or 
symptoms of Candida eye infection during the course of the study 
• Laboratory assessments 
○ Obtain culture from blood and/or normally sterile tissue/fluid if clinically 
indicated.  
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
○ Obtain blood samples for hematology/serum chemistry tests (Appendix 3); in 
general, the laboratory values to be entered into the eCRF will be from the first 
laboratory samples drawn each day with routine morning laboratory samples 
○ Obtain a urine sample for UA and microscopy (Appendix 3) 
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 91 of 128 
 
• Assess, identify, and record any AEs 
9.13 
FOLLOW-UP VISIT (DAYS 45-52 for Subjects with Candidemia 
Only or Days 52-59 for Subjects with Invasive Candidiasis, With 
or Without Candidemia) 
• Clinical assessments 
o Conduct complete physical examination, including weight 
○ Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
− If hospitalized, record the highest and lowest daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), highest and lowest 
heart rate, highest and lowest respiratory rate, and highest and lowest blood 
pressure measured. 
− If not hospitalized, record single measurements for daily temperature and the 
method used (oral, rectal, temporal, tympanic, or core), heart rate, respiratory 
rate, and blood pressure 
○ Repeat retinal examination for Candida eye infection only on subjects with 
candidemia by blood culture and only if the subject develops visual signs or 
symptoms of Candida eye infection during the course of the study 
○ Assess presence or absence of systemic signs and symptoms of infection and 
determine which are attributable to candidemia and/or IC 
• Laboratory assessments 
○ Obtain blood samples for hematology and serum chemistry tests Appendix 3); in 
general, the laboratory values to be entered into the eCRF will be from the first 
laboratory samples drawn each day with routine morning laboratory samples 
○ Obtain culture from blood, and if feasible from normally sterile tissue/fluid 
− Obtain culture from blood  
− If feasible, and if there was a previous culture from a site positive for Candida 
spp., obtain culture from normally sterile tissue/fluid from the same site 
− All fungal isolates cultured from blood and normally sterile tissue/fluid must 
be sent to the Central Laboratory 
− Record the species and susceptibilities for any new bacteria isolated from 
blood or any other normally sterile site 
○ Perform urine pregnancy test on female subjects of childbearing potential. Do not 
perform on women who are ≥2 years postmenopausal or surgically sterile. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 92 of 128 
 
• PI to assess clinical response. Refer to Table 11 for definitions of clinical cure and 
failure 
• Record all concomitant medications including prescription, OTC, and herbal 
medications 
• If radiologic test performed, record radiologic test type with Findings and 
Interpretation only if radiologic test provides evidence of IC, OR evidence of 
resolution of IC from previous radiographs 
• Assess, identify, and record any AEs 
10.0 
ASSESSMENT OF SAFETY 
10.1 
SAFETY PARAMETERS 
Safety will be assessed from the signing of the ICF at Screening to the FU visit through 
the evaluation of AEs, vital signs, ECGs, and clinical laboratory data (clinical chemistry 
panels and hematology and UA evaluations) according to the Schedule of Assessments 
and Procedures (Table 2) and Appendix 3.  
10.2 
ADVERSE EVENTS 
AEs will be collected for all subjects from informed consent. The Investigator will assess 
all AEs and SAEs and will record the following information on the appropriate eCRF 
page: 
• Date of onset  
• Date of resolution or stabilization 
• Severity 
• Relationship to study drug  
• Action taken with study medication 
Medically indicated laboratory tests (emergency or unscheduled tests) should be 
conducted at the local laboratory. The Investigator should employ best medical judgment 
in determining how to manage AEs and SAEs. Any questions regarding AE or SAE 
management should be directed to the Medical Monitor. 
10.3 
ADVERSE EVENT REPORTING 
The Sponsor has requirements for expedited reporting of SAEs meeting specific criteria 
to worldwide regulatory authorities. Therefore, the Sponsor must be notified immediately 
regarding any SAE that occurs after informed consent.  
All SAEs must be reported to the Medical Monitor by phone or email within 24 hours of 
the investigational site’s knowledge of the event. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 93 of 128 
 
The study site will also transmit a Serious Adverse Event Report (SAER) to the safety 
vendor by facsimile or email within 24 hours. Contact details will be provided to all sites. 
An optional initial report can be made via telephone, but a completed SAER must still be 
faxed or emailed within 24 hours of the site’s knowledge of the event. The 
Investigational site will be provided with SAER forms wherein the following information 
is requested.  
• Subject identification, Investigator name, and site number 
• SAE information: event term, onset date, severity, and causal relationship 
• The outcomes attributable to the event (eg, death, a life-threatening AE, inpatient 
hospitalization, prolongation of existing hospitalization, a persistent or significant 
disability or incapacity, or other important medical event[s]) 
• A summary of relevant test results, pertinent laboratory data, and any other relevant 
medical history 
• The first and last dates of study drug administration. NOTE: as this is a double-blind 
study, SAERs should not indicate specific study drug assignments 
• Indicate if the study drug was discontinued or the study drug administration schedule 
modified 
• Supplemental information may include the following hospital records: laboratory 
results, radiology reports, progress notes, admission and emergency room notes, 
holding and observation notes, discharge summaries, autopsy reports, and death 
certificates 
In addition, relevant case report form pages should be appended to communicate relevant 
study drug and subject outcome information. The SAER should be faxed or emailed 
within 24 hours with as much of the above information as available at the time. The 
following minimum information is required for reporting an SAE: subject identification, 
reporting source, and an event or outcome. Supplemental information may be transmitted 
using a follow-up report and should not delay the initial report. The Sponsor may contact 
the investigational site to solicit additional information or follow up on the event.  
The Investigator must take all therapeutic measures necessary for resolution of the SAE. 
Any medications or procedures necessary for treatment of the SAE must be recorded on 
the appropriate pages of the subject’s eCRF. 
10.4 
DEFINITIONS 
10.4.1 
Adverse Event 
An AE means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE (also referred to as an adverse 
experience) can be any unfavorable and unintended sign (eg, a clinically-significant 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 94 of 128 
 
abnormal laboratory finding), symptom, or disease temporally associated with the use of 
a drug, and does not imply any judgment about causality. An AE can arise with any use 
of the drug (eg, off-label use, use in combination with another drug) and with any route 
of administration, formulation, or dose, including an overdose. 
Events that are related to the disease under study, candidemia, should not be considered 
or recorded as AEs unless the event fits the definition for an SAE (Section 10.4.4), in 
which case the SAE form must be submitted for safety reporting in the appropriate 
timeframe and entered as an AE into the eCRF. 
Laboratory abnormalities should not be recorded as AEs or SAEs unless they are 
associated with clinical signs or symptoms, or require medical intervention. However, 
each laboratory abnormality (eg, clinically significant changes detected on hematology, 
comprehensive metabolic panel, UA) independent from any underlying medical condition 
that requires medical or surgical intervention, or that leads to interruption of study drug 
infusion or discontinuation, must be recorded as an AE, or SAE if applicable. If the 
laboratory abnormality is part of a clinical condition or syndrome, it should be recorded 
as the syndrome or diagnosis rather than as the individual laboratory abnormality. In 
addition, laboratory abnormalities or other abnormal test assessments (eg, ECGs) that are 
associated with signs or symptoms must be recorded as AEs or SAEs if they meet the 
definition of an AE (or SAE) as described in Section 10.4.1 (or Section 10.4.4). 
10.4.2 
Suspected Adverse Reaction 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the 
drug caused the AE. For the purposes of IND safety reporting, ‘‘reasonable possibility’’ 
means there is evidence to suggest a causal relationship between the drug and the AE. 
Suspected adverse reaction implies a lesser degree of certainty about causality than 
adverse reaction, which means any AE caused by a drug. 
10.4.3 
Life-Threatening Adverse Event or Life-Threatening Suspected 
Adverse Reaction 
An AE or suspected adverse reaction is considered ‘‘life threatening’’ if, in the view of 
either the Investigator or Sponsor, its occurrence places the patient or subject at 
immediate risk of death. It does not include an AE or suspected adverse reaction that, had 
it occurred in a more severe form, might have caused death. 
10.4.4 
Serious Adverse Event or Serious Suspected Adverse Reaction 
An AE or suspected 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 AE – see definition above  
• Inpatient hospitalization or prolongation of existing hospitalization 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 95 of 128 
 
• A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• A congenital anomaly/birth defect  
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias, or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
Hospitalization for a planned or elective procedure or surgery for a pre-existing condition 
that has not worsened is not considered a serious adverse event.  
10.4.5 
Unexpected Adverse Event or Unexpected Suspected Adverse 
Reaction 
An AE or suspected adverse reaction is considered ‘‘unexpected’’:  
• If it is not listed in the Investigator Brochure or is not listed at the specificity or 
severity that has been observed, or  
• If an Investigator Brochure is not required or available, is not consistent with the risk 
information described in the general investigational plan or elsewhere in the current 
application, as amended  
• If it is not listed in the Prescribing Information (for marketed products) 
For example, under this definition, hepatic necrosis would be unexpected (by virtue of 
greater severity) if the Investigator Brochure referred only to elevated hepatic enzymes or 
hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis would be 
unexpected (by virtue of greater specificity) if the Investigator Brochure listed only 
cerebral vascular accidents.  
‘‘Unexpected,’’ as used in this definition, also refers to AEs or suspected adverse 
reactions that are mentioned in the Investigator Brochure as occurring with a class of 
drugs or as anticipated from the pharmacological properties of the drug, but are not 
specifically mentioned as occurring with the particular drug under investigation. 
10.5 
ADVERSE EVENT CLASSIFICATION 
10.5.1 
Relationship to Investigational Drug 
The Investigator’s assessment of causality must be provided for all AEs (serious and non-
serious) (Table 7). An Investigator’s causality assessment is the determination of whether 
there exists a reasonable possibility that the study drug caused or contributed to an AE. 
Clinical failure that qualifies as an AE without evidence of study drug toxicity should be 
considered unrelated to study drug. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 96 of 128 
 
