Covid-19 roundup: Roger Perl­mut­ter hus­tles up hu­man vac­cine tri­als as Mer­ck looks to catch up on Covid-19; Chi­na hacked Mod­er­na, per of­fi­cial

Mer­ck, the late­com­er to the Covid-19 vac­cine race, said to­day that it will push its first can­di­date in­to the clin­ic this quar­ter and move the oth­er one there by the end of the year.

They are like­ly go­ing to be sin­gle-dose reg­i­mens, Mer­ck not­ed, as op­posed to the prime-boost ap­proach be­ing adopt­ed in Phase III stud­ies by Mod­er­na, Pfiz­er/BioN­Tech and As­traZeneca/Ox­ford.

Roger Perl­mut­ter

For the first time since the com­pa­ny threw its name in­to the hat with one li­cens­ing deal and an ac­qui­si­tion, R&D chief Roger Perl­mut­ter al­so of­fered his thoughts on how the fron­trun­ners are do­ing, why he didn’t go with an mR­NA ap­proach de­spite a long­stand­ing part­ner­ship with Mod­er­na, and what gaps Mer­ck’s pro­grams might fill.

Bot­tom line: There will like­ly still be plen­ty to do in 2021, when Mer­ck ex­pects to have avail­able hun­dreds of mil­lions of dos­es that it’s now man­u­fac­tur­ing at risk.

“There’s rea­son to be­lieve that mul­ti­ple vac­cines will be re­quired in or­der to man­age this ex­tra­or­di­nary glob­al pan­dem­ic, in par­tic­u­lar when one thinks about the het­ero­gene­ity of the pop­u­la­tion that we want to vac­ci­nate,” he said on Mer­ck’s Q2 earn­ings call.

Both of the can­di­dates his team is now ad­vanc­ing are vi­ral vec­tors that de­liv­er the gene for the spike pro­tein of the coro­n­avirus to cells. Themis, which is now a Mer­ck sub­sidiary, us­es a measles vec­tor; it will move in­to Phase I in Q3. The one li­censed from In­ter­na­tion­al Aids Vac­cine Ini­tia­tive, mean­while, us­es the re­com­bi­nant vesic­u­lar stom­ati­tis virus tech­nol­o­gy de­ployed for Mer­ck’s ap­proved Ebo­la vac­cine. Backed with a $38 mil­lion BAR­DA grant, the pro­gram will en­ter the clin­ic lat­er this year.

Clin­i­cal da­ta from oth­er vac­cine de­vel­op­ers sug­gest the spike pro­tein in­duces good im­mune re­spons­es — some­thing that was not guar­an­teed.

“We have to say that from our start­ing po­si­tion, know­ing very lit­tle about SARS-CoV-2 at the be­gin­ning, the re­sults we have seen thus far from a va­ri­ety of ear­ly stud­ies, Phase I stud­ies, are as good as one could hope for, re­al­ly,” Perl­mut­ter said.

The speed en­abled by mR­NA tech­nol­o­gy has been crit­i­cal for that. But look­ing at the long game, Mer­ck has oth­er con­cerns: Can they make a vac­cine po­tent enough that one dose is suf­fi­cient? What about one that can be ad­min­is­tered oral­ly? Do you need dif­fer­ent vac­cines for dif­fer­ent pop­u­la­tions, say the el­der­ly ver­sus some­one in their 20s?

When asked why he was so con­fi­dent about sin­gle-dose ac­tiv­i­ty, he went deep­er in­to the sci­ence:

We have a lot of con­fi­dence in the sin­gle dose ac­tiv­i­ty of both vac­cines be­cause these are repli­cat­ing vac­cines. So they repli­cate in you. They are very po­tent im­muno­gens, and they have sin­gle ad­min­is­tra­tion ac­tiv­i­ty in oth­er set­tings. So of course with the V590, that’s the vesic­u­lar stom­ati­tis virus vac­cine, that’s been demon­strat­ed for Ebo­la virus dis­ease very ef­fec­tive­ly. A sin­gle dose, you know, pro­vides in the field — in the set­ting of civ­il strife of a large mag­ni­tude — greater than 97.5% ef­fi­ca­cy in a sin­gle dose. Now I can’t tell you that that’s ex­act­ly how it will be­have when we put a dif­fer­ent gene, in this case SARS-CoV-2 spike pro­tein en­cod­ing nu­cle­ic acids, in­to the con­struct. But the in­ter­est­ing thing about the VSV plat­form is that this is ac­tu­al­ly a vac­cine in which the spike pro­tein be­comes part of the vac­cine. The repli­ca­tion of the virus is com­plete­ly de­pen­dent on the spike pro­tein, it be­comes the en­ve­lope pro­tein of the vac­cine. Which is — it’s dif­fer­ent from sim­ply ex­press­ing the pro­tein wher­ev­er one ex­press­es it. That has big ef­fects, and pre­clin­i­cal­ly the mag­ni­tude of the re­sponse fol­low­ing sin­gle ad­min­is­tra­tion is very im­pres­sive. Sim­i­lar­ly the measles plat­form has been shown in a va­ri­ety of dif­fer­ent set­tings, most re­cent­ly with re­spect to the chikun­gun­ya ad­min­is­tra­tion, to be a very po­tent im­muno­gen.

