Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

An­oth­er Big Phar­ma is en­ter­ing the Covid-19 an­ti­body hunt.

Ab­b­Vie has an­nounced a col­lab­o­ra­tion with the Nether­lands’ Utrecht Uni­ver­si­ty and Eras­mus Med­ical Cen­ter and the Chi­nese-Dutch biotech Har­bour Bio­med to de­vel­op a neu­tral­iz­ing an­ti­body that can treat Covid-19. The an­ti­body, called 47D11, was dis­cov­ered by Ab­b­Vie’s three part­ners, and Ab­b­Vie will sup­port ear­ly pre­clin­i­cal work, while prepar­ing for lat­er pre­clin­i­cal and clin­i­cal de­vel­op­ment. Re­searchers de­scribed the an­ti­body in Na­ture Com­mu­ni­ca­tions last month.

Al­though ear­ly in the out­break, Ab­b­Vie con­tributed its HIV an­tivi­ral cock­tail Kale­tra to clin­i­cal tri­als, this is the drug com­pa­ny’s first for­ay in­to de­vel­op­ing new treat­ments for the nov­el virus. Al­though the Illi­nois-based phar­ma has lit­tle ap­par­ent ex­pe­ri­ence in de­vel­op­ing an­ti­bod­ies for virus­es, much of their com­mer­cial and re­search work cen­ters on an­ti­bod­ies, in­clud­ing with the block­buster TNF-block­ing an­ti­body Hu­mi­ra.

Last Au­gust, an NIH-fund­ed clin­i­cal tri­al found two dif­fer­ent an­ti­body treat­ments to be the first and on­ly ef­fec­tive treat­ments for Ebo­la, and when the new coro­n­avirus emerged in De­cem­ber, re­searchers jumped in ear­ly to be­gin de­vel­op­ing an­ti­bod­ies for it. Most promi­nent­ly, Re­gen­eron, which de­vel­oped one of the ef­fec­tive Ebo­la treat­ments, and Vir, which owns the plat­form that helped de­vel­op the oth­er one, an­nounced pro­grams in late Jan­u­ary and ear­ly Feb­ru­ary.

Ab­Cellera, a com­pa­ny known for help­ing Big Phar­ma and ma­jor biotechs de­vel­op their an­ti­bod­ies, then fol­lowed up with a pro­gram in part­ner­ship with Eli Lil­ly. Ear­li­er this week, that pro­gram was the first to en­ter clin­i­cal tri­als, al­though Vir and Re­gen­eron are each ex­pect­ed to start their own pro­grams short­ly. David Ho, the renowned HIV re­searcher and Co­lum­bia Uni­ver­si­ty pro­fes­sor, is work­ing on his own an­ti­body project, as are a long list of oth­er re­searchers and small biotechs.

Neu­tral­iz­ing an­ti­bod­ies are a part of the body’s nat­ur­al re­sponse to in­fec­tion, as B cells cre­ate mol­e­cules that match re­cep­tors on the virus and, ide­al­ly, block its abil­i­ty to en­ter cells while re­cruit­ing oth­er im­mune cells to at­tack. That process though can take days or weeks, dur­ing which time the in­fec­tion can spread. Over the last few decades, re­searchers have de­vel­oped pro­grams to cre­ate these an­ti­bod­ies ar­ti­fi­cial­ly through trans­genic mice or by ex­tract­ing them from the blood of sur­vivors. You can then give them to pa­tients as a treat­ment or a pre­ven­ta­tive mea­sure.

Cre­at­ing a can­di­date an­ti­body, though, is on­ly step one, and the one that Ab­b­Vie has part­nered on still has sig­nif­i­cant steps to take. The com­pa­ny holds an op­tion to li­cense for com­mer­cial and clin­i­cal de­vel­op­ment. — Ja­son Mast

As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

For­get 1 bil­lion. As­traZeneca is now promis­ing to sup­ply 2 bil­lion dos­es of Ox­ford Uni­ver­si­ty’s Covid-19 vac­cine around the world per year.

Three new part­ners are com­ing on board to help reach that goal, as well as a broad­er vi­sion to en­sure ac­cess for na­tions that have been large­ly left out of the bar­gain­ing ta­ble.

CEPI — the coali­tion that’s been dol­ing out grants to sup­port oth­er vac­cine projects — is pro­vid­ing $383 mil­lion to sup­port man­u­fac­tur­ing of 300 mil­lion dos­es, while Gavi the Vac­cine Al­liance will chip in $367 mil­lion and be in charge of the pro­cure­ment and dis­tri­b­u­tion, a spokesper­son told Wall Street Jour­nal. A sep­a­rate li­cens­ing agree­ment di­rects the Serum In­sti­tute of In­dia to pro­duce 1 bil­lion dos­es for low- and mid­dle-in­come coun­tries, with the first 400 mil­lion due be­fore the end of the year.

