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

 

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

With lumasir­an on the FDA's doorstep, Al­ny­lam reads out new PhI­II da­ta in PH1

Just over a month away from its December PDUFA date, Alnylam flaunted new data from two Phase III studies to back lumasiran in primary hyperoxaluria type 1 (PH1), a rare liver condition.

The Cambridge, MA-based biotech snagged a priority review for the candidate back in June, and got positive feedback from the EMA’s Committee for Medicinal Products for Human Use just last week. Lumasiran uses RNA interference (RNAi) to silence the gene for glycolate oxidase, an enzyme used in the production of oxalate.

Stephen Hoge, Moderna president (Moderna)

On morn­ing of FDA Covid-19 ad­comm, Mod­er­na com­pletes PhI­II en­roll­ment, putting them neck-and-neck with Pfiz­er

Weeks away from a potential EUA application, Moderna announced they have completed enrollment in their 30,000-person Phase III Covid-19 vaccine trial, with over a third of volunteers non-white and a quarter over the age of 65.

The announcement caps what has been the most closely-watched recruitment race in the history of drug development, as Pfizer and Moderna rushed to get enough volunteers to prove whether or not experimental vaccines could actually protect people from contracting Covid-19. Pfizer reached that mark on Sept. 15. Moderna said around the same time that they would slow down enrollment to ensure they enrolled enough participants from minority and at-risk groups.

Pfiz­er scoops up an an­tibi­ot­ic in rare M&A deal, bag­ging a vir­tu­al start­up op­er­at­ing on a shoe­string bud­get

Pfizer is stepping up with a rare antibiotics buyout deal today, grabbing Palo Alto, CA-based Arixa Pharmaceuticals in a bid to add a new oral version of avibactam, a beta lactamase inhibitor — or BLI — approved back in 2015 as part of the IV treatment Avycaz.

The Arixa acquisition follows some encouraging Phase I responses demonstrating that 60% to 80% of the oral drug is absorbed into the bloodstream. Only 7% of the IV version is absorbed orally, far below the 30% threshold Arixa has pointed to as a therapeutic threshold. The buyout gives Pfizer’s hospital group a line on a new oral combo with antibiotics like ceftibuten to go after drug-resistant cases of urinary tract infections and other ailments.

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News brief­ing: UK biotech 4D phar­ma heads for Nas­daq via SPAC; Dr. Red­dy's shuts down man­u­fac­tur­ing af­ter cy­ber­at­tack

Another pharma company is intending to use a SPAC to join the Nasdaq.

4D pharma, a UK-based biotech, is reverse-merging with a blank check company in a deal worth up to $37.6 million. The move will give 4D pharma a new Nasdaq ticker, which will be $LBPS, using the American Depositary Share program.

As a result of the move, 4D pharma will gain $14.6 million in cash held by the blank check company, dubbed Longevity. The merger is expected to be completed in early 2021, after which shares will be immediately tradeable.

Can B cells break the bound­aries of cell ther­a­py? Long­wood start­up has $52M to prove a new en­gi­neer­ing tech

Back in December 2017, as the cell therapy world was still basking in the virtually back-to-back approvals of two pioneering CAR-Ts, researchers at Seattle Children’s Research Institute reported a scientific first in a different corner of the field: engineer B cells to treat disease.

The team, led by David Rawlings and Richard James, eventually worked with Longwood Fund to start a biotech around those findings. And now Atlas Venture and RA Capital Management are coming on board to lead a $52 million launch round, joined by Alta Partners, for Be Biopharma.

Jason Kelly, Gingko Bioworks CEO (Mike Blake/Reuters via Adobe)

Ex­clu­sive: Eye­ing big Covid-19 test­ing ex­pan­sion, Gink­go rolls out 50M rapid anti­gen di­ag­nos­tics

In what they hope will be a key part of an extensive effort to boost Covid-19 testing in the US, Ginkgo Bioworks is acquiring and distributing 50 million rapid antigen tests that can potentially be used for virus surveillance in schools and communities and for quick, on the ground diagnoses.

The tests, developed by SD Biosensor, are in line with proposals from the Rockefeller Foundation and Harvard epidemiologists, among others, to blanket the country with fast, low-cost tests. Although not yet authorized in the US, they are a key part of testing efforts from the Bill and Melinda Gates Foundation, who announced plans last month to distribute 120 million of them in low and middle income countries. Roche has commercialized the diagnostic in Europe.

Bo Cumbo, AavantiBio CEO (file photo)

Bo Cum­bo jumps from the top com­mer­cial post at Sarep­ta to the helm of a gene ther­a­py start­up with some in­flu­en­tial back­ers, big plans and $107M

After a 7-year stretch building the commercial team at Sarepta, longtime drug salesman Bo Cumbo is jumping to the entrepreneurial side of the business, taking the helm of a startup that’s got several deep-pocket investors. And he’s not just bringing his experience in selling drugs.

He tells me that when he told Sarepta CEO Doug Ingram about it, his boss got excited about the venture and opted to jump in with a $15 million investment from Sarepta to add to the launch money, alongside 3 of the busiest investors in biotech.

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