Discovery of OATD 01 , a First in Class Chitinase Inhibitor as Potential New Therapeutics for Idiopathic Pulmonary Fibrosis

Chitotriosidase CHIT1 and acidic mammalian chitinase AMCase are the enzymatically active chitinases that have been implicated in the pathology of chronic lung diseases such as asthma and interstitial lung diseases ILDs , including idiopathic pulmonary fibrosis IPF and sarcoidosis. The clinical and preclinical data suggest that pharmacological inhibition of CHIT1 might represent a novel therapeutic approach in IPF. Structural modification of an advanced lead molecule 3 led to the identification of compound 9 OATD 01 , a highly active CHIT1 inhibitor with both an excellent PK profile in multiple species and selectivity against a panel of other off targets. OATD 01 given orally once daily in a range of doses between 30 and 100 mg kg showed significant antifibrotic efficacy in an animal model of bleomycin induced pulmonary fibrosis. OATD 01 is the first in class CHIT1 inhibitor, currently completed phase 1b of clinical trials, to be a potential treatment for IP