As­traZeneca CEO Pas­cal So­ri­ot stressed in a state­ment that the vac­cines will be pro­vid­ed “at no prof­it” dur­ing the pan­dem­ic.

The al­lo­ca­tion of vac­cines has be­come a top con­cern as gov­ern­ments scram­ble to se­cure first dibs for their cit­i­zens, trig­ger­ing fears that peo­ple in poor­er coun­tries — pop­u­la­tions who are most vul­ner­a­ble to out­breaks — will be left out.

Ox­ford re­searchers al­so ap­pear to be keep­ing that in mind as they or­ga­nize the clin­i­cal tri­als, an­nounc­ing to­day that Brazil­ian health au­thor­i­ties have cleared an ap­pli­ca­tion to in­clude Brazil in the Phase III tri­al of the re­com­bi­nant ade­n­ovirus vac­cine can­di­date.

The uni­ver­si­ty has be­gun re­cruit­ing 10,000 par­tic­i­pants in the UK while As­traZeneca en­rolls 30,000 in the US. For Brazil, the goal is to test the vac­cine in 2,000 vol­un­teers.

“Brazil is a pri­or­i­ty for the study be­cause of the as­cen­dant curve of the COVID-19,” they wrote. — Am­ber Tong

CSL com­mits to fund­ing, man­u­fac­tur­ing Aus­tralian vac­cine can­di­date

Aus­tralian phar­ma gi­ant CSL is throw­ing its weight be­hind a Covid-19 vac­cine de­vel­oped at the Uni­ver­si­ty of Queens­land, help­ing fund the de­vel­op­ment and sign­ing up as the man­u­fac­tur­er.

UQ re­searchers are work­ing with a “mol­e­c­u­lar clamp” en­abled vac­cine, whose core idea is to “lock” the un­sta­ble, pre­fu­sion ver­sion of the sur­face pro­teins on en­veloped virus to gen­er­ate syn­thet­ic pro­teins that can elic­it a more ef­fi­cient im­mune re­sponse. They have been ex­per­i­ment­ing with a cou­ple of ad­ju­vants, one from GSK and an­oth­er pro­vid­ed by CSL sub­sidiary Se­qirus.

To­geth­er with CEPI — which had backed the tech­nol­o­gy plat­form with a $10.6 mil­lion grant in ear­ly 2019, and lat­er came back to fund a Covid-19 project — CSL will sup­port the up­com­ing Phase I safe­ty study as well as lat­er-stage tri­als.

They will al­so prep their fa­cil­i­ties in Mel­bourne for large-scale man­u­fac­tur­ing. Should the vac­cine be proven ef­fec­tive, they ex­pect to scale the pro­duc­tion to 100 mil­lion dos­es to­ward the end of 2021, while sub­con­tract­ing out to oth­er CMOs around the world.

“We’ll go as fast as we can, we’re em­pha­sis­ing it is a high-risk project,” CSO An­drew Cuth­bert­son told the Syd­ney Morn­ing Her­ald. — Am­ber Tong

Lancet, NE­JM re­trac­tions height­en scan­dal around pa­pers tied to con­tro­ver­sial da­ta an­a­lyt­ics firm

In the world of aca­d­e­m­ic re­search, the coro­n­avirus cri­sis has glo­ri­fied the adage: Shoot first, ask ques­tions lat­er.

Sci­en­tists, des­per­ate to sep­a­rate the wheat from the chaff to has­ten the search for a vi­able ther­a­peu­tic, have been lean­ing heav­i­ly on preprint servers to vault their find­ings in­to the pub­lic sphere even be­fore their peers have a chance to re­view their work. But now, the first big re­search ca­su­al­ty of the cri­sis has emerged from two pres­ti­gious med­ical jour­nals.

It all start­ed with a May 22 pa­per in the Lancet, which de­pict­ed the re­sults of a large ret­ro­spec­tive study on 96,000 Covid-19 pa­tients, us­ing hos­pi­tal records pro­cured by a lit­tle-known da­ta an­a­lyt­ics com­pa­ny Sur­gi­sphere. The con­clu­sion — that coro­n­avirus pa­tients tak­ing chloro­quine or hy­drox­y­chloro­quine were more like­ly to ex­pe­ri­ence ir­reg­u­lar heart rhythms and were more like­ly to die — erod­ed al­ready wan­ing sci­en­tif­ic in­ter­est in the malar­ia ther­a­pies cham­pi­oned by Pres­i­dent Don­ald Trump to such a de­gree that a num­ber of key ran­dom­ized, place­bo-con­trolled tri­als test­ing them, in­clud­ing one by the WHO, ground to a halt.

