The business of microbiomes is--well, a bit dirty. Microbiome therapeutics are typically sourced from healthy human fecal matter. That enables a complex grouping of organisms that serves well for orphan disease patients who have severe conditions, but limits production to enough for only a few patients.
Now, Seres Therapeutics ($MCRB) is taking an additional approach to the microbiome. It’s putting the first synthetically created designer microbiome therapeutic into the clinic.
The candidate is SER-262, an oral capsule that contains 12 bacterial strains in spore form. The strains were selected based upon multiple criteria including analysis of human microbiome data, efficacy in animal models of Clostridium difficile infection (CDI), and bacterial strain level characterization.
The Phase Ib study, a 24-week randomized, placebo-controlled, dose escalation trial, is expected to enroll about 60 patients. The primary endpoint is a comparison of the CDI recurrence rate between the drug and placebo group at up to 8 weeks after dosing.
Instead of relying solely upon the assemblage of microbiomes found in healthy humans, it’s put its own microbiome therapeutic together by drawing upon its immense library of more than 14,000 well-characterized strains of bacteria. Seres believes it has the largest available microbiome library--larger, in fact, than that of the National Institutes of Health.
“Antibiotics do very little for an orphan condition,” Seres Chairman, President and CEO Dr. Roger Pomerantz told FierceBiotech. "There, we need to get to these patients rapidly. They need a very robust, very complex group of organisms in the drug. There are about 50 different strains of bacterium. Some of these patients have the worst microbe we’ve ever seen. They need the full Monty."
He continued, “But we want to use and develop a drug for large groups of patients--like all of primary C. diff. To treat those patients, that’s 850,000 patients. It kills 30,000 people a year in the U.S. We’d rather not biologically source for the ability to get to large numbers of patients. 262 is the tip of the spear.”
Pomerantz, a former SVP and worldwide head of licensing and acquisitions at Merck Research Laboratories, joined Seres to lead it a few years ago.
Seres plans to continue working with biologically sourced microbiome drugs and has two ongoing trials with them. Its lead candidate is SER-109, an oral microbiome therapeutic to prevent CDI in adults who have had three or more episodes within the previous 9 months.
This indication afflicts an estimated 85,000 to 110,000 patients in the U.S. annually and is caused by antibiotic disruption of the microbiome. SER-109 is in Phase II testing and has already received a Breakthrough Therapy designation from the FDA. Data are expected in mid-2016.
In December, it also started a Phase Ib trial for SER-287, another biologically sourced candidate, to treat mild to moderate ulcerative colitis.
Not only does Seres now expect to be able to create both biologically and synthetically derived microbiome therapeutics, but it also plans to be able to work with both spores and the bacteria themselves.
“In the first drug, we used bacterial spores. Now, we have developed how to use the bacteria themselves,” Pomerantz said, pointing to June partnerships with the Mayo Clinic to develop a treatment for nonalcoholic steatohepatitis (NASH) and with Massachusetts General Hospital and Harvard Medical School to identify microbiome therapeutics for obesity and metabolic syndrome.
“We can get into more complex metabolic diseases being able to have a lot of different approaches for putting together drugs and manufacturing,” he concluded.
- here is the release