Canaan backs Pathios’ search for small molecule drugs that hit ‘orphan’ GCPR

December 18, 2019

As fruitful as G protein-coupled receptors have proved for modern medicine — by common estimates, more than 30% of FDA-approved drugs target this class of proteins — there are still dozens of “orphan” GPCRs whose endogenous ligands are poorly understood. One of them is GPR65, a pH sensing receptor that British biotech Pathios believes plays a crucial role in both cancer and autoimmune diseases.

Oxford-based Pathios was founded in 2017 by Tom McCarthy, a biotech vet and one-time VC who has two other ventures to his name: Spinifex Pharmaceuticals, a pain-focused company ultimately acquired by Novartis; and the immuno-oncology upstart Grey Wolf. With $8.8 million in Series A funding and Stuart Hughes coming on board as CEO, Pathios is well on the way to generating its first leads.

Hughes most recently headed pharmacology at Vertex’s Oxfordshire office, having cut his teeth in drug discovery at Eli Lilly. The emphasis on lean and effective project leadership he’s used to is very much present at Pathios, he said, where he will be managing a small team working with a cadre of external partners.

“It really is a very focused technical small molecule drug discovery effort,” Hughes told Endpoints News.

Earlier this year the biotech brought in Sygnature Discovery to hunt for modulators of GPR65, leveraging the CRO’s medicinal chemistry expertise and screening tools. The CRO took a small stake in Pathios as part of the payment.

The idea behind their laser-focused pursuit of GPR65 has two dimensions: Not only does GPR65 appear to be characteristic of certain T helper 17 cell populations that reportedly contribute to the pathology of autoimmune conditions such as ankylosing spondylitis and psoriatic arthritis, but it also appears to drive tumor associated macrophages “to adopt a phenotype that supports cancer immune evasion,” according to the company.

As GPR65 tends to be active in acidic environments, Hughes added, cancers that are particularly glycolytic — ones that produce lactic acid — such as advanced melanoma could be especially suited for this approach.

“We are now on the verge of clearly defining the biological processes GPR65 controls, (its) genetic links to disease and how small molecules can modulate its signalling,” McCarthy said in a statement.

While the special properties of GPR65 present some unique challenges, “the good thing is GPCRs obviously are a very druggable target class,” Hughes said.

Canaan Partners, which led the Series A for Grey Wolf in February and had backed Spinifex, also played a prominent role here alongside Canaan and Australia’s Medical Research Commercialisation Fund managed by Brandon Capital.

Amber Tong
18 December, 2019

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