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

A new num­ber 1 drug? Keytru­da tapped to top the 10 biggest block­busters on the world stage by 2024

Analysts may be fretting about Keytruda’s longterm prospects as a host of rival therapies elbow their way to the market. But the folks at Evaluate Pharma are confident that last year’s $7 billion earner is headed for glory, tapping it to beat out the current #1 therapy Humira as AbbVie watches that franchise swoon over the next 5 years.

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John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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In­vestor day prep at Mer­ck in­cludes a new strat­e­gy to pick up the pace on M&A — re­port

Mer­ck’s re­cent deals to buy up two bolt-on biotechs — Ti­los and Pelo­ton — weren’t an aber­ra­tion. In­stead, both ac­qui­si­tions mark a new strat­e­gy to beef up its dom­i­nant can­cer drug op­er­a­tions cen­tered on Keytru­da while look­ing to ad­dress grow­ing con­cerns that too many of its eggs are in the one I/O bas­ket for their PD-1 pro­gram. And Mer­ck is go­ing af­ter more small- and mid-sized buy­outs to calm those fears.

Dave Barrett, Brian Chee, Amir Nashat, Amy Schulman. Polaris

Bob Langer's first port of call — Po­laris Part­ners — maps $400M for ninth fund

Health and tech ven­ture group Po­laris Part­ners, which counts Alec­tor, Al­ny­lam and Ed­i­tas Med­i­cine as part of its port­fo­lio, is set­ting up its ninth fund, rough­ly two years af­ter it closed Po­laris VI­II with $435 mil­lion in the bank, sur­pass­ing its tar­get by $35 mil­lion.

The Boston-based firm, in an SEC fil­ing, said it in­tends to raise $400 mil­lion for the fund. Po­laris — which rou­tine­ly backs com­pa­nies mold­ed out of the work done in the lab of pro­lif­ic sci­en­tist Bob Langer of MIT  — typ­i­cal­ly in­vests ear­ly, and sticks around till com­pa­nies are in the green. Like its peers at Flag­ship and Third Rock, Po­laris is all about cham­pi­oning the lo­cal biotech scene with a steady flow of start­up cash.

Partners Innovation Fund

David de Graaf now has his $28.5M launch round in place, build­ing a coen­zyme A plat­form in his lat­est start­up

Long­time biotech ex­ec David de Graaf has the cash he needs to set up the pre­clin­i­cal foun­da­tion for his coen­zyme A me­tab­o­lism com­pa­ny Comet. A few high-pro­file in­vestors joined the ven­ture syn­di­cate to sup­ply Comet with $28.5 mil­lion in launch mon­ey — enough to get it two years in­to the plat­form-build­ing game, with­in knock­ing dis­tance of the clin­ic.

Canaan jumped in along­side ex­ist­ing in­vestor Sofinno­va Part­ners to co-lead the round, with par­tic­i­pa­tion by ex­ist­ing in­vestor INKEF Cap­i­tal and new in­vestor BioIn­no­va­tion Cap­i­tal.

Right back at you, Pfiz­er: BeiGene and a Pfiz­er spin­out launch a new­co to de­vel­op a MEK/BRAF in­hibitor that could ri­val $11.4B com­bo

A day af­ter Pfiz­er bought Ar­ray and its ap­proved can­cer com­bo, BeiGene and Pfiz­er spin­out Spring­Works have part­nered in launch­ing a new biotech that has an eye on the very same mar­ket the phar­ma gi­ant just paid bil­lions for. And they’re plan­ning on us­ing an ex-Pfiz­er drug to do it.

In a nut­shell, Chi­na’s BeiGene is toss­ing in a pre­clin­i­cal BRAF in­hibitor — BGB-3245, which cov­ers both V600 and non-V600 BRAF mu­ta­tions — for a big stake in a new, joint­ly con­trolled biotech called Map­Kure with Bain-backed Spring­Works.

Step­ping on Roche's toes, Mer­ck cuts in­to SCLC niche with third-line Keytru­da OK

In the in­creas­ing­ly crowd­ed check­point race, small cell lung can­cer has been a rare area where Roche, a sec­ond run­ner-up, has a lead over the en­trenched lead­ers Mer­ck and Bris­tol-My­ers Squibb. But Mer­ck is fi­nal­ly mak­ing some head­way in that di­rec­tion with the lat­est ap­proval for its PD-1 star.

The lat­est green light en­dors­es Keytru­da in the third-line treat­ment of metasta­t­ic SCLC, where it would be giv­en to pa­tients whose dis­ease ei­ther don’t re­spond to or re­lapse af­ter chemother­a­py, which would have fol­lowed at least one pri­or line of ther­a­py.

Sanofi aligns it­self with Google to stream­line drug de­vel­op­ment

Tech­nol­o­gy is bleed­ing in­to health­care, and big phar­ma is rid­ing the wave. Sanofi $SNY ap­point­ed its first chief dig­i­tal of­fi­cer this Feb­ru­ary, fol­low­ing the foot­steps of its peers. By May, the French drug­mak­er and some of its big phar­ma com­pa­tri­ots joined forces with Google par­ent Al­pha­bet’s Ver­i­ly unit to aug­ment clin­i­cal tri­al re­search. On Tues­day, the Parisian com­pa­ny tied up with Google to ac­cess its cloud com­put­ing and ar­ti­fi­cial in­tel­li­gence tech to spur the de­vel­op­ment of new ther­a­pies.