Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations

Approximately 11% of CF patients have premature termination codons (PTC), causing truncated
CFTR with little to no function. No approved therapies exist for patients with PTC mutations
including W1282X, a unique mutation exhibiting partial CFTR activity even in its truncated
form. CFTR modulators alone enhanced CFTR function in patient cells from W1282X/G542X CFTR.
Several published studies have shown CFTR modulators alone and/or in combination with
readthrough (RT) agents benefit W1282X CFTR. Clinical studies further support an aspect of
this notion, where two W1282X patients showed beneficial effect to Ivacaftor treatment.

Inclusion Criteria:

- Evidence of signed and dated informed consent/assent document(s) indicating that the
subject (and/or his parent/legal guardian) has been informed of all pertinent aspects
of the trial

- Age ≥ 18 yrs

- Body weight ≥ 16 kg

- Diagnosis of CF and documentation of the presence of a nonsense mutation of the
CFTR gene, as determined by historical genotyping

- Ability to perform a valid, reproducible spirometry with demonstration of FEV1 ≥
30% and ≤ 90% of predicted for age, gender, and height

- In 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

- Willingness and ability to comply with all study procedures and assessments

Exclusion Criteria:

- 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 2 weeks prior
to screening

- Ongoing participation in any other therapeutic clinical trial

- Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection
(including viral illnesses) within 2 weeks prior to screening

- Ongoing tobramycin (inhaled), immunosuppressive, warfarin, phenytoin, or tolbutamide
therapy

- History of solid organ or hematological transplantation; positive hepatitis B surface
antigen test; hepatitis C antibody test; or human immunodecifiency

- Major complication of lung disease (including massive hemoptysis, pneumothorax, or
pleural effusion) within 4 weeks prior to screening

- Pregnancy or breast-feeding

- Current smoker or a smoking history of ≥ 10 pack-years (number of cigarette packs/day
x number of years smoked)

- Prior or ongoing medical condition (eg, renal failure, alcoholism, drug abuse,
psychiatric condition), medical history, physical findings, ECG findings, or
laboratory abnormality that, in the investigator's opinion, could adversely affect the
safety of the subject, makes it unlikely that the course of treatment or follow-up
would be completed, or could impair the assessment of study results