LONDON – It's the technology that keeps on giving, and the Heptares unit of Sosei Group Corp. has attracted a further partner to its G protein-coupled receptor (GPCR) platform, signing up Takeda Pharmaceutical Ltd., in a deal worth up to $1.2 billion.

That figure is some way down the line, if and when there are marketed products, but for starters there is $26 million in up-front and near-term milestone payments, in addition to full funding for all the research Cambridge, U.K.-based Sosei Heptares carries out on Takeda's account.

Sosei Heptares also is eligible to receive tiered royalties on any products that make it to market. Takeda has exclusive global rights to all programs.

The agreement takes Sosei Heptares' GPCR stabilization technology in a new direction partnering-wise, with this being the first deal it has done in gastroenterology, one of Takeda's specialist areas.

While the collaboration initially will focus on gastrointestinal (GI) targets, the agreement leaves room to expand into other indications.

"There is a strong start in GI, and that's the major thrust to the deal. It's our first in GI and certainly one that is led by Takeda's strengths there, and the strengths of our platform," Malcolm Weir, chief R&D officer of Sosei Heptares, told BioWorld Asia.

Weir said Sosei and Takeda already have shared roots, with the venture arm of Takeda investing in Heptares following its formation in 2007. That led to Sosei acquiring the U.K. Medical Research Council spinout for up to $400 million in February 2019.

None of the targets in the new partnership are being disclosed. However, Sosei Heptares has two early in-house programs in inflammatory bowel disease (IBD). "We are not specifying what [targets] are in, or are out, or at what stage, but Takeda is very committed to GI and they have got embedded translational capabilities that will work backwards, to speed up our discovery work," said Weir.

Gareth Hicks, head of the gastroenterology drug discovery unit at Takeda, said GPCRs provide "an exciting avenue" for discovery in gut inflammation and motility disorders.

Recent research has uncovered a diverse and complex range of possible GI targets, with GPCRs of epithelial cells, myocytes, enteric neurons and immune cells shown to be involved in cell-to-cell communication in the GI tract. Those are variously involved in secretion, motility, transport, inflammation and pain.

According to Weir, there are as yet only symptomatic drugs targeting GPCRs in the digestive system, such as loperamide (Imodium) for diarrhea or domperidone (Motilium) for constipation. "There is nothing targeting IBD pathophysiology," he said.

Sosei Heptares' in-house IBD programs are aimed at G protein-coupled receptor 35 and EP4 (E-type prostanoid receptor 4). Both are small molecules that Sosei Heptares said have limited systemic exposure and are aimed to act locally in the inflamed gut.

Takeda has one disclosed pipeline program in IBD, EB-8018 (now TAK-018), a treatment for Crohn's disease, which it in-licensed from Enterome SA in a $640 million deal last year. The product is a first-in-class small-molecule antagonist of FimH, an adhesion protein expressed by gram-negative Enterobacteriaceae in the gut, which are implicated in Crohn's pathology. (See BioWorld, Oct. 24, 2018.)

The deal with Takeda comes within weeks of signing a similar-size agreement with Genentech Inc., with Sosei Heptares again in line to receive $26 million in up-front and near-term payments, plus R&D funding, and a potential future value of $1 billion. (See BioWorld, July 17, 2019.)

Before that, Sosei Heptares spun out two drug development programs for narcolepsy into two standalone companies, Orexia Ltd. and Inexia Ltd., after securing up to $40 million funding from the Medicxi venture capital firm.

"The Takeda deal is a very healthy block of revenue, coming straight on top of Genentech," Weir said. "If you add the two together, it is very significant."

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