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.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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Albert Bourla, Pfizer CEO (Evan Vucci, AP Images)

Covid-19 roundup: Pfiz­er ex­pands in­to France; Omi­cron-spe­cif­ic ver­sion of Mod­er­na's boost­er com­ing soon 

As the hype surrounding Pfizer’s antiviral Covid-19 pill swirls, the pharma announced that it will build a production facility in France to make the drug as a part of a five-year investment.

Pfizer will team up with Novasep to install equipment and initiate tech transfer and on-site development at Novasep’s Mourenx facility. The move is a part of a $594 million investment in France.

“We are of course proud to contribute to the manufacturing of this medicine which has shown in clinical trials to have a positive impact on hospitalization among at-risk Covid-19 patients,” Novasep’s CEO Michel Spagnol said in a statement. “This contract also validates our investment strategy for several years and our focus on small molecules.”