Covid-19 roundup: J&J gives deep­est look yet at vac­cine; As­traZeneca shies away from dis­cussing vac­cine com­mer­cial op­por­tu­ni­ty

J&J has giv­en its deep­est look yet in­to its coro­n­avirus vac­cine can­di­date.

The NJ phar­ma and Op­er­a­tion Warp Speed mem­ber pub­lished the pre­clin­i­cal re­sults for their vac­cine in Na­ture Thurs­day morn­ing, show­ing that a sin­gle dose pro­vid­ed “com­plete or near-com­plete pro­tec­tion” from SARS-CoV-2 in rhe­sus macaques. The re­sults bol­stered a Phase I tri­al that is al­ready un­der­way, hav­ing launched in Bel­gium and the US.

Al­though it’s dif­fi­cult to say how the pre­clin­i­cal re­sults will trans­late in­to hu­mans, the study is no­table be­cause it sug­gests that J&J’s vac­cine might be able to pro­vide pro­tec­tion af­ter just a sin­gle dose. The most ad­vanced vac­cine ef­forts out­side of Chi­na — from Mod­er­na, As­traZeneca, and Pfiz­er — all re­quire two dos­es, mak­ing them more dif­fi­cult to ad­min­is­ter and cut­ting the po­ten­tial sup­ply in half.

J&J us­es an ade­n­ovirus vec­tor to de­liv­er a gene for a coro­n­avirus anti­gen in­to cells, trig­ger­ing an im­mune re­sponse. They cre­at­ed sev­en can­di­dates with slight­ly dif­fer­ent anti­gens and test­ed them in 52 dif­fer­ent mon­keys, in­oc­u­lat­ing them and then chal­leng­ing them 6 weeks lat­er with the virus. The can­di­date they will ul­ti­mate­ly bring in the clin­ic ful­ly pro­tect­ed 5 of 6 mon­keys from in­fec­tion. The 6th mon­key had low vi­ral lev­els.

J&J has tak­en that vac­cine in­to Phase I, where they are test­ing both a sin­gle dose and mul­ti­ple dos­es. They hope to be­gin Phase III in Sep­tem­ber. They’ve re­ceived $456 mil­lion from BAR­DA for re­search and de­vel­op­ment, and have pledged to sell their vac­cine at cost while the pan­dem­ic is still rag­ing. — Ja­son Mast

Might Sin­ga­pore have the best Covid-19 an­ti­body?

A young com­pa­ny that was one of the first to bring a Covid-19 an­ti­body in­to the clin­ic is prepar­ing to move in­to Phase III, as its plat­form gets its first val­i­da­tion in the New Eng­land Jour­nal of Med­i­cine. 

Ty­chan, a small biotech set up and backed by the Sin­ga­pore gov­ern­ment dur­ing the 2014-2016 West African Ebo­la cri­sis to re­spond quick­ly to emerg­ing in­fec­tions, pub­lished in NE­JM a mon­o­clon­al an­ti­body they de­vel­oped for yel­low fever virus, show­ing it was safe and neu­tral­ized the virus in pa­tients ex­posed to the in­ac­ti­vat­ed vac­cine in a Phase Ib tri­al.

There were no ma­jor yel­low fever out­breaks in Brazil this year, so the com­pa­ny did not launch the an­ti­body as they thought they might. Still, as sci­en­tif­ic founder Ram Sasisekha­ran said, the an­ti­body could be used if an emerg­ing out­break in Africa wors­ens. And the re­sults help val­i­date their ap­proach for Covid-19.

Like sev­er­al big­ger name com­pa­nies, Ty­chan de­vel­oped an an­ti­body that can bind to and neu­tral­ize SARS-CoV-2 and which can hope­ful­ly in­oc­u­late healthy peo­ple for a lim­it­ed pe­ri­od of time and treat pa­tients with ear­ly-stage or even late-stage dis­ease. They start­ed a Phase I on June 10, 9 days af­ter Eli Lil­ly start­ed the first Covid-19 an­ti­body tri­al in the world. They have since com­plet­ed dos­ing, Sasisekha­ran said.

