Covid-19 roundup: Carl June on hav­ing Covid-19 and his plan to treat it; NIH preach­es cau­tion; 2 new vac­cines en­ter clin­ic

Carl June had Covid-19. Now he’s try­ing to fig­ure out how the world can treat it.

In an in­ter­view with the Philadel­phia In­quir­er, the CAR-T pi­o­neer and Uni­ver­si­ty of Penn­syl­va­nia im­mu­nol­o­gist re­vealed that he had been sick with a “mild to mod­er­ate” case of the virus for 3 weeks. Now re­cov­ered, he is try­ing to do­nate his plas­ma and he has some thoughts about how the bio­med­ical com­mu­ni­ty should pur­sue new treat­ments.

Promis­ing ex­per­i­men­tal treat­ments ex­ist, he said, but they are be­ing pur­sued in an in­ef­fi­cient man­ner, with hun­dreds of dif­fer­ent tri­als for ther­a­pies rang­ing from holis­tic reme­dies to ex­per­i­men­tal an­tivi­rals to re­pur­posed ap­proved drugs. Many of those tri­als are test­ing the same treat­ments.

“There are many re­dun­dant tri­als, not pri­or­i­tized based on sci­ence but on com­pa­nies’ port­fo­lios,” June told the In­quir­er. “They use pa­tients up. It doesn’t al­lo­cate ba­sic re­sources wise­ly.”

For ex­am­ple, he named the more than a dozen tri­als be­ing run on Actem­ra, the Roche drug that blocks the im­mune sig­nal IL-6. June orig­i­nal­ly used the drug in 2013 to suc­cess­ful­ly treat the over­ac­tive im­mune re­sponse — called cy­tokine storms — that emerged as a com­pli­ca­tion of his CAR-T can­cer treat­ment. Doc­tors be­lieve cy­tokine storms, prompt­ed by the virus but re­main­ing even af­ter the virus is large­ly gone, are caus­ing some of the life-threat­en­ing symp­toms seen in some Covid-19 pa­tients.

June said he was con­fi­dent Actem­ra would be ef­fec­tive, but said it was too ex­pen­sive to be the panacea for a glob­al pan­dem­ic. “They can’t af­ford it in In­dia,” he said. “They need some­thing cheap.”

So June is try­ing to or­ga­nize a tri­al for a dif­fer­ent im­mune-sup­press­ing drug: cy­closporine. The com­pound, used to pre­vent re­jec­tion in or­gan trans­plant pa­tients, is a gener­ic and al­ready ex­ists in large sup­ply, mak­ing it an ide­al can­di­date for the de­vel­op­ing world. In a tri­al, it would be giv­en to pa­tients when they are first hos­pi­tal­ized to see if it pre­vents an im­mune over­re­ac­tion. The Penn ethics re­view board is cur­rent­ly re­view­ing the tri­al.

Both drugs, though, have the po­ten­tial to back­fire, turn­ing down the im­mune sys­tem’s abil­i­ty to fight the virus it­self. Roche said to­day they ex­pect re­sults on Actem­ra in June. — Ja­son Mast

Ox­ford’s Covid-19 vac­cine pro­gram to en­ter PhI to­mor­row

An­oth­er Covid-19 vac­cine will en­ter the clin­ic to­mor­row.

A group at Ox­ford Uni­ver­si­ty led by im­mu­nol­o­gist Sarah Gilbert and backed by the UK gov­ern­ment will be­gin test­ing their vac­cine can­di­date in health vol­un­teers, with the hope of ex­per­i­men­tal­ly vac­ci­nat­ing 500 peo­ple by the mid­dle of May. The vac­cine, made of re­com­bi­nant DNA and de­liv­ered through an ade­n­ovirus, has been in de­vel­op­ment since short­ly af­ter the se­quence of the nov­el coro­n­avirus be­came avail­able in ear­ly Jan­u­ary.

The UK gov­ern­ment has made £20 mil­lion (rough­ly $25 mil­lion) avail­able to back the ef­fort, Sec­re­tary of State for Health & So­cial Care Matt Han­cock an­nounced this week. They al­so made £22.5 mil­lion avail­able for an RNA vac­cine project at the Im­pe­r­i­al Col­lege of Lon­don.

Gilbert, who has pre­vi­ous­ly worked on vac­cines for out­breaks such as SARS and Zi­ka, has laid out an an ag­gres­sive time­line for the vac­cine, telling The Lancet last week that in a best-case sce­nario she hoped to have both Phase III ef­fi­ca­cy da­ta on 5,000 vol­un­teers and the abil­i­ty to man­u­fac­ture large dos­es by the fall, with the caveat that “these best-case time­frames are high­ly am­bi­tious and sub­ject to change.”

The fall is al­so when Mod­er­na — which built the first vac­cine to en­ter clin­i­cal tri­als — has said they could have a vac­cine ready for emer­gency use, al­though the com­pa­ny has said it’s un­clear if those would be giv­en as part of a tri­al, un­der com­pas­sion­ate use, or a dif­fer­ent pro­to­col.