These criteria, in addition to good clinical judgment, should be used as a guide for 
determining the causal assessment. If the event is thought to be unrelated to study drug 
administration, then an alternative explanation should be provided. 
Table 9:  
Guidelines for Assessing Relationship of Event to Study Drug  
Unrelated 
There is little or no chance that the Investigational Product 
caused the AE; other conditions, including concurrent illnesses, 
progression or expression of the disease state, or a reaction to a 
concomitant medication best explain the event 
Related 
The association of the AE with the Investigational Product is 
unknown, however, the AE is not clearly due to another 
condition, or a reasonable temporal association exists between 
the AE and treatment administration and, based on the 
Investigator's clinical experience, the association of the AE with 
the Investigational Product seems likely 
AE = adverse event. 
10.5.2 
Severity  
All AEs will be graded for severity (Table 8). 
The Investigator will use the terms: Mild, Moderate, or Severe to describe the maximum 
intensity of the AE. For purposes of consistency, these intensity grades are defined as 
follows: 
Table 10: 
Guidelines for Severity Assessments 
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated 
Moderate 
Minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental activities of daily 
living 
Severe 
Disabling; limiting self-care activities of daily living; 
urgent intervention indicated; death related to an AE 
AE = adverse event. 
10.5.3 
Serious Adverse Event 
Any adverse experience occurring at any dose of study medication that occurs between 
the time of informed consent and the FU visit (Days 45 to 52 for subjects with 
candidemia only or Days 52-59 for subjects with IC, with or without candidemia) that 
results in any of the following outcomes: 
• Death  
• Life-threatening situation (subject is at immediate risk of death) 
• Inpatient hospitalization or prolongation of existing hospitalization 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 97 of 128 
 
• Persistent or significant disability/incapacity 
• Congenital anomaly/birth defect in the offspring of a subject who received study drug 
• Events that jeopardize the subject sufficiently that medical or surgical intervention 
may be required to prevent one of the above outcomes. Examples may include, but 
are not limited, to: 
○ Intensive treatment in an emergency room or at home for allergic bronchospasm 
○ Blood dyscrasias that do not result in hospitalization 
○ Seizures that do not result in hospitalization 
10.5.3.1 
SAE definition clarifications 
• Death is an outcome of an AE, and not an AE in itself 
• All deaths during study drug administration or up to the FU visit (Days 45 to 52 for 
subjects with candidemia only or Days 52-59 for subjects with IC, with or without 
candidemia), regardless of cause or relationship, must be reported 
• “Occurring at any dose” does not imply that the subject is actively receiving study 
drug at the time of the event 
• “Life-threatening” means that the subject was at immediate risk of death from the 
event as it occurred. This does not include an event that might have led to death, had 
it occurred with greater severity. 
• Complications that occur during hospitalizations are AEs. If an AE prolongs 
hospitalization, it is an SAE. 
• “Inpatient hospitalization” means the subject has been formally admitted to a hospital 
for medical reasons, for any length of time. This may or may not be overnight. It does 
not include presentation and care within an emergency department (although an 
emergency department visit may define a medically important event, which is also 
considered an SAE). 
• The Investigator should attempt to establish a diagnosis of the event based on signs, 
symptoms, and other clinical information. In such cases, the diagnosis should be 
documented as the AE or SAE, rather than as the individual signs or symptoms. 
10.6 
ADVERSE EVENT FOLLOW-UP 
All unresolved SAEs (“ongoing” at discharge) will be followed by the study staff until 
resolution or deemed stable. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 98 of 128 
 
10.7 
ADVERSE EVENTS OF SPECIAL INTEREST  
10.7.1 
CD101 IV Intolerability 
Events that, in the opinion of the Investigator, may represent intolerance of the IV 
infusion of IV study drug must be recorded as AEs on the eCRF. In general, these events 
will be temporally related to IV echinocandin infusion.  
10.7.2 
Phototoxicity 
Results from a phototoxicity study in rats indicate evidence of phototoxicity at elevated 
CD101 exposures (Section 4.3). Although there is not yet any evidence of risk to humans, 
Investigators should advise subjects to avoid sun exposure without adequate protection 
and to report any AE potentially related to phototoxicity to the Sponsor. 
10.7.3 
Neuropathy and Tremors 
In a CD101 3-month toxicity study in monkeys, there were observations of tremors, 
intention tremors, and histology consistent with Schwann cell hyperplasia/hypertrophy 
and axonal degeneration (potentially consistent with clinical presentation of neuropathy) 
first appearing at week 6 of dosing and at 11-fold the exposure for Group 2. Ataxia, 
axonal neuropathy, hypoesthesia, paresthesia, peripheral motor neuropathy, peripheral 
neuropathy, peripheral sensory neuropathies, peripheral sensorimotor neuropathy, 
polyneuropathy, toxic neuropathy, and tremors will be included in adverse events of 
special interest. 
10.8 
TOXICITY MANAGEMENT  
The Investigator should employ best medical judgment in determining how to manage 
AEs. Any questions regarding AE management should be directed to the Medical 
Monitor. 
10.9 
RISKS FOR WOMEN OF CHILD-BEARING POTENTIAL OR 
DURING PREGNANCY 
The risks of CD101 IV administration during pregnancy have not been evaluated. 
Pregnant or lactating females who are nursing are excluded from this study.  
Subjects must be instructed to inform the Investigator immediately if they or their partner 
becomes pregnant during the study. Partners must complete informed consent to allow 
the investigator to follow them for the outcome of the pregnancy. In the event of a 
confirmed pregnancy, the following actions should be taken: 
• Study drug should be discontinued immediately in all (and in only) female subjects  
• The pregnancy should be reported within 24 hours of notification using the applicable 
Pregnancy Report Form 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 99 of 128 
 
• The Investigator should counsel the subject regarding the possible effects of prior 
CD101 IV exposure on the fetus and the need to inform the study site of the outcome 
of the pregnancy 
• The subject or subject’s partner (if consented) should be monitored until the 
immediate postnatal period or until termination of the pregnancy. The outcome 
should be reported using the Pregnancy Outcome or Abnormal Pregnancy Outcome 
form. 
Pregnancy is not an AE, in and of itself. However, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be recorded as an AE or 
SAE. A spontaneous abortion is always considered an SAE and will be reported as 
described in the AE and SAE sections. Furthermore, any SAE occurring as an adverse 
pregnancy outcome post-study must be reported to the Medical Monitor. 
10.10 
RISKS FOR MALES OF CHILDBEARING POTENTIAL 
Recent results from a CD101 nonclinical rat fertility study indicated adverse effects on 
sperm morphology and motility without interference with reproduction at 2.5 times the 
exposure of rezafungin Group 2. The risks for CD101 effects on spermatogenesis in non-
human primates and in humans have yet to be defined. Partner pregnancies of male 
subjects should be followed according to Section 10.9, when possible. 
11.0 
ASSESSMENT OF EFFICACY PARAMETERS 
Mycological response will be programmatically determined at Day 5, Day 14 (±1 day), 
Day 28 (±2 days; only for subjects with IC), and FU (Days 45-52 for subjects with 
candidemia only or Days 52-59 for subjects with IC, with or without candidemia) in the 
mITT population as defined in Table 9. 
Table 11:  
Mycological Outcome Categories at Day 5, Day 14 (±1 day), 
Day 28 (±2 days; only for subjects with invasive candidiasis), 
and Follow-up Visit 
Outcome 
Definition 
Success  
(eradication/  
presumed  
eradication) 
• If positive blood culture at baseline: 
o 
The last blood culture drawn on or prior to the day of assessment and 
another blood culture drawn at least 12 hours prior are both negative for 
Candida spp. 
AND 
o 
Any intervening blood cultures drawn between the 2 qualifying negative 
blood cultures are also negative for Candida spp.  
OR 
• If positive culture from a normally sterile site: 
o 
Documented mycological eradication: most recent culture on or prior to 
the day of assessment from all normally sterile sites of baseline Candida 
infection (if accessible) is negative 
OR 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 100 of 128 
 
Table 11:  
Mycological Outcome Categories at Day 5, Day 14 (±1 day), 
Day 28 (±2 days; only for subjects with invasive candidiasis), 
and Follow-up Visit 
Outcome 
Definition 
o 
Presumed mycological eradication: follow-up culture is not available 
(eg, normally sterile baseline site of Candida infection not accessible) in 
a subject with a successful clinical outcome (ie, did not receive rescue 
antifungal treatment and has resolution of systemic signs of invasive 
candidiasis that were present at baseline) and resolution or improvement 
of any baseline radiographic abnormalities due to invasive candidiasis 
AND 
• There was no change of antifungal therapy for the treatment of candidemia 
and/or invasive candidiasis 
AND 
• The subject is not lost to follow up on the day of assessment 
Failure  
• If positive blood culture at baseline: 
o 
The last blood culture drawn on or prior to the day of assessment or any 
blood culture drawn prior to and within 12 hours of the last blood culture 
is positive for Candida spp. 
OR 
o 
The most recent blood culture drawn at least 12 hours prior to the last 
blood culture is positive for Candida spp. 
OR 
• If positive culture from a normally sterile site: 
o 
Documented mycological persistence: most recent culture on or prior to 
the day of assessment from all normally sterile sites of baseline Candida 
infection (if accessible) is positive 
OR 
o 
Presumed mycological persistence: follow-up culture is not available 
(eg, normally sterile baseline site of Candida infection not accessible) in 
a subject without a successful clinical outcome or with continued (from 
baseline) radiographic abnormalities due to invasive candidiasis 
OR 
• The subject requires a change of antifungal therapy to treat candidemia  
OR 
• The subject dies of any cause prior to or on the day of assessment 
Indeterminate 
• If positive blood culture at baseline: A blood specimen was not available to 
culture or the result was not available 
• If positive culture from a normally sterile site: A sterile site tissue/fluid 
specimen was not available to culture or the result was not available AND an 
assessment of signs of invasive candidiasis was not available 
• Subject is lost to follow up on the day of assessment 
The primary efficacy outcome is overall response and is determined programmatically 
from the mycological response and assessment of systemic signs attributable to 
candidemia and/or IC (Table 10). The signs that may be present at baseline and 
attributable to candidemia and/or IC include fever, hypothermia, hypotension, 
tachycardia, and tachypnea (Section 7.1.2). Subjects who require a change of antifungal 
therapy to treat candidemia and/or IC prior to a given day of the overall response 
assessment (Day 5, Day 14, or FU visit) should have the assessment of systemic signs 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 101 of 128 
 
