Study of Rezafungin Compared to Caspofungin in Subjects With Candidemia and/or Invasive Candidiasis

A Phase 3, multicenter, prospective, randomized, double-blind, efficacy and safety study of
Rezafungin for Injection versus an active comparator regimen of caspofungin followed by
optional oral fluconazole step-down therapy in subjects with candidemia and/or invasive
candidiasis.

Inclusion Criteria:

1. 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 his/her behalf.

2. Males or females ≥18 years of age.

3. Established mycological diagnosis of candidemia and/or invasive candidiasis from a
sample taken ≤4 days (96 hours) before randomization defined as

- ≥1 blood culture positive for yeast or Candida OR

- Positive test for Candida from a Sponsor-approved rapid IVD OR

- Positive gram stain (or other method of direct microscopy) for yeast or positive
culture for Candida spp. from a specimen obtained from a normally sterile site.

4. Presence of one or more systemic signs attributable to candidemia or invasive
candidiasis appearing from ≤12 hours prior to the qualifying positive culture through
time of enrollment.

5. Willing to initiate or continue medical treatment to cure infections, including
receipt of antibiotics and surgical procedures, if required.

6. Female subjects of childbearing potential <2 years post-menopausal must agree to and
comply with using one barrier method (e.g., female condom with spermicide) plus one
other highly effective method of birth control, or sexual abstinence while
participating in this study. Male subjects must be vasectomized, abstain from sexual
intercourse, or agree to use barrier contraception, and also agree not to donate sperm
while participating in the study and for 90 days thereafter.

Exclusion Criteria:

1. Any of the following forms of invasive candidiasis at baseline:

1. Septic arthritis in a prosthetic joint (septic arthritis in a native joint is
allowed)

2. Osteomyelitis

3. Endocarditis or myocarditis

4. Meningitis, endophthalmitis, chorioretinitis, or any central nervous system
infection

5. Chronic disseminated candidiasis

6. Urinary tract candidiasis due to ascending Candida infection secondary to
obstruction or surgical instrumentation of the urinary tract

2. Received systemic treatment with an antifungal agent at approved doses for treatment
of candidemia for >48 hours (e.g., >2 doses of a once daily antifungal agent or >4
doses of a twice daily antifungal agent) ≤4 days (96 hours) before randomization

a. Exception: Receipt of antifungal therapy to which any Candida spp. isolated in
culture is not susceptible

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. Presence of an indwelling vascular catheter or device that cannot be removed or an
abscess that cannot be drained and is likely to be the source of candidemia or
invasive candidiasis

6. Known hypersensitivity to Rezafungin for Injection, caspofungin, any echinocandin, or
to any of their excipients

7. Meets National Cancer Institute Common Terminology Criteria for Adverse Events,
version 5, criteria for ataxia, tremor, motor neuropathy, or sensory neuropathy of
Grade 2 or higher

8. History of severe ataxia, tremor, or neuropathy or a diagnosis of multiple sclerosis
or a movement disorder (including Parkinson's Disease or Huntington's Disease)

9. Planned or ongoing therapy at Screening with a known neurotoxic medication

10. Previous participation in this or any previous rezafungin study

11. Current participation in another interventional treatment trial with an
investigational agent

12. 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.

13. Pregnant or lactating females

14. The Principal Investigator (PI) is of the opinion the subject should not participate
in the study

15. Severe renal impairment during Screening (Creatinine Clearance < 30 mL/min by
Cockcroft-Gaul) including patients on hemodialysis or chronic renal replacement
therapy.