Chitinase-1 (CHIT1) is an activated macrophage-specific enzyme implicated in pathology of several interstitial lung diseases in particular regarding granuloma formation in lung sarcoidosis. CHIT1 expression and activity correlates with severity and progression of lung sarcoidosis.

OATD-01 is a small-molecule inhibitor of CHIT1 with in vivo efficacy demonstrated in several preclinical models of inflammatory diseases, including mouse model of granulomatous inflammation. OATD-01 has been so far administered to 129 healthy volunteers in four Phase 1 clinical studies, with single doses up to 600 mg or multiple doses up to 50 mg q.d. At doses of 25 to 50 mg/day, at steady state, the total time with the inhibition of the blood chitinolytic activity of >80% was maintained for 24h.

Here, we present a study to evaluate the efficacy, safety, tolerability, PD, and PK of OATD-01 in the treatment of patients with active pulmonary sarcoidosis. The primary objective is to evaluate the response to a 12-week treatment with OATD-01 as a reduction of granulomatous inflammation in pulmonary parenchyma evaluated by [¹⁸F]FDG PET/CT imaging. The primary endpoint will be response to treatment from baseline to End-of-Treatment. As secondary objective we quantify these changes in pulmonary parenchyma, mediastinal/hilar nodes and extra-thoracic locations. Secondary endpoints include evaluation of granulomatous inflammation quantified by PET/CT SUV and volume of the lesions, assessment of pulmonary function, quality of life and safety parameters. Exploratory endpoints include sarcoidosis biomarkers activity namely CHIT1 and ACE.