Study of N91115 in CF Patients Who Are Heterozygous for F508del-CFTR and a Gating Mutation and Being Treated With Ivacaftor

Assess the effect of N91115 on lung function when added to preexisting treatment with
ivacaftor in adult patients with CF who are heterozygous for F508del-CFTR and a gating
mutation that is approved for treatment with ivacaftor (G551D, G1244E, G1349D, G178R, G551S,
S1251N, S1255P, S549N, or S549R).

Inclusion Criteria:

- Confirmed diagnosis of CF, heterozygous for F508del-CFTR and a gating mutation that
is approved for treatment with ivacaftor (G551D, G1244E, G1349D, G178R, G551S,
S1251N, S1255P, S549N, or S549R)

- Have been treated with chronic ivacaftor twice daily for at least 6 months prior to
Screening (date of consent) and are currently being treated with commercially
available Ivacaftor

- Negative serum pregnancy test

- Weight ≥ 40 kg at screening

- Oxygen saturation by pulse oximetry ≥ 90% breathing ambient air, at screening

Exclusion Criteria:

- Any acute infection, including acute upper or lower respiratory infections and
pulmonary exacerbations that require treatment that has completed within 2 weeks of
Study Day 1 or hospitalization discharge within 2 weeks of Study Day 1

- Recent infection (per investigator discretion) with organisms associated with more
rapid decline in pulmonary status, for example: 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

- Blood hemoglobin < 10 g/dL at screening

- Serum albumin < 2.5 g/dL at screening

- Abnormal liver or renal function

- 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 (> 450 msec for men; > 470 msec for women)

- History of solid organ or hematological transplantation

- History of alcohol abuse or drug abuse (including cannabis, cocaine, and opioids) in
the year prior to screening

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