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

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.

Tom Mc­Carthy

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.

Stu­art Hugh­es

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.

The Price of Re­lief: Ex­plor­ing So­lu­tions to the Ris­ing Costs of On­col­o­gy Drugs

In 2020, The National Cancer Institute estimated about 1.8 million new cases of cancer diagnosed in the United States, while the costs associated with treatment therapies continued to escalate. Given the current legislative climate on drug pricing, it’s never been more important to look at the evolution of drug pricing globally and control concerns of sustainable and affordable treatments in oncology.

Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

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Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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