First Therapeutically Engineered Gut Bacteria Enters Clinical Trials

First Therapeutically Engineered Gut Bacteria Enters Clinical Trials
Gut healthy bacteria 3d illustration.

A genetically engineered strain of Bacteroides bacteria, designed to treat the kidney disease enteric hyperoxaluria, has gone into clinical trials.

Developed by the San Francisco-based biotech Novome Biotechnologies, the engineered bacteria treatment, combined with a botanically derived polysaccharide, is designed to colonize the gut and degrade excessive amounts of oxalate that are present in individuals with this condition.

It has shown good results in multiple animal trials, according to the company, and while still at an early stage of development, will be the first such therapy to be tested in humans.

Enteric hyperoxaluria affects 200,000-250,000 people in the U.S. and tends to first present with kidney stones caused by excessively high levels of oxalate excreted in the urine. In contrast to primary hyperoxaluria, which can be genetic, it occurs in people who have undergone gastrointestinal surgery such as a gastric bypass or part colon removal.

Although the symptoms can be somewhat controlled by reducing intake of food high in oxalate such as spinach, rhubarb and sorrel, and by increasing calcium intake, there is no specific cure or treatment and if left unchecked can result in a need for a kidney transplant.

This ‘genetically engineered microbial medicine’ (GEMM) is the lead candidate for Novome and, according to the company, the first example of this kind of therapy to go into clinical trials. Should it be successful, the company is also using the platform technology to develop GEMM’s to target irritable bowel syndrome, ulcerative colitis and even cancer.

The company was founded in 2016 by scientists at Stanford University and the University of California, Berkeley, based on research from the lab of Justin Sonnenberg, scientific co-founder of the company and an assistant professor at Stanford.

Sonnenberg’s research focuses on the gut microbiome, the multiple species of microbes that are known to colonize our guts. In recent years it has become clear how big an impact the gut microbiome has on human health.

While microbiome research and development has increased exponentially over the last few years, there are still few viable and clinically validated therapeutic options available.

Arguably the most famous of these to date is the success of fecal transplantation for treatment of recurrent Clostridium difficile infection. This essentially involves transplantation of ‘healthy’ gut bacteria (via feces) into the gut of the person with the infection. While fecal transplantation has proven surprisingly successful for treatment of C. difficile, the exact mechanisms behind its efficacy are not totally clear.

Novome’s therapy is one of the first of a new generation of more targeted live microbial medicines. The enteric hyperoxaluria GEMM works by colonizing the gut in a controlled manner –non-engineered Bacteroides species are common in the human gut. The engineered bacteria were able to efficiently degrade oxalate in the gut in animal studies and the company hopes the same effect will be seen in humans.

The combined Phase I/IIa clinical trial aims to recruit 63 participants. The Phase I section of the trial will evaluate safety and tolerability of the treatment in healthy volunteers, as well as assessing degree of strain colonization. The Phase II section will be a randomized, single-blinded, placebo-controlled study in patients with enteric hyperoxaluria to assess efficacy and confirm safety and efficacy.

Phase I results are expected later this year and if effective the company will move straight into the Phase IIa section of the study, the results of which are expected in 2022.

“With this significant milestone—starting our first-in-human clinical trial with therapeutically engineered bacteria—we are advancing towards our goal of becoming a leader in the field of living therapeutics,” said Blake Wise, CEO of Novome.

“We are eager to see the results of this groundbreaking study and its potential to validate our approach to controllably and safely colonize the human gut with therapeutically engineered bacteria.”