By Julia Karow
French startup Enterome has set out to translate intestinal microbial biomarkers discovered during a large European gut metagenomics project into diagnostics for metabolic and bowel diseases.
Last month, the Paris-based company raised €5 million ($6.6 million) in a series A financing round that was co-led by Seventure and Lundbeckfond Ventures (GWDN 3/23/2012), following an earlier seed funding of €1.5 million from Seventure Partners and INRA Transfert.
Enterome was founded in July of 2011 with the mission to develop and commercialize gut microbial biomarkers discovered by the Metagenomics of the Human Intestinal Tract, or MetaHIT, consortium, a four-year European project that started in 2008 and was funded with €11.4 million from the European Commission (IS 3/9/2010 and IS 6/24/2008).
Dusko Ehrlich, coordinator of the MetaHIT project and a research director at the Institut National de la Recherche Agronomique in Jouy-en-Josas, France, is the company's chief scientific officer and a scientific founder, and Peer Bork, who co-heads the structural and computational biology unit at the European Molecular Biology Laboratory in Heidelberg, is the other scientific founder.
CEO Pierre Bellchard and COO Marie-Laure Bouttier were former managers at Fovea Pharmaceuticals, which was acquired by Sanofi in 2009. The company plans to double its staff to about 10 by the end of the year.
Enterome has a collaboration agreement with INRA, providing it with exclusive access to discoveries made by MetaHIT's metagenomic platform for selected diseases, including type 2 diabetes and liver and bowel diseases.
Using metagenomic sequencing of DNA prepared from the human gut, MetaHIT has developed a catalog of about 4 million microbial genes discovered in hundreds of individuals.
Rodolphe Clerval, Enterome's chief business officer, said that the company is sequencing whole DNA — 99 percent of which is microbial DNA — from human gut samples and matching the reads against the MetaHIT gene catalog to establish lists of genes, or gene abundance profiles, that reflect the bacterial diversity in the gut and can serve as biomarkers.
"The use of NGS here is not to detect gene mutations or polymorphisms," he said. "It's really a macroscopic use of these tools to detect the abundance of microbial genes."
MetaHIT, he said, demonstrated that within groups of patients with certain metabolic or bowel diseases, some can have low and some high gut bacterial diversity, and that these profiles correlate with clinical phenotypes and disease evolution.
The consortium is about to publish two studies, one on obesity in two cohorts from France and Denmark, the other on patients with inflammatory bowel disease, but he declined to disclose the results at this time.
Based on the results of these proof-of-concept studies, Enterome plans to develop diagnostic tests to monitor the development of two diseases: non-alcoholic fatty liver disease and inflammatory bowel disease. The company has already identified gene abundance profiles that correlate with certain disease states and plans to validate these biomarkers in a multicenter trial in the second half of this year.
For NAFLD, studies have shown that the gut microbiome composition impacts the development of the disease to a more serious inflammatory form. "Fatty liver itself is not a big issue; that itself doesn't increase your mortality or morbidity risk," Clerval said. "If the fatty liver becomes inflammatory, then you have an increased morbidity or mortality risk."
Today, he said, the only way to determine whether a patient suffers from the inflammatory form of the disease is a liver biopsy, so a biomarker test based on stool samples would make it easier to manage NAFLD patients appropriately.
Right now, Enterome is outsourcing its sequencing to INRA, which runs Life Technologies' SOLiD platform, but it is also collaborating with other academic groups that are using Illumina's sequencing platform. In addition, it plans to test Life Tech's Ion Torrent in the near future, as well as other sequencers.
Enterome will also be a partner in an incubator called MetaGenoPolis that will open next year, which will be housed at INRA and funded by the French government. MetaGenoPolis, which will have a budget of €19 million, will have a number of next-gen sequencers as well as stool biobanking and informatics capabilities available, Clerval said.
Over the next few months, Enterome will validate its gene abundance profiles on large cohorts of more than 100 patients. Next year, the company plans to launch a laboratory-developed test for NAFLD in the US, while in parallel carrying out a clinical validation study of the test's clinical utility. A launch of the test in Europe is planned for 2014 or 2015.
Most likely, that test will be based on a next-gen sequencing platform, Clerval said, although Enterome might switch it over to a qPCR platform if the list of relevant bacterial genes turns out to be small.
In addition to developing its test, Enterome is looking for partnerships with pharmaceutical or nutrition companies. Patients could be stratified for clinical trials based on their gut microbiome composition, the company believes, for example to focus on those patients at high risk of developing inflammatory forms of metabolic disorders.
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