“There [have been] no ad­verse events,” he told End­points News, not­ing that they test­ed high dos­es.”The mol­e­cule looks very safe.”

Ty­chan is now prepar­ing to launch Phase III tri­als in Au­gust, a place that would put them in line with Eli Lil­ly and Re­gen­eron, the oth­er ma­jor an­ti­body com­pa­ny that has al­ready hit the clin­ic.

Ty­chan makes their an­ti­bod­ies dif­fer­ent­ly than most com­pa­nies. Rather than ex­tract an­ti­body-pro­duc­ing B cells from the blood of pa­tients who sur­vived the virus or from ge­net­i­cal­ly mod­i­fied mice and then tweak­ing the an­ti­bod­ies those B cells pro­duce, Ty­chan draws from in­ter­nal and pub­lic data­bas­es of dif­fer­ent an­ti­body se­quences to stitch to­geth­er one they think has the best prop­er­ties. That might mean en­gi­neer­ing their an­ti­body by com­bin­ing a head of one an­ti­body and a tail of an­oth­er, while tweak­ing both. (An FAB and an FC, for our im­mu­nol­o­gist read­ers, among oth­er parts).

“We’ve al­ways looked at them as Lego pieces,” Sasisekha­ran said. “Our ap­proach is more like an as­sem­bly, we as­sem­ble dif­fer­ent com­po­nents that come from dif­fer­ent sources.”

If the an­ti­body proves suc­cess­ful in Phase III, Sasisekha­ran said they have enough man­u­fac­tur­ing ca­pac­i­ty to sup­ply an­ti­bod­ies both in Sin­ga­pore and abroad. — Ja­son Mast 

In­ovio touts non-pub­lished an­i­mal da­ta 

In­ovio is tout­ing its own an­i­mal da­ta for its Covid-19 vac­cine, al­though those da­ta have yet to be peer-re­viewed. In a pre-print post­ed to BioRx­iv،the com­pa­ny said that its DNA vac­cine INO-4800 pro­tect­ed rhe­sus macaques from be­ing in­fect­ed by a SARS-CoV-2 virus for 13 weeks af­ter vac­ci­na­tion. It al­so showed an­ti­body and T cell re­spons­es for 13 months.

Al­though one of the first com­pa­nies to an­nounce a Covid-19 vac­cine pro­gram and one of the first to get fund­ing from the coali­tion of epi­dem­ic pre­pared­ness to do so, the biotech has in­creas­ing­ly found it­self on the fringes of the fight. The vac­cine’s de­vel­op­ment has been stalled in part by a dis­pute with the CD­MO li­censed to man­u­fac­ture its vac­cines. And, al­though In­ovio said in June that it had been “se­lect­ed for the U.S. Gov­ern­ment’s Op­er­a­tion Warp Speed” – one of a cou­ple small biotechs to make the claim, along­side Vaxart and Patrick Soon-Sh­iong’s Nan­tk­west –  they did not clar­i­fy un­til to­day’s re­lease that they had on­ly been se­lect­ed for the an­i­mal chal­lenge stud­ies, which nu­mer­ous com­pa­nies have re­ceived aid for.

In­ovio’s stock was up 11%, or $2.23 on the news. They be­gan the year at $2.98 per share. — Ja­son Mast

As­traZeneca shies away from dis­cussing vac­cine com­mer­cial op­por­tu­ni­ty

Pas­cal So­ri­ot isn’t think­ing about the prof­its an ap­proved Covid-19 vac­cine can bring As­traZeneca now — and he won’t be for quite some time.

“The num­ber 1 thing we’ve learned about this virus is that it is in­cred­i­bly un­pre­dictable,” he told re­porters on a me­dia call. ”So it’s re­al­ly hard to un­der­stand — in fact I would say at this stage im­pos­si­ble to an­swer your ques­tion about po­ten­tial long-term com­mer­cial op­por­tu­ni­ty. […] Give us a few more months and then maybe we can talk about it.”