attributable to candidemia and/or IC moved forward to the early EOT evaluation. 
Assessments of systemic signs performed prior to the early EOT will be unaffected. 
Table 12:  
Overall Response Categories at Day 5, Day 14 (±1 day), Day 28 (±2 
days; only for subjects with invasive candidiasis), and Follow-up 
Visit 
Overall 
Response 
Definition 
Mycological Response 
Clinical Signs  
Success  
Success 
(eradication/presumed 
eradication) 
Resolution of attributable systemic signs of candidemia 
and/or invasive candidiasis that were present at baseline 
Failure 
 
Success 
(eradication/presumed 
eradication) 
Recurrence or lack of resolution of attributable systemic 
signs of candidemia and/or invasive candidiasis 
Failure 
Resolution of attributable systemic signs of candidemia 
and/or invasive candidiasis that were present at baseline 
Failure 
Recurrence or lack of resolution of attributable systemic 
signs of candidemia and/or invasive candidiasis 
Failure 
Assessment of systemic signs was not completed for any 
reason (including death) 
 
Indeterminate 
Indeterminate 
Resolution of attributable systemic signs of candidemia 
and/or invasive candidiasis that were present at baseline 
Success 
(eradication/presumed 
eradication) 
Assessment of systemic signs was not completed for any 
reason  
The Investigator will make an assessment of clinical response at Day 14 (±1 day), Day 28 
(±2 days; only for subjects with IC), and FU, as detailed in Table 11. Subjects whose 
disease is progressing or who receive rescue antifungal therapy for candidemia prior to 
the Day 14 (±1 day) visit will be considered a clinical failure at the Day 14, Day 28 (±2 
days; only for subjects with IC), and FU visits. Subjects who are a clinical cure at Day 14 
(±1 day) and whose systemic signs or symptoms recur between Day 14 (±1 day) and Day 
28 (±2 days; only for subjects with IC) or FU, and who receive antifungal therapy, will be 
considered a failure at Day 28 (±2 days; only for subjects with IC) or FU. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 102 of 128 
 
Table 13: 
Investigator’s Assessment of Clinical Response at Day 14 (±1 day), 
Day 28 (±2 days; only for subjects with invasive candidiasis), and 
Follow-up Visit 
Clinical 
Response 
Definition 
Cure 
• Resolution of attributable systemic signs and symptoms of candidemia and/or IC that 
were present at baseline  
AND 
• No new systemic signs or symptoms attributable to candidemia and/or IC 
AND 
• No additional systemic antifungal therapy administered for candidemia and/or IC 
AND 
• The subject is alive  
Failure 
• Progression or recurrence of attributable systemic signs or symptoms of candidemia 
and/or IC  
OR 
• Lack of resolution attributable systemic signs or symptoms of candidemia and/or IC 
OR 
• Requirement for new or prolonged therapy to treat candidemia and/or ICa 
OR 
• An AE requires discontinuation of study drug (IV and IV/oral) on or prior to the day of 
assessment 
OR 
• The subject died of any cause  
Indeterminate 
Study data are not available for the evaluation of efficacy for any reason including: 
• 
Lost to follow up  
• 
Withdrawal of consent  
• 
Extenuating circumstances that preclude the classification of clinical outcome of 
candidemia and/or IC  
AE = adverse event; IC = invasive candidiasis; IV = intravenous 
a. 
Prolonged antifungal therapy is defined as therapy for the treatment of candidemia extending beyond 
the allowable 21 days of study drug or for the treatment of IC extending beyond the allowable 28 days 
of study drug. The determination of prolonged therapy will only apply to the Follow-up visit clinical 
response assessment. 
12.0 
ASSESSMENT OF PHARMACOKINETIC PARAMETERS (Part A 
only) 
Blood PK samples will be drawn from the OPPOSITE arm of the infusion at the 
following specified time points. 
Blood for PK analyses will be drawn on Day 1 (within 10 minutes [ie, >0 to 10 minutes] 
before the end of infusion, between 15 minutes and 1 hour after the end of infusion, and 
between 2 hours and 12 hours after the end of infusion), Day 2 (random draw with date of 
sample same as Day 2 date of dose, with safety labs if possible), Day 4 (random draw 
with date of sample same as Day 4 date of dose, with safety labs if possible), Day 8 
(predose only), and Day 15 (predose only). Day 8 and Day 15 PK draws should be 
performed within 30 minutes before the second and third dose of study drug, regardless 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 103 of 128 
 
of the exact day and time of these infusions. If therapy is stopped on or before Day 14 
and there is no Day 15 dose, then the Day 15 PK sample should be drawn with the safety 
laboratory samples for the Day 14 visit. Ideally, PK samples would be drawn with the 
safety laboratory samples for that day to prevent multiple needle sticks. 
For the purpose of maintaining the blind, blood samples will be collected from all 
subjects, when possible, in all 3 treatment groups in Part A, but only PK samples from 
the CD101 IV groups will be analyzed (using a validated assay) by an independent, 
central bioanalytical laboratory. When >1 assessment occurs at any time point, the PK 
blood sample will be given priority and taken at the correct protocol-specified time. 
Procedures for collection, storage, and shipping of PK samples are described in 
Appendix 7. 
Plasma samples from all subjects who received CD101 IV will be analyzed by liquid 
chromatography- tandem mass spectrometry (LC-MS/MS) for the concentration of 
CD101. The plasma PK parameters of CD101 IV will be determined based upon the 
CD101 concentrations. 
13.0 
STATISTICAL METHODS 
This is an exploratory study and, therefore, it is not powered for inferential statistical 
analyses. 
Descriptive statistics, including the numbers and percentages for categorical variables, 
and the numbers, means, standard deviations, medians, minimums and maximums for 
continuous variables, will be provided by study drug (CD101 IV or caspofungin). All 
data will be summarized separately by study drug. Listings of individual subject data will 
also be produced. All analyses will be completed for Part A. Selected analyses will be 
completed only for Part B and for Part A and B combined. 
To demonstrate preliminary efficacy and safety of CD101 and to confirm the correct 
CD101 dose regimen is utilized in Part B, an unblinded interim analysis will be 
performed after approximately 40 to 60 subjects in the mITT population have been 
enrolled and completed study drug therapy. This unblinded interim analysis of a few key 
efficacy and safety outcomes will be performed by an independent unblinded statistician. 
Interim efficacy and safety summary tables will be produced, but the identity of the group 
assignment for each individual subject will remain blinded until the completion of the 
study and the database for both Parts A and B are locked. Once Part A is completed, the 
database will be locked and a full unblinded analysis with all summary tables will be 
performed on Part A alone. As with the initial interim analysis and to help avoid bias, the 
full Part A analysis will be performed by an independent unblinded statistician, keeping 
the identity of the group assignment for each individual subject blinded until the 
completion of the study and the database for both Parts A and B are locked. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 104 of 128 
 
A Statistical Analysis Plan (SAP) will be prepared and finalized before the interim 
analysis. Any changes to the SAP from the time of the interim analysis to the final 
database lock of Part B will be documented in an addendum to the SAP. Any deviations 
from the final SAP/addendum will be described and justified in the study report. All 
statistical analyses will be performed using SAS®. All analyses will be completed for 
Part A. Selected analyses will be completed only for Part B and for Part A and B 
combined. 
13.1 
ANALYSIS POPULATIONS 
Analysis populations are: 
• Intent-to-Treat (ITT) population: all randomized subjects 
• Safety population: all subjects who receive any amount of study drug 
• The Microbiological Intent-to-treat (mITT) population: all subjects who had 
documented Candida infection based on Central Laboratory evaluation of a blood 
culture obtained within 96 hours of randomization, or from a specimen obtained from 
a normally sterile site, and received ≥1 dose of study drug 
o  
13.2 
ANALYSIS OF STUDY POPULATION AND SUBJECT 
CHARACTERISTICS 
Demographics (including age, race, and gender), diagnosis (candidemia and/or IC), 
medical history including Candida risk factors, baseline assessments (including height, 
weight, BMI, modified APACHE II score, and Glasgow coma score), mycological data, 
systemic signs and symptoms, and administration of study drug will be summarized in 
the ITT and mITT populations. All analyses will be conducted for Part A only. The SAP 
will detail which analyses are conducted for Part B and for Parts A and B combined. 
13.3 
SAFETY ANALYSES  
All subjects who receive any amount of study drug (Safety population) will be included 
in the safety analyses. All safety analyses will be conducted for Part A only and for Parts 
A and B combined. 
Safety will be evaluated by presenting summaries of AEs, clinical laboratory evaluations 
(hematology evaluation, chemistry panel, and UA), vital signs, and ECGs. Safety 
variables will be tabulated by treatment group.  

