Chitinase-1 (CHIT1) is an enzyme implicated in the pathology of several ILDs, particularly in pulmonary sarcoidosis granuloma formation. CHIT1 expression and activity correlates with sarcoidosis severity and progression.

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

Here, we present an ongoing proof-of-concept clinical study to evaluate the efficacy, safety, PD, and PK of OATD-01 in active pulmonary sarcoidosis patients. Primary objective is to evaluate the response to 12-week OATD-01 treatment as reduction of granulomatous inflammation in pulmonary parenchyma on [18F]FDG PET/CT, used as a primary readout based on our previous demonstration of reduced glucose uptake in OATD-01-treated macrophages. The primary endpoint is treatment response from baseline to End-of-Treatment, attributed to OATD-01 alone in this placebo-controlled and no standard-of-care-treatment approach. As a secondary objective we quantify the changes of granulomatous inflammation in pulmonary parenchyma, mediastinal/hilar nodes and extra-thoracic locations using PET/CT SUV for secondary endpoint. Other endpoints include assessment of pulmonary function, QoL, safety and sarcoidosis biomarkers (CHIT1 activity, sIL-2R, CCL18, TNF-?).