PK Study of N91115 in Cystic Fibrosis Patients

This is an open-label pharmacokinetic (PK) study of twice daily doses of 50 mg of N91115
administered for 14 days in F508del-CFTR homozygous CF patients. Six patients are planned
for enrollment. Each patient will undergo screening (Day 28 to Day 3) and, if eligible, will
return to the clinical site on Day 1 or optionally on Day 1. Eligibility will be reconfirmed
and the patient will be admitted to a clinical research unit (CRU). Patients will stay
overnight from Day 1 to Day 2 and will be discharged on Day 2 after all procedures and
assessments are completed. Patients will return to the CRU as outpatients on Days 4, 7, 11,
14, and 15 for PK sample collection and other assessments. They will receive an oral dose of
investigational medicinal product (IMP), N91115, twice daily on Days 1 through 14 and will
be followed for PK through Day 15. Telephone calls to assess safety and ensure compliance
with dosing will be made on days that patients do not make clinic visits (Days 3, 5, 6, 8,
9, 10, 12, and 13). Follow-up safety calls will then be made on Day 21 (adverse events) and
Day 28 (serious adverse events only). Participation of an individual patient may last
approximately 56 days from the time of screening until the end-of-study (Day 28) follow-up
call.

Inclusion Criteria:

1. Confirmed diagnosis of CF, homozygous for the F508del-CFTR mutation

2. Weight ≥ 40 kg at screening

3. FEV1 ≥ 40% of predicted normal for age, gender, and height (Hankinson standards) pre
or post-bronchodilator value, at screening

4. Hematology, clinical chemistry, and urinalysis results with no clinically significant
abnormalities that would interfere with the study assessments at screening

Exclusion Criteria:

1. History of any illness or condition that in the opinion of the investigator could
confound the results of the study or pose additional risk when administered IMP

2. Any acute infection, including acute upper or lower respiratory infections and
pulmonary exacerbations that require treatment or hospitalizations within 4 weeks of
Study Day 1

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

4. History, including the screening assessment, of ventricular tachycardia or
ventricular arrhythmias

5. History, including the screening assessment, of prolonged QT and/or QTcF
(Fridericia's correction) interval (> 450 msec)

6. History of solid organ or hematological transplantation

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

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