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 105 of 128 
 
Adverse events will be coded using Medical Dictionary for Regulatory Activities 
(MedDRA). AEs will be collected for each subject from the signing of the ICF at 
Screening through the last study visit at FU (Days 45 to 52 for subjects with candidemia 
only or Days 52-59 for subjects with IC, with or without candidemia). A treatment-
emergent adverse event (TEAE) is defined as an AE that occurs during or after study 
drug administration and up through the FU visit. The incidence of TEAEs will be 
presented by system organ class (SOC) and preferred term, by SOC, preferred term, and 
relationship to the study drug administration, and by SOC, preferred term, and severity. 
In addition, the incidence of serious TEAEs and TEAEs leading to discontinuation of 
study drug (IV and IV/oral) will be presented by SOC and preferred term.  
Descriptive statistics for clinical laboratory test results, ECG parameters and vital signs, 
and for changes from baseline, will be presented by time point. Baseline is defined as the 
measurement closest to, but prior to, the administration of study drug. Incidences of 
potentially clinically significant clinical laboratory results, ECG parameters, and vital 
signs, as defined in the SAP, will also be summarized by time point.  
13.4 
EFFICACY ANALYSES 
The number and percentage of subjects with an overall success (mycological 
eradication/presumed eradication and resolution of systemic signs of candidemia and/or 
IC that were present at baseline), failure, and indeterminate response at Day 14 in the 
mITT population will be presented. Exact 2-sided 95% CIs for the point estimates of 
overall success in each treatment group will be determined using the Clopper-Pearson 
method. Additional analysis of the primary efficacy outcome will be conducted. The 
number and percentage of subjects with each overall response (success, failure, 
indeterminate) will be determined separately for subjects with candidemia and with IC in 
the mITT population. Analyses will be conducted for Part A, Part B, and for Parts A and 
B combined. 
The number and percentage of subjects with each overall response (success, failure, 
indeterminate) will be determined in those subjects in the mITT population who did not 
receive concomitant antifungal therapy in addition to study drug and will be determined 
in those subjects with and without a positive blood culture at baseline for Candida spp. 
For this analysis, a baseline culture is defined as one taken within 12 hours before 
randomization. Subjects will be included in the positive culture at baseline group if the 
baseline blood culture is negative, or not done and the first blood culture after receipt of 
study drug is positive. Exact 2-sided 95% CIs for the point estimates of success in each 
treatment group will be determined using the Clopper-Pearson method. Analyses will be 
conducted for Part A and for Parts A and B combined. 
The number and percentage of subjects with an overall success, failure, and indeterminate 
response at Day 5, Day 28 (±2 days; only for subjects with IC), and at FU in the mITT 
population will be presented by treatment group. Exact 2-sided 95% CIs for the point 
estimates of success in each treatment group will be determined using the Clopper-
Pearson method. Analyses will be conducted for Part A, Part B, and for Parts A and B 
combined. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 106 of 128 
 
An additional analysis of overall response at FU will be conducted in which subjects who 
received a non-study antifungal after Day 21 for the treatment of an infection other than 
the candidemia (or after Day 28 for the treatment of an infection other than IC) will be 
excluded. Analyses will be conducted for Part A and for Parts A and B combined. 
Mycological outcome will be summarized by treatment group in the mITT population. 
The number and percentage of subjects with a success (mycological 
eradication/presumed eradication), failure, and indeterminate response at Day 5, Day 14, 
Day 28 (±2 days; only for subjects with IC) and at FU in the mITT population will be 
presented. Exact 2-sided 95% CIs for the point estimates of success in each treatment 
group will be determined using the Clopper-Pearson method. Analyses will be conducted 
for Part A, Part B, and for Parts A and B combined. Mycological outcome will also be 
analyzed in the subgroup of subjects with only a positive rapid in vitro diagnostic result 
and with only a positive baseline blood culture. 
The number and percentage of subjects with a clinical cure, failure, and indeterminate 
response based on the Investigator's assessment at Day 14, Day 28 (±2 days; only for 
subjects with IC), and at FU in the mITT population will be presented by treatment 
group. Exact 2-sided 95% CIs for the point estimates of success in each treatment group 
will be determined using the Clopper-Pearson method. Analyses will be conducted for 
Part A, Part B, and for Parts A and B combined. 
An additional analysis of Investigator's assessment of clinical response at FU will be 
conducted in which subjects who receive a non-study antifungal after Day 21 for the 
treatment of an infection other than the candidemia (or after Day 28 for the treatment of 
an infection other than IC) will be excluded. Analyses will be conducted for Part A and 
for Parts A and B combined. 
The number and percentage of subjects who died up through the FU Visit (all-cause 
mortality) will be presented by treatment group. Kaplan-Meier methods will be utilized to 
analyze the time to the first negative blood culture (for those subjects enrolled with a 
positive blood culture). Time to negative blood culture will be defined as the time to the 
first of the 2 negative blood cultures drawn ≥12 hours apart, without an intervening 
positive culture. Subjects will be censored if they receive an alternative antifungal (ie, 
other than study drug) for the treatment of the candidemia, or if they are lost to follow up 
prior to having 2 negative blood cultures. Analyses will be conducted for Part A and for 
Parts A and B combined. 
13.5 
PHARMACOKINETIC ANALYSES (Part A only)  
Plasma samples from subjects who received ≥1 complete dose of CD101 IV will be 
analyzed for the concentration of CD101 by a validated LC-MS/MS method in the PK 
Analysis population. Due to the sparse sampling for PK in this protocol, plasma 
concentrations will primarily be used to support population PK modeling in patients. PK 
parameter assessment will be reported separately for the PK Analysis population and may 
include: Cmax, Tmax, AUC0-168, and area under the CD101 concentration time curve from 
time zero to infinity [AUC0-∞], if applicable. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 107 of 128 
 
13.6 
DETERMINATION OF STUDY SAMPLE SIZE 
This is an exploratory study and therefore, is not powered for inferential statistical 
analyses. A sufficient number of subjects are randomized to the CD101 IV and 
caspofungin groups in Part A to provide an initial, substantive analysis of safety, 
tolerability, and estimate efficacy. 
In Part A, subjects will be randomized (1:1:1) until there are approximately 30 subjects in 
the CD101 IV treatment Group 1, 30 subjects in the CD101 IV treatment Group 2, and 30 
subjects in the comparator group in the mITT population. It is expected that 
approximately 114 subjects will need to be randomized to achieve 90 subjects in the 
mITT population (assuming 80% of randomized subjects will be included in the mITT 
population). 
In Part B, subjects will be randomized (2:1) until there are ≥30 subjects in the CD101 IV 
treatment groups at any dose and ≥15 subjects in the comparator group (≥45 additional 
subjects and no more than 120 subjects). Total enrollment will depend on the enrollment 
rate for the 6- to 8-month period between the end of Part A and the start of the Phase 3 
study, which is the trigger for Part B to stop enrollment. 
In Part A, assuming a 73% overall success rate, the sample size of 30 subjects in each 
CD101 IV group will yield a 95% CI of 53.8% to 87.5%. With the addition of Part B 
subjects and assuming a 73% overall success rate, a total approximate sample size of 60 
subjects in the CD101 treatment group (consisting of Group 1 from Amendment 5 and 
Group 2 from Amendment 6) will yield a 95% CI of 60.0% to 83.7%, and a total 
approximate sample size of 110 subjects in the CD101 treatment group (consisting of 
Group 1 from Amendment 5 and Group 2 from Amendment 6) will yield a 95% CI of 
63.7% to 81.0%. 
13.7 
HANDLING OF DROPOUTS AND MISSING, UNUSED, AND 
SPURIOUS DATA 
Every effort will be made to collect all data at specified times. For the primary and 
secondary efficacy outcomes, subjects with missing outcome data are considered to have 
an indeterminate response. Subjects with an indeterminate response are included in the 
denominator of the response calculation and thus, are treated in the same manner as 
failures in the analysis. Substitutions for other missing data will be specified in the SAP.  
13.8 
TERMINATION CRITERIA 
Enrollment and withdrawals from the study and from study drug will be summarized by 
treatment group. 
13.9 
DEVIATION REPORTING 
Protocol deviations will be summarized by treatment group. Protocol deviations are 
defined as any variation from the protocol, including enrollment of a subject who did not 
meet all inclusion and exclusion criteria and failure to perform the assessments and 
procedures within the required time frame. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 108 of 128 
 
14.0 
INVESTIGATOR REQUIREMENTS 
14.1 
PROTOCOL ADHERENCE 
The Investigator must adhere to the protocol as detailed in this document (Appendix 8) 
and agree that the Sponsor must approve any change to the protocol before seeking 
approval from the IRB/IEC. The Investigator will be responsible for enrolling only those 
subjects who have met the protocol inclusion and exclusion criteria. 
14.2 
ELECTRONIC CASE REPORT FORMS 
The eCRF will be supplied by the contract research organization or designee for the 
recording of all information and study data as specified by this protocol. All eCRFs must 
be completed by trained study personnel. The Investigator is responsible for ensuring that 
the eCRF data are entered and completed in a timely manner. 
Once all data queries and issues have been resolved for each subject, the Investigator will 
electronically sign each subject’s eCRF to attest to the accuracy of the data.  
The data from Part A will be locked separately from the data from Part B. 
14.3 
SOURCE DOCUMENT MAINTENANCE 
Source documents are defined as documentation related to original observations and 
activities of a clinical investigation. Source documents may include, but are not limited 
to, study progress notes, study- or subject-specific e-mail correspondence, computer 
printouts, laboratory data, and recorded data from automated instruments. All source 
documents produced in this study will be maintained by the Investigator and made 
available for inspections by the Sponsor and by regulatory authorities. The original 
signed ICF for each participating subject shall be filed with records kept by the 
Investigator, and a copy shall be given to the subject. 
14.4 
STUDY MONITORING REQUIREMENTS 
An authorized Sponsor representative will conduct site visits to inspect study data, 
subjects’ medical records, and eCRFs in accordance with International Conference on 
Harmonisation (ICH) guidelines, GCPs, and the foreign regulations and guidelines, as 
applicable. A monitor will be utilized for monitoring ongoing drug accountability and 
adherence to protocol procedures. 
The Investigator will allow representatives of the Sponsor and regulatory authorities to 
inspect facilities and records relevant to this study. 
14.5 
STUDY COMPLETION 
The Sponsor requires the following data and materials before a study can be considered 
complete or terminated: 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 109 of 128 
 
