COMPOSER-1 trial makes sweet music for Microbiotica

The study of MB310 (an investigational precision microbiome medicine taken orally once daily) met its primary and secondary study objectives being safe and well tolerated, with successful engraftment of the MB310 bacteria and statistically significant improvements in efficacy parameters compared with placebo at the end of study assessments. Notably, MB310 achieved clinical remission that was indicative of disease modification.

Professor Herbert Tilg, Medical University, Innsbruck, Austria and Scientific Advisory Board member, said: “These early results are encouraging. Ulcerative colitis is a debilitating inflammatory bowel disease that affects over 1.4 million people globally.

“By dosing with healthy bacterial species shown to be associated with clinical improvements in ulcerative colitis, MB310 has the potential to be a transformative medicine that could be disease modifying and change the underlying natural pathology of the condition.”

COMPOSER-1 was a randomised, placebo-controlled, double-blind, clinical trial that recruited 29 adult patients at clinical centres in five countries across Europe (UK, Austria, Bulgaria, Poland and Spain), with active, mild-to-moderate UC.

The patients took two capsules of study medication (active or matched placebo) once a day for 12 weeks in addition to their standard of care medication, with a 12-week follow-up period.

The study met its primary objective, demonstrating that MB310 had a similar safety profile as placebo. The bacterial strains within MB310 successfully engrafted into patients as early as the first week into treatment. All eight bacteria of the MB310 consortium persisted throughout the 3-month treatment period and were also maintained during the 3-month post dosing follow-up period. This indicates patients had full exposure to MB310 for the entire study, including both dosing and 3-month follow-up period.

Initial signals of efficacy were measured using standard clinical endpoints, including assessment of clinical signs and symptoms, endoscopy, histology and inflammatory biomarkers. MB310 demonstrated:-

• Improvement in remission for patients on MB310 (12 out of 19, i.e., 63%) compared with those on placebo (3 out of 10, i.e., 30%) as measured by partial Mayo score (the standard disease activity index)

• All 12 patients who completed MB310 treatment and entered the follow-up stage were in clinical remission at the end of study. Notably rectal bleeding, a symptom known to be of importance in UC, was completely resolved

• Improvement of histological markers of disease activity, and particularly those relating to gut epithelial barrier integrity compared to baseline and placebo

• Improvement of the key biomarker of active bowel inflammation, faecal calprotectin, consistent with the observed improvement in clinical signs and symptoms compared to placebo

• Withdrawal rates similar in both arms

These data are supportive of preclinical studies that have demonstrated that the MB310 consortium acts via at least three independent mechanisms that are central to the pathology of UC: promoting the healing of the damaged gut epithelial barrier; regulating the balance of cytokines that are inflammatory (TNF) and immune-modulatory (IL-10); and inducing a regulatory T-cell response.

Dr Robert Tansley, Microbiotica’s Chief Medical Officer, said: “We are encouraged by these positive data from our Phase 1b study of MB310 in ulcerative colitis. Our clinic-led approach to the discovery of live biotherapeutic products results in a defined, consistent and reproducible product, which we believe has the best chance of producing clinical benefit by becoming safely established in the microbiome of patients and addressing key underlying causes of ulcerative colitis.

“Our first-in-human study has demonstrated safety and tolerability together with encouraging efficacy data. It supports the hypothesis that MB310 has the potential to deliver disease modifying, long lasting remission with an excellent tolerability profile.

“The highly encouraging clinical remission rates at 6 months, is more impressive than any ulcerative colitis therapy I have seen to date. If confirmed in larger studies, MB310 has the potential to transform the management of ulcerative colitis by addressing a key factor behind the pathophysiology of the disease not currently treated. We are planning our Phase 2/3 studies where such potential is evaluated in combination with standard of care therapies.”

Tim Sharpington, CEO of Microbiotica, added: “We are very excited about these promising results. MB310 has the potential to be a new, differentiated treatment modality for patients with ulcerative colitis, offering the hope of long-lasting disease remission without side effects.

“The study results also provide validation of our clinic-first microbiome discovery platform which brings new precision in the identification of bacterial strains associated positive outcomes from clinical trial data. Combined with our increased understanding of the mechanisms by which our microbiome interact with host cells, this gives us the opportunity to design differentiated, precision microbiome medicines in different disease settings.

“During 2026, we will explore partnering and financing options to determine the best route to fund our products through later studies and towards commercialisation.”

Future plans

Microbiotica is conducting additional analysis of COMPOSER-1 data, to further explore the impact of MB310 and to inform the design of the adaptive Phase 2/3 study. It is anticipated that this study will explore the disease modifying ‘slower-onset longer-acting’ potential of MB310 in combination with anti-inflammatory and/or immuno-modulatory induction agents.

Spun out of the Wellcome Sanger Institute in 2016, Microbiotica is based in purpose-built facilities at the Chesterford Research Park near Cambridge. Microbiotica has raised more than £62 million equity investment, including a £50m Series B in 2022, with venture investors including British Patient Capital, Cambridge Innovation Capital, Flerie Invest, IP Group plc, Seventure Partners and Tencent. The company has also received financial support from the US-based Crohn’s and Colitis Foundation.