Ear­li­er this week, how­ev­er, con­cerns about the ret­ro­spec­tive study and oth­er tri­als by the same lead au­thor and Har­vard pro­fes­sor Man­deep Mehra us­ing Sur­gi­sphere da­ta sur­faced. Af­ter an open let­ter signed by 150 doc­tors called in­to ques­tion the pa­per’s con­clu­sions and asked for pub­lic ac­cess to peer re­view com­men­tary that pre­ced­ed pub­li­ca­tion, on Tues­day Lancet ed­i­tors ac­knowl­edged that “im­por­tant sci­en­tif­ic ques­tions have been raised about da­ta re­port­ed” and that an in­de­pen­dent au­dit had been com­mis­sioned. On Wednes­day, the WHO restart­ed its tri­al. Yes­ter­day, the Lancet pa­per was re­tract­ed.

Sur­gi­sphere, the Chica­go-based com­pa­ny found­ed by the fourth au­thor of the Lancet pa­per Sapan De­sai, re­fused to trans­fer the full dataset, client con­tracts, and the full ISO au­dit re­port to their servers for analy­sis, cit­ing con­fi­den­tial­i­ty rea­sons. “As such, our re­view­ers were not able to con­duct an in­de­pen­dent and pri­vate peer re­view and there­fore no­ti­fied us of their with­draw­al from the peer-re­view process…based on this de­vel­op­ment, we can no longer vouch for the ve­rac­i­ty of the pri­ma­ry da­ta sources,” the first three au­thors of the Lancet study wrote in their re­trac­tion state­ment.

Mean­while, an­oth­er study led by Mehra us­ing Sur­gi­sphere da­ta in the New Eng­land Jour­nal of Med­i­cine (NE­JM) was al­so re­tract­ed on Thurs­day.

Mehra con­nect­ed with the vas­cu­lar sur­geon and sci­ence fic­tion writer De­sai through a co-au­thor, and per­son­al­ly re­viewed the Sur­gi­sphere analy­ses for both the Lancet and NE­JM pa­pers, he told the news di­vi­sion of the jour­nal Sci­ence.

But in the rush to pub­lish dur­ing the Covid-19 cri­sis, he con­ced­ed he “did not do enough to en­sure that the da­ta source was ap­pro­pri­ate for this use. For that, and for all the dis­rup­tions—both di­rect­ly and in­di­rect­ly—I am tru­ly sor­ry.” — Na­tal­ie Grover

Re­port­ed­ly snubbed by Op­er­a­tion Warp Speed, No­vavax gets up to $60M in DoD fund­ing 

If re­ports by the New York Times and Bloomberg are on the mon­ey, then No­vavax may not have made it to the whit­tled down short­list for fi­nan­cial and lo­gis­ti­cal sup­port from Op­er­a­tion Warp Speed — the White House-led am­bi­tious pub­lic-pri­vate ini­tia­tive to se­cure vac­cine ac­cess for Amer­i­cans be­fore the end of this year.

As a con­so­la­tion prize, how­ev­er, the Covid-19 vac­cine de­vel­op­er has been award­ed a con­tract of up to $60 mil­lion by the US De­part­ment of De­fense (DoD) to pro­duce of sev­er­al com­po­nents of the vac­cine in the coun­try. The deal in­cludes a 2020 de­liv­ery of 10 mil­lion dos­es of the vac­cine — called NVX‑CoV2373 — for DoD that could be used in Phase 2/3 clin­i­cal tri­als or un­der an emer­gency use au­tho­riza­tion (EUA) if grant­ed by the FDA, the com­pa­ny said.

No­vavax, which has a pipeline of ex­per­i­men­tal vac­cines for RSV, in­fluen­za and Ebo­la, has not yet man­aged to score any FDA vac­cine ap­provals akin to some oth­er Covid-19 vac­cine hope­fuls such as Mod­er­na and In­ovio. To make its can­di­date, No­vavax gen­er­at­ed an anti­gen de­rived from the spike pro­tein of SARS CoV 2, the virus that caus­es Covid-19, and added an ad­ju­vant to en­hance the im­mune re­sponse to the vac­cine.

An ear­ly-stage study was kicked off last month, and pre­lim­i­nary da­ta should be avail­able by Ju­ly. CEPI is putting in up to $388 mil­lion to fund the de­vel­op­ment.