The plan is to elu­ci­date the prop­er­ties of each in the up­com­ing clin­i­cal tri­als and fig­ure out the best de­vel­op­ment paths for both, rather than choos­ing one over the oth­er.

On top of its vac­cine work, Mer­ck dis­closed to­day that it’s plan­ning to send MK-4482, the Ridge­back-part­nered an­tivi­ral, in­to large-scale Phase III stud­ies in Sep­tem­ber. — Am­ber Tong and Ja­son Mast

Chi­na-backed hack­ers tried to steal Mod­er­na’s Covid-19 re­search, per of­fi­cial

Ear­li­er this week, Mod­er­na ac­knowl­edged it had re­moved sig­nage around its Nor­wood, MA man­u­fac­tur­ing plant due to un­spec­i­fied se­cu­ri­ty is­sues. Now, the cul­prit has ap­par­ent­ly emerged, and it doesn’t come as a sur­prise.

Chi­nese-backed hack­ers at­tempt­ed to steal some of Mod­er­na’s Covid-19 vac­cine re­search, ac­cord­ing to an anony­mous US se­cu­ri­ty of­fi­cial cit­ed by Reuters. The of­fi­cial did not pro­vide fur­ther de­tails, and the FBI and HHS de­clined to iden­ti­fy which com­pa­nies had been the tar­get of Chi­nese es­pi­onage.

The rev­e­la­tion comes a week af­ter the New York Times re­port­ed that the US Jus­tice De­part­ment had for­mal­ly in­dict­ed a pair of Chi­nese na­tion­als and ac­cused them of plot­ting to steal tech IP from a wide range of Amer­i­can com­pa­nies, in­clud­ing those work­ing on vac­cines. Ac­cord­ing to the in­dict­ment, the in­di­vid­u­als “con­duct­ed re­con­nais­sance on the com­put­er net­work of a Mass­a­chu­setts biotech firm pub­licly known to be re­search­ing a po­ten­tial COVID-19 vac­cine” on Jan­u­ary 27.

Re­con­nais­sance can mean a va­ri­ety of things, per cy­ber­se­cu­ri­ty ex­perts cit­ed by Reuters, in­clud­ing prob­ing web­sites for vul­ner­a­bil­i­ties and search­ing for im­por­tant ac­counts.

Mod­er­na re­moved sev­er­al signs around its Nor­wood plant a cou­ple months ago, but on­ly ad­dressed the is­sue af­ter the Boston Globe re­port­ed the com­pa­ny had al­so cov­ered up the sign on its head­quar­ters in what ap­peared to be white shrink wrap. Com­pa­ny spokes­peo­ple re­spond­ed vague­ly to those in­quiries.

Ray Jor­dan

“About two months ago, much of the sig­nage there was ei­ther ad­just­ed or re­moved out of an abun­dance of cau­tion for se­cu­ri­ty and for the safe­ty of our em­ploy­ees once it was clear that the pro­duc­tion fa­cil­i­ty would be­come a pri­ma­ry man­u­fac­tur­ing point for our vac­cine can­di­date,” chief cor­po­rate af­fairs of­fi­cer Ray Jor­dan told the Globe on Tues­day. “That was with­out any spe­cif­ic se­cu­ri­ty threats pre­cip­i­tat­ing the ac­tion.”

Rus­sia has al­so been ac­cused by the US, UK and Cana­di­an gov­ern­ments of at­tempt­ing to steal Covid-19 vac­cine da­ta from west­ern drug­mak­ers. It re­mains un­clear what, if any, in­for­ma­tion had been stolen, how­ev­er.

Mod­er­na this week launched a piv­otal Phase III study to de­ter­mine whether or not two 100 µg dos­es of their mR­NA vac­cine can pre­vent Covid-19 symp­toms from man­i­fest­ing. The com­pa­ny has emerged as one of the lead­ers in the vac­cine race, and BAR­DA com­mit­ted $472 mil­lion to help get that tri­al off the ground and scale up pro­duc­tion. — Max Gel­man

Remde­sivir buoys a down quar­ter for Gilead

The Covid-19 pan­dem­ic hit Gilead hard in the sec­ond quar­ter, but the phar­ma com­pa­ny ex­pects that to change for the bet­ter thanks to remde­sivir.

