Scot Roberts, Altimmune CSO

Why mu­cos­al im­mu­ni­ty may be re­quired to end the pan­dem­ic

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

Fol­low­ing the re­cent emer­gency use au­tho­riza­tions of mul­ti­ple vac­cines for COVID-19, the first wave of peo­ple have al­ready be­gun the vac­ci­na­tion process — a tru­ly re­mark­able mile­stone. As some­one who has ded­i­cat­ed his ca­reer to drug de­vel­op­ment and dis­cov­ery fo­cused on vi­ral vec­tors and an­tivi­ral ther­a­pies, I can tell you that the sci­ence has moved fast, and we have every rea­son to cel­e­brate. The da­ta on these vac­cines are good. They are well stud­ied and their po­ten­tial for pub­lic health is promis­ing.

How­ev­er, I can al­so tell you that this is like­ly on­ly the be­gin­ning. I wor­ry that the roll­out of the cur­rent vac­cines will cre­ate a false sense of se­cu­ri­ty among a large pop­u­la­tion of peo­ple. There is a sce­nario that we need to be pre­pared for and one that could pos­si­bly de­rail our fight against this virus: These first-gen­er­a­tion vac­cines will be able to ef­fec­tive­ly block dis­ease, but not the trans­mis­sion of the SARS-CoV-2 virus.

Pfiz­er, Mod­er­na and near­ly every oth­er phar­ma­ceu­ti­cal com­pa­ny are pro­duc­ing in­jectable vac­cines. Their pro­tec­tive pow­er re­sults from sys­temic im­mu­ni­ty, mean­ing that they gen­er­ate an­ti­bod­ies that cir­cu­late in the blood to oth­er parts of the body. They were au­tho­rized based on their abil­i­ty to block the de­vel­op­ment of dis­ease, which is not the same as the abil­i­ty to in­hib­it vi­ral in­fec­tion or trans­mis­sion.

The best way to block both vi­ral in­fec­tion and trans­mis­sion is by in­duc­ing a spe­cial type of im­mune re­sponse called mu­cos­al im­mu­ni­ty. Mu­cos­al im­mu­ni­ty pro­tects the parts of the body that are in con­tact with the en­vi­ron­ment, and in the case of a res­pi­ra­to­ry pathogen, that means the nasal cav­i­ty and the lungs. Be­cause it is a lo­cal­ized type of re­sponse, a vac­cine needs to be de­liv­ered to the ap­pro­pri­ate com­part­ment if mu­cos­al im­mu­ni­ty is to be stim­u­lat­ed. In the case of a res­pi­ra­to­ry pathogen like SARS-CoV-2 that means in­tranasal vac­cine ad­min­is­tra­tion.

With­out mu­cos­al im­mu­ni­ty, the virus may con­tin­ue to thrive in a per­son’s nasal cav­i­ty al­low­ing for easy trans­mis­sion. This is why wear­ing a mask, even af­ter vac­ci­na­tion with an in­tra­mus­cu­lar vac­cine, will re­main crit­i­cal.

Thank­ful­ly, sci­en­tists, in­clud­ing our team, are work­ing on next gen­er­a­tion vac­cines that can elic­it mu­cos­al im­mu­ni­ty, in­clud­ing in­tranasal vac­cines that have the po­ten­tial to elic­it an im­mune re­sponse in the nose as well as sys­tem­i­cal­ly. This type of broad­er im­mune re­sponse could de­fend against in­fec­tion, dis­ease and trans­mis­sion. In fact, an in­tranasal vac­cine could al­so be used in com­bi­na­tion with an in­tra­mus­cu­lar vac­cine to elic­it mu­cos­al im­mu­ni­ty and serve as a boost­er for sys­temic im­mu­ni­ty.

We have a prece­dent. Flu­Mist is a live but weak­ened in­fluen­za vac­cine de­liv­ered by in­tranasal spray and this type of mu­cos­al vac­cine has been shown to de­crease the trans­mis­sion of in­fluen­za to close con­tacts.

Be­cause of their po­ten­tial to block trans­mis­sion, vac­cines that stim­u­late nasal mu­cos­al im­mu­ni­ty may be es­sen­tial to bring the pan­dem­ic to an end. How­ev­er, it will take a lit­tle more time to de­vel­op and test these new­er vac­cines as we can’t sac­ri­fice ef­fi­ca­cy and safe­ty for speed.

