Study of N91115 in Patients With CF Homozygous for the F508del-CFTR Mutation

Primary Objective:

- Assess the efficacy of N91115 at 12 weeks when added to preexisting treatment with
lumacaftor/ivacaftor in adult patients with CF who are homozygous for the F508del-CFTR
mutation

Secondary Objectives:

- Assess the effect of N91115 added to lumacaftor/ivacaftor on safety

- Assess the effect of lumacaftor/ivacaftor added to N91115 on the pharmacokinetics of
N91115, lumacaftor, and ivacaftor

Inclusion Criteria:

- Patients must have been treated with lumacaftor/ivacaftor for at least 8 weeks prior
to Day 1 (start of dosing)

- A history of Sweat Chloride (SC) ≥ 60 mEq/L by quantitative pilocarpine iontophoresis
test (QPIT) (either before or after starting lumacaftor/ivacaftor treatment)

- Body weight ≥ 40 kg

- ppFEV1 40 - 85 % predicted (inclusive) at screening

- Oxygen saturation ≥ 90% breathing ambient air at screening

Exclusion Criteria:

- Any acute infection that requires treatment or hospitalization within 2 weeks of
Study Day 1

- Colonization with organisms associated with more rapid decline in pulmonary status,
such as Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus

- Any change in the regimen for chronic therapies for CF lung disease (e.g.,
Pulmozyme®, hypertonic saline, Azithromycin, TOBI®, Cayston®) within 4 weeks of Study
Day 1

- Are pregnant, planning a pregnancy, or breast-feeding at screening

- Blood hemoglobin < 10 g/dL at screening

- Serum albumin < 2.5 g/dL at screening

- Abnormal liver function defined as ≥ 3 x upper limit of normal (ULN)

- History of abnormal renal function within 3 months of screening

- History of ventricular tachycardia or other clinically significant ventricular
arrhythmias

- History, including the screening assessment, of prolonged QT and/or QTcF
(Fridericia's correction) interval

- History of solid organ or hematological transplantation

- History of alcohol abuse or drug abuse

- Ongoing participation in another therapeutic clinical trial

- Use of continuous (24 hr/day) or nocturnal supplemental oxygen