NZ-97

NZ-97 is a locally delivered, lung-persistent **small molecule** dipeptidyl peptidase 4 (DPP4) inhibitor engineered to stimulate the proliferation of type 2 alveolar epithelial cells (AEC2s)—the principal stem cells responsible for repair of the gas exchange epithelium in the lower airways[1][4][5][7][12]. By inhibiting DPP4 activity within the lung, NZ-97 augments levels of local regulators such as IGF-1 and IL-6, both required for AEC2 expansion, promoting regenerative repair in acute and progressive pulmonary diseases such as idiopathic pulmonary fibrosis (IPF) and potentially chronic obstructive pulmonary disease (COPD)[1][4][5][7][9][12]. NZ-97 is designed with chemical modifications (a polar polyol group and a lipophilic C8 chain) for high lung retention, minimal peripheral exposure, and increased safety/tolerability relative to systemic DPP4 inhibitors[7][10]. It is administered locally via direct intratracheal delivery or via inhaled mist, and shows efficacy at low and infrequent doses in mouse models[1][4][7][12]. This prototype is chemically related to saxagliptin and was developed as a proof-of-concept for regenerative agents, with CMR316 as a next-generation clinical candidate.