Nkarta CEO Paul Hastings at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Nkar­ta un­der­scores safe­ty of CAR-NK, boasts ear­ly re­spons­es

The first gen­er­a­tion of per­son­al­ized CAR-T ther­a­pies made big waves in the treat­ment of lym­phoma for their stun­ning ef­fi­ca­cy. Nkar­ta is hop­ing its off-the-shelf nat­ur­al killer cell ap­proach will stand out on safe­ty — while keep­ing some of those im­pres­sive num­bers on re­spons­es.

In a new up­date from its Phase I dose es­ca­la­tion study, the South San Fran­cis­co-based biotech re­port­ed that sev­en out of 10 pa­tients treat­ed with the high­est dos­es of its NK cell ther­a­py, NKX019, achieved a com­plete re­sponse, trans­lat­ing to a com­plete re­sponse rate of 70%.

“The emerg­ing safe­ty pro­file of NKX019 is po­ten­tial­ly game-chang­ing,” said CEO Paul Hast­ings on an in­vestor call.

NKX019 hits the same tar­get as Yescar­ta and Kym­ri­ah, the first ap­proved CAR-Ts. But there are some key dif­fer­ences: It con­sists of NK cells that are al­lo­gene­ic, mean­ing doc­tors don’t need to go through the long process of har­vest­ing cells from pa­tients them­selves and en­gi­neer­ing them. And while most CAR-Ts are on­ly in­fused once, some pa­tients in the Nkar­ta tri­al were giv­en mul­ti­ple cy­cles of NKX019.

The new da­ta build on an ini­tial read­out in April, when the com­pa­ny re­port­ed ear­ly re­spons­es. This time around, they have six more pa­tients in the pool and a longer fol­low-up.

Specif­i­cal­ly, Nkar­ta sin­gled out the ab­sence of cy­tokine re­lease syn­drome or neu­ro­tox­i­c­i­ties, which have been the hall­mark of ear­ly CAR-T drugs.

“While oc­ca­sion­al tran­sit and man­age­able in­fu­sion-re­lat­ed re­ac­tions were ob­served and some were even la­beled as CRS by our in­ves­ti­ga­tors, the ear­ly on­set and prompt res­o­lu­tion of symp­toms, some­times with­out any in­ter­ven­tion at all, is clear­ly not the clas­sic CRS that is seen with CAR-T cell ther­a­pies,” Hast­ings added.

Hav­ing en­rolled and dosed 19 pa­tients in the tri­al so far, in­ves­ti­ga­tors ob­served five com­plete re­spons­es across all dose lev­els af­ter just a sin­gle cy­cle — with ad­di­tion­al cy­cles, three par­tial re­spons­es deep­ened to com­plete re­spons­es.

Ten of the pa­tients were in the high­est dose co­horts, get­ting ei­ther three week­ly dos­es of a bil­lion cells or three week­ly dos­es of 1.5 bil­lion cells per cy­cle. Ei­ther of those achieved an ob­jec­tive re­sponse, in­clud­ing sev­en com­plete re­spons­es.

Ex­ecs al­lud­ed to dura­bil­i­ty by not­ing in the call that five pa­tients had com­plete re­spons­es that ex­ceed­ed six months, in­clud­ing one pa­tient with LB­CL who has main­tained CR for over nine months.

Nkar­ta added that it’s ad­min­is­ter­ing what it calls con­sol­i­da­tion dos­ing to sev­en pa­tients with CRs, with the goal of erad­i­cat­ing resid­ual tu­mor cells and pro­long­ing re­sponse.

“Hav­ing the abil­i­ty to ad­min­is­ter mul­ti­ple treat­ment cy­cles gives us the op­por­tu­ni­ty to deep­en re­spons­es in those pa­tients who are show­ing a clin­i­cal ben­e­fit and to con­sol­i­date com­plete re­mis­sions with an ad­di­tion­al cy­cle for those pa­tients that achieve a CR,” said David Shook, vice pres­i­dent of clin­i­cal de­vel­op­ment.

If the re­spons­es hold up, Nkar­ta sees a wide range of po­ten­tial ways for the drug to be de­ployed: as an op­tion for pa­tients who don’t have ac­cess or can’t tol­er­ate CAR-T; as a next-line treat­ment for those who have re­lapsed af­ter CAR-T; and in com­bi­na­tion with oth­er drugs, such as Roche’s Rit­ux­an.

Ed­i­tor’s note: A pre­vi­ous ver­sion of this sto­ry in­cor­rect­ly stat­ed that Nkar­ta did not of­fer num­bers on dura­bil­i­ty. It’s been up­dat­ed to in­clude de­tails pro­vid­ed in a pre­sen­ta­tion.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints Premium

Premium subscription required

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

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.