Mucus hypersecretion has been shown to be an important cause of airway obstruction in COPD and
asthma, and has been associated with fatal asthma. Previous in-vitro and in-vivo studies have provided direct evidence that
the myristoylated alanine-rich C kinase substrate (MARCKS) is a central regulatory molecule linking secretagogue stimulation
at the goblet cell surface to mucin granule release. BIO-11006 is a novel, highly soluble, aerosolized peptide that
inhibits MARCKS function and results in reduced mucus secretion and improved airway obstruction. BIO-11006 is being
tested in Phase 2 clinical studies of COPD.
To determine access of BIO-11006 to the intracellular compartment of normal human bronchial epithelial
(NHBE) cells, and assess the effectiveness of BIO-11006 inhalation solution in inhibiting airway obstruction caused by
mucus hypersecretion as a function of dose and time.
Biotin labeled BIO-11006 was incubated with NHBE cells and visualized with fluorescein-labeled streptavidin.
Ovalbumin-sensitized and challenged mice with airway inflammation and hyperresponsiveness to methacholine (MCh)
were treated with aerosolized BIO-11006 solution prior to MCh challenge, and effects on airway obstruction and mucus
secretion were measured.
A 30-minute aerosol exposure to a 10 mM BIO-11006 solution was maximally effective in inhibiting MChinduced
airway obstruction and mucus hypersecretion. There was a long-lasting effect on inhibition of airway obstruction
after a single treatment with BIO-11006 (t1/2~4 hrs). The duration of effect on inhibition of mucin secretion was shorter
The pharmacodynamic properties of aerosolized BIO-11006 Inhalation Solution are suitable for therapeutic
use. Inhaled BIO-11006 effectively inhibits mucin secretion and improves airway obstruction.