Spyryx’s lead investigational product is an inhaled peptide in clinical development to treat CF-related lung disease for all disease-causing mutations. SPX-101 has demonstrated compelling evidence of the ability to enhance airway liquid volumes in CF patient cells and to restore mucus clearance in animal models of dehydration induced lung disease.
SPX-101 specifically targets epithelial sodium channels (ENaC) on the airway surface, causing reduction in channel density by cellular internalization. This novel mechanism mimics the airway’s normal regulation of ENaC surface density, decreasing absorption so that fluid is retained on the airway surface. Enhancing fluid levels restores hydration to the resident mucus and promotes its clearance via airway cilia, a process called mucociliary clearance.
Building on the strength of the preclinical and toxicology data for SPX-101, Spyryx initiated clinical development, completing Phase 1 studies in healthy volunteers and subjects with CF. These studies indicated a safety and tolerability profile for SPX-101 supporting further investigation.
A Phase 2 efficacy study in people with CF is now enrolling for SPX-101 in Canada, the United Kingdom, France and Portugal: HOPE-1 – Hydration for Optimal Pulmonary Effectiveness (www.clinicaltrials.gov/show/NCT03229252; https://www.cysticfibrosis.org.uk/get-involved/trialstracker/2017/09/99066). HOPE-1 is a 28-day placebo-controlled study with the goal of establishing safety and efficacy for SPX-101 in the treatment of CF.
Cystic Fibrosis is a genetic disease that impacts the body’s ability to regulate the flow of salt and water across epithelial membranes, resulting in loss of fluid volume. The respiratory tract is one of the most profoundly affected, causing dehydration-induced lung disease that begins with depleted airway surface liquid and accumulations of dry, sticky mucus and leads to chronic inflammation, recurrent infections, and reduced ability to breathe. Airway fluid dehydration in CF is mediated by ENaC, which are dramatically over-expressed in this disease.
Spyryx is developing SPX-250, a novel peptide designed to address dehydration induced lung disease in indications where administration via a dry powder inhaler is desirable. Leveraging Spyryx’s peptide-mediated ENaC internalization mechanism, the compound has demonstrated the ability to robustly remove ENaC from the apical surface and to enhance surface fluid volume in human airway cells. In vivo data in animal models of mucus clearance is pending.