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Spyryx Biosciences Emerging Company Profile in BioCentury

EMERGING COMPANY PROFILE

GOING SPLUNCING

BY EMILY CUKIER-MEISNER, SENIOR WRITER

Spyryx Biosciences Inc. is developing inhaled peptides for
cystic fibrosis that inhibit the sodium channel responsible
for regulating fluid volume in the lungs. The peptides could
offer a pan-genotypic treatment that is more efficacious than
therapies targeting CFTR.

CF is caused by defects in the cystic fibrosis transmembrane
conductance regulator (CFTR) channel that result in
depletion of airway surface liquid and abnormally adherent
mucus. Spyryx’s peptides target the epithelial sodium
channel (ENaC), which conducts sodium and water away
from the airway surface, and becomes hyperactive when
CFTR is defective.

Scientific founder Robert Tarran discovered how defects in
CFTR lead to excessive ENaC activity. Namely, the inability
of defective CFTR to conduct chloride and bicarbonate
ions results in the airway surface fluid becoming acidic. The
acidity in turn causes a conformational change in SPLUNC1
(BPI fold containing family A member 1; BPIFA1; PLUNC;
LUNX), a secreted protein that normally binds to and
deactivates ENaC by causing its subunits to dissociate and
internalize.

The conformational change in SPLUNC1 makes its ENaC
binding domain inaccessible, which allows ENaC to be
activated by proteases.

Spyryx is developing small peptides based on the SPLUNC1
ENaC binding domain to prevent ENaC activation.

“When you isolate the regulatory peptide from the rest of
the protein, it maintains its binding affinity for ENaC, but
it’s pH independent,” said CEO John Taylor. [FULL STORY]