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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Gilead bol­sters its case for block­buster hope­ful fil­go­tinib as FDA pon­ders its de­ci­sion

Before remdesivir soaked up the spotlight amid the coronavirus crisis, Gilead’s filgotinib was the star experimental drug tapped to rake in billions competing with other JAK inhibitors made by rivals including AbbVie and Eli Lilly.

Now, long term data on the drug — discovered by Gilead’s partners at Galapagos and posted as part of a virtual medical conference — have solidified the durability and safety of filgotinib in patients with rheumatoid arthritis, spanning data from three late-stage trials. An FDA decision on the drug is expected this year.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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