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

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to 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.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

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Paul Hudson, Sanofi CEO (via Getty)

Sanofi's $20B buy­out of Gen­zyme pays off again with Eu­ro­pean OK for first Nie­mann-Pick drug

Sanofi CEO Paul Hudson has made clear his intention to develop new rare disease drugs and broaden his company’s offerings. That effort leaped forward on Friday with the EMA’s signing off on the company’s — and the EU’s — first drug to treat the non-central nervous system manifestations of the rare and debilitating Niemann-Pick disease.

The enzyme replacement therapy, developed to replace patients’ deficient or defective enzyme, known as acid sphingomyelinase, was first developed by Genzyme, which Sanofi acquired for more than $20 billion in 2011. That acquisition has also helped Sanofi pull in sales in the field of MS.

Proac­tive­ly pre­vent­ing short­ages: New FDA guid­ance spells out which drugs re­quire risk man­age­ment plans

As the majority of drug shortages are still associated with manufacturing-related quality issues, the FDA on Thursday published new draft guidance spelling out how to proactively assess risks to manufacturing processes and supply chains, while understanding the market’s vulnerabilities.

While drug shortages peaked in 2011, the FDA says in its new 18-page draft guidance that the number of new drug shortages “has declined significantly since” that peak, reaching a low in 2015 and 2016, thanks in part to a new law’s enactment, known as FDASIA, which helped the agency better prevent or mitigate drug supply disruptions and shortages, and clarified cGMP requirements.