Park­er In­sti­tute sum­moned the neoanti­gen pi­o­neers to com­pare their pre­dic­tion al­go­rithms. And they have some sug­ges­tions for the field

What makes a good neoanti­gen?

For all the promis­es of the bold new ap­proach to can­cer vac­cines and ther­a­pies — ze­ro­ing in on spe­cif­ic mu­tat­ed anti­gens ex­pressed on­ly by tu­mors — com­pa­nies and aca­d­e­mics have lit­tle way of know­ing how good they are at pre­dict­ing which neoanti­gens rep­re­sent the best tar­gets. There’s no stan­dard or base­line for play­ers to stack them­selves against ri­vals in the nascent field, and by the time they find out, it could be too late.

No sin­gle group could re­al­ly build that bench­mark. Pre­cious pro­pri­etary in­for­ma­tion is at stake, not to men­tion tremen­dous re­sources re­quired.

Dan­ny Wells

But four years ago, just as the con­cept was tak­ing off, it struck the Park­er In­sti­tute for Can­cer Im­munother­a­py as the ex­act kind of prob­lem its col­lab­o­ra­tive mod­el was built to solve.

“We’re like Switzer­land of neoanti­gens,” Dan­ny Wells, the prin­ci­pal da­ta sci­en­tist at PI­CI, told End­points News.

So work­ing with the Can­cer Re­search In­sti­tute and a non­prof­it named Sage Bionet­works, it brought to­geth­er over 40 bio­phar­ma com­pa­nies and aca­d­e­m­ic labs, gave them the same melanoma and non-small cell lung can­cer tis­sue, and asked each team to sub­mit its most promis­ing neoanti­gen pre­dic­tions. PI­CI re­searchers then went in­to the lab and cross-com­pared the pre­dic­tions, check­ing whether the neoanti­gens were in­deed rec­og­nized by T cells. The re­sult is a base­line dataset that the ini­tia­tive — named TES­LA, short for Tu­mor Neoanti­gen Se­lec­tion Al­liance — is mak­ing pub­lic to the sci­en­tif­ic world to­day.

To the re­searchers’ sur­prise, the dif­fer­ences be­tween the pre­dic­tion al­go­rithms were “tremen­dous,” said Wells, a co-se­nior au­thor in the pa­per pub­lished in Cell. No team man­aged to iden­ti­fy every neoanti­gen or even a large ma­jor­i­ty of them: “The over­lap be­tween pre­dic­tions, no mat­ter how we sliced it, was re­al­ly low.”

It high­lights the need for new knowl­edge in the field, he added, and PI­CI be­lieves TES­LA has yield­ed some in­sights.

Na­dine De­fra­noux

A set of five dis­tinct fea­tures, it turned out, could pre­dict good neoanti­gens with high ac­cu­ra­cy and speci­fici­ty when in­te­grat­ed in­to a mod­el. They are bind­ing affin­i­ty, tu­mor abun­dance and bind­ing sta­bil­i­ty, which has to do with how the neoanti­gens are pre­sent­ed; as well as agre­topic­i­ty and for­eign­ness, which re­lates to their recog­ni­tion by im­mune cells.

“These are all fea­tures that had been talked about, but I think we were sur­prised that just by in­te­grat­ing them to­geth­er in­to this sin­gle mod­el that it works so well,” Wells said.

When par­tic­i­pat­ing teams reap­plied these char­ac­ter­is­tics in­to their al­go­rithms, PI­CI re­port­ed, the pre­dic­tions im­proved. A da­ta mod­el em­pha­siz­ing all five fea­tures came out of a test against an­oth­er set of can­cer sam­ples ac­cu­rate­ly pre­dict­ing 75% of ef­fec­tive neoanti­gen tar­gets and fil­ter­ing out 98% of in­ef­fec­tive ones. De­pend­ing on the ther­a­peu­tic strat­e­gy drug de­vel­op­ers may cal­i­brate their al­go­rithms dif­fer­ent­ly, Wells said. But the hope he and co-se­nior au­thor Na­dine De­fra­noux have is that they can pro­vide a com­mon base­line both for those al­ready in the field and oth­ers look­ing to jump in.

Lisa But­ter­field

“This re­search has the po­ten­tial to im­prove drug mak­ers’ and re­searchers’ math­e­mat­i­cal al­go­rithms,” Lisa But­ter­field, vice pres­i­dent of re­search and de­vel­op­ment at PI­CI, said in a state­ment. “It can pri­or­i­tize anti­gens most like­ly to be present on each pa­tient’s can­cer and most vis­i­ble to the im­mune sys­tem while de­pri­or­i­tiz­ing the ones that aren’t.”

