Ar­mored CAR-Ts? Memo­r­i­al Sloan Ket­ter­ing en­gi­neers CAR-T loaded with check­point in­hibitors

Sci­en­tists at Memo­r­i­al Sloan Ket­ter­ing have en­gi­neered a hy­brid can­cer ther­a­py that might just bring two of hottest ar­eas of on­col­o­gy sci­ence to­geth­er in one pack­age: CAR-T and check­point in­hibitors.

Sar­wish Rafiq

That’s the hope of a team of MSK re­searchers work­ing in the labs of Re­nier Bren­t­jens, a renowned physi­cian-sci­en­tist in New York City. They just pub­lished a pa­per in Na­ture — au­thored by Sar­wish Rafiq, Oladapo Yeku, and Hol­lie Jack­sonout­lin­ing their suc­cess in an­i­mal mod­els.

“We took a step back and said, ‘How can we make CAR T cells bet­ter?’ That’s when we de­cid­ed to try to com­bine these two promis­ing ap­proach­es,” Bren­t­jens said. “This proves — at least in a mouse mod­el — that we can now have our cake and eat it too.”

Oladapo Yeku

The ear­ly re­search is promis­ing. Here’s how it works: MSK’s new­ly de­signed CAR-T cells come loaded with a minia­ture ver­sion of a check­point-block­ing an­ti­body, sim­i­lar to drugs al­ready on the mar­ket like Op­di­vo and Keytru­da. When the loaded CAR-T is de­liv­ered to the tu­mor en­vi­ron­ment, the an­ti­bod­ies are se­cret­ed — bind­ing to PD-1 pro­teins and slam­ming the brakes on im­mune cells. This al­lows the CAR-Ts to bet­ter fight the can­cer cells, with an army of an­ti­bod­ies by their side.

MSK is call­ing this new tech an “ar­mored CAR T.” They made two ver­sions of it: one that rec­og­nizes CD19 (found in cer­tain blood can­cers), and the oth­er that rec­og­nizes MUC16, which is found in some ovar­i­an and pan­cre­at­ic can­cers.

In mouse mod­els, the re­searchers found that mice on the ar­mored CAR treat­ment lived sig­nif­i­cant­ly longer than those on reg­u­lar CARs, and the ar­mored CARs stuck around in the body longer, too. Plus, the check­point drugs re­leased by the CAR-Ts cre­at­ed a help­ful by­stander ef­fect, and PD-1 an­ti­bod­ies were low in cir­cu­lat­ing blood (hope­ful­ly in­di­cat­ing that the treat­ment wasn’t spread­ing be­yond the tu­mor site).

“An ar­mored CAR T ap­proach rep­re­sents the next phase of in­no­va­tion in T cell ther­a­pies,” Bren­t­jens said in a news re­lease. “These da­ta, to­geth­er with in vi­vo mod­els, sug­gest that this is an ear­ly step to­ward ex­plor­ing how we can make the first it­er­a­tions of CAR T cell ther­a­pies even bet­ter.”

MSK says it’s in the process of de­sign­ing clin­i­cal tri­als in hu­mans.


Pho­to: Re­nier J. Bren­t­jens. Memo­r­i­al Sloan Ket­ter­ing

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.

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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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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Pfizer CEO Albert Bourla (Drew Angerer/Getty Images)

Pfiz­er is on the verge of claim­ing a multi­bil­lion-dol­lar first-mover ad­van­tage with their Covid-19 vac­cine — an­a­lyst

From the beginning, Pfizer CEO Albert Bourla eschewed government funding for his Covid-19 vaccine work with BioNTech, willing to take all the $2 billion-plus risk of a lightning-fast development campaign in exchange for all the rewards that could fall its way with success. And now that the pharma giant has seized a solid lead in the race to the market, those rewards loom large.

SVB Leerink’s Geoff Porges has been running the numbers on Pfizer’s vaccine, the mRNA BNT162b2 program that the German biotech partnered on. And he sees a $3.5 billion peak in windfall revenue next year alone. Even after the pandemic is brought to heel, though, Porges sees a continuing blockbuster role for this vaccine as people around the world look to guard against a new, thoroughly endemic virus that will pose a permanent threat.

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UP­DAT­ED: CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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Giovanni Caforio, Bristol Myers Squibb CEO (Christopher Goodney/Bloomberg via Getty Images)

Here's how Bris­tol My­er­s' CEO Gio­van­ni Caforio com­plet­ed a $13B buy­out: He moved fast, upped the bid quick­ly and de­mand­ed every­one to keep up

Bristol Myers Squibb CEO Giovanni Caforio does not waste time. He also likes everyone around him to keep up.

Anyone reading over the insider account filed with the SEC of the back-and-forth over his $13 billion buyout of MyoKardia $MYOK could reach only one conclusion: The CEO who had willingly crafted a $74 billion Celgene acquisition had found something else he liked — and he was willing to pay a nice premium to get it.

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Roche finds a home for a new, $500M man­u­fac­tur­ing lo­gis­tics hub, promis­ing 500 jobs

Roche is pouring $500 million into its Canadian headquarters in Mississauga, Ontario to set up a new hub that will coordinate logistics for its global supply chain.

Over the 5-year investment, the Swiss pharma giant expects to add 200 jobs over next year and another 300 by the end of 2023.

Introduced as a $190 million global pharmaceutical development site in 2011, the campus currently houses Roche’s Canadian commercial unit as well as product development, global procurement and pharma informatics. The new expansion will see it organize manufacturing across 13 plants and 11 sites, according to FiercePharma.

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