Christoph Lengauer, Thrive co-founder (Third Rock Ventures)

Third Rock-backed star­tup's blood test can sniff out can­cer in pa­tients with no his­to­ry of dis­ease

The myr­i­ad of liq­uid biop­sy com­pa­nies work­ing on blood tests for ear­ly can­cer de­tec­tion have been con­duct­ing ret­ro­spec­tive stud­ies, look­ing at how ef­fec­tive and sen­si­tive their tech­nol­o­gy is in spot­ting can­cer in pa­tients that have al­ready been di­ag­nosed. Now, a Third Rock Ven­tures-backed start­up has al­so shown its blood test can per­form in a large prospec­tive study in­volv­ing pa­tients with no per­son­al his­to­ry of can­cer.

The com­pa­ny, apt­ly named Thrive Ear­li­er De­tec­tion, is bet­ting on Can­cerSEEK — its blood test-in-de­vel­op­ment de­signed to sniff out a wide va­ri­ety of can­cer types by in­ter­ro­gat­ing ge­nom­ic mu­ta­tions in cir­cu­lat­ing tu­mor DNA (ctD­NA) as well as pro­tein mark­ers in plas­ma that have been im­pli­cat­ed in can­cer.

The tri­al — chris­tened DE­TECT-A — eval­u­at­ed the blood test in more than 9,900 women aged 65 to 75 with no ev­i­dence or his­to­ry of can­cer.

Can­cerSEEK is en­gi­neered to not on­ly be pow­ered to iden­ti­fy the pres­ence of rel­a­tive­ly ear­ly can­cer, but it us­es ma­chine learn­ing to lo­cal­ize the or­gan of ori­gin of can­cer — even­tu­al­ly, the hope is the test will be used as part of the ar­se­nal of rou­tine med­ical screen­ing tools to com­ple­ment ex­ist­ing dis­ease-spe­cif­ic screen­ing meth­ods such as mam­mog­ra­phy and colonoscopy.

“The mo­ti­va­tion for this study was, how does this look like in a re­al-world set­ting? How does the blood test per­form in nor­mal in­di­vid­u­als, which means they have co­mor­bidi­ties?” said Christoph Lengauer, the com­pa­ny’s co-founder and chief in­no­va­tion of­fi­cer. “It’s the first in­ter­ven­tion­al study, which means that the re­sults of the test are giv­en back to the physi­cian and then shared with the pa­tient and then de­ci­sions (on treat­ment) get made.”

Over­all, 96 cas­es of can­cer were iden­ti­fied among the 9,911 par­tic­i­pants with­in 12 months of en­roll­ment. Da­ta showed that Can­cerSEEK de­tect­ed 26 can­cers — 17 can­cers were di­ag­nosed at an ear­ly stage (lo­cal­ized or re­gion­al to the area it orig­i­nat­ed from), of which 12 were able to be sur­gi­cal­ly re­moved. The di­ag­noses were con­firmed by PET-CT scans.

Stan­dard screen­ing meth­ods, such as mam­mog­ra­phy or colonoscopy, pin­point­ed an­oth­er 24 can­cers. The re­main­ing 46 cas­es were not first de­tect­ed by ei­ther blood test­ing or by stan­dard screen­ing — in most of those cas­es di­ag­nos­tic tests were ini­ti­at­ed on the ba­sis of pa­tient symp­toms.

“We didn’t know ba­si­cal­ly how our test fits in­to re­al­i­ty … and the re­al­i­ty is that to­day 75% of all can­cers that hap­pen are iden­ti­fied by symp­toms. With the in­tro­duc­tion of colono­scopies and mam­mo­gra­phies, that changed, be­cause now you can de­tect some of those can­cers ear­li­er,” Lengauer said. “We want­ed to see what our test can add to it in ad­di­tion to stan­dard-of-care (screen­ing) … that was sur­pris­ing be­cause our test end­ed up dou­bling the num­ber of what can be de­tect­ed by screen­ing.”