J&J, which has a $1 bil­lion part­ner­ship with BAR­DA, and CanSi­no, the lead­ing Chi­nese Covid-19 vac­cine pro­gram, al­so use ade­n­ovirus-based vac­cines. — Ja­son Mast

NIH guide­lines preach cau­tion, pa­tience on treat­ments

The NIH has post­ed its of­fi­cial treat­ment guide for Covid-19, and the ma­jor take­away is a mes­sage many sci­en­tists have been preach­ing: Wait for more ev­i­dence be­fore lean­ing one way or an­oth­er. De­vel­oped by a pan­el of ex­perts, many of whom are front­line clin­i­cians, the “liv­ing doc­u­ment” cov­ers two wide­ly-dis­cussed cat­e­gories of ther­a­pies: an­tivi­rals, which tar­get the virus, and host mod­i­fiers and im­mune-based ther­a­pies, which may tar­get the pa­tient.

In the an­tivi­ral realm, the pan­el con­clud­ed that there are in­suf­fi­cient clin­i­cal da­ta to rec­om­mend ei­ther for or against the three hottest drugs: the an­ti­malar­i­al drugs chloro­quine and hy­drox­y­chloro­quine, or Gilead’s re­pur­posed Ebo­la drug remde­sivir.

The guide­lines stand in sharp con­trast with Pres­i­dent Trump’s en­thu­si­as­tic en­dorse­ment of hy­drox­y­chloro­quine and chloro­quine. Every turn of events sur­round­ing the pair of drugs — which are al­so tak­en by pa­tients with au­toim­mune dis­eases such as lu­pus and rheuma­toid arthri­tis — have elicit­ed strong opin­ions, from the FDA’s con­tro­ver­sial emer­gency use au­tho­riza­tion to the re­sults from the small stud­ies con­duct­ed thus far.

Out­side of a clin­i­cal tri­al, the NIH ex­perts sug­gest physi­cians don’t pre­scribe hy­drox­y­chloro­quine plus azithromycin for fear of tox­i­c­i­ty. The same ad­vice ap­plies to HIV pro­tease in­hibitors such as lopinavir/ri­ton­avir “be­cause of un­fa­vor­able phar­ma­co­dy­nam­ics and neg­a­tive clin­i­cal tri­al da­ta.”

Im­mune-based ther­a­pies didn’t of­fer clear­er an­swers. The pan­el sim­i­lar­ly con­clud­ed it’s too ear­ly to say ei­ther yay or nay on con­va­les­cent plas­ma, hy­per­im­mune im­munoglob­u­lin, IL-6 in­hibitors or IL-1 in­hibitors. As for in­ter­fer­ons and JAK in­hibitors — a class that en­com­pass­es Eli Lil­ly’s Olu­mi­ant, now be­ing test­ed in pa­tients — they’re not rec­om­mend­ed un­less in a tri­al set­ting. — Am­ber Tong

Roche’s Sev­erin Schwan lam­basts an­ti­body test ‘dis­as­ter’

Roche’s mild man­nered CEO has some harsh words re­served for the de­vel­op­ers be­hind some of the an­ti­body tests cur­rent­ly on the mar­ket. “It’s a dis­as­ter,” Schwan was cit­ed as say­ing on a con­fer­ence call.

Hav­ing got­ten the green light ear­ly to de­ploy its coro­n­avirus tests, the Swiss phar­ma gi­ant is plan­ning to re­lease an an­ti­body test in May. By an­a­lyz­ing peo­ple’s blood and de­tect­ing any an­ti­bod­ies against SARS-CoV-2, the di­ag­nos­tic is sup­posed to tell whether they have ever been in­fect­ed.

A num­ber of such tests, al­so known as sero­log­i­cal tests, have al­ready been rolled out to the mar­ket. They come from about 90 com­pa­nies, many based in Chi­na, and were au­tho­rized be­fore get­ting re­viewed. Mul­ti­ple news out­lets have re­port­ed that ex­perts are con­cerned about their ac­cu­ra­cy, ques­tion­ing whether the FDA — chid­ed for its slow re­sponse to the nasal swab tests — set the qual­i­ty stan­dards too low this time around in pur­suit of speed.

“These tests are not worth any­thing, or have very lit­tle use,” Schwan said, ac­cord­ing to Reuters. “Some of these com­pa­nies, I tell you, this is eth­i­cal­ly very ques­tion­able to get out with this stuff.” — Am­ber Tong

BioN­Tech, Pfiz­er moves in­to hu­man tri­al with mR­NA vac­cine can­di­date in Ger­many

BioN­Tech and Pfiz­er have se­cured ap­proval from Ger­man au­thor­i­ties to be­gin test­ing its four vac­cine can­di­dates in hu­mans. The Phase I/II tri­al will en­roll 200 healthy vol­un­teers to find the op­ti­mal dose.

