Ex­clu­sive: Gink­go teams with un­known up­start in hunt for Covid-19 an­ti­body

Gink­go Bioworks, with its vast ware­hous­es of au­to­mat­ed ro­bots and biore­ac­tors, has played a be­hind-the-scenes role in the an­ti-Covid fight since the start of the pan­dem­ic. They’ve helped pro­duce the mR­NA for Mod­er­na’s mR­NA vac­cine, joined a con­sor­tium to help dis­cov­er and an­a­lyze an­ti­bod­ies, and they’ve qui­et­ly laid out grand plans to use Il­lu­mi­na ma­chines to test mil­lions of Amer­i­cans per day.

Now, for the first time, the syn­thet­ic bi­ol­o­gy be­he­moth is back­ing a Covid-19 drug, join­ing forces with a biotech you’ve nev­er heard of to do so.  They’ll work with To­tient, an an­ti­body-fo­cused start­up that is just emerg­ing from stealth mode to­day, to turn their al­ter­nate means of gen­er­at­ing virus-neu­tral­iz­ing in­to a treat­ment that could po­ten­tial­ly treat or tem­porar­i­ly pre­vent in­fec­tion. It’s a small part of a larg­er strat­e­gy Gink­go hopes can both make a broad im­pact on the lat­ter sea­son of the pan­dem­ic.

Naren­dra Ma­heshri

“We’re hop­ing Gink­go be­comes a house­hold name in the next 5 months,” Naren­dra Ma­heshri, Gink­go’s head of mam­malian bi­ol­o­gy, told End­points News. 

Gingko hasn’t his­tor­i­cal­ly de­vel­oped drugs in­de­pen­dent­ly, but rather part­nered with oth­er com­pa­nies that might ben­e­fit from ac­cess to their syn­thet­i­cal bi­ol­o­gy and an­a­lyt­i­cal plat­forms. Ac­cord­ing­ly, when the pan­dem­ic start­ed, they didn’t pur­sue an in­di­vid­ual pro­gram but in­stead be­gan reach­ing out to a host of com­pa­nies, of­fer­ing $25 mil­lion worth of work at their foundry for Covid-19 di­ag­nos­tic, ther­a­peu­tic and vac­cine projects. Specif­i­cal­ly, on drugs, they de­cid­ed to fo­cus on neu­tral­iz­ing an­ti­bod­ies — the same place Eli Lil­ly, Vir, As­traZeneca, Am­gen and Re­gen­eron were throw­ing their weight.

Most of these com­pa­nies de­rive neu­tral­iz­ing an­ti­bod­ies from the blood of sur­vivors, sam­pling which pro­teins the body nat­u­ral­ly made in re­sponse to in­fec­tion and sift­ing out the best ones. Ma­heshri said most of the re­searchers they spoke to used that ap­proach.

By con­trast, To­tient de­rives an­ti­bod­ies from what are known as ter­tiary lym­phoid struc­tures — ba­si­cal­ly ac­cu­mu­la­tions of im­mune cells that can form in places of height­ened in­flam­ma­tion, such as near a tu­mor or at the site of in­fec­tion. In the case of Covid-19, that’s the lungs. So in­stead of an­a­lyz­ing B cells in the blood for an­ti­bod­ies, they look for an­ti­bod­ies from flu­id in the lungs.

The idea both To­tient and Gink­go are bank­ing on — one they say has al­ready been borne out in cell lines — is that be­cause these are the an­ti­bod­ies that were in the hu­man–SARS-CoV-2 bat­tle­field, they will be most at­tuned to neu­tral­iz­ing the virus.

Deniz Kur­al

“We are sam­pling these an­ti­bod­ies that were di­rect­ly in­volved in the tis­sues un­der at­tack,” To­tient CEO Deniz Kur­al told End­points. “At least in our ex­per­i­ments … a lot of them are binders and they tend to be more dis­ease rel­e­vant.”

To­tient is al­so able to de­rive an­ti­bod­ies by look­ing at RNA from across tis­sue, as op­posed to just from a sin­gle cell, which both com­pa­nies say can be an ad­van­tage. Ma­heshri al­so not­ed the feed­back loop they’ve de­vel­oped to im­prove on ini­tial can­di­dates.

