Faecalibacterium prausnitzii EXL01 for the Maintenance of Steroid-induced Clinical Response or Remission in Patients with Crohn’s Disease: a first in human trial

A marked decrease in Faecalibacterium prausnitzii is a hallmark of Crohn's disease (CD)-associated dysbiosis and predicts disease relapse. Here, we present the development and first-in-human evaluation of F. prausnitzii strain EXL01 for CD treatment. The EXL01-strain demonstrates anti-inflammatory effects in four models of colitis in rodents. A first-in-human, open-label, single-arm study of oral EXL01 was conducted in eight adult participants with mild to moderate CD, following corticosteroids-induced clinical response or remission. The primary endpoint was safety, and secondary endpoints included clinical, endoscopic, histological, molecular, and microbiome assessments. Exploratory endpoints included mucosa transcriptome and cytokine levels. EXL01 is well-tolerated with no treatment-related adverse events. Six participants completed the study; two discontinued treatment due to disease flare. While gut microbiota composition remains largely stable, transcriptomic analyses reveal distinct changes in ileal gene expression following EXL01 treatment, notably modulation of immune-related genes and upregulation of energy metabolism pathways. Compared to participants who remained in remission, those who flared show higher baseline systemic inflammation markers and innate immunity gene expression. These findings demonstrate that oral administration of EXL01 is feasible and well tolerated and establishes proof-of-concept for F. prausnitzii as a first-in-class live biotherapeutic for CD. ClinicalTrials.gov registration: NCT05542355.