Cell ther­a­py play­er Gam­maDelta spins off Adap­tate to di­rect body's sur­veil­lance sys­tem

If al­pha be­ta T-cells — the foun­da­tion of CAR-T cell ther­a­py — are “killer cells,” trained in the bi­o­log­i­cal­ly an­cient art of ex­e­cut­ing in­trud­ers, think of their gam­ma delta cousins as armed guards, ca­pa­ble of en­gag­ing an in­ter­lop­er but al­so of sound­ing an alarm to kick the rest of the body’s de­fens­es in­to ac­tion.

“The key role they play is to con­duct im­mune sur­veil­lance,” Na­tal­ie Mount told End­points News.  And once they find an in­trud­er “they can stim­u­late a whole im­mune re­sponse as well as be cy­to­tox­ic [cell-killing].”

Na­tal­ie Mount Gam­maDelta

On­ly dis­cov­ered in 1985, these gam­ma delta T-cells (γδ) have al­ready be­come a pop­u­lar tar­get in can­cer im­munother­a­py. This morn­ing, a top British biotech ex­plor­ing po­ten­tial γδ ap­pli­ca­tions found­ed a new com­pa­ny to help reach that goal as Gam­maDelta Ther­a­peu­tics spun off Adap­tate Bio­ther­a­peu­tics with Mount at its helm.

While Gam­maDelta will con­tin­ue to fo­cus on a CAR-T-like cell ther­a­py ap­proach, the new com­pa­ny will de­vel­op an­ti­bod­ies that guide the γδ cells as they pa­trol a pa­tient, Mount said. Both have the same aim: get­ting these cel­lu­lar guards to no­tice and ef­fec­tive­ly strike can­cers.

“We are de­vel­op­ing an­ti­bod­ies that are able to rec­og­nize the gam­ma delta cells and tar­get those and mod­u­late their ac­tiv­i­ties,” Mount said. “We’ve dis­cov­ered a range of sub­strates and what we can do now is take that for­ward in non-clin­i­cal de­vel­op­ment.”

Gam­ma delta cells have risen in pop­u­lar­i­ty in on­col­o­gy re­search large­ly be­cause they show po­ten­tial to bring cell ther­a­py’s ef­fec­tive­ness in blood can­cers to sol­id tu­mors, al­though they present oth­er po­ten­tial ad­van­tages, in­clud­ing broad­er tar­get­ing and faster re­sponse.

Pao­lo Pao­let­ti Gam­maDelta

Gam­maDelta Ther­a­peu­tics got in on the ground floor, open­ing its doors in 2016. Since then, new and big­ger play­ers have en­tered the game. Last week, Re­gen­eron dropped $25 mil­lion as part of an $80 mil­lion fund­ing round for Adicet Bio, an­oth­er com­pa­ny look­ing to use an­ti­bod­ies to guide gam­ma delta T cells.

“Just in the last 2 to 3 years there’s been a re­al sol­id in­ter­est,” Mount said.

The broad idea of tar­get­ing these cells for on­col­o­gy is not new. Clin­i­cal tri­als have been con­duct­ed eval­u­at­ing gam­ma delta T cell treat­ments on sev­er­al can­cers, in­clud­ing leukemia and sar­co­ma. They were safe but with high­ly lim­it­ed ef­fi­ca­cy, al­though some ap­peared for not-ful­ly-un­der­stood rea­sons to ac­tu­al­ly fu­el tu­mors.

But Gam­maDelta and Adap­tate say they work on a dif­fer­ent sub­set of cells than these ear­li­er tri­als did, one called γδ1. γδ1 is found in the tis­sues, mak­ing it an in­tu­itive weapon for at­tack­ing sol­id tu­mors.

The an­ti­body con­cept be­hind Adap­tate is an in­creas­ing­ly pop­u­lar form of ther­a­py. Ab­b­Vie, Eli Lil­ly, Re­gen­eron, and Sanofi, among a long list of oth­ers, are de­vel­op­ing a form of an­ti­body ther­a­py called bis­pe­cif­ic. They’re still in the ear­ly stage, but last year Baird’s Bri­an Sko­r­ney ar­gued that the class of drugs has huge po­ten­tial.

“Our bias is that bis­pecifics pose an ex­is­ten­tial risk to the cel­lu­lar ther­a­pies,” he wrote. “If a reg­u­lar­ly ad­min­is­tered ther­a­peu­tic can keep an­ti-tu­mor pres­sure on by con­sis­tent­ly en­gag­ing and ac­ti­vat­ing T-cells, we think the much more ex­pen­sive CART would be­come an even hard­er sell than it al­ready is.”

The ex­haus­tive CAR-T process is like a spe­cial­ized mas­ter­class in tu­mor-killing, with doc­tors with­draw­ing cells, equip­ping them with a spe­cif­ic anti­gen re­cep­tor to iden­ti­fy ma­lig­nan­cies and re-in­ject­ing them. The an­ti­body ap­proach for Adap­tate can be thought of more as di­rec­tives from a com­mand cen­ter guid­ing the sur­veilling im­mune cells.

Gam­maDelta will fo­cus on a cell ther­a­py process sim­i­lar to CAR-T, while Adap­tate fo­cus­es on an­ti­bod­ies. But Mount ar­gued one of the big ad­van­tages for Gam­maDelta Ther­a­peu­tics and gam­ma delta cells is that they can iden­ti­fy can­cer cells based on pat­terns as op­posed to the spe­cif­ic anti­gens that CAR-T (chimeric anti­gen re­cep­tor T-cells) ther­a­pies use, open­ing up the po­ten­tial for a range of tar­gets.

Gam­maDelta is much clos­er to the clin­ic than the Adap­tate spin­off, al­though they have yet to re­veal ex­act­ly when they will be­gin tri­als, and for what in­di­ca­tions. Mount said they were at least 12 months from eval­u­at­ing whether they were ready to en­ter the clin­ic.

So­cial im­age: Adap­tive CEO Na­tal­ie Mount via Gam­maDelta

 

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.

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.

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.

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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Eliot Forster, F-star CEO (Rachel Kiki for Endpoints News)

F-star gets down to the wire with $161M sale to Chi­nese buy­er as na­tion­al se­cu­ri­ty con­cerns linger

With the clock ticking on F-star Therapeutics’ takeover by a Chinese buyer, the companies are still scrambling to remove a hold on the deal from the US government’s Committee on Foreign Investment in the United States.

F-star and invoX Pharma said they are “actively negotiating” with CFIUS “about the terms of a mitigation agreement to address CFIUS’s concerns regarding potential national security risks posed by the transaction.”

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