• Laboratory findings, clinical data, and all special test results from Screening 
throughout the study until the FU visit (Days 45-52 for subjects with candidemia only 
or Days 52-59 for subjects with IC, with or without candidemia)  
• eCRFs (including data queries) properly completed by appropriate study personnel 
and signed and dated by the Investigator 
• Copies of complete drug accountability records (drug inventory log and an inventory 
of returned or destroyed clinical material) 
• Copies of protocol amendments and IRB/IEC approval and notification, if appropriate 
• A summary of the study prepared by the Investigator (an IRB/IEC summary letter is 
acceptable) 
15.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
Written standard operating procedures (SOPs) will be followed to ensure that the study is 
conducted and data are generated, documented (recorded), and reported in compliance 
with the protocol, GCP, and the applicable regulatory requirements. Quality control will 
be applied to each stage of data handling. Regular monitoring, as defined in ICH GCP, 
Section 1.8, “The act of overseeing the progress of a clinical trial, and of ensuring that it 
is conducted, recorded, and reported in accordance with the protocol, SOPs, GCP, and the 
applicable regulatory requirement(s)”, will be conducted throughout the conduct of the 
study. 
The purpose of monitoring is to verify that: 
• Rights and well-being of the human subjects are protected 
• The reported study data are accurate, complete, and verifiable from source documents 
• The conduct of the study is in compliance with the currently approved 
protocol/amendment(s), with GCP, and with the applicable regulatory requirements 
• Monitoring is an integral role in the quality control of a clinical trial and is designed 
to verify the quality of the study 
 
To fulfill the Quality Assurance requirements of GCP, audits will be conducted to assess 
and assure the reliability and integrity of a study’s quality control systems and recognized 
standards. 
The purpose of an audit is to: 
• Ensure participant safety 
• Assure compliance to study protocol procedures, regulatory requirements, and SOPs 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 110 of 128 
 
• Assure data quality 
16.0 
PROTECTION OF HUMAN SUBJECTS 
This study will be conducted in compliance with the ICH Technical Requirements for 
Registration of Pharmaceuticals for Human Use E6 GCP: Consolidated Guidelines, the 
ethical principles of the Declaration of Helsinki, FDA GCP guidelines, and any additional 
national or IRB/IEC-required procedures. 
16.1 
INFORMED CONSENT 
This study will be conducted in compliance with ICH E6 GCP: Consolidated Guidelines 
pertaining to informed consent. Subjects will give written consent to participate in the 
study at the first visit, prior to initiation of any study-related procedures, after having 
been informed about the nature and purpose of the study, participation and termination 
conditions, risks, and benefits. If a subject is unable to provide written informed consent, 
the subject’s legally acceptable representative may provide written consent, as approved 
according to institution-specific guidelines. The ICF must be signed and dated by the 
subject, or the subject’s legally acceptable representative, prior to study participation. A 
copy of the ICF must be provided to the subject or the subject’s legally acceptable 
representative. If applicable, it will be provided in certified translation for non-English-
speaking subjects. Signed ICFs must remain in the subject’s study file and be available 
for verification by Sponsor at any time. 
16.2 
IRB/IEC APPROVAL 
This protocol, the ICF, and all relevant supporting data must be submitted to the IRB/IEC 
for approval. The protocol, ICF, and any advertisement used to recruit study subjects 
must be approved by the IRB/IEC. Approval by the IRB/IEC of the protocol and ICF 
must be obtained before the study may be initiated. 
The Investigator is responsible for informing the IRB/IEC of any changes made to the 
protocol, and to advise them, at least once a year, about the progress of the study. The 
Investigator is also responsible for notifying the IRB/IEC of any significant AEs that 
occur during the study. 
17.0 
DATA HANDLING AND RECORD KEEPING 
Training sessions, regular monitoring of Investigators by Sponsor-designated personnel, 
instruction manuals, data verification, crosschecking, and data audits will be performed to 
ensure quality of all study data. Investigator meetings will be performed to prepare 
Investigators and other study personnel for appropriate collection of study data. 
The Sponsor will review and validate study data as defined in the monitoring plan. 
It will be the responsibility of the Investigator to ensure that the essential documents are 
available at the Investigator or institutional site. Any or all of these documents may be 
subject to, and should be available for, monitoring by the Sponsor or inspection by the 
regulatory authorities as defined in the monitoring plan. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 111 of 128 
 
17.1 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION 
The Investigator agrees by his/her participation that the results of this study may be used 
for submission to national or international registration. If required, these authorities will 
be provided with the name of the Investigator and his or her address, qualifications, and 
extent of involvement. It is understood that the Investigator is required to provide 
Sponsor with all study data, complete reports, and access to all study records. 
Data generated by this study must be available for inspection by any regulatory 
authorities, by Sponsor and by the IRB/IEC as appropriate. At a subject’s request, 
medical information may be given to his or her personal physician or other appropriate 
medical personnel responsible for his or her welfare. Medical information obtained from 
subjects during the course of this study is confidential and disclosure to third parties other 
than those noted above is prohibited. 
17.2 
STUDY DRUG ACCOUNTABILITY 
All supplies of CD101 IV, caspofungin, and fluconazole required for completion of this 
study will be provided by the Sponsor. It is the responsibility of the unblinded Pharmacy 
staff or unblinded study staff to ensure that a current record of drug inventory and drug 
accountability is maintained. Inventory and accountability records must be readily 
available for inspection by the unblinded monitor and are open to inspection at any time 
by applicable regulatory authorities. 
17.3 
RETENTION OF RECORDS 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product and shipment and 
delivery of the drug for investigational use is discontinued. These documents should be 
retained for a longer period, however, if required by the applicable regulatory 
requirements of specific ICH- and non-ICH countries, or by an agreement with the 
Sponsor. The Sponsor will inform the Investigator/institution as to when these documents 
no longer need to be retained. 
18.0 
FINANCING AND INSURANCE 
The financing and insurance for this study are outlined in the Clinical Trial Agreement. 
19.0 
PUBLICATION POLICY 
The data generated in this clinical study are the exclusive property of the Sponsor and are 
confidential. Authorship on any publication of the results from this study will be based on 
contributions to study design, enrollment, data analysis, and interpretation of results. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 112 of 128 
 
20.0 
REFERENCES 
Alastruey-Izquierdo A, Melhem MS, Bonfietti LX, Rodriguez-Tudela JL. Susceptibility 
test for fungi: clinical and laboratorial correlations in medical mycology. Rev Inst Med 
Trop Sao Paulo. 2015 Sep;57 Suppl 19:57-64.  
Alexander BD, Johnson MD, Pfeiffer CD, Jiménez-Ortigosa C, Catania J, Booker R, 
Castanheira M, Messer SA, Perlin DS, Pfaller MA. Increasing echinocandin resistance in 
Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated 
minimum inhibitory concentrations. Clin Infect Dis 2013; 56:1724–32. 
Alexander BD, Wingard JR. Study of renal safety in amphotericin B lipid complex-
treated patients. Clin Infect Dis. 2005 May 1;40 Suppl 6:S414-21. 
Andes DR, Safdar N, Baddley JW, Playford G, Reboli AC, Rex JH, Sobel JD, Pappas 
PG, Kullberg BJ, Mycoses Study Group. Impact of treatment strategy on outcomes in 
patients with candidemia and other forms of invasive candidiasis: a patient-level 
quantitative review of randomized trials. Clin Infect Dis 2012; 54:1110–22. 
Arendrup MC, Dzajic E, Jensen RH, Johansen HK, Kjaeldgaard P, Knudsen JD, 
Kristensen L, Leitz C, Lemming LE, Nielsen L, Olesen B, Rosenvinge FS, Røder BL, 
Schønheyder HC. Epidemiological changes with potential implication for antifungal 
prescription recommendations for fungaemia: data from a nationwide fungaemia 
surveillance programme. Clin Microbiol Infect 2013; 19: E343–53. 
Arendrup MC, Sulim S, Holm A, Nielsen L, Nielsen SD, Knudsen JD, Drenck NE, 
Christensen JJ, Johansen HK. Diagnostic issues, clinical characteristics, and outcomes for 
patients with fungemia. J Clin Microbiol. 2011 Sep;49(9):3300-8. 
Azie N, Neofytos D, Pfaller M, Meier-Kriesche HU, Quan SP, Horn D. The PATH 
(Prospective Antifungal Therapy) Alliance registry and invasive fungal infections: update 
2012. Diagn Microbiol Infect Dis 2012; 73: 293–300. 
Bader JC, Andes DR, Castanheira M, Ambrose PG, Bhavnan SM. ID Week 2017, San 
Diego, California. Poster 833. 2017Oct4-8. 
Beyda ND, John J, Kilic A, Alam MJ, Lasco TM, Garey KW. FKS mutant Candida 
glabrata: risk factors and outcomes in patients with candidemia. Clin Infect Dis. 
2014;59(6):819-25. 
Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC. Hidden killers: 
human fungal infections. Sci Transl Med 2012; 4:165rv13. 
Cancidas (caspofungin) New Drug Application 21-227. Center for Drug Evaluation and 
Research Approval Package: Pharmacology Review. FDA, Washington, DC. 2001. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 113 of 128 
 