Re­port­ed­ly, No­vavax was in­clud­ed in the ini­tial 18-name short­list for Op­er­a­tion Warp Speed.

Five groups — Mod­er­na, J&J, the joint As­traZeneca-Ox­ford, the Pfiz­er, BioN­Tech part­ner­ship and Mer­ck — who have made it to whit­tled down short­list as re­port­ed by the NYT and Bloomberg. But vac­cines made by No­vavax, Sanofi, In­ovio, Med­ica­go, the U.S. Army, British Amer­i­can To­bac­co, Coda­genix, In­sti­tut Pas­teur, Vaxart, Nan­tK­west, Geo­vax, Gr­ef­fex, and the Uni­ver­si­ty of Queens­land, were on the ini­tial 18-name short­list, ac­cord­ing to a Sci­ence re­port.

In mid-May how­ev­er, the HHS put out a state­ment say­ing it had a list of 14 ef­forts — from the more than 100 can­di­dates in de­vel­op­ment at com­pa­nies and uni­ver­si­ties — as a start­ing point. The of­fi­cial word from the HHS on what groups the short­er short­list con­tains is ex­pect­ed short­ly.

“It’s typ­i­cal Op­er­a­tion Warp Speed, where every­thing is sort of cryp­tic and it’s un­clear what they’re ac­tu­al­ly say­ing,” said Pe­ter Hotez, a vac­cine re­searcher at the Bay­lor Col­lege of Med­i­cine who is part of a team de­vel­op­ing a COVID-19 vac­cine in an in­ter­view with Sci­ence and serves on the vac­cine com­mit­tee of a pub­lic-pri­vate part­ner­ship or­ga­nized by the NIH that is sup­posed to as­sist Op­er­a­tion Warp Speed run clin­i­cal tri­als of cho­sen vac­cines.

But he and sev­er­al oth­er mem­bers of this com­mit­tee told Sci­ence that Op­er­a­tion Warp Speed did not ask for their in­put in the se­lec­tion. “We’re sort of like two par­al­lel uni­vers­es,” Hotez said. — Na­tal­ie Grover

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

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George Yancopoulos (Regeneron)

UP­DAT­ED: Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

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Pfiz­er shares surge on pos­i­tive im­pact of their mR­NA Covid-19 vac­cine — part­nered with BioN­Tech — in an ear­ly-stage study

Pfizer and their partners at the mRNA specialist BioNTech have published the first glimpse of biomarker data from an early-stage study spotlighting the “robust immunogenicity” triggered by their Covid-19 vaccine, which is one of the leaders in the race to vanquish the global pandemic.

Researchers selected 45 healthy volunteers 18-55 years of age for the study. They were randomized to receive 2 doses, separated by 21 days, of 10 µg, 30 µg, or 100 µg of BNT162b1, “a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD.” Their responses were compared against the effect of a natural, presumably protective defense offered by a regular infection.

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Covid-19 roundup: Vac­cines will need to beat place­bo by 50% to qual­i­fy for FDA OK; UK tri­al drops Kale­tra

The FDA will set the bar for approving a Covid-19 vaccine at 50% efficacy, the Wall Street Journal reported, meaning any successful candidate will have to reduce the risk of coronavirus disease by at least half compared to placebo.

That requirement is part of guidance that the agency is set to release later today, laying out detailed criteria for vaccine developers — some of whom are eyeing an OK by the end of the year, in line with expectations at Operation Warp Speed.

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Covid-19 has roiled clin­i­cal tri­al plans around the world, rais­ing con­cerns over the in­dus­try’s fu­ture on new drug ap­provals

Over the past 4 months, a group of analysts at GlobalData tracked 322 biopharma companies — biotechs, pharmas, CROs and such — reporting on the trouble Covid-19 has caused for their clinical development plans.

Slightly more than half — 179 — are US operations, with about 1 in 4 scattered throughout Europe and in Canada. And the disruptions are clustered around mid-stage development, though a hefty number of late-stage derailments may well blunt the stream of approvals down the road.

An ex­pe­ri­enced biotech is stitched to­geth­er from transpa­cif­ic parts, with 265 staffers and a fo­cus on ‘new bi­ol­o­gy’

Over the past few years, different teams at a pair of US-based biotechs and in labs in Japan have labored to piece together a group of cancer drug programs, sharing a single corporate umbrella with research colleagues in Japan. But now their far-flung operations have been knit together into a single unit, creating a pipeline with 10 cancer drug development programs — going from early-stage right into Phase III — and a host of discovery projects managed by a collective staff of some 265 people.

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