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.

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for their Covid-19 vac­cine in a mat­ter of months

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

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US gov­ern­ment re­port­ed­ly be­gins prepar­ing for Covid-19 chal­lenge tri­als. Are they eth­i­cal?

Controversial human challenge trials for potential Covid-19 vaccines reportedly have a new booster — the US government.

Scientists working for the government have begun manufacturing a strain of the novel coronavirus that could be used in such studies, Reuters reported Friday morning. The trials would enroll healthy volunteers to be vaccinated and then intentionally infected with a weakened coronavirus.

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Sanofi vet Kather­ine Bowdish named CEO of PIC Ther­a­peu­tics; As the world Terns: Liv­er dis­ease biotech makes ex­ec­u­tive changes

PIC Therapeutics hasn’t raised much money, yet. But the fledgling biotech has attracted a high-profile player to the helm.

The Boston-based biotech has handed the reins to Katherine Bowdish as its president and CEO. Bowdish will also join the board of directors of PIC. Bowdish joins from Sanofi where she served as VP and head of R&D strategy, as well as helping launch and lead Sanofi Sunrise, a venture investment and partnering vehicle at Sanofi. Before that, Bowdish held several exec roles at Permeon Biologics, Anaphore, Alexion Pharmaceuticals and Prolifaron (acquired by Alexion).

Charlie Silver (Mission Bio)

'We want to be every­where.' Mis­sion Bio rais­es $70M be­hind re­sis­tance-hunt­ing se­quenc­ing plat­form

Charlie Silver wants to look really, really closely at a lot of your cells. And he just got a lot of money to do so.

Silver’s startup, Mission Bio, raised $70 million in a Series C round Thursday led by Novo Holdings. The money, which brings Mission Bio to $120 million raised since its 2012 founding, will be used to advance the single-cell sequencing platform they built to detect early response or resistance to new cancer therapies.

Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.

Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.

Clockwise from left: Canaccord Genuity principal Michelle Gilson, Canaccord Genuity CSO Brian Mueller and BioMarin CSO Hank Fuchs (Canaccord Genuity webcast)

Bio­Marin CSO diss­es ri­vals for the he­mo­phil­ia A gene ther­a­py crown: Way be­hind, fac­ing big re­cruit­ment chal­lenges and at best a .6 on the gen-one scale

The leader in the race to a hemophilia A gene therapy does not like to be compared unfavorably to the competition. And when their top execs do the comparing, don’t look for any modesty — BioMarin, they say, owns the lead.

As Factor VIII expression wanes over time, quite a few analysts have raised questions about the kind of future BioMarin’s gene therapy — a supposed once-and-done treatment — faces if it stops working. But just 7 days away from their PDUFA date, with high odds of success, the top execs clearly feel that they are way out front, while promising their rivals will discover there’s a tough slog ahead trying to pursue trials where large numbers of patients are ineligible for new therapies.

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Stéphane Bancel speaks to President Donald Trump at the White House meeting on March 2 (AP Images)

UP­DAT­ED: Mod­er­na of­fers steep dis­count in US sup­ply deal — but still takes the crown with close to $2.5B in vac­cine con­tracts

The US pre-order for Moderna’s Covid-19 vaccine is in.

Operation Warp Speed is reserving $1.525 billion for 100 million doses of Moderna’s Phase III mRNA candidate, rounding out to about $15 per dose — including $300 million in incentive payments for timely delivery. Given that Moderna has a two-dose regimen, it’s good for vaccinating 50 million people. The US government also has the option to purchase another 400 million doses for a total of $6.6 billion, or $16.5 per dose.

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