Here’s an overview of the BNT162 pro­gram:

Two of the four vac­cine can­di­dates in­clude a nu­cle­o­side mod­i­fied mR­NA (mod­R­NA), one in­cludes a uri­dine con­tain­ing mR­NA (uR­NA), and the fourth vac­cine can­di­date uti­lizes self-am­pli­fy­ing mR­NA (saR­NA). Each mR­NA for­mat is com­bined with a lipid nanopar­ti­cle (LNP) for­mu­la­tion. The larg­er spike se­quence is in­clud­ed in two of the vac­cine can­di­dates, and the small­er op­ti­mized re­cep­tor bind­ing do­main (RBD) from the spike pro­tein is in­clud­ed in the oth­er two can­di­dates. The RBD-based can­di­dates con­tain the piece of the spike that is thought to be most im­por­tant for elic­it­ing an­ti­bod­ies that can in­ac­ti­vate the virus.

The part­ners are al­so await­ing reg­u­la­to­ry de­ci­sions in the US, while BioN­Tech is work­ing with Fo­s­un to be­gin tri­als in Chi­na. — Am­ber Tong

San Diego biotech tests in­ter­sti­tial lung dis­ease drug for se­vere Covid-19 pa­tients

As the sever­i­ty and dan­ger of res­pi­ra­to­ry com­pli­ca­tions among Covid-19 pa­tients be­come clear, aTyr is join­ing the long line of bio­phar­ma com­pa­nies pitch­ing their an­ti-in­flam­ma­to­ry drugs to the fight. The San Diego-based biotech has re­cent­ly come up with pos­i­tive safe­ty da­ta in a Phase Ib/IIa study in­volv­ing pa­tients with pul­monary sar­coido­sis and will now launch a Phase II study in se­vere Covid-19 pa­tients.

The the­o­ry is that ATYR1923 down­reg­u­lates T-cell re­spons­es, there­by damp­en­ing the in­flam­ma­to­ry cy­tokine and chemokine sig­nal­ing. The drug can al­so im­prove lung func­tion, aTyr added, based on an­i­mal mod­els.

The tri­al will en­roll 30 pa­tients in the US, with 10 pa­tients each ran­dom­ized to take 1mg/kg, 3mg/kg or place­bo. — Am­ber Tong

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

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

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Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

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CEO Harith Rajagopalan (Fractyl)

Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.

You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.

“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”

Michel Sade­lain puts his name and new cell en­gi­neer­ing tech be­hind 'ag­nos­tic' CAR-T start­up chas­ing epi­ge­net­ic anti­gens

It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

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Covid-19 roundup: Re­al world da­ta sug­gest As­traZeneca vac­cine ef­fec­tive against Delta, Al­pha vari­ants; No­vavax hails pos­i­tive study on coro­n­avirus, flu shots com­bo

AstraZeneca’s Covid-19 vaccine, which has been authorized for use in the EU and Japan among many countries but not yet the US, has proved effective against the Delta variant, the company announced on Tuesday.

Real world data from Public Health England showed that the vaccine conferred high levels of protection against the variant that originated in India, as its 2 doses demonstrated 92% efficacy against hospitalization due to this variant. For the Alpha variant, which originated in the UK, the vaccine spurred a 86% reduction in hospitalization, with no deaths reported.

Lynn Fitch, Mississippi Attorney General (Rogelio V. Solis/AP Images)

Mis­sis­sip­pi sues Eli Lil­ly, Sanofi and No­vo over in­sulin prices as in­ter­change­able biosim­i­lars may ar­rive soon

Mississippi Attorney General Lynn Fitch last week sued the top three insulin manufacturers, which collectively cover almost the entire US insulin market, alleging that they’ve colluded to raise their prices in lockstep, and in some cases by more than 1,000% for drugs that are decades old.

“Because of Manufacturer Defendants’ collusive price increases, nearly a century after the discovery of insulin, diabetes medications have become unaffordable for many diabetics,” the lawsuit says.

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Andrew Hopkins, Exscientia CEO

Ex­sci­en­tia spends Soft­Bank's cash in bid to edge out AI ri­vals

Exscientia is sprinting to win the great AI biotech race.

The UK company, having long labored on small discovery deals with large pharmas, raised up to $525 million in a Series D led by the infamous Japanese conglomerate SoftBank in April and followed it up less than a month later with a Bristol Myers Squibb deal that paid $50 million cash and $1.2 billion in milestones.

Now, the Oxford spinout is splurging on a shiny new tool. On Monday they announced they purchased the three-year-old molecule-screening biotech Allcyte, a longtime collaborator, for $60.6 million in cash and stock.

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As­traZeneca's Covid-19 an­ti­body cock­tail miss­es the mark in pre­vent­ing symp­toms post-ex­po­sure

As the field for monoclonal antibody treatments of Covid-19 grows more crowded, AstraZeneca has announced a study of its own cocktail AZD7442 did not meet its main goal of preventing symptomatic Covid-19.

The company’s long-acting antibody combo was used in a trial with unvaccinated adults about the age of 18 with confirmed exposure. AZD7442 reduced the risk by just 33%, a figure that was not statistically significant.