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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Af­ter sell­ing to Genen­tech, the old Je­cure team is back at an RNA-fo­cused start­up — and more en­thu­si­as­tic than ever

When Genentech swooped in to buy NASH-focused Jecure Therapeutics back in 2018, a handful of the startup’s executives weren’t quite ready to disperse.

It had been just three years since Jecure launched with a preclinical portfolio of NLRP3 inhibitors — and the takeover came sooner than anyone, including CEO Jeff Stafford, had expected. So he got talking with James Veal and Gretchen Bain, two serial entrepreneurs in charge of Jecure’s R&D.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.