Novavax R&D chief Gregory Glenn (Novavax)

Af­ter Mod­er­na and Pfiz­er's stel­lar re­sults, the come­back play­ers at No­vavax face big ques­tions about their best-in-class hunt in a fren­zied Covid-19 vac­cine race

On Nov. 9, No­vavax R&D chief Gre­go­ry Glenn was awak­ened on his fam­i­ly farm to a news alert: Pfiz­er and BioN­Tech’s vac­cine was more than 90% ef­fec­tive at pre­vent­ing Covid-19.

It was in­cred­i­ble news for the world, and Glenn texted con­grat­u­la­tions to old friends on the Pfiz­er-BioN­Tech team. But he al­so knew that it was com­pli­cat­ed news for No­vavax.

“I was not sur­prised that it worked, but to have 90, 95% ef­fi­ca­cy? That’s re­al­ly great,” Glenn told End­points News. “Ad­mit­ted­ly, it puts a lit­tle ad­di­tion­al pres­sure on me in oth­er ar­eas.”

No­vavax, a tiny 33-year-old biotech that was tee­ter­ing on in­sol­ven­cy be­fore the coro­n­avirus broke out, had emerged as one of the pan­dem­ic’s un­like­li­est win­ners. Backed with $2.2 bil­lion in new cap­i­tal, in­clud­ing $1.6 bil­lion from Op­er­a­tion Warp Speed, they were prepar­ing for their own Phase III tri­als and lay­ing the ground­work to pro­duce up to 2 bil­lion dos­es of the year.

The com­pa­ny’s pro­tein-based tech­nol­o­gy was old­er and less flashy than the mR­NA Pfiz­er and Mod­er­na used, and it had failed be­fore, in one no­to­ri­ous­ly dif­fi­cult dis­ease. But pro­tein-based vac­cines were known to be par­tic­u­lar­i­ty im­muno­genic and over the sum­mer, No­vavax’s Phase I da­ta ap­peared to show that their vac­cine pro­duced more neu­tral­iz­ing an­ti­bod­ies than its ri­vals.

That raised the prospect that mR­NA would be first but No­vavax might be best. Shares peaked at $178, a near­ly 4000% in­crease from the $4.44 share price on Jan. 3.

“Be­fore this re­sult, every­one was think­ing, well No­vavax should have the best da­ta,” Glenn said. “And mR­NAs could be in­ter­me­di­ate and vec­tors might be a lit­tle be­hind that.”

The Pfiz­er-BioN­Tech and Mod­er­na re­sults, though, all but elim­i­nat­ed that pos­si­bil­i­ty be­fore No­vavax could even start a piv­otal tri­al. It’s hard to im­prove on 95%.

Be­cause all the ma­jor vac­cine de­vel­op­ers tar­get the same coro­n­avirus S pro­tein, the Pfiz­er-BioN­Tech news gave Glenn more con­fi­dence in a can­di­date than he’s had in three decades de­sign­ing and de­vel­op­ing vac­cines. Yet it al­so dra­mat­i­cal­ly changed No­vavax’s po­si­tion in the race. In­stead of gun­ning to be the best vac­cine, at least in the short-term they will have to set­tle to be one of sev­er­al good ones try­ing to sup­ply the world, while al­so deal­ing with the all but in­evitable de­lays that come from a small biotech try­ing to be­come a large one overnight.

Glenn, a self-de­scribed “gris­tled vac­ci­nol­o­gist” who found­ed his first biotech more than two decades ago and has led the com­pa­ny’s R&D since 2010, is in charge of guid­ing the can­di­date through.

Bryce Chack­er­ian

“I thought that if any­thing, their vac­cine could be as good or per­haps even bet­ter — of course, when you’re at 95%, it’s gonna be hard to beat that,” Bryce Chack­er­ian, a vac­ci­nol­o­gist at the Uni­ver­si­ty of New Mex­i­co, told End­points. Still,”any ef­fec­tive vac­cine is go­ing have a place in the mar­ket­place, be­cause it’s go­ing to be a while be­fore there’s enough.”

No­vavax was hit with an­oth­er set­back Mon­day, when they an­nounced that the launch of the Phase III US tri­al would be de­layed for a sec­ond time, po­ten­tial­ly push­ing it in­to 2021.  The Gaithers­burg, MD-based com­pa­ny has strug­gled in late stages in the past, rais­ing hopes among in­vestors and pub­lic health hopes around an RSV can­di­date that ul­ti­mate­ly failed a 2016 tri­al.

The de­lay al­so raised ques­tions about pre­cise­ly how No­vavax could run a Phase III study. Was it eth­i­cal to run a place­bo-con­trolled study now that two vac­cines ap­pear to be high­ly ef­fec­tive? If it were, would peo­ple sign up? Memo­r­i­al Sloan Ket­ter­ing’s Pe­ter Bach ar­gued that at this stage, the com­para­tor arm should be Pfiz­er or Mod­er­na’s vac­cine.

Glenn said the com­pa­ny was just work­ing to get FDA clear­ance for com­mer­cial-scale man­u­fac­tur­ing. They’ve spent a year try­ing to come from be­hind in that de­part­ment, af­ter they sold their pro­duc­tion fa­cil­i­ties to Catal­ent last year to keep the com­pa­ny alive. He said the cur­rent de­lays were min­i­mal.

“No one would even know,” he said, if it weren’t for the Covid mi­cro­scope. “It’s a nor­mal process to scale up, cre­ate as­says, cre­ate pack­ag­ing around that.”

He said the Phase III US tri­al would be place­bo-con­trolled as vac­cines are still in short sup­ply, but he ac­knowl­edged that the study might nev­er be com­plet­ed.

