Cel­lec­tis preps for ground­break­ing US tri­als for an off-the-shelf CAR-T ther­a­py


Cel­lec­tis is ramp­ing up the first-ever US tri­al launch­es for an off-the-shelf CAR-T ther­a­py.

The Paris-based biotech $CLLS, which has a siz­able R&D group in Man­hat­tan, says the FDA has signed off on their IND for a Phase I study of UCART123 in acute myeloid leukemia and blas­tic plas­ma­cy­toid den­drit­ic cell neo­plasm.

The plan now is to get start­ed in the next few months, wrap up their ear­ly-stage work in ear­ly 2018 and then launch what they hope will be a reg­is­tra­tional Phase II tri­al in mid-2018 — pro­vid­ed the FDA signs off, Dr. Loan Hoang-Sayag, Cel­lec­tis’ chief med­ical of­fi­cer, tells End­points News via email.

Servi­er and part­ner Pfiz­er have been col­lab­o­rat­ing with Cel­lec­tis on an on­go­ing Phase I study for the lead ther­a­py, UCART19, in the UK. UCART123 is a sole­ly-owned Cel­lec­tis pro­gram us­ing TAL­EN en­gi­neered T cells.

The biotech is com­ing in be­hind lead au­tol­o­gous CAR-T play­ers Kite and No­var­tis, both of which are an­gling for the first-ever ap­proval this year for reengi­neered cells ex­tract­ed from pa­tients. Cel­lec­tis, helmed by CEO An­dre Chouli­ka, has been steadi­ly ad­vanc­ing these off-the-shelf ther­a­pies as an eas­i­er to man­u­fac­ture and de­liv­er can­cer treat­ment that could be a nat­ur­al suc­ces­sor to the first CAR-Ts to hit the mar­ket.

It’s a tricky process though. Their ther­a­py has been test­ed in com­pas­sion­ate use cas­es, and in one in­stance re­quired steroids to tamp down on an im­mune re­sponse, which is one re­ac­tion they def­i­nite­ly don’t want to see in an al­lo­gene­ic ap­proach. The au­tol­o­gous lead­ers have been us­ing pa­tient-de­rived cells pre­cise­ly in or­der to avoid any im­mune re­sponse.

UCART123 is a gene-edit­ed T-cell in­ves­ti­ga­tion­al drug that tar­gets CD123, an anti­gen ex­pressed at the sur­face of leukemic cells in AML, tu­moral cells in BPD­CN. The clin­i­cal re­search for AML will be led at Weill Cor­nell by prin­ci­pal in­ves­ti­ga­tor Dr. Gail J. Roboz, sirec­tor of the Clin­i­cal and Trans­la­tion­al Leukemia Pro­grams. The UCART123 clin­i­cal pro­gram for BPD­CN will be led at the MD An­der­son Can­cer Cen­ter by Dr. Naveen Pem­mara­ju, an as­sis­tant pro­fes­sor, and Pro­fes­sor Hagop Kan­tar­jian, de­part­ment chair of the De­part­ment of Leukemia, Di­vi­sion of Can­cer Med­i­cine.

Hoang-Sayag called the move “a ma­jor mile­stone not on­ly for the com­pa­ny but al­so for the med­ical com­mu­ni­ty, glob­al biotech and phar­ma­ceu­ti­cal in­dus­tries at large. Cel­lec­tis’ al­lo­gene­ic UCART prod­ucts have the po­ten­tial to cre­ate an im­por­tant shift with re­gard to avail­abil­i­ty, and cost-ef­fec­tive­ness, to make these ther­a­pies wide­ly ac­ces­si­ble to pa­tient pop­u­la­tion across the world.”

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,900+ biopharma pros reading Endpoints daily — and it's free.

Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,900+ biopharma pros reading Endpoints daily — and it's free.

Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,900+ biopharma pros reading Endpoints daily — and it's free.

George Yancopoulos (L) and Len Schleifer (Regeneron)

Re­gen­eron touts pos­i­tive pre­lim­i­nary im­pact of its Covid an­ti­body cock­tail, pre­vent­ing symp­to­matic in­fec­tions in high-risk group

Regeneron flipped its cards on an interim analysis of the data being collected for its Covid-19 antibody cocktail used as a safeguard against exposure to the virus. And the results are distinctly positive.

The big biotech reported Tuesday morning that their casirivimab and imdevimab combo prevented any symptomatic infections from occurring in a group of 186 people exposed to the virus through a family connection, while the placebo arm saw 8 of 223 people experience symptomatic infection. Symptomatic combined with asymptomatic infections occurred in 23 people among the 223 placebo patients compared to 10 of the 186 subjects in the cocktail arm.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,900+ biopharma pros reading Endpoints daily — and it's free.

Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

As­traZeneca scores new goal on the pipeline front, adding its first AI-gen­er­at­ed tar­get to the port­fo­lio

As more and more biopharmas develop artificial intelligence platforms, the drug discovery process is being reshaped to fit new goals on cutting down the prodigious amount of time, energy and money that go into a drug program. Now one of the most ambitious players in the drive to improve on ROI, AstraZeneca, is marking a milestone on that front by adding the first target generated by AI to its portfolio.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,900+ biopharma pros reading Endpoints daily — and it's free.