Cancidas (caspofungin acetate) [Prescribing Information]. Whitehouse Station, NJ: 
Merck & Co., Inc.; 2014 September. Available at 
https://www.merck.com/product/usa/pi_circulars/c/cancidas/cancidas_pi.pdf. Accessed 
09May2015. 
Castanheira M, Messer SA, Rhomberg PR, Jones RN, Pfaller MA. Activity of a Novel 
Echinocandin Biafungin (CD101) Tested against Most Common Candida and 
Aspergillus Species, Including Echinocandin- and Azole-resistant Strains. Interscience 
Conference of Antimicrobial Agents and Chemotherapy 2014; Poster M-1082. 
Chapeland-Leclerc F, Hennequin C, Papon N, Noël T, Girard A, Socié G, Ribaud P, 
Lacroix C. Acquisition of flucytosine, azole, and caspofungin resistance in Candida 
glabrata bloodstream isolates serially obtained from a hematopoietic stem cell transplant 
recipient. Antimicrob Agents Chemother. 2010 Mar;54(3):1360-2. 
CDC 2013. Antibiotic resistance threats in the United States, 2013. 
http://www.cdc.gov/drugresistance/threat-report-2013/  
CDC Clinical Alert to U.S. Healthcare Facilities: Global emergence of invasive 
infections caused by the multidrug-resistant yeast Candida auris. 
http://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-alert.html, accessed 
19JUL2016 
Cleveland AA, Farley MM, Harrison LH, Stein B, Hollick R, Lockhart SR, Magill SS, 
Derado G, Park BJ, Chiller TM. Changes in incidence and antifungal drug resistance in 
candidemia: results from population- based laboratory surveillance in Atlanta and 
Baltimore, 2008–2011. Clin Infect Dis 2012; 55: 1352–61. 
Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, Meersseman 
W, Akova M, Arendrup MC, Arikan-Akdagli S, Bille J, Castagnola E, Cuenca-Estrella 
M, Donnelly JP, Groll AH, Herbrecht R, Hope WW, Jensen HE, Lass-Flörl C, Petrikkos 
G, Richardson MD, Roilides E, Verweij PE, Viscoli C, Ullmann AJ; ESCMID Fungal 
Infection Study Group. ESCMID* guideline for the diagnosis and management of 
Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012 
Dec;18 Suppl 7:19-37. 
Ecalta [anidulafungin] European Medicines Agency Summary of Product Characteristics, 
23AUG2012. Available at 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/000788/WC500020673.pdf. Accessed 20JUL2017. 
Eraxis (anidulafungin) New Drug Applications 21-632 and 21-948. Center for Drug 
Evaluation and Research Approval Package: Pharmacology Review. FDA, Washington, 
DC. 2006. 
Eraxis (anidulafungin) [Prescribing Information]. New York, NY; Pfizer Roerig; 2013 
November. Available at http://labeling.pfizer.com/showlabeling.aspx?id=566. Accessed 
09May2015. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 114 of 128 
 
Executive Office of the President, President’s Council of Advisors on Science and 
Technology. Report to the President on Combating Antibiotic Resistance. September 
2014. 
Falagas ME, Apostolou KE, Pappas VD. Attributable mortality of candidemia: a 
systematic review of matched cohort and case-control studies. Eur J Clin Microbiol Infect 
Dis. 2006 Jul;25(7):419-25. 
Gudlaugsson O, Gillespie S, Lee K et al. Attributable mortality of nosocomial 
candidemia, revisited. Clin Infect Dis. 2003 37:1172–7. 
Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK; 
National Healthcare Safety Network Team; Participating National Healthcare Safety 
Network Facilities. NHSN annual update: antimicrobial-resistant pathogens associated 
with healthcare-associated infections: annual summary of data reported to the National 
Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-
2007. Infect Control Hosp Epidemiol. 2008 Nov;29(11):996-1011. Erratum in: Infect 
Control Hosp Epidemiol. 2009 Jan;30(1):107. 
Kett DH, Azoulay E, Echeverria PM, Vincent JL; Extended Prevalence of Infection in 
ICU Study (EPIC II) Group of Investigators. Candida bloodstream infections in intensive 
care units: analysis of the extended prevalence of infection in intensive care unit study. 
Crit Care Med. 2011 Apr;39(4):665-70. 
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease 
classification system. Critical Care Medicine 1985 13(10):818–29. 
Krogh-Madsen M, Arendrup MC, Heslet L, Knudsen JD. Amphotericin B and 
caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient. 
Clin Infect Dis. 2006 Apr 1;42(7):938-44. 
Labelle AJ, Micek ST, Roubinian N, Kollef MH. Treatment-related risk factors for 
hospital mortality in Candida bloodstream infections. Crit Care Med. 2008 
Nov;36(11):2967-72. 
Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, Lynfield R, 
Maloney M, McAllister-Hollod L, Nadle J, Ray SM, Thompson DL, Wilson LE, Fridkin 
SK; Emerging Infections Program Healthcare-Associated Infections and Antimicrobial 
Use Prevalence Survey Team. Multistate point-prevalence survey of health care-
associated infections. N Engl J Med 2014;370:1198–208. 
Menzin J, Meyers JL, Friedman M, Perfect JR, Langston AA, Danna RP, Papadopoulos 
G. Mortality, length of hospitalization, and costs associated with invasive fungal 
infections in high risk patients. Am J Health Syst Pharm 2009; 66: 1711–7. 
Mikulska M, Del Bono V, Ratto S, Viscoli C. Occurrence, presentation and treatment of 
candidemia. Expert Rev Clin Immunol. 2012 Nov;8(8):755-65. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 115 of 128 
 
Mycamine (micafungin sodium) New Drug Application 21-754. Center for Drug 
Evaluation and Research Approval Package: Pharmacology Review. FDA, Washington, 
DC. 2005. 
Mycamine (micafungin sodium) [Prescribing Information]. Northbrook, IL: Astellas 
Pharma US, Inc.; 2013 June. Available at 
http://www.us.astellas.com/docs/mycamine.pdf. Accessed 09May2015. 
Mylonakis E, Clancy CJ, Ostrosky-Zeichner L, Garey KW, Alangaden GJ, Vazquez JA, 
Groeger JS, Judson MA, Vinagre YM, Heard SO, Zervou FN, Zacharioudakis IM, 
Kontoyiannis DP, Pappas PG. T2 Magnetic Resonance Assay for the Rapid Diagnosis of 
Candidemia in Whole Blood: A Clinical Trial. Clin Infect Dis. 2015 Jan 12 [Epub ahead 
of print]. 
Ostrosky-Zeichner L. Candida glabrata and FKS mutations: witnessing the emergence of 
the true multidrug-resistant Candida. Clin Infect Dis. 2013 Jun;56(12):1733-4. 
Ostrosky-Zeichner L, Pappas PG, Shoham S, Reboli A, Barron MA, Sims C, Wood C, 
Sobel JD. Improvement of a clinical prediction rule for clinical trials on prophylaxis for 
invasive candidiasis in the intensive care unit. Mycoses. 2009 Jan;54(1):46-51. 
Ostrosky-Zeichner L, Sable C, Sobel J, Alexander BD, Donowitz G, Kan V, Kauffman 
CA, Kett D, Larsen RA, Morrison V, Nucci M, Pappas PG, Bradley ME, Major S, 
Zimmer L, Wallace D, Dismukes WE, Rex JH. Multicenter retrospective development 
and validation of a clinical prediction rule for nosocomial invasive candidiasis in the 
intensive care setting. Eur J Clin Microbiol Infect Dis. 2007 Apr;26(4):271-6. 
Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, 
Reboli AC, Schuster MG, Vazquez JA, Walsh TJ, Zaoutis TE, Sobel JD. Clinical 
Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious 
Diseases Society of America. Clin Infect Dis. 2016 Feb 15;62(4):409-17. 
Pfaller MA. Antifungal drug resistance: mechanisms, epidemiology, and consequences 
for treatment. Am J Med 2012; 125: S3–13. 
Pfaller MA, Castanheira M, Lockhart SR, Ahlquist AM, Messer SA, Jones RN. 
Frequency of decreased susceptibility and resistance to echinocandins among 
fluconazole-resistant bloodstream isolates of Candida glabrata. J Clin Microbiol 2012; 
50: 1199–203. 
Pfaller MA, Castanheira M, Messer SA, Moet GJ, Jones RN. Variation in Candida spp. 
distribution and antifungal resistance rates among bloodstream infection isolates by 
patient age: report from the SENTRY Antimicrobial Surveillance Program (2008-2009). 
Diagn Microbiol Infect Dis. 2010a;68(3):278-83. 
Pfaller MA, Diekema DJ. Epidemiology of invasive mycoses in North America. Crit Rev 
Microbiol 2010; 36: 1–53. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 116 of 128 
 
