SPX-101 is an experimental peptide designed to block the function of the sodium channels in the lungs. These channels move sodium and water from the airway surface. Blocking these channels may help maintain fluid within the airways, improving mucus clearance in patients with cystic fibrosis (CF).1
How SPX-101 Works
SPX-101 is a SPLUNC1-derived peptide that mimics the S18 binding site of SPLUNC1, replicating its natural functions of binding to, disrupting, and internalizing of epithelial sodium channels (ENaC). SPX-101’s mechanism of action, according to its developer, Spyryx Bioscience, results in a robust and durable reduction in the cell membrane concentration of active ENaC and in lower sodium absorption.
Restoring control over these sodium channels and sodium absorption in the lungs of people of CF has the potential to improve airway surface hydration and promote mucus clearance, as well as the bacteria, viruses, or other particles mucus contains.
SPX-101 is said to be the first therapy aiming to influence a natural, biological mechanism important to the maintenance of normal mucus clearance.
SPX-101 was tested in in vitro and in vivo preclinical models of CF, and clearly showed effectiveness in both models. The therapy achieved nearly 100% survival in a 14-day inhaled study in beta-ENaC mic, dosed once-daily, and dose-dependent restoration of tracheal mucus velocity in a single dose study in a sheep model.2
Three poster presentations at the 30th Annual North American Cystic Fibrosis Conference featured different aspects of SPX-101 research. The first poster, “SPX-101 is a potent promoter of ENaC internalization, capable of regulating mucus hydration in vitro and in vivo,” demonstrated that CF animal models given SPX-101, as an inhaled aerosol once or twice daily, survived longer and more easily cleared airway mucus easier. The second, “The scale-up and productization of SPX-101 for preclinical inhaled toxicology” detailed studies characterizing drug properties, such as its chemical stability and purity. The third, “SPX-101 demonstrates safety as an ENaC-affecting therapy for the treatment of CF,” showed that daily inhalation of the drug did not produce systemic or airway side effects in dogs and rats treated for 28 days, and did not increase levels of potassium — important because potassium and sodium levels are closely linked in the body.3
SPX-101’s mechanism of action is also independent of the mutations in CFTR, meaning it has the potential to benefit all CF patients.
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