It’s been three months since the phar­ma gi­ant took on the re­spon­si­bil­i­ty to de­vel­op as well as lin­ing up man­u­fac­tur­ing and dis­tri­b­u­tion for the ade­n­ovirus-based vac­cine in­vent­ed by Ox­ford Uni­ver­si­ty. Along­side J&J, As­traZeneca is among the on­ly fron­trun­ning vac­cine de­vel­op­ers to have pledged to sup­ply its prod­uct at no prof­it.

Based on a sup­ply agree­ment with the Nether­lands, Ger­many, France and Italy, SVB Leerink an­a­lyst Ge­of­frey Porges has cal­cu­lat­ed the price to be $3 to $4 a dose — a fig­ure echoed by Pam Cheng, the VP of op­er­a­tions and IT who’s tasked with pro­cure­ment.

“So from a COGS per­spec­tive we are able to man­u­fac­ture such a vac­cine at a few dol­lars per dose,” she said. “Now ob­vi­ous­ly the ex­act cost is de­pen­dent on the sup­ply chain, but we’re look­ing in gen­er­al a few dol­lars a dose. So that’s very good news.”

That sug­gests a treat­ment course cost­ing un­der $10 even if it’s a two-dose reg­i­men, which is be­ing tak­en in­to Phase III.

Pfiz­er, mean­while, has con­firmed that it’s charg­ing $39 for its own two-dose course of its BioN­Tech-part­nered mR­NA vac­cine, al­low­ing it­self to make a prof­it. Mod­er­na is re­port­ed­ly look­ing to go high­er with a price tag go­ing in­to the $50 to $60 range.

As the un­of­fi­cial Oc­to­ber dead­line for an emer­gency ap­proval looms, vac­cine mak­ers have found them­selves un­der con­flict­ing pres­sure from politi­cians ar­gu­ing for “fair pric­ing” to en­sure ac­cess and an­a­lysts press­ing why com­pa­nies shouldn’t make mon­ey for help­ing solve a glob­al health­care cri­sis.

As­traZeneca has sug­gest­ed that it would charge a dif­fer­ent price once the pan­dem­ic is over. But when asked how they would de­ter­mine when that is, the CEO left it up to “a va­ri­ety of in­put.”

“The re­al­i­ty is that if our vac­cine or sev­er­al vac­cines work, there should not be a pan­dem­ic any­more,” So­ri­ot said. “If there is still a pan­dem­ic, it means the vac­cines are not work­ing.”

The pri­or­i­ty, he em­pha­sized, is work­ing with the net­work of more than 20 con­tract man­u­fac­tur­ers to en­sure they can de­liv­er the 2 bil­lion dos­es they have pledged to dis­trib­ute glob­al­ly on time. Ox­ford’s tech­nol­o­gy al­so gives them an edge; as it stands, the vac­cine can­di­date can be stored in “nor­mal cold chain” at 2 to 8 de­grees Cel­sius.

From So­ri­ot:

Peo­ple tend to fo­cus these days on­ly on safe­ty and ef­fi­ca­cy. But if you have a vac­cine that works and is safe, but is ex­pen­sive to make or you can­not scale it up, or you have to keep it un­der -60 or -20 de­grees — I mean imag­ine how prac­ti­cal it is to dis­trib­ute these in Latin Amer­i­ca, Africa etc. So if you want the vac­cine to have bril­liant im­pact to make a dent on this pan­dem­ic, it has to be safe and ef­fec­tive. You have to be able to scale it up in bil­lions of dos­es which is a mas­sive ef­fort, it has to be at a rea­son­able price, as cheap as pos­si­ble, you have to dis­trib­ute to every­body, and it has to be easy to keep at nor­mal fridge tem­per­a­ture … that’s what this team hopes to de­liv­er.

