STOCKHOLM —
The eight-strain live biotherapeutic product (MB310, Microbiotica) is due to enter its first clinical trial later this year.
In patients with UC who showed clinical benefit after fecal microbiota transplantation (FMT), these eight specific bacterial strains were shown to be consistently elevated, reported Ron Carter, MD, chief medical officer at Microbiotica, Cambridge, UK, the company developing the product.
In addition, “in lab studies, we’ve found they exhibit anti-inflammatory effects when incubated with different cells of the immune system,” he explained. With the biotherapeutic product, “we want to prompt the immune system to realign the gut inflammation” in UC.
On February 23, at the annual congress of the European Crohn’s and Colitis Organisation, Dr. Carter presented the work-to-date and the near-term plans for a phase 1b randomized, placebo-controlled, double-blind trial to be conducted across roughly 20 sites in Europe (Abstract DOP 67). The trial, COMPOSER-1, will investigate the engraftment and initial signs of clinical activity of MB310 in 30 patients with active, mild to moderate UC (modified Mayo score 4-7; endoscopic subscore ≥ 2).
Calming Inflammation With Specific Bacteria
To date, the researchers have focused on identifying bacterial species that correlate with clinical outcomes in individual patients with UC after treatment with FMT. Dr. Carter and colleagues worked in collaboration with Sam Costello, MBBS, gastroenterologist at The Queen Elizabeth Hospital in Adelaide, Australia.
The initial research involved analyzing stool samples from a round 70 patients diagnosed with mild to moderate UC, who were randomly assigned to receive either pooled, anaerobically prepared, healthy donor FMT, or their own autologous FMT as a comparative control. FMT was delivered via colonoscopy and two enemas over 7 days. The primary endpoint of the study was achieving steroid-free remission of UC on the basis of specific Mayo scores, at the end of week 8.
“Results indicated that the group receiving the pooled donor FMT showed a 32% success rate with respect to the primary outcome compared with only 9% of the control group,” said Dr. Carter. “This suggested a promising therapeutic strategy.”
Based on these outcomes, Microbiotica then decided to conduct a local study in which they analyzed fecal samples from FMT donors and from pre-FMT and post-FMT recipients in order to precisely identify which bacterial species were associated with clinical response.
“With our precision microbiome analysis platform, we determined eight bacterial species that were consistently elevated in FMT responders, but absent or not elevated in non-responders,” reported Dr. Carter.
Next, they carried out subspecies-level bioinformatic analysis and identified one bacterial strain from each of the eight species, which were then cultured individually, freeze-dried, and combined into a custom delayed-release capsule.
The researchers tested the resulting live biotherapeutic product in cellular assays using human cell lines to confirm that they effectively modulated immune functions.
The cellular assays showed that in epithelial cell monolayer tests, MB310 not only enhanced barrier integrity but also protected the cellular barrier from inflammation.
The eight bacterial strain combination also exhibited anti-inflammatory effects when incubated with different primary innate immune cells, dendritic cells, and M1 macrophages.
And, Dr. Carter emphasized, the specific MB310 bacterial strains were found to regulate T-cells directly or via metabolites.