Gastroenterology · Medical Literature
Faecalibacterium prausnitzii EXL01 for the Maintenance of Steroid-induced Clinical Response or Remission in Patients with Crohn's Disease: a first in human trial.
Abstract
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.
Clinical relevance
Is oral administration of the live biotherapeutic F. prausnitzii strain EXL01 safe and biologically active for maintaining steroid-induced clinical response or remission in adults with mild-to-moderate Crohn's disease? __SNAPSHOT__ {"studyDesign":"Phase 1, first-in-human, open-label, single-arm trial (Part A of the two-part MAINTAIN study; NCT05542355)","setting":"Multicentre study; country/institution not specified in abstract or available supplementary data","sampleSize":"n=8 enrolled; n=6 completed the study","population":"Adults aged 18–74 years with a diagnosis of Crohn's disease with ileal involvement (≥3 months), mild-to-moderate disease activity (CDAI 180–350), who achieved clinical response or remission following standard-of-care corticosteroid induction therapy","intervention":"Oral EXL01 (gastro-resistant capsule targeting jejunal release, once daily) for up to 24 weeks, administered alongside progressive corticosteroid taper","comparator":"Not applicable (single-arm, no control group in Part A)","primaryOutcome":"Safety and tolerability of oral EXL01","followUp":"Up to 24 weeks of treatment plus 30 days post-treatment monitoring","fundingSource":"Not reported in abstract; study was conducted by Exeliom Biosciences (industry-affiliated sponsor, based on ClinicalTrials.gov registration)"}
Key findings
Primary safety endpoint: EXL01 was well-tolerated with no treatment-related adverse events (TEAEs) reported. One serious TEAE (Grade 2 calculus bladder) occurred in one participant and was assessed by the investigator as unrelated to EXL01. No deaths were reported. AEs were consistent with the known corticosteroid safety profile and the background CD population. Six of eight participants (75%) completed the study; two (25%) discontinued due to disease flare. Endoscopic outcomes: The Simple Endoscopic Score for Crohn's Disease (SES-CD) did not significantly change at Week 24, and no participants achieved endoscopic response or mucosal healing. Biomarker/molecular findings (exploratory): Corticosteroid induction significantly reduced CDAI scores prior to EXL01 initiation (Wilcoxon rank test, p=0.002). Ileal transcriptomic analyses revealed distinct changes in gene expression following EXL01 treatment — including modulation of immune-related genes and upregulation of energy metabolism pathways — without major taxonomic shifts in gut microbiota composition. The two participants who experienced disease flare had higher baseline and post-corticosteroid-induction systemic inflammation markers compared with those remaining in remission, and showed transcriptomic evidence of persistent mucosal inflammatory pathway activation. No absolute or relative effect sizes, confidence intervals, or NNT/NNH values are calculable or reported for clinical or endoscopic endpoints in this single-arm safety study.
Practice implications
This first-in-human Phase 1 trial establishes that oral EXL01 can be safely administered to adults with mild-to-moderate Crohn's disease following corticosteroid-induced remission, with no treatment-related adverse events identified. The finding of ileal transcriptomic changes — specifically immune gene modulation and upregulation of energy metabolism pathways without significant shifts in overall microbiota composition — provides proof-of-concept for a direct mucosal immunological effect. However, the study was not designed or powered to establish efficacy; the absence of a control arm means that observed clinical, endoscopic, and molecular changes cannot be attributed to EXL01 with any confidence. No participant achieved endoscopic response or mucosal healing, though this was not a primary objective of Part A. The observation that participants who flared had higher baseline systemic inflammation is hypothesis-generating and supports the concept that this drug class may be best positioned for maintenance of remission rather than induction — but this is explicitly speculative given n=2 in the flare subgroup. Patients with active mucosal inflammation, prior biologic failure, or extraintestinal CD manifestations were not adequately represented. Generalizability is severely limited by sample size, single-arm design, open-label methodology, and the early termination of the planned placebo-controlled Part B due to low recruitment. Only the abstract was available for full review, and access to complete data tables, figures, and statistical outputs was not possible — this constitutes a critical limitation in interpreting all secondary and exploratory endpoints. __LIMITATIONS__ Critically small sample size (n=8 enrolled, n=6 completing), precluding any inferential statistical comparison for efficacy endpoints.,Open-label, single-arm design with no control group; all observed changes in clinical, endoscopic, histological, and transcriptomic parameters are uncontrolled and unattributable to EXL01 with certainty.,Part B of the MAINTAIN study — a planned randomized, double-blind, placebo-controlled study in 42 participants — was never initiated due to low recruitment, removing the primary vehicle for efficacy evaluation.,No endoscopic response or mucosal healing was observed in any participant, raising questions about meaningful disease modification at the mucosal level within the study duration.,Transcriptomic and microbiome findings are exploratory; without a placebo arm, it is impossible to distinguish EXL01-specific effects from natural disease trajectory or corticosteroid withdrawal effects.,Subgroup analysis of flare vs. remission participants involved n=2 vs. n=6, making any mechanistic or predictive inferences unreliable.,Industry-affiliated sponsorship (Exeliom Biosciences) introduces potential reporting bias.,Selection bias: only patients who responded to corticosteroids were enrolled, limiting applicability to steroid-refractory populations.,Follow-up duration of 24 weeks may be insufficient to evaluate durable remission maintenance.,Only the abstract was available for full evaluation; complete methods, statistical analyses, and data tables were not accessible, limiting assessment of analytical rigor. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ EXL01, an oral live biotherapeutic formulation of F. prausnitzii, was well-tolerated in eight adults with mild-to-moderate Crohn's disease with no treatment-related adverse events, and produced exploratory transcriptomic signals of ileal immune modulation. However, no endoscopic response or mucosal healing was observed, no control arm exists, and the planned placebo-controlled phase was never initiated, making any efficacy conclusion premature. This study establishes a safety signal sufficient to support further investigation; it does not support changes to current clinical practice.