A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis

Inclusion Criteria:

- Willing and able to comply with scheduled visits, treatment pan, study restrictions,
laboratory tests, contraceptive guidelines, and other study procedures.

- Body weight ≥35 kg.

- Sweat chloride value ≥ 60 mmol/L from test results obtained during screening.

- Subjects must have an eligible CFTR genotype:

- Cohorts 1A, 1B, 1C: Heterozygous for F508del and a minimal function mutation
known or predicted not to respond to TEZ and/or IVA.

- Cohorts 2A, 2B: Homozygous for F508del.

- Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
at the Screening Visit.

- Stable CF disease as judged by the investigator.

- Willing to remain on a stable CF medication regimen through the planned end of
treatment or if applicable the Safety Follow-up Visit.

Exclusion Criteria:

- History of any comorbidity that in the opinion of the investigator might confound the
results of the study or pose an additional risk in administering study drug to the
subject.

- History of cirrhosis with portal hypertension.

- Risk factors for Torsade de Pointes.

- History of hemolysis.

- Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.

- Clinically significant abnormal laboratory values at screening.

- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in
therapy for pulmonary disease within 28 days before the first dose of study drug.

- Lung infection with organisms associated with a more rapid decline in pulmonary
status.

- An acute illness not related to CF within 14 days before the first dose of study drug.

- A standard digital ECG demonstrating QTc >450 msec at screening.

- History of solid organ or hematological transplantation.

- History or evidence of cataract or lens opacity determined to be clinically
significant by the ophthalmologist or optometrist, based on the ophthalmologic
examination during the Screening Period.

- History of alcohol or drug abuse in the past year, including but not limited to,
cannabis, cocaine, and opiates, as deemed by the investigator.

- Ongoing or prior participation in an investigational drug study with certain
exceptions.

- Use of commercially available CFTR modulator within 14 days before screening (applies
only to Cohorts 1A, 1B, and 1C).

- Pregnant or nursing females: Females of childbearing potential must have a negative
pregnancy test at screening and Day 1.