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.

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.

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’ 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.

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.