Study to Evaluate Efficacy of LAI When Added to Multi-drug Regimen Compared to Multi-drug Regimen Alone

This is an ongoing randomized, open-label, multicenter study of LAI in adult subjects with
NTM lung infections caused by MAC that were refractory to treatment. Subjects received either
LAI 590 mg administered QD by inhalation plus a multidrug regimen, hereafter referred to as
LAI + MDR or a multidrug regimen alone, hereafter referred to as MDR alone for a minimum of 8
months. Subjects who demonstrated culture conversion by Month 6 went on to complete a
treatment course of 12 months, starting from the first of 3 negative cultures that defined
culture conversion.

Sputum culture results were made available to the site after the Month 6 sputum result was
known, in time for the Month 8 visit. Prior to the Month 8 visit, the culture results from
Baseline to Month 6 inclusively were blinded to the site and Sponsor. The results were
blinded to reduce the potential for bias in an open-label study. At Month 8 (-28 to +7 days),
after all sputum culture results were made available to the site only, up to and including
Month 6, subjects were assessed as converters or non-converters.

A converter was defined as a subject who had 3 consecutive monthly MAC-negative sputum
cultures at any time within the first 6 months of the study.

"Relapse or recurrence" was defined as having MAC-positive sputum cultures in liquid broth
media (agar negative) for 3 or more consecutive months, or having at least 1 MAC-positive
sputum culture on solid media (agar positive) after achieving culture conversion.

A non-converter was defined as a subject who did not have 3 consecutive monthly MAC-negative
sputum cultures at any time within the first 6 months of the study.

All converters remained in the study. Converters who, after culture conversion, subsequently
had MAC-positive sputum cultures in liquid broth media (agar negative) for 1 or 2 consecutive
months only by Month 6 also remained in the study. Subjects who remained in the study
continued their randomized treatment regimen until they completed a total of 12 months of
treatment (EOT), starting from the first of 3 negative cultures that defined culture
conversion. These subjects returned after the EOT visit for 28 days, 3, 6, and 12 months
off-treatment follow-up visits. The 12 months off-treatment follow-up visit was the EOS
visit. No NTM treatment was administered during the off-treatment phase.

At Month 8, all non-converters as assessed at the Month 6 visit were discontinued from Study
INS-212. Subjects who experienced a relapse or recurrence by Month 6 also discontinued from
Study INS-212 at their Month 8 visit. These subjects were potentially eligible to enter a
separate open-label study of LAI (Study INS-312), provided all entry criteria were met for
that study.

Inclusion Criteria:

1. Be continually positive for MAC on sputum culture while adhering to a multi-drug
treatment regimen for a minimum duration of 6 months which is either ongoing or was
completed no more than 12 months before screening

2. Be diagnosed with MAC NTM lung infection with evidence of nodular bronchiectasis
and/or fibrocavitary disease by chest CT

3. Be willing to adhere to multi-drug treatment regimen during the course of the study

Exclusion Criteria:

1. Patients with cystic fibrosis

2. Positive pregnancy test or lactation at screening. All women of child bearing
potential will be tested. Women not of childbearing potential are defined as
postmenopausal (i.e., amenorrheic for at least 1 year), or surgically or naturally
sterile.

3. Active pulmonary tuberculosis requiring treatment at screening

4. History of lung transplantation

5. Prior exposure to LAI (including clinical study).