Af­ter Ro­va-T bust, Ab­b­Vie plans new sol­id tu­mor as­sault, li­cens­ing next-gen CAR-T tech from Cal­i­br

Af­ter its dis­ap­point­ing Ro­va-T flop last month, Ab­b­Vie is shoring up its sol­id tu­mor bets with a fresh­ly inked re­search deal that should elic­it new strate­gies for tu­mor at­tack. This time, Ab­b­Vie is hop­ing to use po­ten­tial­ly safer, next-gen CAR-Ts that have been cook­ing in the labs of a San Diego re­search in­sti­tute for the past few years.

The phar­ma gi­ant is buy­ing an ex­clu­sive four-year li­cense to tech de­vel­oped at the Cal­i­for­nia In­sti­tute for Bio­med­ical Re­search — bet­ter known as Cal­i­br — to in­ter­ro­gate some of its own can­cer tar­gets, in­clud­ing sol­id tu­mors. Cal­i­br is bring­ing to the ta­ble a plat­form based on a “switch­able” CAR-T cell. I talked with Travis Young, Cal­i­br’s di­rec­tor of pro­tein sci­ences, last Fri­day to find out what that ac­tu­al­ly means. Young tells me it’s about re­duc­ing tox­i­c­i­ty and get­ting a more durable re­sponse from CAR-Ts, which are known to cause safe­ty is­sues.

Travis Young

“CAR-Ts are po­tent, and they can cause tox­i­c­i­ty in the clin­ic,” Young said. “This is about tun­abil­i­ty. We’re call­ing this a switch, but it’s re­al­ly more like a light dim­mer. We want to tune ac­tiv­i­ty and elim­i­nate can­cer cells with­out caus­ing that tox­i­c­i­ty.”

They do that by us­ing an­ti­body-based switch mol­e­cules to con­trol the ac­ti­va­tion and anti­gen speci­fici­ty of CAR-T cells. Young said it’s im­por­tant to note this ap­proach dif­fers from the in­creas­ing­ly pop­u­lar “kill switch” tac­tic, which has been tout­ed as a way to make CAR-Ts safer.

“Rather than killing off the cells in the case of an ad­verse event, this is more proac­tive,” Young said.

The part­ner­ship has both Cal­i­br and Ab­b­Vie do­ing pre­clin­i­cal work, while Ab­b­Vie alone will be re­spon­si­ble for clin­i­cal de­vel­op­ment and com­mer­cial­iza­tion. Cal­i­br, of course, will get mile­stones and roy­al­ties if cer­tain tar­gets are met, but the duo was tight-lipped on fi­nan­cial de­tails of the deal.

The main fo­cus of the col­lab­o­ra­tion will be Ab­b­Vie’s can­cer tar­gets, but Cal­i­br is al­so work­ing on a liq­uid tu­mor pro­gram of its own that might come in­to play down the road. Young said the yet-named pro­gram is a CD19 tar­get­ed switch­able CAR-T ther­a­py, which the in­sti­tute plans to take in­to Phase I for lym­phoma in 2019. As part of the deal, Ab­b­Vie has the op­tion to li­cense that pro­gram (and oth­ers at Cal­i­br). That op­tion ex­pires in four years, how­ev­er.

You didn’t used to see re­search in­sti­tutes mov­ing pro­grams in­to the clin­ic, but its be­com­ing an in­creas­ing­ly pop­u­lar strat­e­gy for non-prof­it re­search cen­ters and uni­ver­si­ties. The idea is that it helps them cre­ate a source of rev­enue in­de­pen­dent from the fed­er­al gov­ern­ment and phil­an­thropy.

Matt Trem­blay

“We’re at the head of this new theme to take your as­sets — your IP orig­i­nat­ed at the in­sti­tute — and take them for­ward in­to clin­i­cal de­vel­op­ment,” Cal­i­br and Scripps Re­search COO Matt Trem­blay told me. 

This is some­thing I dis­cussed with Dave Gib­bons, who han­dles com­mer­cial li­cens­ing at the biotech-heavy cam­pus at UC San Diego, last year. By de-risk­ing pro­grams and de­vel­op­ing up to IND, “you’d have a tremen­dous­ly more valu­able as­set for li­cens­ing,” Gib­bons said.

Ab­b­Vie’s on­col­o­gy and clin­i­cal de­vel­op­ment ex­per­tise will be a boon to the re­source-slim Cal­i­br, but the phar­ma gi­ant was al­so in need of this deal. The com­pa­ny dis­ap­point­ed in­vestors in March when news that its Ro­va-T pro­gram post­ed poor mid-stage re­sults for third-line non-small cell lung can­cer. That was a re­al blow, con­sid­er­ing it was hoped to be a $5 bil­lion earn­er for the com­pa­ny.

Ge­of­frey Porges at Leerink post­ed a scathing as­sess­ment of Ab­b­Vie’s sit­u­a­tion short­ly af­ter the news.

“On­col­o­gy is the key growth busi­ness seg­ment for Ab­b­Vie af­ter the loss of ex­clu­siv­i­ty for Hu­mi­ra in 2023, and to­day’s re­sults and reg­u­la­to­ry de­ci­sion call in­to ques­tion the vi­a­bil­i­ty of the com­pa­ny’s cur­rent sol­id tu­mor strat­e­gy,” he wrote.

Per­haps Cal­i­br’s tech will give their sol­id tu­mor strat­e­gy more hope.

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.

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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.”

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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.

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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.

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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.

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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.

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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.

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