Clinica Medtech Ventures: Enterome

Specialty area: Gut microbiome (drugs and diagnostics)

Based in: Paris, France

Founded in: 2012

No. of employees: 20

Total investment received to date: €17.5m ($21.5m)

Investors: Seventure, , Lundbeckfond Ventures,  Omnes Capital, Shire, Danone

The gut microbiome is becoming a bit of a buzzword in healthcare, amid growing evidence of its importance in diseases ranging from Crohn’s and diabetes to multiple sclerosis. French venture capitalist Seventure Partners even has a fund dedicated to microbiome-based investments.

Among the companies in Seventure’s microbiome portfolio is Enterome,  and its CEO Pierre Belichard stressed that his firm is not a flash in the pan. “The science we’re based on started 20 years ago – we haven’t just come out of the blue,” he told Clinica.

Enterome is initially focused on diagnostics and therapies for Crohn’s disease, using its technology for profiling the bacteria found in the gut. The firm maps the total fecal bacterial gene content and functions, giving a personal metagenome (which it calls the metagenotype) for each person. This metagenotype can indicate certain disease states, or be measured in one patient over time, for example to monitor changes that might lead to an acute episode in Crohn’s disease.

Mr Belichard explained that Enterome has developed an automated and standardized method for extracting DNA from the stool, meaning testing can be carried out in any lab around the world with consistent results. Patients collect their own stool samples and send them to labs where the DNA is extracted using Enterome’s technology; the gene content can then be measured using any available genome sequencer.

“Fecal matter is 90% living bacteria, and a good representation of what’s going on in the gastrointestinal tract,” the CEO said. “But the quality of the DNA [sampled] is the key.”

AbbVie partnership

The firm currently has two projects ongoing in Crohn’s. Closest to the market is a partnership with pharma company AbbVie, inked in November 2014, to develop a biomarker to measure the level of activity in patients with the disease. Currently, Crohn’s patients undergo regular colonoscopies to look for inflammation that could herald an exacerbation. But there is a need for a noninvasive test to support colonoscopy and allow more frequent testing, Mr Belichard said – although he acknowledged that it is unlikely to replace colonoscopy completely.

The ultimate aim is to develop a routine monitoring device for Crohn’s that will “monitor patients’ gut microbiome and assess disease progression and response to therapeutics,” the companies stated at the time of the agreement. This could help prevent relapse of symptoms through early intervention or, conversely, help patients avoid taking unnecessary drugs if their gut microbiome is stable.

The test would be used in conjunction with drugs from AbbVie’s inflammatory bowel disease (IBD) franchise, which includes the blockbuster Humira (adalimumab), used in Crohn’s as well as other inflammatory diseases such as rheumatoid arthritis.

To this end, Enterome studied a longitudinal cohort of 100 Crohn’s disease patients that were followed for both microbiome composition and disease activity for one year, and discovered a bacterial signature indicative of the level of inflammatory activity of the disease. This metagenomic signature is currently under validation through a collaboration with AbbVie, which is funding a study in 300 patients with Crohn’s; this study will compare the results of bacterial signature found by stool exam and colonoscopy. The pharma company will support further studies if the data are encouraging, Mr Belichard said. He hopes that Enterome’s test will be clinically available by the end of 2016.

Drug-diagnostic combo

Further down the line, Enterome is developing its own drug-companion diagnostic combination in Crohn’s. The drug, EP-8018, which is currently at the preclinical stage, is a small molecule designed to limit binding of a type of bacteria called AIEC (adherent-invasive E coli) to the CEACAM6 receptor.

AIEC takes advantage of the inflammatory crisis that upsets the normal microbiome, Mr Belichard explained. The microbiome does not normally allow these bacteria to adhere to the gut wall, but in its absence they can invade and produce TNF (tumor necrosis factor), which leads to further inflammation.

TNF blockers such as Humira only treat the symptoms, the CEO added, while Enterome’s drug could target the underlying cause of the disease.

The corresponding test, which will look for the AIEC bacteria in the stool, will be closely developed alongside the drug and approved at the same time, via the companion diagnostic pathway. Mr Belichard is anticipating getting the go-ahead for both in 2019 or 2020.

Obesity, MS

Even further into the future, Enterome’s technology has potential application in other diseases, the CEO believes. The gut microbiome could be implicated in obesity, he says, adding that a weak microbiome, in combination with bad food habits, is a “big risk factor” for becoming obese. This raises the possibility of a new obesity treatment targeting defects in the microbiome.

More surprisingly, it may also play a role in multiple sclerosis (MS). Local inflammation can cause the gut microbiome to leak into the blood stream, and there is a particular bacteria that has a similar gene sequence to the myelin sheaths that insulate nerve cells and are destroyed in MS. The body, in trying to attack these bacteria, actually attacks the myelin, which leads to MS, Mr Belichard said.

As for competition, the CEO mentioned Vedanta Biosciences and Seres Health, both of which have taken a slightly different approach to Enterome, he believes. Its rivals are replacing the missing bacteria, while Enterome is focused on the products the bacteria are producing, Mr Belichard claimed. “We don’t really believe in probiotics as a magic bullet,” he said, adding that the regulatory hurdles for getting such products approved are very high, while there is a risk that the “missing” bacteria may be rejected as foreign by the patient, stopping any potential beneficial effects.

These advantages mean that Enterome is seeing interest from various quarters: in addition to the deal with AbbVie, it counts pharma company Shire among its investors, as well as food multinational Danone. “We’re backed by good science, and the blessing of key people in the field,” Mr Belichard concluded.



Pierre Belichard, CEO. Email: [email protected]

Enterome, 94/96 avenue Ledru-Rollin,  75011 Paris, France

www.enterome.fr