Mino-Lok Therapy (MLT) for the Treatment of CRBSI/CLABSI

This is a Phase 3, multi-center, randomized, double-blind study to determine the efficacy and
safety of MLT, a novel antibiotic lock therapy that combines minocycline with edetate
disodium in 25% ethanol solution.

Mino-Lok Therapy is being developed as an adjunctive therapy for the treatment of
catheter-related or central line associated bloodstream infection (CRBSI/CLABSI) in
combination with appropriate systemic antibiotic(s), to preserve central venous access and to
avoid the complications and morbidities associated with catheter removal and reinsertion.

Approximately 700 subjects who have been diagnosed with CRBSI/CLABSI and who meet all
necessary criteria for the study will be randomized in a 1:1 ratio to 1 of 2 treatment arms:

- MLT Arm: MLT + SOC intravenous (IV) antibiotic therapy; or

- Control Arm (subjects randomized to the Control Arm will receive treatment based on the
type and virulence of the infecting organism as documented by the Investigator prior to
randomization): The antibiotic lock should be comprised of the best available therapy at
the sites. Prior to randomization, the Investigator at each site will determine the
antibiotic used in the lock, the dose, the dwell time, and the number of days of
administration (minimum of 7 days) based on standard institutional practices or
recommendations from the Infectious Diseases Society of America (IDSA) guidelines. In
the event that the subject is being treated with more than 1 systemic SOC IV antibiotic,
the Investigator will specify a single antibiotic that should be used for the antibiotic
lock. It is acceptable for the SOC antibiotic lock to differ from the SOC IV
antibiotics, as necessary per local SOC.

All infecting organism types are permitted (eg, S. aureus, S. epidermidis, Candida spp.,
Pseudomonas aeruginosa). Randomization will be stratified by type of CVC, presence of
neutropenia, and by virulence of the infecting organism.

The primary endpoint is the proportion of subjects in the ITT Population who have Overall
Success at TOC (Week 8). Success is defined as any subject who demonstrates eradication of
the pathogen, stabilization or improvement in signs and symptoms of the infection, catheter
salvage, AND survival at termination of the study. Analysis for the primary endpoint will
compare the overall success rate between the MLT Arm and the Control Arm.

Note: Patients who have had their catheters removed and replaced due to a CLABSI/CRBSI may be
eligible for entry into the observation arm.

Inclusion Criteria:

1. Male or female at least 12 years of age;

2. Subject must have a bloodstream infection with no other apparent source that is not
related to an infection at another site that meets one of the following:

1. A recognized single pathogen cultured from 1 or more blood cultures; OR

2. A common skin contaminant cultured from 2 or more blood cultures drawn on the
same or consecutive calendar days from a subject with fever (greater than 38.0
degrees C), chills, or hypotension (systolic blood pressure less than 90 mmHg);

3. Inpatient or outpatient with presence of indwelling CVC (ie, totally implantable port,
tunneled or non-tunneled CVC, hemodialysis catheter, or peripherally inserted CVC)
that has been in place for greater than5 days from which a bloodstream infection has
been documented within 96 hours prior to enrollment (and from which an isolate of the
baseline pathogen(s) is still available for analysis at the central laboratory) and
demonstrates the protocol definition of CRBSI/CLABSI; NOTE: For the treatment arm only
(MLT Arm and Control Arm), the CVC is expected to be in place through the end of
treatment.

4. Subjects who refuse to have their catheter removed or subjects for whom, in the
Investigator's opinion, catheter retention for the duration of the study is reasonable
or required;

5. Female subjects of childbearing potential must have a negative urine and/or serum
pregnancy test within 5 days prior to randomization (MLT Arm and Control Arm) ;

6. Male subjects must agree to refrain from sperm donation throughout the duration of the
study and for 90 days following the last dose of study drug;

7. Subjects eligible for the Observation Arm must have had their central line removed and
replaced within 96 hours of the qualifying blood culture (120 hours with Medical
Monitor approval);

Exclusion Criteria:

1. Subjects with hypersensitivity or allergy to tetracycline antibiotics or edetate
disodium;

2. Subjects with septic shock that requires inotropic support or is unresponsive to fluid
resuscitation;

3. Subjects taking disulfiram or disulfiram-like drugs;

4. Subjects with prosthetic cardiac valves, vascular grafts, pacers, or other
non-removable vascular foreign body, with the exception of coronary stents and
peripheral stents;

5. Subjects with the presence of a deep-seated intravascular source of infection (eg,
endocarditis [as evidenced by vegetations on an echocardiogram or clinical suspicion]
or septic thrombosis);

6. Subjects with bacteremia with documented microbiological evidence of another source of
infection (eg, osteomyelitis, pneumonia, skin infection, urinary tract infection,
joint infection, or abdominal infection) known to be due to the same organism cultured
from the blood;

7. Subjects with polymicrobial CRBSI/CLABSI caused by pathogens that would require
multiple antibiotics to be used for adequate lock therapy treatment. For example, a
subject with methicillin-resistant Staphylococcus aureus and Escherichia coli
requiring treatment with vancomycin and meropenem would be excluded from the study. A
subject with S. aureus and Staphylococcus epidermidis, where both are identified as
pathogens and where both could be treated with vancomycin, would be eligible;

8. Subjects with the presence of a tunnel or catheter exit site infection or an infusion
port pocket abscess as manifested by purulence at the exit site, or inflammation with
erythema, or induration of greater than 1 cm in diameter;

9. Subjects who have been previously randomized into the present study;

10. Subjects who are pregnant or lactating;

11. Subjects with proven or suspected persistent bacteremia despite 72 hours of both
systemic antibiotic therapy and lock therapy to which the infecting organism is
susceptible;

12. Subjects with short-term CVCs indwelling less than 5 days;

13. Subjects with a central line-related mycobacterial infection; or

14. Subjects who, in the opinion of the Investigator, have a high probability of death
within 3 months of randomization due to a disease process other than the CRBSI/CLABSI