Vertex Pharmaceuticals, a global biotechnology company based in Boston, and Parion Sciences, a development stage biopharmaceutical company based in Durham, N.C., will collaborate to develop investigational epithelial sodium channel (ENaC) inhibitors for the potential treatment of cystic fibrosis (CF) and other pulmonary diseases.

Vertex gains worldwide development and commercial rights to Parion's investigational ENaC inhibitors, including P-1037 and P-1055, for CF and other pulmonary diseases. P-1037 currently is being evaluated in an exploratory phase IIa study in people with CF, regardless of genotype. Vertex and Parion plan to begin an additional phase IIa study that adds P-1037 to treatment with the investigational combination of lumacaftor and ivacaftor for people with CF who have two copies of the F508del mutation. This Phase 2a study is expected to begin in early 2016.

Parion will receive an $80 million up-front payment from Vertex with the potential to receive additional development and regulatory milestone payments and tiered royalties related to P-1037 and P-1055 in CF and other pulmonary diseases. Parion has the potential to receive up to an additional $490 million in development and regulatory milestone payments for development of ENaC inhibitors in CF, including $360 million related to global filing and approval milestones.

Jeffrey Chodakewitz, M.D., executive vice president and chief medical officer at Vertex, said, "The goal of these planned studies of P-1037 is to determine whether ENaC inhibition can improve lung function in people with CF, including those with mutations unlikely to respond to treatment with the investigational combination of lumacaftor and ivacaftor. Beyond CF, this agreement helps to diversify our pipeline by providing opportunities to evaluate P-1037 as part of phase IIa studies in multiple other diseases that impact the lungs."

Cystic fibrosis is a rare genetic disease that is caused by defective or missing cystic fibrosis transmembrane conductance regulatory (CFTR) proteins resulting from mutations in the CFTR gene. The defective or missing CFTR proteins result in poor flow of salt and water into and out of the cell in a number of organs, including the lungs. The defective CFTR protein that causes CF is also believed to increase the function of ENaC, which may contribute to dehydration of the cell surface of lungs in people with CF. In CF, the poor flow of salt and water in cells prevents cilia on the surface of the cell from beating properly, which leads to a buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage, eventually leading to death.

Parion has the potential to receive up to $370 million in additional development and regulatory milestones for P-1037 and P-1055 in non-CF pulmonary indications. Parion also may receive an additional $230 million in development and regulatory milestones should Vertex elect to develop an additional ENaC inhibitor from Parion's research program. Parion will receive tiered royalties on potential sales of P-1037 and P-1055 in CF and other pulmonary diseases that range from the low double digits to mid-teens as a percentage of sales. Vertex will lead future development activities for P-1037 and P-1055 in CF and other pulmonary diseases.

Parion recently initiated an exploratory phase IIa study of inhaled P-1037 in approximately 120 people with CF. The study is enrolling people with a confirmed diagnosis of CF and any CFTR mutation, including those who have mutations not expected to respond to ivacaftor alone. The study is evaluating the use of P-1037, with and without hypertonic saline, compared to placebo. Patients in the study will continue to receive standard CF medicines.

Beyond CF, Vertex and Parion plan to conduct additional phase IIa studies of P-1037 across multiple other pulmonary diseases where the disease results in defective hydration of the cell surfaces in the lung. These diseases include chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis (NCFB) and primary ciliary dyskinesia (PCD). Parion will conduct phase IIa development in these diseases and retains an option to participate in co-development and co-commercialization activities related to one of these non-CF pulmonary diseases.