Study of Ataluren (PTC124) in Cystic Fibrosis

This is a Phase 3, multicenter, open-label, safety and efficacy study of ataluren in patients
with nonsense mutation cystic fibrosis who participated in the previous Phase 3 study with
ataluren (PTC124-GD-009-CF; Study 009). The primary objective of this study is to determine
the long-term safety and tolerability of ataluren in patients with nmCF, as assessed by
adverse events and laboratory abnormalities. The secondary objective of this study includes
the assessment of the efficacy of ataluren, as measured by FEV1 and pulmonary exacerbation
rate, and change from baseline in other safety parameters (eg, 12-lead ECG measurements,
vital signs). Study subjects will be enrolled at approximately 17 sites in the United States,
Europe and Israel that previously participated in Study PTC124-GD-009-CF. All study subjects
will receive 10-, 10-, and 20-mg/kg ataluren (PTC124) 3 times per day (morning, midday and
evening, respectively) for 192 weeks. Subjects will be evaluated at clinic visits every 16
weeks and supplemented with interim phone calls in between onsite visits. A final 4-week
post-treatment follow-up visit will also be conducted.

Key Inclusion Criteria:

- Ability to provide written informed consent (parental/guardian consent and subject
assent if <18 years of age)

- Evidence of completed participation in the double-blind study, PTC124-GD-009-CF (Study
009)

- Body weight >16 kg.

- Performance of a valid, reproducible spirometry test using the study-specific
spirometer during the screening period.

- Confirmed laboratory values within the central laboratory ranges at screening

- In male and female subjects who are sexually active, willingness to abstain from
sexual intercourse or employ a barrier or medical method of contraception during the
study drug administration and 60-day follow-up period

- Willingness and ability to comply with all study procedures and assessments, including
scheduled visits, drug administration plan, laboratory tests, and study restrictions

Key Exclusion Criteria:

- Chronic use of systemic tobramycin within 4 weeks prior to screening

- Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection
(including viral illnesses) within 3 weeks prior to screening or between screening and
enrollment

- Any change (initiation, change in type of drug, dose modification, schedule
modification, interruption, discontinuation, or re-initiation) in a chronic
treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior
to screening.

- Known hypersensitivity to any of the ingredients or excipients of the study drug

- Exposure to another investigational drug within 4 weeks prior to screening or ongoing
participation in any other therapeutic clinical trial

- Treatment with intravenous antibiotics within 3 weeks prior to screening

- History of solid organ or hematological transplantation

- Ongoing immunosuppressive therapy (other than corticosteroids)

- Positive hepatitis B surface antigen, hepatitis C antibody test or HIV test

- Known portal hypertension

- Pregnancy or breast-feeding