“They not on­ly have an­ti­body se­quences they re­con­struct but they al­so have in­for­ma­tion about the pa­tient, their im­mune re­sponse, how long they were in the hos­pi­tal,” he said.  “So our hits then help them re­fine their al­go­rithms to po­ten­tial­ly pull out po­ten­tial­ly even bet­ter an­ti­body se­quences, which he can then put back in­to our pipeline.”

So far, Gink­go has al­ready syn­the­sized and an­a­lyzed over 200 an­ti­bod­ies To­tient iden­ti­fied from the lungs of Covid-19 pa­tients, test­ing them against pseudovirus in cell lines. Nei­ther would dis­close the re­sults, but Ma­heshri said “they look very good.”

Gink­go doesn’t bring drugs in­to the clin­ic, so for now To­tient is look­ing for a part­ner to bring in­to the clin­ic in ear­ly 2021. Ma­heshri not­ed, though, that Gink­go is work­ing on meth­ods to scale up an­ti­body pro­duc­tion, leav­ing a door open for a part­ner­ship down the road. Sev­er­al an­ti­bod­ies are al­ready in the clin­ic, with Eli Lil­ly and Re­gen­eron near­ing ef­fi­ca­cy da­ta, but far more will be need­ed to match na­tion­al and glob­al de­mand. The an­ti­bod­ies found in lung flu­id are al­so dif­fer­ent from the ones found in blood, the com­pa­nies said, mean­ing they could be used in com­bi­na­tion with more ad­vanced can­di­dates.

Ankit Sax­e­na

To­tient, mean­while, is al­so work­ing on can­cer — their main longterm fo­cus. Found­ed by Kur­al and CBO James Si­et­stra, a pair of vet­er­ans from the bio­an­a­lyt­ics firm Sev­en Bridges, the com­pa­ny has an­a­lyzed these struc­tures in pa­tient sam­ples to de­vel­op hun­dreds of can­cer an­ti­bod­ies. They’ve set­tled on three pre­clin­i­cal can­di­dates and will use $10 mil­lion in seed fund­ing to ad­vance them fur­ther. A Se­ries A is in the works.

Gink­go, mean­while, has oth­er po­ten­tial ther­a­peu­tic and vac­cine part­ner­ships in the works, said Ankit Sax­e­na, Gink­go’s di­rec­tor of phar­ma busi­ness de­vel­op­ment. They’ve an­nounced plans to open up their first ma­jor test­ing fa­cil­i­ties in Oc­to­ber.

Un­lock­ing ESG strate­gies for growth with Gilead Sci­ences

RBC Capital Markets explores what is material in ESG for biopharma companies with the ESG leads at Gilead Sciences. Gilead has long focused on sustainability but recognized a more robust framework was needed. Based on a materiality assessment, Gilead’s ESG strategy today focuses first on drug access and pricing, while also addressing D&I and climate change. Find out why Gilead’s board is “acutely aware” of the contribution that ESG makes to firm’s overall success.

What con­tro­ver­sy? Eli Lil­ly plots Alzheimer's BLA fil­ing lat­er this year as FDA taps more an­ti-amy­loid drugs as break­throughs

The FDA is keeping the good news coming for Alzheimer’s drug developers. And Eli Lilly is taking them up on it.

Amid continued controversy around whether Biogen’s new flagship drug, Aduhelm, should have been approved at all — and swelling, heated debates surrounding its $56,000 price tag — the agency had no issue handing them and their Japanese partner Eisai a breakthrough therapy designation for a second anti-amyloid beta antibody, lecanemab, late Wednesday.

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Hervé Hoppenot, Incyte CEO (Jeff Rumans)

ODAC echoes FDA con­cern over In­cyte PD-1, as Paz­dur sig­nals broad­er shift for ac­cel­er­at­ed ap­proval

After the FDA lambasted their PD-1 ahead of an adcomm earlier this week, Incyte ran into new trouble Thursday as ODAC panelists voted against an accelerated OK by a wide margin.

Members of the Oncologic Drugs Advisory Committee recommended with a 13-4 vote to defer a regulatory decision on Incyte’s retifanlimab until after more data can be collected from a placebo-controlled trial. The PD-1 therapy is due for a PDUFA date in late July after receiving priority review earlier this year.

