Sen­ti sci­en­tif­ic co-founder Wil­son Wong de­signs the SUPRA — a new, high per­for­mance mod­el CAR-T

Wil­son Wong, one of the sci­en­tif­ic co-founders be­hind Tim­o­thy Lu’s new syn­thet­ic bi­ol­o­gy start­up Sen­ti, has de­signed a new CAR-T that he be­lieves has the po­ten­tial to over­come some of the big is­sues that con­tin­ues to plague the first gen­er­a­tion of drugs now on the mar­ket.

And he’s tricked it out with some in­ter­est­ing new fea­tures.

The Boston Uni­ver­si­ty T-cell en­gi­neer — work­ing with grad­u­ate stu­dent Jang Hwan Cho and MIT’s Jim Collins, a leg­end in syn­thet­ic bio cir­cles and a men­tor to Lu — pub­lished a pa­per in Cell to­day out­lin­ing their work on the re­design, which Sen­ti will now see if it can guide to­ward the clin­ic.

Jim Collins

Work­ing with mouse mod­els, Wong de­vised a CAR he’s dubbed the SUPRA —  which stands for split, uni­ver­sal and  pro­gram­ma­ble. The cen­tral part of its promise is that the re­vised CAR-T is built to go af­ter two mark­ers for the dis­ease, vast­ly im­prov­ing its chance of ex­tend­ing the use of these drugs in­to hard-to-hit sol­id tu­mors while im­prov­ing the speci­fici­ty of the drug to can­cer tis­sue.

It’s al­so a cus­tomiz­able ap­proach, with bet­ter built-in con­trol fea­tures that can be used to go af­ter spe­cif­ic types of blood can­cer and sol­id tu­mors.

“What’s nice,” he tells me, “is that you need two sig­nals to turn on the T cells, not one mag­ic bul­let. The can­cer mark­er can be less spe­cif­ic, re­ly­ing on the in­ter­sec­tion of the two.”

The oth­er key in­gre­di­ent is an added adap­tive mol­e­cule which can be in­clud­ed with the treat­ment to guide the T cells to can­cer cells. With­out these adap­tive mol­e­cules, the T cell won’t be ac­ti­vat­ed, he says. And as they’re cleared even­tu­al­ly, you can add a fresh sup­ply to en­gi­neer a fresh re­sponse to a cho­sen tar­get.

Add it up and you gain a ba­sic on/off switch that can be used to fine tune the ac­tiv­i­ty of the ther­a­py to con­trol tox­i­c­i­ty, pre­vent­ing the kind of over­ac­tiv­i­ty that can launch a dan­ger­ous re­ac­tion in pa­tients. And you can more eas­i­ly spur a fol­lowup re­sponse to pre­vent re­laps­es.

It’s pre­clin­i­cal, which means there’s still plen­ty of work that would need to be done be­fore it could be test­ed in a hu­man. How long?

Maybe two years, says the sci­en­tist, “but you nev­er know.”

The first two CAR-Ts on the mar­ket, Yescar­ta and Kym­ri­ah, work ac­cord­ing to a sim­ple de­sign plan, tak­ing pa­tient cells, en­gi­neer­ing them with a chimeric anti­gen re­cep­tor, and then un­leash­ing a swarm to at­tack can­cer cells.

But it’s lim­it­ed, and not just by the tox­i­c­i­ty of an un­con­trolled re­ac­tion. The first gen­er­a­tion pa­tients are al­so ex­posed to re­laps­es as the ac­tiv­i­ty wears down, and adding a new half-mil­lion dol­lar ther­a­py isn’t fea­si­ble.

The long-term plan is to cre­ate an off-the-shelf ther­a­py with uni­ver­sal fea­tures for each can­cer type, and the re­searchers now are ze­ro­ing in on the types of can­cers which are most like­ly to re­spond to the two-tar­get de­sign.

The grand idea here is that Wong wants to build a “pros­thet­ic im­mune sys­tem,” a mas­ter con­trol tech­nol­o­gy that could pro­vide a new sys­tem that would gov­ern the im­mune re­sponse to any dis­ease, which would have a pow­er­ful and ob­vi­ous role to play on reg­u­la­to­ry T cells that sup­press an im­mune re­sponse as well as in au­toim­mune dis­eases like rheuma­toid arthri­tis. 

That’s a sub­stan­tial­ly big­ger vi­sion than the work on CAR-T 2.0. But these steps fol­low a longer path for Wong that he’s keen to ex­plore.

Im­age: Wil­son Wong. BOSTON UNI­VER­SI­TY

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.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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The fu­ture of mR­NA, J&J's vac­cine ad­comm, Mer­ck­'s $1.85B au­toim­mune bet and more

Welcome to the third installment of Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

If this report was helpful in recapping it all for you, please do share it with your colleagues.

Get ready for FDA’s third Covid-19 vaccine

On the heels of a ringing endorsement from FDA reviewers earlier in the week, J&J‘s single-dose vaccine — which proved 66% effective at preventing symptomatic Covid-19, and 85% effective at stopping severe disease 28 days after administration — the advisory committee convened by the agency voted unanimously to recommend its emergency use authorization. It was “a relatively easy call,” according to one of the committee members — although that doesn’t mean they didn’t have questions. Jason Mast has the highlights from the discussion, including new information from the company, on this live blog.

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With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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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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Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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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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Masayoshi Son, SoftBank CEO (glen photo/Shutterstock)

Japan's Soft­Bank plots bil­lions in biotech in­vest­ments in move that could keep the val­u­a­tion flood ris­ing — re­port

The valuation crazy train in biotech continues to roll into the new year with more than a dozen companies taking a chance on Nasdaq and money flowing in from all sides. Now, a Japanese institutional investor is reportedly weighing an entry into the market in a big way — will it keep the bitcoin-esque flood rising?

Already a part-time investor in biotech, SoftBank could drop billions of dollars into the industry as part of helmsman Masayoshi Son’s plan to spend around $80 billion of the firm’s own assets, according to a report from Bloomberg citing people familiar with the plan.

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