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

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

This is the second biotech buyout pact today, marking a brisk tempo of M&A deals in the lead-up to the big JP Morgan gathering in mid-January. It’s no surprise the acquisitions are both for cancer drugs, where Sanofi will try to make its mark while Merck beefs up a stellar oncology franchise. And bolt-ons are all the rage at the major pharma players, which you could also see in Novartis’ recent $9.7 billion MedCo buyout.

ArQule — which comes out on top after their original lead drug foundered in Phase III — highlighted early data on ‘531 at EHA from a group of 6 chronic lymphocytic leukemia patients who got the 65 mg dose. Four of them experienced a partial response — a big advance for a company that failed with earlier attempts.

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Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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Left top to right: Mark Timney, Alex Denner, Vas Narasimhan. (The Medicines Company, Getty, AP/Endpoints News)

In a play-by-play of the $9.7B Med­Co buy­out, No­var­tis ad­mits it over­paid while of­fer­ing a huge wind­fall to ex­ecs

A month into his tenure at The Medicines Company, new CEO Mark Timney reached out to then-Novartis pharma chief Paul Hudson: Any interest in a partnership?

No, Hudson told him. Not now, at least.

Ten months later, Hudson had left to run Sanofi and Novartis CEO Vas Narasimhan was paying $9.7 billion for the one-drug biotech – the largest in the string of acquisitions Narasimhan has signed since his 2017 appointment.

The deal was the product of an activist investor and his controversial partner working through nearly a year of cat-and-mouse negotiations to secure a deal with Big Pharma’s most expansionist executive. It represented a huge bet in a cardiovascular field that already saw two major busts in recent years and brought massive returns for two of the industry’s most eye-raising names.

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Am­gen puts its foot down in shiny new South San Fran­cis­co hub as it re­or­ga­nizes R&D ops

Amgen has signed up to be AbbVie’s neighbor in South San Francisco as it moves into a nine-story R&D facility in the booming biotech hub.

The arrangement gives Amgen 240,000 square feet of space on the Gateway of Pacific Campus, just a few minutes drive from its current digs at Oyster Point. The new hub will open in 2022 and house the big biotech’s Bay Area employees working on cardiometabolic, inflammation and oncology research.

Ab­b­Vie, Scripps ex­pand part­ner­ship, for­ti­fy fo­cus on can­cer drugs

Scripps and AbbVie go way back. Research conducted in the lab of Scripps scientist Richard Lerner led to the discovery of Humira. The antibody, approved by the FDA in 2002 and sold by AbbVie, went on to become the world’s bestselling treatment. In 2018, the drugmaker and the non-profit organization signed a pact focused on developing cancer treatments — and now, the scope of that partnership has broadened to encompass a range of diseases, including immunological and neurological conditions.

South Ko­rea jails 3 Sam­sung ex­ecs for de­stroy­ing ev­i­dence in Bi­o­Log­ics probe

Three Samsung executives in Korea are going to jail.

The convictions came in what prosecutors had billed as “biggest crime of evidence destruction in the history of South Korea”: a case of alleged corporate intrigue that was thrown open when investigators found what was hidden beneath the floor of a Samsung BioLogics plant. Eight employees in total were found guilty of evidence tampering and the three executives were each sentenced to up to two years in prison.

Nick Plugis, Avak Kahvejian, Cristina Rondinone, Milind Kamkolkar and Chad Nusbaum. (Cellarity)

Cel­lar­i­ty, Flag­ship's $50M bet on net­work bi­ol­o­gy, mar­ries ma­chine learn­ing and sin­gle-cell tech for drug dis­cov­ery

Cellarity started with a simple — but far from easy — idea that Avak Kahvejian and his team were floating around at Flagship Pioneering: to digitally encode a cell.

As he and his senior associate Nick Plugis dug deeper into the concept, they found that most of the models others have developed take a bottom-up approach, where they assemble the molecules inside cells and the connections between them from scratch. What if they opt for a top-down approach, aided by single-cell transcriptomics and machine learning, to gauge the behavior of the entire cellular network?