Precision CMO Alan List (Diane Bondareff/AP Images for Moffitt Cancer Center)

ASH: An­oth­er 'off-the-shelf' cell ther­a­py leader shows dura­bil­i­ty is­sues, rais­ing re­newed con­cerns about emerg­ing field

The next gen­er­a­tion of cell ther­a­pies have fo­cused in large part on the de­vel­op­ment of al­lo­gene­ic — bet­ter known as “off-the-shelf — drugs that can cut man­u­fac­tur­ing times and hope­ful­ly evade a pa­tient’s im­mune sys­tem. One of the ear­ly play­ers in that race has new da­ta at #ASH21 that show deep re­spons­es but will al­so raise fresh con­cerns about these ther­a­pies’ dura­bil­i­ty.

Pre­ci­sion Bio­sciences’ PB­CAR0191, a CD19-di­rect­ed al­lo­gene­ic CAR-T cell ther­a­py, post­ed a com­plete re­sponse rate of 59% in 22 heav­i­ly pre­treat­ed pa­tients with var­i­ous forms of re­lapsed or re­frac­to­ry non-Hodgkin’s lym­phoma and acute lym­pho­cyt­ic leukemia, six of whom had pre­vi­ous­ly re­ceived an au­tol­o­gous CAR-T be­fore dos­ing, the biotech said.

At a Nov. 16 da­ta cut­off, PB­CAR0191 spurred an over­all re­sponse rate of 73% in that ear­ly Phase I/II cut, well in line with cur­rent-gen­er­a­tion CAR-Ts, but dura­bil­i­ty con­cerns in this da­ta set will like­ly raise eye­brows on Pre­ci­sion’s chance to up­set cur­rent CAR-T and re­new con­cerns about the field on the whole.

Among the 17 evalu­able NHL pa­tients in this study, most re­spon­ders re­lapsed be­fore hit­ting the six-month mark, shut­ting down the drug’s chances as a one-time in­fu­sion for most pa­tients.

On the safe­ty front, PB­CAR0191 post­ed no se­ri­ous cy­tokine re­lease syn­drome events and just one Grade 3 neu­ro­tox­i­c­i­ty side ef­fect. There was one in­fec­tious death that in­ves­ti­ga­tors said was pos­si­bly re­lat­ed to treat­ment.

It’s a re­sult that mir­rors read­outs from Pre­ci­sion’s near­est com­peti­tors Al­lo­gene and CRISPR Ther­a­peu­tics, both of which pre­vi­ous­ly un­corked da­ta for their own al­lo­gene­ic CAR-Ts show­ing ques­tions over dura­bil­i­ty. Pre­ci­sion did tout da­ta in a small co­hort of pa­tients who had pre­vi­ous­ly re­ceived an au­tol­o­gous CAR-T, say­ing their dura­bil­i­ty of re­sponse was longer than on that pri­or ther­a­py, but it’s hard not to see PB­CAR0191’s un­der­whelm­ing re­sults as an ap­pe­tiz­er in­to Pre­ci­sion’s move in­to even more next-gen tech with a “stealth” CAR-T dubbed PB­CAR19B.

Pre­ci­sion un­corked very ear­ly Phase I da­ta for that drug this week­end too, which us­es gene edit­ing to knock down be­ta-2 mi­croglob­u­lin, an MHC mol­e­cule that trig­gers a graft vs. host re­sponse, and in­sert an HLA-E trans­gene to evade re­jec­tion from pa­tients’ nat­ur­al killer cells.

A Phase I study in re­lapsed/re­frac­to­ry NHL is en­rolling now, and Pre­ci­sion ex­pects da­ta by the mid­dle of next year, CMO Alan List said in a state­ment.

Mean­while, this week­end Pre­ci­sion al­so rolled out new da­ta for its al­lo­gene­ic BC­MA-di­rect­ed CAR-T can­di­date PB­CAR269A show­ing the drug couldn’t top au­tol­o­gous CAR-T in terms of ef­fi­ca­cy in a Phase I/IIa tri­al. Pre­ci­sion will now push a com­bi­na­tion ap­proach with this drug along­side nirogace­s­tat, a gam­ma sec­re­tase in­hibitor from Spring­Works Ther­a­peu­tics, with da­ta ex­pect­ed by the mid­dle of next year.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; 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.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Ying Huang, Legend CEO

J&J, Leg­end say Carvyk­ti beat stan­dard ther­a­py in ear­li­er-line blood can­cer

J&J and Legend Biotech’s next step in turning their CAR-T therapy Carvykti into a potential megablockbuster has succeeded, the companies said Friday.

Carvykti achieved the primary endpoint — progression-free survival — in an open-label Phase III study testing the treatment in second- to fourth-line multiple myeloma patients. The CARTITUDE-4 trial, for which there aren’t any hard data yet, represents the biggest development for Carvykti’s ability to compete with Bristol Myers Squibb’s Abecma since its approval last February.

No­var­tis' ap­proved sick­le cell dis­ease drug fails to beat place­bo in PhI­II

Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

The Swiss pharma giant unveiled early data from the ongoing STAND Phase III study on Friday, saying that crizanlizumab showed no statistically significant difference between the drug at two different dose levels compared to placebo in annualized rates of vaso-occlusive crises that lead to a healthcare visit over the first year since being randomized into the trial.

Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

Steve Harr, Sana Biotechnology CEO

Four years in, Sana gets first FDA go-ahead to bring can­cer treat­ment in­to the clin­ic

Sana Biotechnology is finally headed to the clinic.

Thursday afternoon, the biotech announced the FDA had cleared its application to start a clinical trial for its allogeneic, or “off-the-shelf,” CAR-T cell therapy targeting the antigen CD19 for patients with B-cell lymphomas and leukemias. Sana said its therapy, dubbed SC291, was designed to evade the immune system, which could help cell therapy produce a more durable response in patients, a concern that has followed such off-the-shelf therapies that use donor cells as opposed to a patient’s own cells.

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Dutch biotech starts liq­ui­da­tion af­ter end­ing PhI­II in GVHD

A 13-year-old Dutch biotech is going through a liquidation process after an unexpected end to its Phase III trial testing whether its combination of two monoclonal antibodies was superior to Incyte’s Jakafi.

Xenikos had hoped to prove its investigational therapy, named T-Guard, was better than Jakafi at garnering a complete response in patients experiencing life-threatening complications in which new cells from a hematopoietic stem cell transplant begin to fight the body. Jakafi was approved for the indication, steroid-refractory acute graft-versus-host disease, in May 2019.

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