Un­til then, the pub­lic must take pre­cau­tions to keep this virus un­der con­trol. Even af­ter vac­ci­na­tion, our best weapon is so­cial dis­tanc­ing, test­ing and masks. They must re­main a core part of our pub­lic health strat­e­gy even as the first-gen­er­a­tion vac­cines roll out.

Robert Bradway (Photographer: Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Am­gen snaps up can­cer drug play­er Five Prime, adding PhI­II-ready FGFR2b drug in $2B M&A play

Amgen is making a long-awaited move on the M&A side, buying South San Francisco-based Five Prime $FPRX for close to $2 billion and adding a slate of new cancer drugs to the pipeline.

Amgen is paying $38 a share, putting the deal value at $1.9 billion. The stock closed at $21.26 last night, giving investors a 78% premium.

The jewel in the crown of this deal is bemarituzumab, which Amgen describes as a first-in-class, Phase III-ready anti-FGFR2b antibody. Amgen was drawn to the bargaining table by Five Prime’s mid-stage data on gastric cancer, satisfied by PFS and OS data helping to validate FGFR2b as a target. Amgen researchers will now expand on the R&D program in other epithelial cancers, including lung, breast, ovarian and other cancers.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,700+ biopharma pros reading Endpoints daily — and it's free.

David Liu (Casey Atkins Photography courtesy Broad Institute)

David Liu has a new big idea: pro­teome edit­ing. It could one day shred tau, RAS and some of the worst dis­ease-caus­ing pro­teins

Before David Liu became famous for inventing new forms of gene editing, he was known around academia in part for a more obscure innovation: a Rube Goldberg-esque system that uses bacteria-infecting viruses to take one protein and turn it into another.

Since 2011, Liu’s lab has used the system, called PACE, to dream up fantastical new proteins: DNA base editors far more powerful than the original; more versatile forms of the gene editor Cas9; insecticides that kill insecticide-resistant bugs; enzymes that slide synthetic amino acids into living organisms. But they struggled throughout to master one of the most common and powerful proteins in the biological world: proteases, a set of Swiss army knife enzymes that cut, cleave or shred other proteins in everything from viruses to humans.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

In the lat­est big in­vest­ment in gene ther­a­py man­u­fac­tur­ing, Bio­gen com­mits $200M to a ma­jor new fa­cil­i­ty in NC

You’d be forgiven for thinking that the only R&D effort of any consequence at Biogen belongs to aducanumab, its controversial Alzheimer’s drug. But behind the uproar around that drug, the big biotech has a full scale pipeline in play that includes a growing focus on developing gene therapies.

Now Biogen plans to build up the kind of manufacturing muscle that will give it an advantage in gaining FDA approvals — where CMC is always key — and then marketing them around the world.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,700+ biopharma pros reading Endpoints daily — and it's free.

Eli Lil­ly claims a TKO in its long-run­ning ti­tle fight with No­vo Nordisk for the block­buster di­a­betes mar­ket — but there’s a hitch

Eli Lilly isn’t just gunning for a better diabetes drug in tirzepatide. They want to cut ahead of Novo Nordisk’s blockbuster rival Ozempic (semaglutide) on the obesity front as well. But a newly-claimed win in a head-to-head Phase III showdown over reducing A1C while shedding pounds — complete with clear evidence of superiority over the approved rival — could prove a tough sell right now.

Let’s start with the latest data from Lilly.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,700+ biopharma pros reading Endpoints daily — and it's free.

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.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,700+ biopharma pros reading Endpoints daily — and it's free.

Cedric Francois, Apellis CEO (Apellis)

Apel­lis joins the grow­ing num­ber of bio­phar­mas scrap­ping a failed Covid-19 pro­gram af­ter an ear­ly flop

The global pandemic set off a frenzy of R&D activity as biotechs around the world scrambled to see if they could come up with a new medication or vaccine to help fight back. But even as the mRNA standouts are highlighting the market El Dorado open to successful teams, the failures are starting to pile up.

Thursday afternoon it was Apellis’ $APLS turn to deep-six a new drug.

The biotech reports that their C3 therapy APL-9 had failed to move the needle on mortality when combined with standard of care, as compared to SOC alone.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,700+ biopharma pros reading Endpoints daily — and it's free.