Enterome CEO Pierre Belichard

Takeda Pharmaceutical has agreed to license, co-develop, and co-promote Enterome’s lead candidate, the Phase Ib Crohn’s disease candidate EB8018, Enterome said today, through a collaboration that could generate more than $690 million for the French biotech focused on treating microbiome-associated diseases.

EB8018 is a novel, first-in-class, oral gut-restricted small molecule designed to selectively disarm virulent bacteria in the gut that can cause inflammation without disrupting the local microbiome. Enterome has been developing EB8018 since licensing the small molecule for an undisclosed amount from its discoverer Vertex Therapeutics in 2016.

EB8018 is designed to work by inhibiting FimH-mediated inflammation induced by the interaction of pathogenic pro-inflammatory bacteria to receptors in the gut wall, thereby potentially reducing the production of inflammatory cytokines including TNF.

Together with Takeda, Enterome plans to launch a Phase II clinical proof-of-concept trial of EB8018 in 2019. The companies are also partnering on a Phase Ib trial (NCT03709628) that has begun recruiting patients, according to an update posted Friday on ClinicalTrials.gov.

The Phase Ib trial will consist of eight patients and two parts: Part 1 is designed to demonstrate that a single oral dose of EB8018 that is safe and tolerable in patients with Crohn’s disease, while Part 2 will characterize the PK profile when administered as multiple oral doses. The new trial is intended to support the development of EB8018 as an add-on therapy, for the treatment of adult patients suffering from Crohn’s disease.

Enterome said its agreement with Takeda covers the development of EB8018 in Crohn’s disease, with the potential to expand to other unspecified gastrointestinal (GI) disorders and liver diseases.

“We are delighted to sign this agreement for EB8018, our most advanced candidate that represents a non-antibiotic, non-steroidal, non-immunomodulatory approach for the treatment of GI disorders including Crohn’s disease,” Enterome CEO Pierre Belichard said in a statement. “We believe we have a world-class partner in Takeda to deliver the best development and commercialization strategy for EB8018 based on their extensive expertise and focus in Crohn’s disease and GI disorders.”

GI is one of Takeda’s three therapeutic areas on which the company focuses R&D efforts—the others are oncology and neuroscience—though Takeda also develops vaccines against infectious diseases.

Positive Phase I Results

A year ago this month, Enterome trumpeted positive Phase I results for a first-in-human trial (NCT02998190) of EB8018, showing it to be safe and well tolerated in healthy volunteers across a wide range of doses tested, with minimal blood absorption.

FimH, a two-domain protein, is an adhesin that is overexpressed on the surface of bacteria that bloom in patients with Crohn’s Disease. FimH was validated as a novel microbiome-derived therapeutic target by Enterome through its proprietary metagenomics platform.

The platform is designed to enable identification of biomarkers and bacteria of interest associated with the development of diseases. The platform allows the characterization of a personal metagenome (metagenotype®) associated with a disease phenotype, based on full sequencing and mapping of total fecal bacterial gene content.

Takeda has agreed to pay Enterome $50 million upfront, and a future unspecified equity investment in the company. Takeda has also agreed to pay Enterome up to $640 million tied to achieving clinical development, regulatory, and commercial milestones with EB8018.

Enterome and Takeda agreed to co-develop EB8018, and if approved, co-promote the treatment in the U.S. under a profit/cost-sharing structure. Takeda will receive an exclusive license to commercialize EB8018 outside the U.S., with Enterome eligible for royalties on net sales generated there.

The collaboration for EB8018 is the second between the companies, and comes nearly three years after Takeda agreed to partner with Enterome in discovering new GI therapies. Takeda agreed in January 2016 to use Enterome’s metagenomic platform to discover new small molecules or biologics derived from gut bacteria and directed against GI targets selected by both companies, including inflammatory bowel disease and motility disorders.

Enterome was established in 2012 in Paris to develop discoveries made by the French National Institute for Agricultural Research (INRA) metagenomic platform. In January, Enterome raised €32 million ($36.7 million) in a Series D financing that attracted new investor Principia SGR—as well as strategic investor and collaboration partner Bristol-Myers Squibb—along with previous investors Seventure, Health for Life Capital, LundbeckFonden Ventures, Omnes Capital, and Nestlé Health Science.

In conjunction with its equity financing, Enterome entered into an agreement with the European Investment Bank for access to a €40 million ($45.9 million) loan facility to further support acceleration of its pipeline and technology development. The loan and financing brought Enterome’s total fundraising to €101.5 million ($116.4 million), according to Crunchbase.

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