Pfaller MA, Diekema DJ. Epidemiology of Invasive Candidiasis: a Persistent Public 
Health Problem Clin. Microbiol. Rev. Jan. 2007, p. 133–163. 
Pfaller MA, Diekema DJ, Gibbs DL, Newell VA, Nagy E, Dobiasova S, Rinaldi M, 
Barton R, Veselov A; Global Antifungal Surveillance Group. Candida krusei, a 
multidrug resistant opportunistic fungal pathogen: geographic and temporal trends from 
the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005. J Clin Microbiol 
2008; 46:515–21. 
Pfaller MA, Diekema DJ, Gibbs DL, Newell VA, Barton R, Bijie H, Bille J, Chang SC, 
da Luz Martins M, Duse A, Dzierzanowska D, Ellis D, Finquelievich J, Gould I, Gur D, 
Hoosen A, Lee K, Mallatova N, Mallie M, Peng NG, Petrikos G, Santiago A, Trupl J, 
VanDen Abeele AM, Wadula J, Zaidi M; Global Antifungal Surveillance Group. 
Geographic variation in the frequency of isolation and fluconazole and voriconazole 
susceptibilities of Candida glabrata: an assessment from the ARTEMIS DISK Global 
Antifungal Surveillance Program. Diagn Microbiol Infect Dis. 2010b;67(2). 
Pfaller MA, Jones RN, Castanheira M. Regional data analysis of Candida non-albicans 
strains collected in United States medical sites over a 6-year period, 2006-2011. 
Mycoses. 2014;57(10):602-11.  
Pfaller MA, Messer SA, Hollis RJ, Boyken L, Tendolkar S, Kroeger J, Diekema DJ. 
Variation in susceptibility of bloodstream isolates of Candida glabrata to fluconazole 
according to patient age and geographic location in the United States in 2001 to 2007. J 
Clin Microbiol. 2009 Oct;47(10):3185-90. 
Pfaller MA, Messer SA, Rhomberg PR, Castanheira M. CD101, a long-acting 
echinocandin, and comparator antifungal agents tested against a global collection of 
invasive fungal isolates in the SENTRY 2015 Antifungal Surveillance Program. 
Int J Antimicrob Agents. 2017 Sep;50(3):352-358. 
Pfaller MA, Messer SA, Woosley LN, Jones RN, Castanheira M. Echinocandin and 
triazole antifungal susceptibility profiles for clinical opportunistic yeast and mold isolates 
collected from 2010 to 2011: application of new CLSI clinical breakpoints and 
epidemiological cutoff values for characterization of geographic and temporal trends of 
antifungal resistance. J Clin Microbiol. 2013;51(8):2571-81.  
Shields RK, Nguyen MH, Press EG, Updike CL, Clancy CJ. Caspofungin MICs correlate 
with treatment outcomes among patients with Candida glabrata invasive candidiasis and 
prior echinocandin exposure. Antimicrob Agents Chemother. 2013;57(8):3528-35. 
Slavin MA, Sorrell TC, Marriott D, Thursky KA, Nguyen Q, Ellis DH, Morrissey CO, 
Chen SC; Australian Candidemia Study, Australasian Society for Infectious Diseases. 
Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death. J 
Antimicrob Chemother. 2010 May;65(5):1042-51. 
Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical 
scale. Lancet. 1974 Jul 13;2(7872):81-4. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 117 of 128 
 
Ullmann AJ, Akova M, Herbrecht R, Viscoli C, Arendrup MC, Arikan-Akdagli S, 
Bassetti M, Bille J, Calandra T, Castagnola E, Cornely OA, Donnelly JP, Garbino J, 
Groll AH, Hope WW, Jensen HE, Kullberg BJ, Lass-Flörl C, Lortholary O, Meersseman 
W, Petrikkos G, Richardson MD, Roilides E, Verweij PE, Cuenca-Estrella M; ESCMID 
Fungal Infection Study Group. ESCMID* guideline for the diagnosis and management of 
Candida diseases 2012: adults with haematological malignancies and after 
haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect. 2012 Dec;18 
Suppl 7:53-67. 
Vincent JL1, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, 
Gomersall C, Sakr Y, Reinhart K; EPIC II Group of Investigators. International study of 
the prevalence and outcomes of infection in intensive care units. JAMA 2009; 302: 2323–
9. 
The White House. National Strategy for Combating Antibiotic Resistant Bacteria. 
September 2014. 
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H,Wenzel RP, Edmond MB. 
Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a 
prospective nationwide surveillance study. Clin Infect Dis 2004; 39:309–17. 
Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The epidemiology and 
attributable outcomes of candidemia in adults and children hospitalized in the United 
States: a propensity analysis. Clin Infect Dis. 2005 Nov 1;41(9):1232-9. 
Zhao Y, Prideaux B, Chen P-Y, Nagasaki Y, Lee M-H, Hough G, Ong V, Perlin DS. 
Tissue Distribution and Pharmacokinetics of CD101 in an Immunocompetent Mouse 
Model of Invasive Candidiasis. 2016 American Society of Microbiology Microbe, 
Session 247. Available at 
http://files.abstractsonline.com/SUPT/1/4060/AllOralAbstracts.pdf. Access 17JAN2017. 
Zilberberg MD, Shorr AF, Kollef MH. Growth and geographic variation in 
hospitalizations with resistant infections, United States, 2000–2005. Emerg Infect Dis 
2008a; 14: 1756–8. 
Zilberberg MD, Shorr AF, Kollef MH. Secular trends in candidemia related 
hospitalization in the United States, 2000–2005. Infect Control Hosp Epidemiol 2008b; 
29: 978–80.

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 118 of 128 
 
21.0 
APPENDICES 
APPENDIX 1: CLINICAL AND LABORATORY STANDARDS INSTITUTE 
(CLSI) AND EUROPEAN COMMITTEE ON ANTIMICROBIAL 
SUSCEPTIBILITY TESTING (EUCAST) BREAKPOINTS FOR 
CANDIDA SPP:  
The following table provides susceptibility breakpoints for both CLSI and EUCAST and 
should be used as guidance in determining susceptibility of different Candida species to 
potential empiric antifungal drugs. Not all species or antifungal drugs are referenced here 
and local determination of susceptibility and resistance may be used when appropriate. 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 119 of 128 
 
MIC Breakpoints (mg/L) 
Antifungal Agent 
Standard 
C. albicans 
C. glabrata 
C. krusei 
C. parapsilosis 
C. tropicalis 
S ≤ 
R > 
S ≤ 
R > 
S ≤ 
R > 
S ≤ 
R > 
S ≤ 
R > 
Amphotericin B 
EUCAST 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
CLSI 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Anidulafungin 
EUCAST 
0.03 
0.03 
0.06 
0.06 
0.06 
0.06 
0.002 
4 
0.06 
0.06 
CLSI 
0.25 
0.5 
0.12 
0.25 
0.25 
0.5 
2 
4 
0.25 
0.5 
Caspofungin 
EUCAST 
 
 
 
 
 
 
 
 
 
 
CLSI 
0.25 
0.5 
0.125 
0.25 
0.25 
0.5 
2 
4 
0.25 
0.5 
Fluconazole 
EUCAST 
2 
4 
0.002 
32 
- 
- 
2 
4 
2 
4 
CLSI 
2 
4 
32 (SDD) 
32 
- 
- 
2 
4 
2 
4 
Itraconazole 
EUCAST 
0.06 
0.06 
IE 
IE 
IE 
IE 
0.12 
0.12 
0.12 
0.12 
CLSI 
0.125 
0.5 
0.125 
0.5 
0.125 
0.5 
0.125 
0.5 
0.125 
0.5 
Micafungin 
EUCAST 
0.016 
0.016 
0.03 
0.03 
IE 
IE 
0.002 
2 
IE 
IE 
CLSI 
0.25 
0.5 
0.06 
0.12 
0.25 
0.5 
2 
4 
0.25 
0.5 
Posaconazole 
EUCAST 
0.06 
0.06 
IE 
IE 
IE 
IE 
0.06 
0.06 
0.06 
0.06 
CLSI 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Voriconazole 
EUCAST 
0.125 
0.125 
IE 
IE 
IE 
IE 
0.125 
0.125 
0.125 
0.125 
CLSI 
0.125 
0.5 
 
 
0.5 
1 
0.125 
0.5 
0.125 
0.5 
CLSI = Clinical and Laboratory Standards Institute; EUCAST = European Committee on Antimicrobial Susceptibility Testing; IE = insufficient evidence; R = 
resistant; S = susceptible; SDD = susceptible dose dependent 
Source: Alastruey-Izquierdo et al., 2015.

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 120 of 128 
 
APPENDIX 2: CREATININE CLEARANCE 
In the event the local laboratory does not calculate creatinine clearance based on the most 
recent serum creatinine value, estimate the patient’s creatinine clearance using the serum 
creatinine value provided by the local laboratory, actual body weight, and the appropriate 
Cockcroft-Gault formula. If necessary, convert serum creatinine values from µmol/L to 
mg/dL by dividing by 88.4. For example, 100 µmol/L divided by 88.4 equals 
1.131 mg/dL: 
 
Males: 
creatinine clearance = (140 – [insert age in years]) × [insert weight in kg]  
                  72 × [insert serum creatinine in mg/dL] 
Females:  
creatinine clearance = 0.85 × (140 – [insert age in years]) × [insert weight in kg]  
                              72 × [insert serum creatinine in mg/dL] 
 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 121 of 128 
 
APPENDIX 3: SAFETY LABORATORY TESTS 
 
Hematology 
Serum Chemistry 
hemoglobin 
blood urea nitrogen 
hematocrit  
bilirubin (total and direct) 
total and differential leukocyte count 
alkaline phosphatase 
red blood cell count 
aspartate aminotransferase 
platelet count 
alanine aminotransferase 
Coagulation 
Prothrombin time/ International Normalized Ratio 
Partial thromboplastin time or activated partial thromboplastin time 
albumin 
sodium 
potassium 
Urinalysis 
chloride 
pH 
glucose 
specific gravity 
creatinine 
protein a 
total protein 
glucose 
calcium 
ketones 
bicarbonate 
procalcitonin c 
bilirubin b 
 
blood a 
 
nitrite a 
Additional Tests 
Urine pregnancy test for females 
of childbearing potential. Do not 
perform on women who are ≥2 
years postmenopausal or 
surgically sterile. 
 
urobilinogen b 
leukocyte esterase a 
a. 
If urinalysis is positive for protein, blood, nitrite and/or leukocyte esterase, a microscopic examination 
(for red blood cells, white blood cells, bacteria, casts, and epithelial cells) will be performed. 
b. Urobilinogen and bilirubin are optional tests. 
c. 
Procalcitonin is an optional test to be performed only at Screening 
 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 122 of 128 
 
