Study of the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis and the G551D Mutation

Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance
regulator (CFTR) gene. The encoded protein, CFTR, is an epithelial chloride ion channel
responsible for aiding in the regulation of salt and water absorption and secretion in
various tissues. Although the disease affects multiple organs, the leading cause of
mortality is the progressive loss of lung function. Obstruction of airways with thick
mucous, chronic bacterial infection of the airways, and inflammatory response are all
thought to play a role in causing lung damage. Through its function as a chloride channel,
CFTR is believed to be integral in epithelial ion and water transport and hence, maintaining
the normal hydration of lung secretions.

VX-770 is a potent and selective potentiator of wild-type, G551D, F508del, and R117H forms
of human CFTR. Based on in vitro studies and pharmacologic, pharmacokinetic (PK), and safety
profiles, VX-770 has been selected for clinical development as a possible treatment for
patients with CF.

Hyperpolarized noble gas magnetic resonance imaging (HG-MRI) is a promising new means of
assessing lung function by direct imaging of certain non-radioactive isotopes of an inert
noble gas, such as helium or xenon. Through this technique, high-resolution 3-dimensional
images of lung ventilation can be obtained in both pediatric and adult patients during a
single short breath-hold following inhalation of the gas.

The objectives of this study are to evaluate the effect of VX-770 on hyperpolarized 3He-MRI,
and to evaluate the safety and efficacy of VX-770 in subjects aged 12 years and older with
CF who have the G551D-CFTR mutation.