Full-spectrum microbiome drug for IBS with constipation clears phase II trial

The next-generation oral full-spectrum microbiome drug EBX-102-02 appears to have an acceptable safety profile in patients with irritable bowel syndrome with constipation (IBS-C) while yielding improvements in symptom severity, abdominal pain, and stool consistency, according to the results of the phase IIa TrIuMPH* study.

Analysis of the first raw dataset of the study showed that EBX-102-02 was well tolerated, with treatment-emergent adverse events (TEAEs) being mostly mild, transient, and gastrointestinal in nature. Nausea was the most common TEAE, occurring in 31.7 percent of patients who received the investigational drug and in 14.3 percent of those who received placebo. [DDW 2025, abstract 987b]

Study author Dr Anthony Hobson, who serves as the director of the Functional Gut Clinic in Great Chesterford, Essex, UK, reported that one participant on EBX-102-02 withdrew from the study after experiencing severe adverse events including headache and vomiting. Apart from this, there were no reports of serious TEAEs.

Symptom improvements

In terms of efficacy, patients on EBX-102-02 showed marked improvements and favourable trends across multiple endpoints compared with those on placebo.

Mean IBS Symptom Severity Scale scores (range of 0–500, with higher scores indicating greater severity) from baseline dropped by 68 points at week 3 and by 78 points at week 7 in the EBX-102-02 group. These reductions were greater than the 34- and 53-point drop documented at the respective time points in the placebo group.

EBX-102-02 treatment also resulted in a quicker and more pronounced reduction in abdominal pain. Hobson noted that IBS-SSS pain scores were diminished by 14.1 points at week 7 with the investigational drug vs 9.3 points with placebo. The frequency of abdominal pain days over the past 10 days decreased more rapidly for patients who received EBX-102-02, with this improvement lasting through week 7.

By week 3, the weekly average number of hard stools (Bristol Stool Form Scale 1 or 2) had been halved in the EBX-102-02 group, dropping from 69 percent at baseline to 30 percent, as opposed to a more modest decrease from 69 percent to 54 percent in the placebo group. However, Hobson acknowledged that the difference in the weekly average numbers began to narrow at week 7. Results for straining scores followed a similar pattern, with a faster and more pronounced reduction in the EBX-102-02 group at weeks 1 through 5 then subsequently rising, converging with those in the placebo group at week 7.

Patients in both treatment groups experienced an increase in complete bowel movement frequency, although the magnitude of increase was greater with EBX-102-02, with an average increase of over one bowel movement per week in 4 out of 6 weeks of follow-up compared with 2 out of 6 weeks in the placebo group, according to Hobson.

Finally, metagenomic sequencing of the microbiome of stool samples showed a notable shift. The patients’ endogenous microbiota composition began to resemble the composition of EBX-102-02 itself, with the shift already occurring after receiving a single dose in the first week and continuing in the third week after the second dose, Hobson said. This effect persisted through week 7.

EBX-102-02

Despite the microbiome’s involvement in IBS-C, standard treatments are hindered by suboptimal efficacy and tolerability issues, as Hobson pointed out. Faecal microbiota transplants, on the other hand, have been shown to be safe and well-tolerated in six small trials, but challenges persist due to inconsistent clinical improvement across studies and the absence of a standardized delivery method, he said.

EBX-102-02 is sourced from screened human stool donations and consists of a diverse consortium of viable microorganisms, formulated as an off-white, odourless powder encapsulated into oral capsules. Hobson emphasized that the drug was developed to address variations in medicine delivery and increase species diversity.

The positive data from TrIuMPH demonstrate the potential of EBX-102-02 in the treatment of IBS-C and support further investigation in a larger population of patients.

TrIuMPH involved 120 patients with IBS-C or IBS with diarrhoea (IBS-D) (confirmed by Rome IV grading criteria and IBS-SSS inclusion of ≥175). These patients were randomly assigned to receive two doses (8 capsules at each dosing) of EBX-102-02 or placebo, administered 1 week apart.

Safety and efficacy were assessed at weeks 1, 3, and 7. Patients had to complete a daily bowel habit diary throughout follow-up. Stool samples were collected at each visit for metagenomic sequencing of the microbiome and targeted metabolomics.

The current analysis included 62 patients in the IBS-C cohort, of which 41 were in the EBX-102-02 group and 21 were in the placebo group. Most patients were young and female with severe IBS, with a mean IBS-SSS score of 306.

Results from the IBS-D cohort are expected in second quarter of 2025.