APPENDIX 4: CHILD-PUGH SCORE 
Calculate the Child-Pugh score only if the subject has a history of chronic cirrhosis.  
The Child-Pugh score employs 5 clinical measures of liver disease. Each measure is 
scored 1 to 3, with 1 indicating the least severe and 3 indicating the most severe score. 
The sum of the 5 measures is the total Child-Pugh point score. 
Parameter 
Points 
1 
2 
3 
Ascites 
None 
Medically controlled 
Poorly controlled 
Encephalopathy a 
None 
Medically controlled 
Poorly controlled 
Total bilirubin (mg/dL) 
<2 
2 – 3 
>3 
Albumin (g/dL) 
>3.5 
2.8 – 3.5 
<2.8 
International Normalized Ratio 
OR 
PT prolongation in seconds 
<1.7 
 
<4 
1.7 – 2.3 
 
4 – 6 
>2.3 
 
>6 
a. 
If sedated, use last known encephalopathy status before sedation. 
 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 123 of 128 
 
APPENDIX 5: MODIFIED ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION (APACHE) II SCORE 
Point Value 
4 
3 
2 
1 
0 
1 
2 
3 
4 
Total 
Glasgow Coma Score 
Score = 15 minus actual Glasgow Coma Score 
 
Temperature (rectal, ºC) 
≥41 
39-40.9 
 
38.5-38.9 
36-38.4 
34-35.9 
32-33.9 
30-31.9 
≤29.9 
 
Mean Arterial Pressure 
(mmHg) a 
≥160 
130-159 
110-129 
 
70-109 
 
50-69 
 
≤49 
 
Heart Rate (bpm) 
≥180 
140-179 
110-139 
 
70-109 
 
55-69 
40-54 
≤39 
 
Respiration Rate 
≥50 
35-49 
 
25-34 
12-24 
10-11 
6-9 
 
≤5 
 
Alveolar-Arterial Oxygen 
Gradient (if FiO2 ≥50%) 
OR 
PaO2 (mmHg) 
OR 
Oxygen Saturation, % 
≥500 
 
 
 
 
350 to 499 
 
 
 
 
200 to 349 
 
 
 
 
 
 
 
 
 
<200 
 
 
>70 
 
 
≥92 
 
 
 
61-70 
 
 
88-91 
 
 
 
 
 
 
 
 
55-60 
 
 
85-87 
 
 
 
<55 
 
 
<85 
 
Arterial pH 
OR 
Serum HCO3 (mEq/L) -
(venous- if ABG not 
performed) 
≥7.7 
 
 
≥52 
7.6-7.69 
 
 
41-51.9 
 
7.5-7.59 
 
 
32-40.9 
7.33-7.49 
 
 
22-31.9 
 
7.25-7.32 
 
 
18-21.9 
7.15-7.24 
 
 
15-17.9 
<7.15 
 
 
<15 
 
Serum Na+ (mMol/L) 
≥180 
160-179 
155-159 
150-154 
130-149 
 
120-129 
111-119 
≤110 
 
Serum K+ (mMol/L) 
≥7.0 
6.0-6.9 
 
5.5-5.9 
3.5-5.4 
3.0-3.4 
2.5-2.9 
 
<2.5 
 
Serum creatinine (mg/dL) 
≥3.5 
2.0-3.4 
1.5-1.9 
 
0.6-1.4 
 
<0.6 
 
 
 
Acute renal failure b 
×2 creatinine point score if patient has acute renal failure 
 
Hematocrit, % 
≥60 
 
50-59.9 
46-49.9 
30-45.9 
 
20-29.9 
 
<20 
 
WBC, (109 cells/L or mm3) 
≥40 
 
20-39.9 
15-19.9 
3-14.9 
 
1-2.9 
 
<1 
 
Severe organ failure  
(liver, heart, or lung) or 
immunocompromised c 
Add 5 points if patient is medical (no surgery) or postoperative for emergency surgery 
Add 2 points if patient is postelective surgery  
 
Age (years) points 
≤44=0, 45-54=2, 55-64=3, 65-74=5, ≥75=6 
 
 
Sum of all rows 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 124 of 128 
 
 
Source: Modified from Knaus et al., 1985. 
a. 
Mean arterial pressure = (systolic blood pressure + 2 diastolic blood pressure)/3 
b. Acute Renal Failure = a 0.5 mg/dL increase in serum creatinine if the baseline serum creatinine was ≤1.9 mg/dL, a 1.0 mg/dL increase in serum creatinine 
if the baseline serum creatinine was 2.0 to 4.9 mg/dL, and a 1.5 mg/dL increase in serum creatinine if the baseline serum creatinine was ≥5.0 mg/dL. 
c. 
Organ insufficiency or immunocompromised state must have been evident prior to this hospital admission and conform to the following criteria:  
• Liver – biopsy proven cirrhosis and documented portal hypertension; episodes of past upper gastrointestinal bleeding attributed to portal hypertension; 
or prior episodes of hepatic failure/encephalopathy/coma.  
• Cardiovascular – New York Heart Association Class IV.  
• Respiratory – Chronic restrictive, obstructive, or vascular disease resulting in severe exercise restriction (ie, unable to climb stairs or perform household 
duties; or documented chronic hypoxia, hypercapnia, secondary polycythemia, severe pulmonary hypertension (>40 mmHg), or respirator 
dependency.  
• Renal – receiving chronic dialysis.  
• Immunocompromised – the patient has received therapy that suppresses resistance to infection (eg, immunosuppression, chemotherapy, radiation, long 
term or recent high dose steroids, or has a disease that is sufficiently advanced to suppress resistance to infection, eg, leukemia, lymphoma, AIDS). 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 125 of 128 
 
APPENDIX 6: GLASGOW COMA SCORE 
Sedating and paralytic agent use may confound the assessment of the Glasgow Coma 
Score. If sedation is reduced and patients awakened daily to perform neurologic 
assessments, assess the score during the period when the patient is not sedated. If daily 
awakenings are not performed, please record the score as if the patient did not have 
sedating or paralytic agents preventing response. 
 
Neurologic Response 
Score 
Best Eye Response (E) 
Spontaneous-open with blinking at baseline 
4 
Opens to verbal command, speech or shout 
3 
Opens to pain (not applied to face) 
2 
None 
1 
Best Verbal Response (V) 
Oriented 
5 
Confused conversation, but can answer questions 
4 
Inappropriate responses, words discernible 
3 
Incomprehensible speech 
2 
None 
1 
Best Motor Response (M) 
Obeys commands for movement 
6 
Purposeful movement to painful stimulus 
5 
Withdraws from pain 
4 
Abnormal (spastic) flexion, decorticate posture 
3 
Extensor (rigid) response, decerebrate posture 
2 
None 
1 
Total Score 
 
Source: Teasdale and Jennet, 1974. 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 126 of 128 
 
APPENDIX 7: PHARMACOKINETIC SAMPLE PROCESSING AND 
SHIPMENT (Part A only) 
Plasma PK sample collection and processing procedure  
1. Draw blood into a 4 mL lavender top potassium ethylenediaminetetraacetic acid 
(K2EDTA) Vacutainer tube. Label the tube. 
2. Mix the blood with the anticoagulant by gently inverting the tube 8 to 10 times, 
and then immediately place the tube on wet ice. It is preferable to leave the 
sample on wet ice for 5 to 10 minutes before centrifuging.   
3. Centrifuge the blood samples for approximately 10 minutes at approximately 
1006g in a centrifuge within approximately 60 minutes after blood sample 
collection.  
4. Immediately following centrifugation, gently remove the plasma from the packed 
cells and aliquot into 2 transfer vials. Into the first, aliquot ≥0.5 mL of plasma, 
and, into the second, aliquot the rest. 
5. Replace the caps on the transfer vials and freeze the samples immediately at 
approximately -20°C or colder.  
6. Note: No more than 60 minutes should elapse between blood collection and 
freezing the plasma samples. 
7. Keep the samples frozen at approximately -20°C or colder until shipment. 
8. Ship the primary sample on dry ice; retain the frozen backup sample until receipt 
of instructions regarding its shipment. 
Note: Wet ice is defined as a mixture of ice and water. 
Pharmacokinetic Sample Shipment 
Procedures for the shipping of PK samples, including contact information, is provided in 
the Pharmacokinetics Manual. 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 127 of 128 
 
 
 
 
Radius 
(cm) 
G-Force 
RPM 
10 
1006 
3000 
12 
1006 
2738 
14 
1006 
2535 
16 
1006 
2371 
18 
1006 
2236 
20 
1006 
2121 
22 
1006 
2022 
24 
1006 
1936 
26 
1006 
1860 
28 
1006 
1793 
 
 

Cidara Therapeutics, Inc.  
 
 
 
 
 
Protocol CD101.IV.2.03 A6 
Intravenous CD101 
 
 
Protocol Amendment 6 
Confidential  
Page 128 of 128 
 
APPENDIX 8: INVESTIGATOR SIGNATURE 
I have read and understand protocol CD101.IV.2.03 and the Investigator Brochure. I 
agree to the following: 
1. To conduct the trial in compliance with GCP, with applicable regulatory 
requirement(s), with the protocol agreed to by the Sponsor and given 
approval/favorable opinion by the IRB/IEC 
2. To comply with procedures for data recording and reporting 
3. To permit monitoring, auditing, and inspection by the Sponsor, its designated 
representatives, and regulatory authorities  
4. To retain the essential documents in the Investigator/institution files until the 
Sponsor informs the Investigator or institution that these documents are no longer 
needed 
 
INVESTIGATOR SIGNATURE: 
 
 
 
_____________________________________    ___________________________ 
[Investigator Signature] 
 
 
 
 
Date 
 
_____________________________________    
[Investigator Name]  
 
 
[Site Number] 
 
 
[Site Name] 
 
 
[Site Address]