Neu­vo­gen un­cloaks with broad plan of at­tack for whole-cell can­cer vac­cines, clin­i­cal hopes with­in the year

Af­ter about four stealthy years in the de­vel­op­ment phase, San Diego-based Neu­vo­gen is emerg­ing with a new ap­proach to whole-cell can­cer vac­cines and nine sol­id tu­mor pro­grams bound for the clin­ic.

Whole-cell tu­mor vac­cines are de­vel­oped by tak­ing can­cer cells from pa­tients and mod­i­fy­ing them to make them im­muno­genic.

“What’s dif­fer­ent from what we do, is most peo­ple use one cell line. We use six,” CEO Todd Binder said. From there, the com­pa­ny builds out six mod­i­fi­ca­tions to elim­i­nate prob­lem­at­ic im­muno­sup­pres­sive fac­tors, and add what the ex­ec­u­tive called three “stim­u­la­to­ry fac­tors” to gen­er­ate a prime and over­come pe­riph­er­al tol­er­ance.

Im­mune prim­ing ef­forts are typ­i­cal­ly di­rect­ed at one or a hand­ful of tar­gets. But if some can­cer cells with­in the tu­mor don’t ex­press those tar­gets, the tu­mor can es­cape. So at Neu­vo­gen, the fo­cus is breadth.

“I came from the CAR-T cell ther­a­py world,” said Binder, who hails from Ze­taRx. “And the one thing that was crit­i­cal is that CAR-T cell ef­fi­ca­cy seems to be tight­ly cor­re­lat­ed with the per­cent of can­cer cells you can di­rect­ly tar­get.”

His ap­proach now is to tar­get as many can­cer cells as pos­si­ble in a sol­id tu­mor — the chal­lenge be­ing that the sol­id tu­mor en­vi­ron­ment is “in­cred­i­bly het­ero­ge­neous.”

“In essence, we’re try­ing to repli­cate CAR-T cell ef­fi­ca­cy in blood can­cers in sol­id tu­mors us­ing a can­cer vac­cine,” he said.

To get the de­sired im­mune re­sponse, the team en­gi­neers its can­di­dates with those “stim­u­la­to­ry fac­tors,” de­signed to over­come pe­riph­er­al tol­er­ance. One of them en­hances the traf­fick­ing of den­drit­ic cells to the vac­ci­na­tion site in the hopes of achiev­ing an ef­fi­cient up­take. An­oth­er en­hances den­drit­ic-cell mat­u­ra­tion to help op­ti­mize anti­gen pre­sen­ta­tion in the drain­ing lymph node. And the third skews the prim­ing of the naive T cells in­to an in­ter­fer­on gam­ma-pro­duc­ing an­ti-tu­mor T cell.

The out­come was “bet­ter than ex­pect­ed,” Binder said. “So that opened up the pos­si­bil­i­ty of adding in ad­di­tion­al tar­get­ing method­olo­gies.”

The team added in can­cer stem cell tar­gets, as well as non­syn­ony­mous mu­ta­tions and dri­ver mu­ta­tions, which are tu­mor spe­cif­ic anti­gens, Binder said.

Binder ex­pects the first pro­gram for non-small cell lung can­cer to hit the clin­ic by the end of this year. The start­up is al­so go­ing af­ter prostate can­cer, al­though Binder de­clined to com­ment on a time­line for that pro­gram. The CEO is keep­ing the re­main­ing sev­en in­di­ca­tions un­der wraps for now.

“This is no small feat to do mul­ti­ple mod­i­fi­ca­tions to a sin­gle bi­o­log­i­cal prod­uct… the team was able to just keep ex­tend­ing it to im­prove the ad­ju­vant ef­fect and al­so to im­prove the breadth that we’re ca­pa­ble of,” said CMO Mark Bagarazzi, who comes by way of In­ovio and Mer­ck.

Neu­vo­gen has an­oth­er In­ovio vet­er­an, Bernadette Fer­raro, as its head of im­muno-on­col­o­gy, and for­mer Am­gen CEO Gor­don Binder as strate­gic ad­vi­sor and board chair­man. Kendall Mohler, for­mer CSO of Juno Ther­a­peu­tics, is al­so join­ing the board.

“Our goal is to put at least four in­di­ca­tions in­to the clin­ic over the next few years,” Binder said. Now, we watch.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Joe Nolan, Jaguar

Sean Nolan gath­ers AveX­is alum­ni to launch an­oth­er biotech. Is it an­oth­er race-to-IPO?

The old AveXis crew is launching another company. And they may once again look to cash in quick.

Armed with patents and a steady stream of cash from Deerfield Management, Sean Nolan and five ex-Avexis executives have launched Jaguar Gene Therapy to develop AAV9 gene therapies for a small constellation of disparate disorders, from autism to diabetes. Jaguar remains over a year from the clinic, but CEO Joe Nolan hinted they could look to follow a pace set by Tasyha, the biotech Sean Nolan and other AveXis alumni launched last year and took from Series A to IPO in less than 6 months.

Glax­o­SmithK­line re­thinks strat­e­gy for Covid-19 an­ti­body — not the Vir ones — af­ter tri­al flop. Is there hope in high-risk pa­tients?

In the search for a better Covid-19 therapeutic, GlaxoSmithKline and Vir have partnered up on two antibodies they hope have a chance. GSK is also testing its own in-house antibody, and early results may have shut the door on its widespread use.

A combination of GSK’s monoclonal antibody otilimab plus standard of care couldn’t best standard of care alone in preventing death and respiratory failure in hospitalized Covid-19 patients after 28 days, according to data from the Phase IIa OSCAR study unveiled Thursday.