Re­gen­eron leaps in­to the block­buster race to de­vel­op off-the-shelf im­mune cell can­cer ther­a­pies

A year ago, Sanofi agreed to pay Re­gen­eron $1.8 bil­lion-plus to part­ner on its an­ti-PD1 check­point pro­gram. To­day, biotech heavy­weight Re­gen­eron is jump­ing in­to CAR-Ts and TCR tech, de­ter­mined to leap di­rect­ly in­to a block­buster brawl with a plan to emerge as a leader in the fast-grow­ing im­muno-on­col­o­gy field. And it’s made the lat­est in a hand­ful of rare biotech deals to part­ner on the tech­nol­o­gy it needs.

Re­gen­eron se­lect­ed the start­up Adicet Bio for its col­lab­o­ra­tion. A new face in im­muno-on­col­o­gy, the biotech popped up on­ly last Jan­u­ary with a hefty $51 mil­lion A round to get start­ed. But it’s helmed by Aya Jakobovits, the found­ing pres­i­dent and CEO of Kite Phar­ma, a leader in de­vel­op­ing per­son­al­ized CAR-Ts.

Aya Jakobovits, Adicet Bio

If it was any oth­er biotech oth­er than Re­gen­eron, the news might spur a lit­tle mock­ing from some of the side­line ob­servers who have been watch­ing the fron­trun­ners present a slate of top per­son­al­ized CAR-Ts down the fi­nal stretch to a like­ly near-term set of ap­provals. It may ap­pear late to the par­ty, but Re­gen­eron is a top in­dus­try R&D play­er; a ma­jor biotech out­fit that is well fi­nanced, re­lent­less­ly fo­cused with a track record that now in­cludes a list of ma­jor drugs that are ei­ther on the mar­ket or close to it. And it’s look­ing to catch the next wave form­ing off­shore of I/O.

Jakobovits gets a mod­est $25 mil­lion up­front to get start­ed on en­gi­neer­ing a pipeline of im­mune cells with chimeric anti­gen re­cep­tors and T cell re­cep­tors, a one-two ap­proach aimed at ze­ro­ing in on both sur­face anti­gens found specif­i­cal­ly on tar­get­ed can­cer cells as well as in­tra­cel­lu­lar tar­gets. There’s a sup­port pack­age for re­search as well, with ad­di­tion­al funds to back up the col­lab­o­ra­tion, but no one is dis­clos­ing any of that this morn­ing.

Both com­pa­nies em­pha­size that they’re con­cen­trat­ing on off-the-shelf drugs that will be pri­mar­i­ly fo­cused on sol­id tu­mors, the new new thing in im­muno-on­col­o­gy where first-gen hema­to­log­i­cal im­munother­a­pies have en­coun­tered hard bar­ri­ers.

“There’s a lot of room left to wind up as a leader,” says Michael Aber­man, the strat­e­gy ex­ec at Re­gen­eron. His com­pa­ny wasn’t the first to tack­le check­points, nor the first in cell ther­a­pies. But “it’s very ear­ly in the first wave to know how that’s go­ing to play out. There’s a lot of chal­lenges left ahead and a lot of op­por­tu­ni­ties. And we’re talk­ing a nov­el ap­proach.”

The pact with Re­gen­eron cov­ers a “broad pipeline,” Jakobovits tells End­points, em­pha­siz­ing that the key to cre­at­ing a safe, ef­fec­tive im­mune cell ther­a­py is be­ing “spe­cif­ic to the tu­mor tar­get.” But Jakobovits, who set up the com­pa­ny as a part­ner at Or­bimed, is very care­ful to stay in­side some nar­row bound­aries on ex­plain­ing ex­act­ly what dis­tin­guish­es their work.

I/O in­vest­ment spe­cial­ist Brad Lon­car says the deal high­lights some key points. Re­gen­eron, he says:

1) Sees the promise in cell ther­a­py, which not all com­pa­nies do. For ex­am­ple, Gilead’s CEO said the idea makes him very un­com­fort­able. Many bears be­lieve it will nev­er be com­mer­cial­ly vi­able. So for a com­pa­ny with the sci­en­tif­ic cred­i­bil­i­ty of Re­gen­eron to take a small dive in says some­thing.

