SLS-008: CRTH2 Antagonist Program
Target profile: Orally-bioavailable small molecule antagonists of the Chemoattractant Receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor
Seelos has identified
two advanced lead
compounds with
excellent profiles for
clinical candidate
selection
Selectively
antagonize binding of
prostaglandin D2 to
the CRTH2 receptor
Active in cell based
functional assays of
eosinophil migration
Good pharmacokinetics
in rats and dogs after
oral administration
Favorable ADME
profile predicts once
daily dosing in
humans
Potential biomarker
identified for Phase I
studies in man
No safety issues
observed in preliminary
studies (AMES, hERG,
Micronucleus)
SLS-008: CRTH2 Target Description
Chemoattractant Receptor-homologous
molecule expressed on Th2 cells
A G-protein coupled receptor (Also known as DP2)
CRTH2 binds prostaglandin D2 as well
as many other active arachidonate metabolites
CRTH2 is expressed primarily on immune cells
(Th2 cells, eosinophils, and basophils)
Expression profile is on cells associated with
allergy and inflammation
Therapeutic indications include
pediatric esophagitis, asthma and
atopic dermatitis
Conditions are characterized by increased eosinophil
infiltration in the lung and airways
CRTH2 antagonists inhibit eosinophil migration
Novartis’ fevipiprant, an oral CRTH2 antagonist,
termed a “game changer” in asthma
(Phase III data late 2018)