In idiopathic pulmonary fibrosis (IPF) patients, alveolar epithelium architectures are persistently lost and lung gas transfer function would decline over time, which cannot be rescued by conventional anti-fibrotic therapy. P63+ airway basal progenitor cells are previously reported to have great potential to repair damaged lung epithelium. Here, we successfully cloned and expanded the autologous P63+ progenitor cells from IPF patients to manufacture the cell therapeutic product REGEND001, which were further characterized by cell morphology and single-cell transcriptomic analysis. Subsequently, an open-label, dose-escalation exploratory clinical trial was conducted (CTR20210349). The primary outcome was the incidence and severity of the cell therapy-related adverse events (AEs); secondary outcome included other safety and efficacy evaluation in each dose groups. We treated 12 patients with ascending doses of cells: 0.6x, 1x, 2x and 3.3x 106 cells/kg bodyweight. The data revealed that P63+ basal progenitor cell was safe and well tolerated at all doses, with no dose-limiting toxicity or cell therapy-related severe adverse events observed. Patients in the three higher dose groups showed statistically significant improvement of lung gas transfer function as well as exercise ability after REGEND001 therapy. Resolution of honeycomb lesion was also observed in patients of higher dose groups. Altogether these initial results indicated that REGEND001 has a high safety profile and meanwhile shows preliminary efficacy in IPF patients.

Regend Therapeutics is holding the patent of human lung progenitor cell isolation and expansion technique.

Chinadrugtrials.org Identifier: CTR20210349

This study was funded by National High Level Hospital Clinical Research Funding (2022-PUMCH-B-108 to Z.-J.X.), Jiangsu Province Science and Technology Special Project (Key Research and Development Plan for Social Development) Funding (BE2023727 to W.Z.), National Biopharmaceutical Technology Research Project Funding (NCTIB2023XB01011 to W.Z.) and Non profit Central Research Institute Fund of Chinese Academy of Medical Science (2020-PT320-005 to W.Z.). Regend Therapeutics also funded the study and covered costs associated with the development of this publication

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Medical Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University; Ruijin Hospital Ethics Committee, Shanghai Jiao Tong University School of Medicine; Drug Clinical Trial Ethics Committee of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences gave ethical approval for this work

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The data that support the findings of this study are available from the corresponding author upon reasonable request.