Phase 1 Trial of Peptide to Treat All CF Patients (SPX-101) Shows Safety, Phase 2 Study Planned

Spyryx Biosciences successfully completed a Phase 1 clinical trial of its lead compound, SPX-101, in healthy volunteers and is now planning a Phase 2 study in patients with cystic fibrosis (CF).

SPX-101 is an inhaled SPLUNC1-derived peptide created to regulate epithelial ion channels in the airways. The drug was developed to restore the lungs’ natural ability to regulate hydration and promote mucociliary clearance, which is dysfunctional in CF patients.

This mechanism of action works independently of the genetic mutations that cause CF (mutations in the cystic fibrosis transmembrane conductance regulator [CFTR] gene), meaning it could potentially treat all CF patients.

The Phase 1 trial evaluated SPX-101 for its safety, tolerability, and pharmacokinetics in 64 participants, all of whom completed the study protocol.

SPX-101 was found to be safe and well-tolerated in all single ascending dose (SAD) and multiple ascending dose (MAD) arms. No adverse effects on electrolyte levels, and no indication of hyperkalemia (high concentration of serum potassium), were found, demonstrating that the drug has low systemic exposure and rapid clearance.

“The data from this study validate the safety of SPX-101’s novel mechanism of action; the internalization of epithelial sodium channels with a small, inhaled peptide. We are pleased to confirm the absence of safety or tolerability concerns and the lack of significant systemic exposure following 14-day administration,” Alistair Wheeler, MD, chief medical officer of Spyryx, said in a press release.

“Given the absence of dose-limiting adverse effects in healthy adults, supported by the excellent non-clinical safety data and the strong scientific rationale for a meaningful effect on pulmonary function, we are eager to move the program into the CF patient population,” Wheeler added.

Based on these results, Spyryx is now planning to initiate a multinational Phase 2 trial in people with CF, assessing SPX-101’s ability to improve lung function, as well as its safety and tolerability. This study will enroll patients regardless of underlying CFTR mutation.

A preclinical study found that SPX-101, given to animal models of CF as an inhaled aerosol, helped the animals to survive longer and better clear airway mucus. This study, whose data was presented at the 30th Annual North American Cystic Fibrosis Conference last year, also showed that administering the drug one to two times daily was enough to maintain the effect.