Am­ber Tong

FDA could au­tho­rize con­va­les­cent plas­ma with­in a week

An­ti­body-rich plas­ma from re­cov­ered Covid-19 pa­tients has seen some suc­cess in treat­ing oth­ers with the most se­vere symp­toms, but now the FDA is get­ting clos­er to ap­prov­ing its emer­gency use in mild cas­es.

A de­ci­sion could come as soon as next week, ac­cord­ing to a re­port in the Wall Street Jour­nal. Thus far, on­ly remde­sivir has re­ceived the reg­u­la­to­ry green light for emer­gency au­tho­riza­tion.

Doc­tors and hos­pi­tals have al­ready treat­ed Covid-19 pa­tients with con­va­les­cent plas­ma due to a lack of proven drugs, most­ly un­der com­pas­sion­ate use and as part of stud­ies. An ex­pand­ed ac­cess study at the Mayo Clin­ic in Rochester, MN, has seen more than 48,000 pa­tients treat­ed with plas­ma in­fu­sions.

BAR­DA re­cent­ly fund­ed a tri­al across sev­er­al uni­ver­si­ties, in­clud­ing the Uni­ver­si­ty of Pitts­burgh, the Uni­ver­si­ty of Michi­gan, the Uni­ver­si­ty of South Car­oli­na, and Stan­ford to study the ef­fec­tive­ness of out­pa­tient con­va­les­cent plas­ma treat­ments.

The tri­al, dubbed C3PO, will treat 600 pa­tients with mild symp­toms across 50 hos­pi­tals. Ide­al­ly, these pa­tients will be con­sid­ered high-risk: old­er than 50, with heart dis­ease, lung dis­ease or di­a­betes, or be im­muno­com­pro­mised.

Par­tic­i­pants will be giv­en ei­ther the plas­ma or a saline IV so­lu­tion in the emer­gency room and doc­tors will check up on them with a phone call every oth­er day. The study should have re­sults by the time the flu sea­son rolls around in Sep­tem­ber.

Re­searchers from Johns Hop­kins Uni­ver­si­ty pub­lished a “how-to” guide for Covid-19 plas­ma trans­fu­sions back in April, as the ther­a­py hasn’t been wide­ly used in the US in decades. Though con­va­les­cent plas­ma has been used to treat H1N1 and SARS in past out­breaks, the pro­ce­dure con­tin­ues to leave hos­pi­tals with many ques­tions about its safe­ty and ef­fi­ca­cy.

The pa­per sug­gest­ed a SARS tri­al in Hong Kong in­di­cates pa­tients who re­ceive con­va­les­cent plas­ma treat­ments with­in 14 days of con­tract­ing the virus re­cov­er faster than those giv­en the plas­ma lat­er. Much re­mains un­known about the treat­ments, how­ev­er, in­clud­ing which an­ti­bod­ies best pro­tect against the virus. — Max Gel­man

EU gets a hold of 30,000 remde­sivir treat­ments de­spite US buy­ing up sup­ply

De­spite the Unit­ed States buy­ing al­most the en­tire glob­al sup­ply of remde­sivir, the Eu­ro­pean Union has man­aged to get in on the ac­tion.

The EU com­mis­sion is pay­ing about $74 mil­lion for 30,000 treat­ments of the drug to help ad­dress needs of Covid-19 pa­tients in the short term, Reuters re­port­ed Wednes­day. That’s a rel­a­tive­ly lim­it­ed amount, giv­en that the US gov­ern­ment last month pur­chased enough dos­es — more than 500,000 — to make up for Gilead’s en­tire pro­duc­tion through Sep­tem­ber.

Sold un­der the brand name Vek­lury, the treat­ments will be avail­able be­gin­ning in ear­ly Au­gust. The an­tivi­ral is the on­ly drug au­tho­rized in the EU to treat se­vere cas­es of Covid-19.

