The gam­ma delta T cell gam­bit in­spires a small Lon­don biotech start­up with big ideas

If you run through the whole gamut of cell ther­a­pies be­ing worked on in can­cer re­search these days, gam­ma delta T cells aren’t like­ly to fig­ure promi­nent­ly in your re­view. But for years now Adri­an Hay­day, who runs labs at The Fran­cis Crick In­sti­tute and King’s Col­lege Lon­don, has been fas­ci­nat­ed by their un­usu­al abil­i­ty to pen­e­trate in­to tis­sue, mak­ing them po­ten­tial ther­a­peu­tic can­di­dates.

And now, with the ex­plo­sion of im­muno-on­col­o­gy re­search work, some mar­quee re­search play­ers have set out to take Hay­day’s work — along with con­tri­bu­tions by Oliv­er Nuss­baumer — in­to the clin­ic, seed­ing a start­up which will now nav­i­gate its way through about 18 months of pre­clin­i­cal work iden­ti­fy­ing a lead pro­gram that can be tak­en in­to a hu­man study.

The start­up, ap­pro­pri­ate­ly dubbed Gam­maDelta Ther­a­peu­tics, is be­ing helmed by Raj Mehta from Can­cer Re­search Tech­nol­o­gy, who’s tak­ing a break from his busi­ness de­vel­op­ment role to act as the in­ter­im CEO of a small band of staffers, in league with Hay­day’s big lab, to start piec­ing to­geth­er all the ear­ly-stage work need­ed to get their work to the thresh­old of Phase I. CRT, along with King’s Col­lege and The Crick, are pro­vid­ing as­sis­tance. Tim Haines, the man­ag­ing part­ner at Abing­worth’s Lon­don of­fice, is con­tribut­ing seed cash and in­cu­bat­ing the com­pa­ny.

What’s the big idea? It’s very sim­ple.

Gam­ma delta T cells “have the po­ten­tial to in­vade tis­sue and be bet­ter at in­vad­ing tu­mors,” Mehta tells me. And that makes it a po­ten­tial ground­break­er in all the im­muno-on­col­o­gy work now go­ing on glob­al­ly.

Where the check­point ther­a­pies like Keytru­da and Op­di­vo re­quire an en­vi­ron­ment with a heavy mu­ta­tion load to be ef­fec­tive, gam­ma delta cells – at least in the pre­clin­i­cal work — don’t. And where CAR-Ts — T cells which have been reengi­neered with chimeric anti­gen re­cep­tors — have proved promis­ing ini­tial­ly in blood can­cers, it’s been a chal­lenge get­ting them in­to tu­mors. (And, yes, there’s a lot of work be­ing done to fix that.)

Gam­ma delta cells, though, have the es­sen­tial prop­er­ties to get in­side tu­mors to do their work. Al­so, these cells ev­i­dent­ly aren’t heav­i­ly in­flu­enced by reg­u­la­to­ry T cells, mak­ing them good can­di­dates for sol­id tu­mors with high con­cen­tra­tions of Tregs.

One of the biggest chal­lenges faced by the fledg­ling biotech, says Mehta, will be fig­ur­ing out the CMC side of things. These ther­a­pies won’t be very valu­able if they aren’t po­tent, durable and fair­ly straight­for­ward to make. But the team al­so has a big ad­van­tage: Lon­don has emerged as a glob­al hub for cell man­u­fac­tur­ing, mak­ing their job some­what eas­i­er on that score.

The em­pha­sis here is on the col­lab­o­ra­tion among the re­search in­sti­tutes, with the ven­ture back­ing from Haines’ ven­ture group. They’re not say­ing how much it is cost­ing at this point, but chances are it’s not the kind of fig­ure that would leap out at you with all the big num­bers be­ing thrown around biotech these days.

Mehta is fa­mil­iar with at least two oth­er Eu­ro­pean com­pa­nies that have been op­er­at­ing in this field. Lym­phact in Por­tu­gal is one. And there’s al­so Gade­ta, a Dutch biotech which just raised 7 mil­lion eu­ros in a round led by Medicxi Ven­tures. Gade­ta has been us­ing gam­ma delta T cell re­cep­tors to reengi­neer the more com­mon type of T cells.

Gam­maDelta has a dis­tance to trav­el be­fore it gets close to putting any­thing in­to Phase III. But in the in­tense I/O field right now, it will like­ly start at­tract­ing im­me­di­ate at­ten­tion from some key play­ers.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Deborah Dunsire. Lundbeck

Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

A year after taking the reins as CEO of Lundbeck, Deborah Dunsire is making a bold bid to beef up the Danish biotech’s portfolio of drugs in what will likely be a direct leap into an intense rivalry with a group of giants now carving up a growing market for new migraine drugs.

Bright and early European time the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation for a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.