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.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

Pssst: That big Bio­haven Alzheimer's study? It was a bust. Even the sub­group analy­sis ex­ecs tout­ed was a flop

You know it’s bad when a biopharma player plucks out a subgroup analysis for a positive take — even though it was way off the statistical mark for success, like everything else.

So it was for Biohaven $BHVN on MLK Monday, as the biotech reported on the holiday that their Phase II/III Alzheimer’s study for troriluzole flunked both co-primary endpoints as well as a key biomarker analysis.

The drug — a revised version of the ALS drug riluzole designed to regulate glutamate — did not “statistically differentiate” from placebo on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).  The “hippocampal volume” assessment by MRI also failed to distinguish itself from placebo for all patients fitting the mild-to-moderate disease profile they had established for the study.

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Hal Barron, GSK R&D chief (GSK via YouTube)

Glax­o­SmithK­line's $4B bis­pe­cif­ic can­cer drug al­liance with Mer­ck KGaA hit by set­back with a fail­ure on NSCLC

Close to 2 years ago, GSK’s R&D team eagerly agreed to pay up to $4 billion-plus to ally itself with Merck KGaA on a mid-stage bispecific called bintrafusp alfa, which intrigued them with the combination of a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein.

But today the German pharma company says that their lead study on lung cancer was a bust, as independent monitors said there was no reason to believe that the experimental drug — targeting PD-L1/TGF-Beta — could beat Keytruda.

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Bris­tol My­ers Squibb gets re­view date for Op­di­vo com­bo in gas­tric can­cer, look­ing to over­turn Keytru­da's 3-year lead

The past two months have been tough for Bristol Myers Squibb and its checkpoint inhibitor Opdivo after setbacks in lung and brain cancers. But in the battle against Merck’s Keytruda, any success matters — and now Bristol could be looking at a quick approval for Opdivo in an unmatched indication.

The FDA will launch a speedy review of a combination of Bristol Myers Squibb’s Opdivo and chemotherapy to treat first-line patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, the drugmaker said Wednesday. The agency set an action date of May 25 for the application.

Covid-19 claims an­oth­er PDU­FA vic­tim as Glax­o­SmithK­line push­es back planned PD-1 roll­out

Bristol Myers Squibb isn’t the only pharma giant that’s been standing in the FDA’s waiting line for site inspections.

GlaxoSmithKline is telling us today that their H2 2020 PDUFA deadline for the PD-1 drug dostarlimab — picked up in its Tesaro buyout — was pushed back due to a delay in the manufacturing site inspection needed for a regulatory decision. And that is forcing the company to revise its timeline.

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The IPO flood keeps ris­ing with 4 more biotechs and a SPAC on their way to Nas­daq

After a record year for biotech IPOs in 2020, forecasts were bullish on another strong year showing for public offerings — and 2021 hasn’t disappointed so far. Now, a clutch of four biotechs chasing rare disease and cancer and a New York SPAC are ready to join the party.

Three more companies filed to head to Nasdaq on Tuesday, as well as a SPAC, with an additional Dutch biotech filing Friday. All in all, early days indicate another big year, at least to start, with 12 companies either pricing or filing their IPOs in the first 20 days of January.

Janet Woodcock and Joshua Sharfstein (AP, Images)

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It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.

Artist rendering of the Assembly Square site in Somerville, MA (BioMed Realty)

Bio­Med Re­al­ty snaps up in­no­va­tion cam­pus site with­in earshot of pricey and bustling Boston biotech hub

On the short list of the premier biotech hubs in the world, the Boston area has transformed into a home for innovation — and ridiculously high rent. Now, a real estate firm is seeking tenants for a major site in neighboring Somerville with more than enough elbow room.

Snapped up by BioMed Realty, the land — which consists of an existing 162,000 square-foot office building and a 7.5 acre site — will serve as an “innovation space” for a variety of research, technology and life science tenants, the real estate company said in a press release. Financial terms weren’t disclosed.

Sanofi protests, AP Images

Paul Hud­son faces down French unions in fight to re­struc­ture Sanofi

Sanofi CEO Paul Hudson is facing a familiar adversary in his efforts to cut up to 1,680 jobs from the French pharma giant: French unions.

Around 200 union members staged a one-day strike Tuesday at Sanofi’s main Covid-19 vaccine plant in Marcy-l’Étoile to protest the cuts, The Associated Press reported, with other members joining at other facilities across the country.

France’s finance minister Bruno Le Maire, meanwhile, went on French radio twice this week to talk about the company. On Monday, per Reuters, he told RTL that Sanofi would not close any plants or lay off any employees in the restructuring. But on Wednesday morning, he re-emerged on BFM and said he would like three things from the drugmaker, including confirmation that there will be no site closures and layoffs.