When sell­ing to gov­ern­ments, Gilead $GILD set a price of $2,340 per pa­tient for a five-day course of remde­sivir in late June. That pric­ing ap­pears to match up with the price the EU paid Wednes­day. The bloc is al­ready plan­ning an ad­di­tion­al pur­chase for Oc­to­ber should a sec­ond wave hit Eu­ro­pean cities.

So far, remde­sivir has proved to be one of on­ly two treat­ments ef­fec­tive at treat­ing Covid-19 symp­toms, in ad­di­tion to a gener­ic steroid called dex­am­etha­sone. An ob­ser­va­tion­al study ear­li­er this month in­di­cat­ed that pa­tients with se­vere symp­toms tak­ing remde­sivir had a 62 per­cent bet­ter chance at sur­viv­ing than those not on the drug.

Gilead is ex­pect­ed to re­port its sec­ond quar­ter earn­ings Thurs­day evening, and its stock price is al­ready up al­most 12 per­cent, peak­ing as high as $84. The com­pa­ny’s first quar­ter sales reached $5.5 bil­lion and an­a­lysts ex­pect sales north of $5 bil­lion for the sec­ond quar­ter, ac­cord­ing to Bar­ron’s. — Max Gel­man

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

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

DFC CEO Adam Boehler and Kodak CEO Jim Continenza (Kodak)

Covid-19 roundup: Cure­Vac beefs up its uni­corn IPO dreams as bil­lion­aire own­er takes this Covid-19 mR­NA play­er on a forced march to Nas­daq; Ko­dak's $765M deal is put on hold

When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

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Warren Huff, Reata CEO

Rea­ta sug­gests Friedre­ich's atax­ia pro­gram could be de­layed, send­ing stock plung­ing

Reata Pharmaceuticals $RETA made waves last October when its drug omaveloxolone produced positive trial results in treating a rare neurological disorder, but the candidate’s path forward became much murkier Monday.

In a report of quarterly earnings, the biotech divulged that the FDA is considering delaying omaveloxolone’s NDA pending completion of a second trial. That could push back approval by at least a year given that the target population, individuals with Friedreich’s ataxia, is limited and progression of the hard-to-treat illness is notoriously slow. The Covid-19 pandemic would also hinder Reata’s ability to complete an additional trial.

Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

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Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

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Vi­da Ven­tures co-leads Dyne's $115M megaround for next-gen oli­go ther­a­pies aimed square­ly at mus­cles

Dyne Therapeutics started out last April with a modest $50 million to mine targeted muscle disease therapies from its in-house conjugate technology. The biotech has now convinced more investors that it’s got gems on its hands, closing $115 million in fresh financing to push its next-gen oligonucleotide drugs into the clinic.

Vida Ventures and Surveyor Capital led the round, joined by a group of other new backers including Wellington Management Company, Logos Capital and Franklin Templeton.

Eli Lil­ly teams with Pieris on HER2+ tu­mors; Op­di­vo + Yer­voy best chemo in mesothe­lioma

Despite the FDA putting a partial clinical hold on its lead program only a few weeks ago, Boston-based Pieris Pharmaceuticals is plowing forward with a new collaboration.

Pieris will work with Eli Lilly to further advance studies on PRS-343, a 4-1BB/HER2 bispecific for HER2-positive tumors, in combination with the latter’s ramucirumab and paclitaxel for the second-line treatment of patients with HER2-positive gastric cancer in a single-arm, Phase II study.

In­novent and Eli Lil­ly chal­lenge Mer­ck­'s mega-block­buster Keytru­da in non-small cell lung can­cer field

China-based Innovent Biologics and its multinational ally Eli Lilly shared Phase III evidence that their PD-1 inhibitor combo can delay the progression of nonsquamous non-small cell lung cancer.

But the drugmakers will face stiff competition in China from Merck’s Keytruda, the ruling PD-1 which is already approved to treat both squamous and nonsquamous NSCLC and boasts positive overall survival rates.

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