The purpose of the study is to evaluate

1. The microbiological response and clinical efficacy of SPR720 compared with placebo in participants with nontuberculous mycobacteria pulmonary disease (NTM-PD).
2. The safety and tolerability of SPR720 in participants with NTM- PD
3. The pharmacokinetic (PK) of SPR719, active moiety, following orally (po) administered prodrug SPR720 in participants with NTM-PD.

Inclusion Criteria:

1. Has a prior diagnosis of NTM-PD due to MAC according to American Thoracic Society (ATS) criteria

2. Has at least one prior lower respiratory culture (sputum or bronchoalveolar lavage [BAL]) positive for MAC in the 12 months prior to consent

3. Has an induced sputum culture at Screening positive for MAC by quantitative culture on solid agar

4. Is either treatment naïve and has not received any prior treatment for MAC, OR if previously treated for MAC and meets all of the following criteria:

   1. Has a history of successful treatment with sputum culture conversion to negative
   2. Has recent sputum or BAL culture evidence of recurrent or relapsed disease and
   3. Has been off therapy for at least 3 months prior to consent

5. Has clinical signs and symptoms within the 6 weeks prior to consent that are consistent with NTM-PD with ≥2 of the following:

   1. chronic cough
   2. fatigue
   3. frequent throat clearing
   4. shortness of breath (dyspnea)
   5. coughing up of blood (hemoptysis)
   6. excessive mucus (sputum) production
   7. fever (temperature >38ºC or >100.4ºF)
   8. night sweats
   9. loss of appetite
   10. unintended weight loss
   11. wheezing
   12. chest pain

6. Has a measured forced expiratory volume in the first second following maximal inhalation (FEV1) % predicted ≥30% within 3 months prior to consent. If prior FEV1% predicted test result is not available, obtain FEV1% predicted at Screening to confirm eligibility

Exclusion Criteria:

1. In the opinion of the Investigator, is not a candidate for a 5-month delay in initiation of standard multidrug therapy to participate in a placebo-controlled clinical trial (e.g., participant has severe symptoms or, extensive disease burden)

2. Has disseminated or extrapulmonary NTM disease

3. Has end-stage NTM-PD or treatment-refractory NTM-PD

4. Has isolation on lower respiratory (sputum or BAL) cultures of any Mycobacterium species other than those included in MAC within the 6 months prior to consent

5. Has any other condition or prior therapy, which, in the opinion of the Investigator, would make the participant unsuitable for this study, including compliance with all study assessments and adherence to the protocol schedule of assessment

6. Prior exposure to SPR720. Participants who are unable to comply with the requirements of the study or who in the opinion of the Investigator should not participate in the study are not eligible

   • Other inclusion and exclusion criteria as per protocol may apply.