Jo­han­na Merci­er

Af­ter an­nounc­ing a 10 per­cent drop in sales in a quar­ter­ly earn­ings call with in­vestors Thurs­day af­ter­noon, Gilead re­vised its 2020 rev­enue pro­jec­tions up­ward, fore­cast­ing as much as $2.8 bil­lion more in year-end yield. Huge de­mand for remde­sivir is the biggest rea­son, as CCO Jo­han­na Merci­er hopes to meet the glob­al need by Oc­to­ber, ac­cord­ing to a Wall Street Jour­nal re­port.

Gilead re­ceived emer­gency FDA ap­proval for remde­sivir to treat Covid-19 back in May, with the com­pa­ny do­nat­ing treat­ments to the US gov­ern­ment for dis­tri­b­u­tion. The phar­ma start­ed sell­ing the drug this month, charg­ing $3,120 per course in the US and $2,340 in the EU.

The de­part­ment of Health and Hu­man Ser­vices makes up for al­most all of Gilead’s remde­sivir sales, as HHS sec­re­tary Alex Azar an­nounced a pur­chase of 500,000 cours­es of the drug on June 29. This ac­counts for all Ju­ly pro­duc­tion and 90 per­cent of pro­duc­tion in each of Au­gust and Sep­tem­ber.

SVB Leerink’s Ge­of­frey Porges cit­ed this HHS con­tract as a rea­son for op­ti­mism, ex­pect­ing Gilead to re­bound lat­er this year.

Due to remde­sivir’s com­pli­cat­ed man­u­fac­tur­ing process, Gilead has strug­gled to keep up with ear­ly de­mand for the drug. The pan­dem­ic has al­so af­fect­ed sup­ply chains around the world, and Gilead has not gone un­touched in this re­gard.

Dur­ing the earn­ings call, Gilead said it ex­pects to sell about one mil­lion to 1.5 mil­lion remde­sivir treat­ments in the sec­ond half of 2020. With these sales po­ten­tial­ly off­set­ting sec­ond-quar­ter loss­es, Gilead projects rev­enue to fall be­tween the $23.3 bil­lion and $25 bil­lion range, up from $21.8-22.2 bil­lion.

The Wall Street Jour­nal al­so cit­ed an an­a­lyst from Cred­it Su­isse who not­ed that Gilead is in­di­cat­ing full remde­sivir sales to be around $3 bil­lion and $4.5 bil­lion.

Over­all, Gilead post­ed a $3.34 bil­lion loss in the sec­ond quar­ter, large­ly dri­ven by ex­pens­es re­lat­ed to their $4.9 bil­lion ac­qui­si­tion of Forty Sev­en back in March. Be­cause Covid-19 al­so af­fect­ed how and when pa­tients de­cid­ed to seek rou­tine health care, sales for Gilead’s Bik­tarvy and De­scovy were al­so down for the quar­ter. — Max Gel­man

Japan pur­chas­es 120 mil­lion dos­es of Pfiz­er/BioN­Tech vac­cine can­di­date

The Covid-19 vac­cine can­di­date be­ing de­vel­oped by Pfiz­er and BioN­Tech has found a new buy­er — Japan.

The two com­pa­nies an­nounced Fri­day morn­ing that the Japan­ese gov­ern­ment has agreed to ac­quire 120 mil­lion dos­es of their mR­NA vac­cine, which would cov­er al­most 95 per­cent of the coun­try’s pop­u­la­tion. Fi­nan­cial terms of the deal were not dis­closed but are con­tin­gent on the tim­ing of de­liv­ery and vol­ume of dos­es.

The deal is al­so sub­ject to the can­di­date’s reg­u­la­to­ry ap­proval. As re­quest­ed by Japan, de­liv­er­ies of the vac­cine will start in the first half of 2021.

Pfiz­er is work­ing with BioN­Tech on four vac­cine pro­grams, two of which have re­ceived Fast Track des­ig­na­tion from the FDA. Ear­li­er this week, the com­pa­nies an­nounced the start of en­roll­ment for a Phase II/III study for the can­di­date BNT162b2, putting them on track for reg­u­la­to­ry re­view as ear­ly as Oc­to­ber.

That’s not the can­di­date most an­a­lysts ex­pect­ed to pro­vide the foun­da­tion for Pfiz­er’s vac­cine pro­gram, as BNT162b1 ap­peared more ex­cit­ing when pre­lim­i­nary da­ta dropped on Ju­ly 1. But BNT162b2 demon­strat­ed a bet­ter tol­er­a­bil­i­ty pro­file in Phase I/II, which end­ed up be­ing the de­cid­ing fac­tor along with T cell re­sponse. — Max Gel­man

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

So­cial im­age: Daniel O’Day, Bloomberg via Get­ty

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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