Phase 2a Trial of Microbiome Therapy With Allo-HSCT Completes Enrollment

Enrollment has been completed for a phase 2a randomized clinical trial evaluating the investigational microbiome therapeutic EBX-102-02 in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), according to a news release from EnteroBiotix.¹

The MAST trial (NCT06355583) will assess whether preemptive administration of the microbiome therapy prior to conditioning chemotherapy can preserve gut microbial diversity during transplantation and potentially influence posttransplant outcomes.

The investigator-initiated trial enrolled 50 adult patients with defined hematologic malignancies who are scheduled to undergo allo-HSCT. Participants are randomly assigned in a 1:1 ratio to receive a single oral dose of EBX-102-02 or matched placebo prior to the initiation of conditioning chemotherapy. Patients will be followed for 12 months after transplantation. The trial is sponsored by Imperial College London and funded by the UK Medical Research Council.

The primary end point of the study evaluates change in gut microbiota alpha diversity from baseline to posttransplant timepoints. Secondary and exploratory end points include safety, tolerability, clinical transplant outcomes, and translational analyses examining microbiome composition and immune parameters. Topline results from the study are expected in the first half of 2027.

“Profound disruption of the intestinal microbiome is common during allogeneic stem cell transplantation and has been strongly associated with adverse outcomes,” said Julian Marchesi, PhD, co-chief investigator and professor of digestive health at Imperial College London. “MAST builds on prior promising work from the Imperial team utilising traditional FMT [fecal microbiota transplantation] approaches and has been designed to assess whether pre-emptive microbiota restoration using EBX-102-02 can preserve microbiome diversity during the transplant period and potentially improve post-transplant outcomes. We are pleased to have completed enrolment and thank the patients and clinical teams involved.”

Gut Microbiome Disruption in Allo-HSCT

Allo-HSCT remains a potentially curative therapy for several hematologic malignancies, including acute leukemias, myelodysplastic syndromes, and certain lymphomas. However, the procedure is associated with substantial treatment-related morbidity and mortality. Infectious complications, graft-vs-host disease (GVHD), and other transplant-related toxicities continue to limit outcomes despite improvements in conditioning regimens, supportive care, and GVHD prophylaxis strategies.²

Increasing evidence suggests that the intestinal microbiome plays an important role in transplant outcomes. During the transplantation process, patients often experience profound disruption of the gut microbial ecosystem due to chemotherapy conditioning, antibiotic exposure, mucosal injury, and hospitalization. This loss of microbial diversity has been associated with higher rates of bloodstream infections, increased incidence and severity of GVHD, and reduced overall survival after allo-HSCT.³

EBX-102-02 is an investigational, orally administered microbiome therapeutic designed to restore microbial ecosystem diversity. The product is manufactured using proprietary processing technologies intended to maintain a broad spectrum of microorganisms while enabling standardized dosing and stability.

Prior studies have explored microbiota restoration strategies to counteract microbiome depletion during allo-HSCT, with some preliminary evidence suggesting that such interventions may improve microbial diversity and potentially influence clinical outcomes.

In addition to the trial’s primary goal, investigators will also assess whether microbiome restoration correlates with changes in transplant-related clinical outcomes, although these endpoints are exploratory in the current study.¹

The trial’s translational analyses will examine microbial community composition and immune parameters over time. Such analyses may help clarify mechanistic links between microbiome composition and immune responses during the transplantation process.

Identifying Role for EBX-102-02

Microbiome-based therapies are an emerging area of investigation in oncology and transplant medicine. Interest in these approaches has increased as research continues to demonstrate interactions between the gut microbiome and host immune function. Investigators have reported associations between microbiome diversity and outcomes in patients receiving immune checkpoint inhibitors as well as those undergoing hematopoietic stem cell transplantation.³

In January, EnteroBiotix announced positive phase 2 results from the TrIuMPH trial [ISRCTN65517362] of EBX-102-02 as therapy for irritable bowel syndrome with constipation; durable clinical improvements were seen vs placebo were shown in 7 weeks with no serious treatment-related adverse events.⁴ The therapy was also investigated in the phase 1b IMPuLCE trial in patients with liver cirrhosis, where it demonstrated a dose-dependent shift in microbiota composition and favorable tolerability.⁵

Although EBX-102-02 remains investigational, the study reflects broader efforts to incorporate microbiome-directed strategies into supportive care and complication prevention in high-risk oncology populations. If successful, approaches aimed at preserving microbial diversity during transplantation could represent an adjunctive strategy to reduce complications associated with allo-HSCT.

Investigators will continue to follow participants for safety and longitudinal microbiome changes over the 12-month post-transplant period. Results from the trial are expected to provide insight into the feasibility and biologic activity of preemptive microbiome restoration in the transplant setting.¹

REFERENCES

1. EnteroBiotix Announces Completion of Enrolment in Phase 2a Trial Evaluating EBX-102-02 Prior to Allogeneic Stem Cell Transplantation. News release. EnteroBiotix. March 10, 2026. Accessed March 11, 2026. https://tinyurl.com/2bhh9phd

2. K Kim HT, Soiffer RJ, Cutler C, et al. Reduced incidence of relapse and graft-versus-host disease in acute myeloid leukemia after allogeneic hematopoietic cell transplantation. Haematologica. 2025;110(9):1998-2008. doi:10.3324/haematol.2025.287390

3. van Lier YF, Vos J, Blom B, Hazenberg MD. Allogeneic hematopoietic cell transplantation, the microbiome, and graft-versus-host disease. Gut Microbes. 2023;15(1):2178805. doi:10.1080/19490976.2023.2178805

4. EnteroBiotix announces positive Phase 2 TrIuMPH results supporting EBX-102-02 as a potential first-in-class, oral, full-spectrum microbiome therapy for irritable bowel syndrome. News release. EnteroBiotix. January 8, 2026. Accessed March 11, 2026. https://tinyurl.com/yu3efnht

5. OS-036 A multicentre randomised double-blind placebo-controlled phase 1b clinical trial evaluating the safety and mechanism of action of EBX-102, an oral pooled intestinal microbiota product, in liver cirrhosis: the IMPuLCE trial. J Hepatology. 2025;82(S1):S31. doi:10.1016/S0168-8278(25)00351-4