Vertex Pharmaceuticals and Parion Sciences said they have initiated an up-to-$1.17 billion-plus collaboration to develop investigational epithelial sodium channel (ENaC) inhibitors as a potential treatment of cystic fibrosis (CF) and other pulmonary diseases.

The deal, disclosed yesterday, gives Vertex worldwide development and commercialization rights to Parion’s investigational ENaC inhibitors. They include P-1037 and P-1055, indicated for CF and other pulmonary diseases.

An inhaled version of P-1037 is being evaluated in a recently-launched exploratory Phase IIa study. The study is assessing use of P-1037, with and without hypertonic saline, compared to placebo in approximately 120 people with CF, regardless of genotype. The study is enrolling people with a confirmed diagnosis of CF and any cystic fibrosis transmembrane conductance regulatory (CFTR) protein CFTR mutation, including those who have mutations not expected to respond to ivacaftor alone.

Vertex and Parion reason that 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.

Parion and Vertex said they plan to launch early next year 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. The study will assess whether adding P-1037 to lumacaftor and ivacaftor provides additional benefit compared with lumacaftor and ivacaftor alone.

“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,” Jeffrey Chodakewitz, M.D., evp and CMO at Vertex, said in a statement. “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.”

The additional study will be based on preclinical results showing that adding P-1037 to lumacaftor and ivacaftor resulted in an additional increase in both airway surface liquid and cilia beat frequency compared to baseline, and to P-1037 or lumacaftor or ivacaftor alone. The companies surmise that improved lung function may result from enhancing the ability of cilia to clear mucus from the cell surface through the combo of P-1037 with lumacaftor and ivacaftor.

Beyond CF, Vertex and Parion plan to conduct additional Phase 2a studies of P-1037 across multiple other pulmonary diseases, including chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis (NCFB), and primary ciliary dyskinesia (PCD). Parion will conduct Phase IIa development in these diseases, and will retain an option to participate in co-development and co-commercialization activities related to one of the pulmonary diseases.

Under their collaboration, Vertex agreed to pay Parion $80 million upfront, and up to an additional $490 million in payments tied to development and regulatory milestones—a figure that includes $360 million related to global filing and approval milestones.

Parion could also receive up to $370 million in development and regulatory milestone payments for P-1037 and P-1055 in non-CF pulmonary indications; plus another $230 million in development and regulatory milestones should Vertex develop an additional ENaC inhibitor from Parion's research program.

The deal also includes tiered royalties on sales of P-1037 and P-1055, at percentages ranging from “the low double digits to mid-teens.”








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