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.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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#ES­MO20: 'As good as any PD-1 out there': Re­gen­eron flash­es PD-(L)1 lung can­cer da­ta to ri­val Mer­ck

Regeneron entered the PD-(L)1 game late, so they devised a two-pronged strategy to catch up with Big Pharma rivals: They would push it into cancers where PD-1s had yet been tested, and they would prove that it’s as powerful in the big indications as any other on the market.

They cleared a hurdle on the first goal Friday, showing a 31% response in patients with the rare skin cancer basal cell carcinoma. And with the data they’re rolling out Monday, Regeneron cancer chief Israel Lowy is ready to declare success on the second.

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Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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As­traZeneca pub­lish­es Covid-19 vac­cine PhI­II pro­to­cols in lock­step with Mod­er­na and Pfiz­er. How are they dif­fer­ent?

Following in the steps of Moderna and Pfizer, the other two American drugmakers currently in Phase III trials for their Covid-19 vaccines, AstraZeneca posted its own study protocols over the weekend. The move is the latest in a series of rare peeks behind the curtain, as such blueprints are typically shared once such trials are completed.

“Given the unprecedented global impact of the Coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial. As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials. AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company said in a statement.

Eli Lilly CSO Dan Skovronsky (file photo)

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The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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Sebastian Nijman (file photo)

Roche looks to ge­net­ic mod­i­fiers for new drug tar­gets, team­ing up with Dutch biotech in $375M deal

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A spinout of the Netherlands Cancer Institute and Oxford University, Scenic Biotech set out to pioneer a field that’s gaining some traction among top VCs in the US: to harness the natural protecting powers of genetic modifiers — specific genes that suppress a disease phenotype.

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After decades of failure targeting KRAS, sotorasib offered the first positive look at a new approach that promised to open a door to a whole new approach by targeting a particular mutation to a big target that had remained “undruggable” for decades.

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#ES­MO20: Out to beat Tagris­so, J&J touts 100% ORR for EGFR bis­pe­cif­ic/TKI com­bo — fu­el­ing a quick leap to PhI­II

J&J’s one-two punch on EGFR-mutant non-small cell lung cancer has turned up some promising — although decidedly early — results, fueling the idea that there’s yet room to one up on third-generation tyrosine kinase inhibitors.

Twenty out of 20 advanced NSCLC patients had a response after taking a combination of an in-house TKI dubbed lazertinib and amivantamab, a bispecific antibody targeting both EGFR and cMET engineered on partner Genmab’s platform, J&J reported at ESMO. All were treatment-naïve, and none has seen their cancer progress at a median follow-up of seven months.