Phase 1b Safety, Tolerability, and PK Study to Assess GS-5737 in Subjects With CF

Inclusion Criteria:

- Males or females, ≥ 18 years of age, at Screening

- Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria, with at
least 1 of the following: Documented sweat chloride ≥ 60 mEq/L by quantitative
pilocarpine iontophoresis test OR Abnormal nasal transepithelial potential difference
(NPD) test OR Two well-characterized, disease-causing genetic mutations in the CF
transmembrane conductance regulator (CFTR) gene AND 1 or more accompanying clinical
features consistent with CF

- FEV1 ≥ 40% and ≤ 90% predicted

- BMI ≥ 19 and ≤ 30 kg/m2

- Clinically stable with no evidence of significant new or acute respiratory symptoms

- Chest radiograph without significant acute findings; or chest radiograph, CT, or MRI
obtained and interpreted within 90 days prior to enrollment, without acute findings
and no significant intercurrent illness; chronic, stable findings are allowed

- History of lifetime smoking < 5 pack-years (ie, 1 pack per day x 1 year =

1 pack-year) and non-smokers of at least 60 days duration prior to Screening

- Estimated creatinine clearance ≥ 80 mL/min at Screening

- Negative drug tests; including alcohol

- Hepatitis B, C, & HIV Negative

- Surgically sterile or ≥ 12 months post-menopausal

- Non-pregnant females

Exclusion Criteria:

- Experienced symptoms of recent acute upper or lower respiratory tract infection or
acute pulmonary exacerbation requiring treatment within 2 weeks prior to Screening

- Plasma potassium ≥ 5 mEq/L

- Changes in chronic azithromycin use, bronchodilator (BD), dornase alfa, HS,
physiotherapy technique or regimen, antibiotics or corticosteroid medications within
28 days prior to Screening

- History of sputum or throat swab culture yielding Burkholderia species within 2 years
of Screening