James Peyer, Cambrian

Can a cell ther­a­py treat mus­cu­lar dy­s­tro­phy? A Ger­man bil­lion­aire's an­ti-ag­ing start­up is try­ing to find out

Gene therapy companies have faced huge hurdles trying to deliver healthy genes into muscular dystrophy patients’ muscle cells, so here’s an idea: Why don’t we just replace the muscle cells themselves?

Over the last two years, Vita Therapeutics has been exploring that possibility, building on early stem cell work from Johns Hopkins professor Peter Andersen. And on Tuesday they announced a $32 million Series A to begin to move their first therapy into the clinic, where they hope it will help rebuild muscle in patients with a type of dystrophy that afflicts the arms and legs.

New FDA doc­u­ments show in­ter­nal dis­sent on Aduhelm ap­proval

In a lengthy review document and a pair of memos from top officials, the FDA released on Tuesday night its most detailed argument yet for approving Biogen’s intensely controversial Alzheimer’s drug aducanumab.

The documents amount to an agency attempt to quench the firestorm their decision kindled, as outside advisors members resigned and experts warned that an unproven drug now could stretch Medicare’s budget to a breaking point. Ultimately, the documents show how CDER director Patrizia Cavazzoni and Office of New Drugs director Peter Stein both concurred with FDA neuroscience head Billy Dunn on the accelerated approval while the staff at FDA’s Office of Biostatistics did not think an approval was warranted.

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Karen Flynn, Catalent

Q&A: When the pan­dem­ic struck, Catal­en­t's CCO had just joined the team

Karen Flynn came aboard Catalent’s team just in time.

The company was going through a surge of changes, and she had been brought over from her role as CCO of West Pharmaceutical Services to serve in the same capacity for the New Jersey-based CDMO. Then a few months later, the pandemic was in full-force.

Since then, Catalent’s been in hyper-expansion mode. In early May, it acquired Promethera’s Hepatic Cell Therapy Support SA subsidiary and its 32,40-square-foot facility in Gosselies, Belgium. Prior to that, the company acquired Belgian CDMO Delphi Genetics, wrapped up the expansion of an already-existing site in Madison, WI and added an ultra-low temperature freezer partner in Sterling. As Emergent has botched millions of doses of AstraZeneca’s vaccine, the company has swooped in to move that production to its Maryland plant as well.

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Richard Pazdur (vis AACR)

FDA en­cour­ages in­clud­ing in­cur­able can­cer pa­tients in tri­als, re­gard­less of pri­or ther­a­pies

The FDA on Thursday called to include those with incurable cancers (when there is no potential for cure or for prolonged/near normal survival) in appropriate clinical trials, regardless of whether they have received existing alternative treatments.

Historically, many cancer clinical trials have required that participating patients previously received multiple therapies, according to Richard Pazdur, director of the FDA’s Oncology Center of Excellence.

On heels of Aduhelm ap­proval, Bris­tol My­ers jumps back in­to Alzheimer's race

Bristol Myers Squibb last put major resources behind an Alzheimer’s drug nearly a decade ago, when their own attempt at targeting amyloid flamed out in mid-stage studies. They invented another molecule, a Tau-targeted antibody, but jettisoned it to Biogen in 2017 as they dropped out of neuroscience altogether.

But on Thursday, the New York pharma announced they were getting back in the game. Bristol Myers exercised an $80 million option to bring a tau-targeted antibody from Prothena into a Phase I study. The opt-in, which Bristol Myers triggered ahead of analyst expectations, opens the door for another $1.7 billion in milestones down the road.

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Covid-19 roundup: CDC ad­vi­sors find like­ly link be­tween mR­NA vac­cines and rare cas­es of heart in­flam­ma­tion; NIH launch­es new vac­cine study in preg­nant vol­un­teers 

The FDA will update the fact sheets for the Pfizer/BioNTech and Moderna Covid-19 vaccines, after the CDC advisory group ACIP found that rare cases of heart inflammation in adolescents and young adults are likely linked to the shots, Reuters reported.

According to the CDC’s website, there have been more than a thousand reports of heart inflammation following mRNA vaccination since April. These cases are rare, according to the agency, given the hundreds of millions of doses administered. Most have been mild, and individuals often recover on their own or with minimal treatment, several public health figures said in a joint statement.