Photo Credit: Artemis Diana
Microbiotica’s COMPOSER-1 (MB310), derived from successful fecal microbiota transplantation (FMT), demonstrated efficacy in treating mild-to-moderate ulcerative colitis (UC), showing a therapeutic response signature linked to clinical benefit.
The following is a summary of “From Clinical FMT to a Phase 1 Study with a Defined, Orally Administered Live Bacterial Therapeutic for Mild Moderate Ulcerative Colitis,” published in the January 2024 issue of Gastroenterology by Villemin et al.
Ulcerative colitis (UC) treatment is moving from broad fecal microbiota transplantation (FMT) to a defined bacterial therapeutic (COMPOSER-1) targeting the microbiome-disease link.
Researchers started a retrospective study to assess the efficacy and potential limitations of Microbiotica’s COMPOSER-1, a defined bacterial therapy for mild-to-moderate UC, compared to the variability of traditional FMT.
They conducted a UC trial, treating patients with FMT from healthy donors. In the active group, 32% achieved clinical remission, while the placebo arm had 9%. Shotgun metagenomic sequencing analyzed donor, pre-treatment recipient, and post-FMT recipient samples. Microbiotica’s platform identified bacteria linked to patient response. Using Caco2, dendritic cells, M1 macrophages, and CD4+ T-cells, cellular assays assessed these bacteria.
The results showed a therapeutic response signature based on engrafted bacteria from donors to UC patients, linked to clinical benefit. An analysis at the sub-species level identified 8 bacteria, now part of the defined live bacterial therapeutic, MB310. These consortium bacteria improved epithelial cell monolayer barrier integrity and shielded it from LPS-induced inflammation. In vitro, the bacteria exhibited an anti-inflammatory effect on primary innate immune cells, including dendritic cells and M1 macrophages. Specific MB310 bacteria, directly or via metabolites, could regulate T-cell responses.
Investigators concluded that patient-derived, 8-bacteria consortium MB310 emerged from successful FMT, poised for 2024’s first-in-human UC trial targeting barrier and immune pathways.
Source: academic.oup.com/ecco-jcc/article/18/Supplement_1/i195/7586186?searchresult=1
