Study of Epetraborole in Patients With Treatment-refractory MAC Lung Disease

Inclusion Criteria:

1. Male or female patients who are 18 years of age or older.

2. Willing and able to provide written informed consent.

3. Patients with a diagnosis of treatment-refractory MAC lung disease consisting of allof the following (a) Microbiological, (b) Clinical, and (c) Radiographic criteria:

4. Microbiological criteria:

• One Pre-Study MAC-positive respiratory specimen. Documentation of a MACpositive specimen collected per standard of care within 6 months prior tosigning the informed consent form (ICF).
• One Screening MAC-positive expectorated or induced sputum sample.

2. Clinical criteria: At least 2 of the following patient-reported clinicalsymptoms:

• Cough with sputum production
• Cough without sputum
• Chest congestion
• Hemoptysis
• Dyspnea
• Fatigue
• Night sweats or unusual sweating

3. Radiographic criteria: Non contrast Chest CT scan within 6 months prior tosigning the ICF with abnormalities consistent with MAC lung disease.

4. OBR criteria: An OBR is a combination regimen that consists of ≥2antimycobacterial agents. The patient-specific OBR must be administered for aminimum duration of 6 consecutive months that is either ongoing at the time ofScreening or was stopped or paused no more than 12 months before screening. TheOBR regimen administered during Screening must be continued afterrandomization.

5. Patients who are willing to comply with all the study activities and proceduresthroughout the duration of the study and comply with all planned study visits andstudy procedures from Screening through the LFU Visit.

6. All patients must agree to use an effective method of birth control.

7. Patients expected to survive with continued antimycobacterial therapy andappropriate supportive care from Screening through the LFU Visit, in the judgment ofthe Investigator.

Exclusion Criteria:

1. Patients with a presence of any suspected or confirmed disease or condition atScreening or the time of randomization that, in the opinion of the Investigator, mayconfound the assessment of symptom-based clinical response.

2. Patients with active pulmonary malignancy or any malignancy that required or wouldrequire chemotherapy or radiation therapy within 1 year prior to randomizationthrough the LFU Visit.

3. Patients with creatinine clearance (CrCl) of ≤30 mL/min, as estimated by theCockcroft Gault formula, at Screening.

4. Patients with hemoglobin <10.0 g/dL or <6.2 mmol/L at Screening; donation of bloodor plasma within 28 days prior to randomization; or symptomatic loss of blood orhemorrhage within 28 days prior to randomization.

5. Patients with severe hemoptysis within 28 days prior to randomization, defined as >100 mL over any 24-hour period or severe or extremely severe hemoptysis.

6. Patients with severe hepatic impairment, as evidenced by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) or totalbilirubin >2 × ULN, or clinical signs of cirrhosis or end-stage hepatic disease.

7. Patients who are pregnant or breastfeeding.

8. Patients with a mean QT interval corrected using Fridericia's formula (QTcF) >480msec based on triplicate 12-lead ECGs at Screening.

9. Patients with an immunodeficiency or an immunocompromised condition and risk for anopportunistic pulmonary infection.

10. Patients with an anticipated start of new non-study antimycobacterial therapy to beadministered at any time between Screening and Month 6.

11. Patients who have received any investigational medication during the 30 days or 5half-lives, whichever is longer, prior to randomization.

12. Patients with any prior exposure to epetraborole.

13. Patients with any condition that, in the opinion of the Investigator, interfereswith the ability to safely complete the study or adhere to study requirements,including the patient's inability or unwillingness to comply with all studyassessments and visits.