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.

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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The lat­est Cin­derel­la sto­ry in on­col­o­gy ends with a sud­den rout as up­dat­ed da­ta dis­play spooks in­vestors

NextCure’s turn as the Cinderella of cancer-focused biotechs was short-lived.
Just a few days after its shares $NXTC zoomed up more than 250% on some very early stage results in a SITC abstract, a more complete analysis over the weekend spiked the hype and left investors in high dudgeon as the stock price collapsed back towards earth Monday.
The focus at NextCure is centered on NC318, an antibody that is intended to shut down the immunosuppressive Siglec-15 — or S-15 — target. After adding a small group of patients to the readout, investigators circled 2 clinical responses, a complete and partial response, along with 4 stable disease cases in non-small cell lung cancer.

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Te­va spin­out rais­es $85M in IPO; No­var­tis beefs up gener­ics unit with $440M deal

→ After Teva spinout 89bio recently announced that its IPO was being held up, the company is back in the game offering 5,304,687 shares at a price of $16 per share. The company has raised $84.9 million IPO in gross proceeds and will be listed under the ticker symbol $ETNB. BofA Securities, SVB Leerink and RBC Capital Markets are the joint book-running managers for the offering. Oppenheimer & Co is the co-manager for the offering.
→ Looking to amp up its presence in Japan’s hospitals, Novartis has struck a deal to buy out Aspen’s portfolio of generics in the world’s third largest healthcare market. The pharma giant is paying $440 million for Aspen’s Japanese subsidiary.
→ Novartis said tropifexor, a non-bile acid FXR agonist, has scored on several key biomarkers of NASH in a Phase IIb trial, including reductions in hepatic fat, alanine aminotransferase and body weight compared to a placebo at 12 weeks.

Break­through sta­tus and promise of a speedy re­view ar­rives for Op­di­vo/Yer­voy com­bi­na­tion as Bris­tol-My­ers bites at Bay­er

Its frontline and single-agent aspirations have been set back, but Bristol-Myers Squibb just took a big step forward in its efforts to apply its checkpoint inhibitor Opdivo to liver cancer. The FDA has granted breakthrough status and priority review to a combination, second-line treatment.

The designation is for Opdivo (nivolumab) in combination with Yervoy (ipilimumab),  for treating advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The PD-L1 drug was already approved as a single-agent, second-line treatment for HCC. A PDUFA date was set for March 10, 2020 — just 4 months from now.

Third time un­lucky: Lipocine's lat­est quest to mar­ket their oral testos­terone drug snubbed again by FDA

Lipocine’s latest attempt at securing approval for its oral testosterone drug has fizzled yet again.

The Utah-based drug developer on Monday said the FDA has spurned its marketing application, indicating that some efficacy data on the drug, Tlando, was not up to scratch to treat male hypogonadism, a condition characterized by low production of the hormone testosterone, which is responsible for maintaining muscle bulk, bone growth, and sexual function.

UP­DAT­ED: De­cry­ing 'ar­bi­trary and capri­cious' ac­tion, Re­genxBio sues FDA over clin­i­cal holds on gene ther­a­py

When RegenxBio disclosed that the FDA had placed a partial clinical hold on one of its lead gene therapies, execs outlined several customary next steps: continuing assessment and monitoring, delaying a related IND filing, and working with the FDA to address the matter.

As it turned out, they were planning something much less mundane. Two days after announcing the hold in its Q3 update, RegenxBio filed a lawsuit seeking to set it aside, the FDA Law Blog noted.

Roche's SMA chal­lenge to Bio­gen's Spin­raza fran­chise looms larg­er with piv­otal win

Roche has just landed a crucial advance in scoring a come-from-behind win on the spinal muscular atrophy field, giving Novartis and Biogen a run for their money.

The update was brief, but Roche said risdiplam hit the primary endpoint in the placebo-controlled pivotal SUNFISH trial, meeting the threshold for change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment. The results, which is the second, confirmatory portion of a two-part study, involved 180 patients with type 2 or 3 spinal muscular atrophy between 2 and 25 years old.

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Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is working on putting together a late-stage study for its monoclonal antibody Gazyva in patients with severe kidney disease associated with lupus after a combination approach helped patients in a mid-stage study.

The 125-patient NOBILITY trial evaluated Gazyva, combined with standard-of-care treatment mycophenolate mofetil or mycophenolic acid and corticosteroids, versus standard treatment alone. The combo met the main goal of inducing a statistically superior complete renal response (CRR) of 40% at week 76, versus 18% in patients given standard treatment, Roche said.