Autologous transplantation of P63+ lung progenitor cells (REGEND001) for idiopathic pulmonary fibrosis therapy: phase I clinical trial

<bold>Background:</bold> Idiopathic pulmonary fibrosis (IPF) leads to irreversible loss of alveolar epithelium, challenging conventional therapy and encouraging stem/progenitor cell-based therapy. P63+ airway basal progenitor cells have been identified as a promising candidate for lung epithelium repair, providing new therapeutic option for IPF patients. <bold>Aim:</bold> To evaluate the safety, tolerability, and preliminary efficacy of REGEND001, an autologous P63+ basal progenitor cell product to treat IPF. <bold>Methods:</bold> Autologous P63+ progenitor cells were isolated from the airway basal layer via bronchoscopic brushing, cultured for 4~6 weeks, and transplanted into the lungs via bronchoscopy. Totally 12 IPF patients were enrolled in four cohorts that received ascending doses of cells, and assessed for safety and efficacy 24 weeks afterwards. <bold>Results:</bold> REGEND001 was safe and well tolerated at all doses, with no dose-limiting toxicities observed. The most frequently observed adverse events related to cell therapy were fever (4, 33.33%), hemoptysis (3, 25.00%) and leukocytosis (2, 16.67%), which were likely due to bronchoscopic procedures. Among the four dose groups, the 1 x 10⁶ cell/kg bodyweight dose demonstrated best efficacy, improving DLCO (baseline: 47.85% to 24 weeks: 63.47%), FVC (baseline: 81.39% to 24 weeks: 83.90%) and 6MWD (baseline: 434.00 m to 24 weeks: 513.10 m) and decreased average SGRQ score (baseline: 27.23 to 24 weeks: 19.08). <bold>Conclusions:</bold> REGEND001 was safe in all participants and showed efficacy potential in the 1 x 10⁶ cell/kg bodyweight dose group. These data strongly support further clinical evaluation of REGEND001 as a therapeutic product in IPF patients.