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.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; 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.

I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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BAR­DA slows its $9B en­gine for new Covid-19 ther­a­peu­tics

The Biomedical Advanced Research and Development Authority is cooling its jets in looking for new, potential Covid-19 treatments, at least in the near term.

An HHS spokesperson told Endpoints News via email, “to date, BARDA has obligated more than $9 billion for the development and/or purchase of 13 therapeutics, beginning in February 2020 with support to develop Regeneron’s monoclonal antibody therapeutic. Therapeutics are an important element of the COVID-19 response, and we are focused on the programs currently underway and/or in negotiation using the funds available to us.”

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Severin Schwan, Roche CEO (Georgios Kefalas/Keystone via AP Images)

Covid-19 roundup: High­er an­ti­body counts seen in spaced-out vac­cine in­ter­vals — study; Roche CEO com­pares IP waiv­er to East Ger­man 'ex­per­i­ments'

Near the outset of the UK’s vaccination campaign, the British government outlined plans to space out shots in larger intervals in order to get more people their first shot. Now, a study has come out saying the approach can drive a higher antibody response — at least in older populations.

In a study with 175 people older than 80, the antibody response was 3.5 times higher in individuals who received their second Pfizer/BioNTech shot 12 weeks after their first, compared to those who followed the typical three-week period. Antibody levels were measured about two to three weeks after the follow-up jabs.

Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Brazil­ian Covid vari­ant in Illi­nois leads to a pause in ship­ments of Lil­ly’s mAb com­bo

The US is pausing shipments of Eli Lilly’s Covid-19 treatment combo (bamlanivimab and etesevimab) to Illinois because of the increased frequency of the coronavirus variant that originated in Brazil, known also as the P.1 variant.

The FDA is now recommending that health care providers in Illinois instead use Regeneron’s monoclonal antibody combo therapy of casirivimab with imdevimab, which it said is likely to retain activity against the P.1 variant, until further notice.