New UK start­up pur­sues off-the-shelf CAR-T, can­cer vac­cines through 'dark anti­gen­s'

Sci­en­tists un­furl­ing the hu­man genome at the turn of the cen­tu­ry came across many sur­pris­es but per­haps noth­ing as shock­ing as the per­cent­age of the genome that didn’t ap­pear to code for any­thing. Around 2% wrote pro­teins and the rest ap­peared to be “junk,” “dark,” or, as the New York Times then put it, “the ap­par­ent prod­uct of a typ­ing pool of drunk­en ba­boons. ”

Armed with the sup­po­si­tion ba­boons hadn’t cre­at­ed hu­man DNA, many sci­en­tists have the spent the pre­vail­ing two decades fig­ur­ing out what the so-called junk DNA is for or how it got there. One start­up out of the UK is now by­pass­ing part of that ques­tion and at­tempt­ing to lever­age seg­ments of “dark” DNA for can­cer vac­cines and im­munother­a­pies.

Kevin Po­jasek

Er­vaxx launched out of Lon­don with $17.5 mil­lion in seed and Se­ries A fund­ing on the promise that some non-cod­ing DNA in fact codes pro­teins in can­cer cells and that those pro­teins could be tar­gets for can­cer vac­cines and off-the-shelf CAR–T. The fund­ing is from SV Health In­vestors and an undis­closed glob­al phar­ma­ceu­ti­cal com­pa­ny. They’ve dubbed the tech “Dark Anti­gens” — af­ter the dark genome and a play on cos­mo­log­i­cal dark mat­ter, the vast amount of mat­ter in the uni­verse we’re pret­ty sure is there but re­mains in­vis­i­ble and large­ly in­scrutable.

“What we found is a set of se­quences in the genome that are se­lec­tive­ly tran­scribed and trans­lat­ed in can­cer and not in nor­mal cells,” CEO Kevin Po­jasek told End­points News.  “I think it’s sci­en­tif­i­cal­ly fas­ci­nat­ing that we’re sit­ting here in 2019 and find­ing new pro­teins in can­cer cells and from a ther­a­peu­tic per­spec­tive, it could make great anti­gens or neo-anti­gens for cell ther­a­py.”

Er­vaxx’s plat­form emerged out of a rel­a­tive­ly well-un­der­stood part of the dark genome, en­doge­nous retro­virus­es (ERV). Over mil­len­nia or eons of in­fect­ing hu­mans and our mam­malian an­ces­tors, these an­cient virus­es in­cor­po­rat­ed them­selves in­to our DNA and left a foot­print that ac­counts for about 8% of hu­man ge­net­ic code. Er­vaxx’s pitch is that the rapid dam­age can­cer caus­es to tu­mor DNA can lead pro­teins in these nor­mal­ly dead re­gions to be cod­ed.

It’s not clear what – if any­thing – these pro­teins do, but Po­jasek said they can func­tion as an anti­gen tar­get for tu­mor cells. He said their re­search showed that they are al­ready de­tectable to naive tu­mor cells, in the­o­ry al­low­ing Er­vaxx to use a vac­cine or a CAR-T process to then amp-up the im­mune re­sponse.

Be­cause the same anti­gens ap­pear to be present in dif­fer­ent peo­ple, they might al­low for an off-the-shelf CAR-T ap­proach, al­though Er­vaxx is al­so pur­su­ing a vac­cine and clas­sic CAR-T strat­e­gy. Its lead pro­gram is a vac­cine for melanoma, with oth­er ther­a­pies in the works for non-small cell lung can­cer, ovar­i­an can­cer and breast can­cer, among oth­ers. They hope to ward off re­sis­tance to any po­ten­tial ther­a­py by trig­ger­ing an im­mune re­sponse against mul­ti­ple dark anti­gens.

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.

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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.

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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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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.

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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.

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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.

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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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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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 slapdown, 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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