Robert Schreiber

While TES­LA won’t be mon­i­tor­ing the space lon­gi­tu­di­nal­ly to see how com­pa­nies com­pare over time, Wells does en­vi­sion new evo­lu­tions for the coali­tion. Many ques­tions still need to be an­swered; for in­stance, while they fo­cused on class 1 pre­dic­tion, or how CD8+ T cells see the tu­mor, co-se­nior au­thor Robert Schreiber’s re­search has sug­gest­ed that class 2, or how CD4+ T cells see the tu­mor, are just as im­por­tant.

“Un­til now, neoanti­gen pre­dic­tion has been a black box,” said Schreiber, a pro­fes­sor at the Wash­ing­ton Uni­ver­si­ty School of Med­i­cine in St. Louis. TES­LA has be­gun shed­ding light on it, and it in­tends to con­tin­ue.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Bo Cumbo, AavantiBio CEO (file photo)

Bo Cum­bo jumps from the top com­mer­cial post at Sarep­ta to the helm of a gene ther­a­py start­up with some in­flu­en­tial back­ers, big plans and $107M

After a 7-year stretch building the commercial team at Sarepta, longtime drug salesman Bo Cumbo is jumping to the entrepreneurial side of the business, taking the helm of a startup that’s got several deep-pocket investors. And he’s not just bringing his experience in selling drugs.

He tells me that when he told Sarepta CEO Doug Ingram about it, his boss got excited about the venture and opted to jump in with a $15 million investment from Sarepta to add to the launch money, alongside 3 of the busiest investors in biotech.

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Covid-19 roundup: WSJ of­fers in­side look at Ox­ford-As­traZeneca deal, in­clud­ing fi­nan­cial terms; Lil­ly plant un­der scruti­ny again

Oxford scientists developing a Covid-19 vaccine are working with British drugmaker AstraZeneca, and together the pair have become one of the frontrunners in the race to end the pandemic. But a new Wall Street Journal report out Wednesday offered a behind-the-scenes look at how that deal came together in the wake of a scholar-led revolt over a potential collaboration with Merck, and included previously unreported financial terms of the AstraZeneca deal.

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Jean-Pierre Sommadossi, Atea president and CEO (file photo)

Roche wades deep­er in­to Covid-19 fight, ink­ing an­tivi­ral pact with $350M cash fol­low­ing Re­gen­eron deal

Roche is making its first bet on an antiviral against Covid-19 in style, shelling out $350 million in cash to grab ex-US rights.

The drug comes from Atea Pharmaceuticals, the 7-year-old biotech created by Pharmasset co-founder Jean-Pierre Sommadossi, which essentially rebranded itself as a Covid-19 fighter in May when it closed a whopping $215 million venture round. Over a dozen investors bought in, including marquee names like Bain Capital and RA Capital.

CEO Marc Gleeson (Azura)

Azu­ra Oph­thalmics gets a $20M boost for its R&D work on eye dis­eases

Three years after closing a $16 million Series B, the same group of investors are back to give Azura Ophthalmics a $20 million boost.

That brings the Tel Aviv-Yafo, Israel-based biotech’s total fundraise to $38 million, and should pave the way for a registration study of its lead candidate in Meibomian gland dysfunction (MGD) and related eye diseases, CEO Marc Gleeson told Endpoints News.

The topical candidate, dubbed AZR-MD-001, is designed to address abnormal hyperkeratinization, or the build-up and shedding of proteins at the opening of or within the Meibomian gland. When Meibomian glands become dysfunctional, rapid evaporation of the tear film can occur, leading to dry eye disease.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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Peter Kolchinsky and Raj Shah (file photo)

Pe­ter Kolchin­sky and Raj Shah's RA Cap­i­tal has $461M more to play with, af­ter 'rapid' in­vest­ment in the last 15 months

Just over 15 months after launching its first venture fund, RA Capital Management is ready for more. And this time the firm is bringing an even bigger load of cash to the table.

Announcing the close of its Nexus II fund on Wednesday, RA said it raised $461 million for investments in private companies across the biotech industry. The first venture fund, which raised $300 million, has churned through roughly 80% of its capital already, a pace that managing partner Raj Shah called unusually quick.

David Hung (file photo)

Mas­ter deal­mak­er David Hung re­tools a SPAC sedan in­to a fi­nanc­ing mus­cle ve­hi­cle that leaves his can­cer start­up with $850M and a place on Wall Street

It’s only right that one of the industry’s top dealmakers just completed one of the biggest SPAC-related deals in the pipeline.

David Hung, of Medivation fame, has completed a back flip into the market, merging with EcoR1 Capital’s SPAC Panacea and landing neatly on Wall Street with an $NUVB stock ticker after filling out the blank check in his name. In addition to the $144 million held in the SPAC — provided none of the investors opt out — Hung is getting ahold of $500 million more being chipped in by a slate of institutional investors who feel that Hung could have the keys to another Medivation-style success.

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