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.

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