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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 119,700+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

Endpoints Premium

Premium subscription required

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

Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

Endpoints Premium

Premium subscription required

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

Yao-Chang Xu, Abbisko Therapeutics founder and CEO

Qim­ing-backed Ab­bisko makes $200M+ Hong Kong de­but, as a SPAC and Agenus spin­out al­so price on Nas­daq

Three new entities priced their public debuts late Thursday and early Friday, including a SPAC, a traditional Nasdaq IPO and a Chinese biotech joining the Hong Kong Index.

Shanghai-based Abbisko Therapeutics raised the most money of the triumvirate, garnering $226 million in its Hong Kong debut and pricing at HK$12.46, or roughly $1.60 in US dollars. The blank check company followed up with a $150 million raise, while MiNK Therapeutics priced on Nasdaq at $12 per share and a $40 million raise.

Paul Grayson, Tentarix CEO (Versant)

Phar­ma vet­er­ans re­group with $50M and a plan to dis­cov­er new mul­ti-specifics

While a horde of drugmakers develops bispecific antibodies to more directly target tumor cells — there were about 100 programs in or nearing clinical trials back in May — a new company is emerging to go one step further.

On Thursday, Tentarix Biotherapeutics unveiled a $50 million Series A round to support its next-gen multi-specifics platform. While the field has largely focused on bispecifics, which engage two targets, Tentarix believes its multifunctional programs have the potential to be even more specific, since more conditions must be met for potent activity to occur.

Tillman Gerngross, Adagio CEO

Q&A: Till­man Gern­gross ex­plains why his Covid mAb will have an edge over an al­ready crowd­ed field

If anyone knows about monoclonal antibodies, it’s serial entrepreneur, Adimab CEO, and Dartmouth professor of bioengineering Tillman Gerngross.

Even the name of Gerngross’ new antibody startup Adagio Therapeutics is meant to reflect his vision behind the development of his Covid-19 mAb: slowly, he said, explaining that “everyone else, whether it’s Regeneron, Lilly, or AstraZeneca, Vir, they all valued speed over everything.”

Endpoints Premium

Premium subscription required

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