LONDON – Sosei Heptares has added Genentech Inc. to the list of partners seeking access to its G protein-coupled receptor (GPCR) expertise, signing a collaboration with a headline value of $1 billion with the Roche Group company.

The collaboration brings together Sosei Heptares' GPCR structure-based discovery capabilities and Genentech's development expertise, around a series of targets nominated by Genentech.

The partnership will work on both small molecules and biologics. Malcolm Weir, chief R&D officer at Sosei Heptares, said it will be exciting "to see what the combination of our respective capabilities can deliver."

Sosei Heptares is getting $26 million in up-front and near-term payments. The $1 billion figure will be reached if specified research, development and commercialization milestones are achieved. In addition, royalties will be due on any marketed drugs resulting from the partnership.

The number and type of targets was not disclosed. "It is a collaboration working in areas of interest to each company," Weir said. "The indications are all in areas of very high unmet need, where people are crying out for innovation," he told BioWorld.

The techniques Sosei Heptares has developed for stabilizing GPCRs to make them amenable to structure-based drug design have made an important contribution to opening up that class of drug targets. However, it remains the case that of around 400 known GPCR targets, 56% have not been drugged.

Weir said the company has been adding to its range of tools, most recently installing a cryo-electron microscopy capability at its new R&D center in Cambridge U.K., enabling it to image biomolecules.

"We start with the protein GPCR target; we stabilize it, solve it. We have increased the ways we can do this over the years, staying at the forefront of the field," said Weir. In parallel, the company has got faster at moving from target to preclinical candidate. "The timelines are certainly better than they were in years gone by," Weir said.

This is one of the bigger deals Sosei Heptares has done based on access to its platform technology. "We're not talking about assets we've developed to a later stage and out-licensed. This is very much driven off our discovery capabilities," Weir said.

The largest deal inked by Sosei Heptares to date is a $3.3 billion collaboration with Allergan plc in Alzheimer's disease and other neurological disorders, signed in April 2016. Sosei Heptares received $125 million up front. (See BioWorld, April 8, 2016.)

Weir said as yet, there is "nothing to say" about whether Abbvie Inc.'s proposed $63 billion acquisition of Allergan will have any impact on Sosei Heptares' relationship with the Dublin-based company. The cash-and-share deal, giving Abbvie shareholders 83% of Allergan's equity, will not be completed until early next year.

Part of the program of research between Allergan and Sosei Heptares stalled last year after cynomolgus monkeys in a toxicology study of HTL-0018318 developed neoplastic tumors.

The study was carried out in preparation for Allergan to launch a U.S. phase I study of the small-molecule muscarinic M1 receptor agonist. Before that, around 310 healthy volunteers and patients had received the orally administered product in European studies, with no ill effects. The two companies have put a voluntary hold on the program. (See BioWorld, Sept 19, 2018.)

Since the suspension, Sosei Heptares has seen interim phase I data from the European study, which it says "supports the hypothesis for selective M1 agonism." Work to investigate causes of the toxicity seen in the animal study, which is being fully funded by Allergan, is "progressing well."

The voluntary hold means Sosei Heptares also has delayed the start of a planned phase IIa Japanese trial of HTL-0016878 in dementia with Lewy bodies, a program that it wholly owns.

Allergan and Sosei Heptares are going ahead with an M4 agonist in Alzheimer's disease, and this product is expected to complete phase I in the next 12 to 18 months.

Over the past 10 years, Sosei Heptares has identified or contributed to the discovery of 22 GPCR-targeted drugs, of which three are in clinical development. The most advanced product generated by the platform is AZD-4635, an A2a antagonist, which is being developed in the treatment of multiple solid tumors.

In January, Astrazeneca plc said it was moving the product into phase II, triggering a $15 million milestone payment to Sosei Heptares, and bringing total up-front and milestones paid since the partnerships was formed in 2015 to $47 million.

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