Over­all, the speci­fici­ty of the Thrive test came in at 99.6% — “there were al­most no false pos­i­tives,” said Lengauer.

The re­sults showed Can­cerSEEK aug­ment­ed the ben­e­fit of stan­dard-of-care screen­ing for breast, colon and lung tu­mors im­prov­ing sen­si­tiv­i­ty from 47% to 71% — and al­so al­lowed the de­tec­tion of sev­en oth­er can­cer types (lym­phoma, ap­pen­dix, uter­ine, thy­roid, kid­ney, ovary and can­cers aris­ing from an un­known pri­ma­ry site) that can­not be screened now, with a sen­si­tiv­i­ty of 31%.

In 2018, pub­lished da­ta from a ret­ro­spec­tive study, en­com­pass­ing 1,005 pa­tients with non-metasta­t­ic, clin­i­cal­ly de­tect­ed can­cers of the ovary, liv­er, stom­ach, pan­creas, esoph­a­gus, col­orec­tum, lung or breast, showed that Can­cerSEEK tests were pos­i­tive in a me­di­an of 70% of the eight can­cer types.

Armed with these da­ta, Thrive is gear­ing up to con­duct a reg­is­tra­tional study, which should en­roll an even big­ger num­ber of pa­tients than DE­TECT-A, said Lengauer.

Can­cerSEEK has been grant­ed the FDA’s break­through de­vice sta­tus, as has Grail’s mul­ti-can­cer de­tec­tion blood test, which re­lies on DNA se­quenc­ing to as­sess methy­la­tion, an epi­ge­net­ic change across the genome to ex­pose can­cer sig­nals.

Grail, which was spun out of DNA se­quenc­ing com­pa­ny Il­lu­mi­na $ILMN in 2016, has raised $1.6 bil­lion in fund­ing to fu­el the de­vel­op­ment of its test, which is now be­ing eval­u­at­ed in three large-scale stud­ies that will al­to­geth­er en­roll 165,000 in­di­vid­u­als. Sim­i­lar­ly de­signed as Thrive’s DE­TECT-A study, Grail is cur­rent­ly en­rolling pa­tients in a prospec­tive PATHFIND­ER tri­al, which is de­signed to as­sess the util­i­ty of its ear­ly de­tec­tion blood test in clin­i­cal prac­tice.

Oth­er com­pa­nies such as Guardant Health and Bio­cept are al­so work­ing on their own liq­uid biop­sy tests. Each com­pa­ny is look­ing to cham­pi­on con­sis­ten­cy and ac­cu­ra­cy — false pos­i­tives in­duce un­nec­es­sary anx­i­ety, and are cost­ly. An­oth­er con­cern is, of course, pri­va­cy.

Sin­gle dis­ease tests, such as Ex­act Sci­ence’s Co­lo­guard, car­ry list prices of $600 or $700 and mam­mo­gra­phies cost be­tween $100 to $200 — if ap­proved, Thrive’s mul­ti-can­cer test Can­cerSEEK would be priced “in the hun­dreds of dol­lars com­mer­cial­ly, not thou­sands of dol­lars,” com­pa­ny of­fi­cials sug­gest­ed in an in­ter­view with End­points News last year, when Thrive launched and raised $110 mil­lion in a Se­ries A fi­nanc­ing.

Now, as it works on plans for a large reg­is­tra­tional study, rais­ing cap­i­tal will be im­per­a­tive, Thrive ex­ec­u­tives said.

“We have to raise more mon­ey be­cause this is very ex­pen­sive. And this is part of the chal­lenge in the screen­ing space … we just did (a study with) 10,000 pa­tients, I mean, it costs a lot of mon­ey,” said Lengauer.

“There­fore this sum­mer, we will raise more mon­ey,” he added, with­out dis­clos­ing specifics.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

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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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.

‘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)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

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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