The com­pa­ny is al­so run­ning tri­als in South Africa and the UK, where they’ve now com­plet­ed en­roll­ment. De­pend­ing on the tim­ing, he said, the FDA might ac­cept ef­fi­ca­cy da­ta from those stud­ies, with some im­muno­genic­i­ty and safe­ty da­ta from the US tri­als, of­fer­ing a path to ap­proval even af­ter vac­cines have be­come broad­ly avail­able in the coun­try.

Da­ta from the ex-US stud­ies may come soon­er than ex­pect­ed. Be­cause of Pfiz­er and Mod­er­na’s da­ta, No­vavax short­ened the UK and South Africa stud­ies, Glenn said. They now ex­pect their own vac­cine to be high­ly ef­fec­tive and that there­fore they will need few­er cas­es to get a sta­tis­ti­cal­ly sig­nif­i­cant re­sult.

And al­though those re­sults leave lit­tle room for No­vavax to show bet­ter re­sults against symp­to­matic dis­ease, Glenn thinks there’s a chance their can­di­date may still be able to last longer or pro­vide bet­ter pro­tec­tion from in­fec­tion.

Chack­er­ian said both ideas make sense: The more neu­tral­iz­ing an­ti­bod­ies you de­vel­op im­me­di­ate­ly af­ter be­ing vac­ci­nat­ed, for ex­am­ple, the more you’ll like­ly have a year lat­er. Still, those ques­tions re­main spec­u­la­tive and he said he was more con­cerned about the ap­par­ent man­u­fac­tur­ing is­sue.

While mR­NA has stor­age re­quire­ments that can make it dif­fi­cult to de­liv­er glob­al­ly, the world is al­ready well-equipped to move pro­tein vac­cines. Any de­lay could mean de­lays in de­liv­er­ing bad­ly-need­ed dos­es.

“Whether that rep­re­sents a mo­men­tary glitch or points to more fun­da­men­tal is­sues in scal­ing up pro­duc­tion, I don’t know the an­swer,” he said. “But it’s cer­tain­ly some­thing that’s worth watch­ing.”

A spokesper­son for No­vavax did not di­rect­ly re­spond to a ques­tion about whether the man­u­fac­tur­ing de­lays would change the amount of vac­cine it can pro­duce next year, say­ing on­ly that once pro­duc­tion is ful­ly on­line, they should be able to pro­duce 2 bil­lion dos­es an­nu­al­ly.

Glenn now spends his days in back-to-back meet­ings try­ing to get the clin­i­cal and man­u­fac­tur­ing days run­ning. He has helped de­vel­op can­di­dates for RSV, E. Coli, Ebo­la, and pan­dem­ic flu since he found­ed his first biotech, IOMAI, in 1997. He most re­cent­ly helped No­vavax de­liv­er pos­i­tive Phase III re­sults for a sea­son­al flu vac­cine.

None of it, though, has been like this, and not just be­cause of the scale of the cri­sis. Once the Pfiz­er and Mod­er­na da­ta came in, he said, he was cer­tain they could do the same.

“The like­li­hood of suc­cess here is so high,” he said. “It feels like climb­ing the moun­tain, and it’s hard to wait.”

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

Hal Barron, Endpoints UKBIO19

GSK, Vir's hopes for a Covid-19 an­ti­body fall flat in NIH 'mas­ter pro­to­col' with no ben­e­fit in hos­pi­tal­ized pa­tients

GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan.

The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday.

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UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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As Brain­Storm con­tin­ues to tout ‘clear sig­nal’ on ALS drug, the FDA of­fers a rare pub­lic slap­down on the da­ta

A little more than a week after BrainStorm acknowledged that regulators at the FDA had informed them that the biotech needed more data before it could expect to gain an approval for its ALS treatment NurOwn — while still touting a “clear signal” of efficacy and not ruling out an application — the agency has decided to clarify the record in a most unusual statement.

The FDA statement amounts to a straight slap own, offering a different set of efficacy numbers from the company’s public presentation last November and ruling out any chance of statistical significance.

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Eli Lil­ly claims suc­cess in a new JAK in­di­ca­tion: hair loss

Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one.

Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms.

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In­tro­duc­ing End­points FDA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.

Antoine Papiernik, Sofinnova managing director (Business Wire)

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One of Europe’s most high-profile biopharma investors is getting $540 million to invest in new crossover deals for late-stage companies.

The Paris-based VC says the fresh Sofinnova Crossover Fund raise positions them as the “largest crossover investor in Europe dedicated to late-stage biopharma and medtech investments.”

They got a leg up in France after winning a special “Tibi” designation from the French government, giving them access to a pool of €6 billion that helped them gain an edge with institutional investors. Since they were founded close to 50 years ago, the venture group has backed more than 500 companies and currently has more than €2 billion under management.

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Seattle-based Presage Biosciences, which approaches drug development through its microdosing platform, has some new partnerships and cash to come with them.

Presage closed a $13 million financing round Tuesday, aiming to expand its network of clinical trial sites and advance development of its microdosing injection devices. They also closed partnership deals with Merck and Maverick Therapeutics.

The financing included $7 million from new investors, including the LabCorp Venture Fund, Bristol Myers Squibb, and InHarv Partners. An additional $6 million convertible note from Takeda Ventures will convert to equity.

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Soticlestat made it.

Takeda is bringing the drug back into its fold more than four years after first entrusting the team at Ovid with the mid-stage clinical work. For all that — generating what they saw as positive Phase II data in Dravet syndrome and Lennox-Gastaut syndrome — the biotech has been rewarded with $196 million in upfront cash, with another $660 million reserved for regulatory and commercial milestones.

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