2) Un­der­stands that it’s too late to be a play­er in the au­tol­o­gous (per­son­al­ized) ap­proach or doesn’t be­lieve it can be eco­nom­i­cal­ly vi­able. All of the com­mer­cial op­por­tu­ni­ty has al­ready been tak­en up by ex­ist­ing play­ers.

3) Be­lieves the off the shelf ap­proach is sci­en­tif­i­cal­ly vi­able, which not every­one does.

I’d say the main point is that it’s a good sign for the whole field of cell ther­a­py when a com­pa­ny as cred­i­ble as Re­gen­eron feels like they need to be a play­er in this area. Most peo­ple don’t ap­pre­ci­ate the fact that cell ther­a­py is ba­si­cal­ly ver­sion 1.0 right now and there are many im­prove­ments that will be made over the com­ing years. It has the chance to be very spe­cial and I’m sure Re­gen­eron sees that.

A tech­nol­o­gy arms race of a kind has tak­en shape as var­i­ous com­pa­nies sort out how off-the-shelf ther­a­pies can even­tu­al­ly re­place the first gen­er­a­tion lab-craft­ed per­son­al­ized ther­a­pies that ex­tract cells from pa­tients, reengi­neer them in­to can­cer treat­ments and the in­fuse them back in­to pa­tients. Just days ago Jakobovits’s for­mer com­pa­ny Kite ex­e­cut­ed a deal with UCLA for al­lo­gene­ic tech from the lab of Gay M. Crooks.

Re­gen­eron’s not-so-se­cret weapon in the new front on can­cer in­cludes its unique Ve­locIm­mune mouse mod­els, which are de­scribed as “the largest mam­malian ge­net­ic en­gi­neer­ing project ever ac­com­plished.” It helped them de­vel­op REGN1979, a bis­pe­cif­ic an­ti­body ther­a­py that R&D chief George Yan­copou­los has high­light­ed ex­cit­ed­ly for its abil­i­ty to tar­get the B cell mark­er, CD20, and the CD3 com­po­nent of the T cell re­cep­tor, which trig­gers redi­rect­ed killing of B cells. Its an­ti-PD-1 an­ti­body is REGN2810. Any tar­get­ing mol­e­cules that come out of this new col­lab­o­ra­tion can be redi­rect­ed in­to any oth­er pro­grams Re­gen­eron has, in­clud­ing its pact with Sanofi.

Re­gen­eron doesn’t do many of these pacts, says Aber­man. There was the In­tel­lia deal back in April that brings CRISPR-Cas9 gene edit­ing tech, Avalanche’s gene ther­a­py pact, and now Adicet. But they ex­pect a lot out of the few deals they do with the se­lect biotechs they want to work with.

For Jakobovits, the deal al­so al­lows her to push the quick ex­pan­sion of he new biotech. The staff of 14 is slat­ed to dou­ble, with ad­di­tion­al in­put com­ing from her Is­raeli sub­sidiary.

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.

EQRx chairman Alexis Borisy and CEO Melanie Nallichieri

EQRx, CStone un­furl full lung can­cer da­ta for PD-L1 drug in what the part­ners are call­ing a first

As a self-stylized drug pricing disruptor, EQRx has high hopes for its lead PD-(L)1 to offer proof of concept for the entire business model. After touting a win back in May, the biotech is back with full data in lung cancer that could back up an approval.

Patients dosed with EQRx and CStone Pharmaceuticals’ sugemalimab posted median progression-free survival of 9 months compared with 5.8 months for patients given placebo (p=0.0026), according to full data from the Phase III GEMSTONE-301 study in Stage III non-small cell lung cancer set to be presented at this weekend’s #ESMO21.

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As­traZeneca touts Imfinzi im­munother­a­py com­bos for lung can­cer in push to dri­ve PD-L1 drug up­take

Facing the big dogs in the PD-(L)1 space, AstraZeneca has taken its own contender Imfinzi into blockbuster territory in its four years on the market but sees even bigger things for the drug. Combinations could be the key, and early results from a mid-stage test are adding some fuel to that strategy.

Imfinzi combined with one of two investigational immunotherapies — a CD73 antibody dubbed oleclumab or an Innate’s anti-NGK2a named monalizumab — topped Imfinzi alone in terms of overall response and progression-free survival in patients with stage III non-small cell lung cancer whose tumors had not worsened during concurrent chemoradiation, according to interim data from the Phase II COAST trial set to be presented at #ESMO21.