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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.

Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Stephen Squinto, Gennao Bio chairman

Scoop: Stephen Squin­to’s Yale spin­out is rais­ing a Se­ries B for ge­net­ic med­i­cines

The nucleic acid therapeutics at Stephen Squinto’s Yale-originated biotech are en route to a $40 million R&D payday.

After a Series A of that size in the spring of 2021, Hopewell, NJ-based Gennao Bio is closing on a round of the same amount, Endpoints News has learned. A Series B is in the works, according to an investor’s post on LinkedIn and as confirmed by a spokesperson. An SEC filing on Thursday outlines $15 million in equity sold thus far in the round.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.

WIB22: Lead­ing NK cell re­searcher re­flects on roots in Iran, the UK and Texas

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

In a small but widely-cited 11-person study published in NEJM in 2020, seven patients saw signs of their cancer completely go away after getting a new therapy made from natural killer cells. The study was one of the earliest to provide clinical proof that the experimental treatment method had promise.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.