European investors pour $156M to beat Bluestone, Third Rock and RA Capital in multibillion-dollar race to the clinic

Amid bur­geon­ing ef­forts to cre­ate a new type of cell ther­a­py out of reg­u­la­to­ry T cells — whether by chan­nel­ing or block­ing their im­muno­sup­pres­sive pow­er — Quell Ther­a­peu­tics wants to shoot for a first.

If every­thing goes well, the Syn­cona-backed biotech will be in the clin­ic ear­ly next year, mark­ing what it calls the his­toric feat of dos­ing a pa­tient with a CAR-Treg with mul­ti­ple edit­ed genes.

Hav­ing shied away from the spot­light since clos­ing a mod­est Se­ries A two years ago, Quell is now loud and clear about those next steps with $156 mil­lion in Se­ries B cash.

‘This is the round where peo­ple sit up and take no­tice,’ was how CEO Iain McGill put it to End­points News.

The megaround is just part of it — and like­ly a small part at that. With­in the past year, mul­ti­ple out­fits from Jef­frey Blue­stone’s Sono­ma to RA Cap­i­tal-backed Gen­tiBio to Third Rock’s Aba­ta Ther­a­peu­tics have each bagged im­pres­sive rais­es to fund their re­spec­tive ap­proach­es, and that’s not to men­tion Mozart, Egle, TRex Bio and oth­ers who are all promis­ing to gen­er­ate po­tent, sta­ble, safe and durable cells that can tamp ex­ces­sive au­toim­mune or in­flam­ma­to­ry re­ac­tions.

But come 2022, Quell reck­ons it will be in the ex­clu­sive club of clin­i­cal-stage com­pa­nies de­vel­op­ing a CAR-Treg. Sang­amo is the on­ly oth­er play­er it sees there for now.

The com­pa­ny al­so be­lieves that its plat­form, based on sci­ence out of King’s Col­lege Lon­don, Uni­ver­si­ty Col­lege Lon­don and Han­nover Med­ical School, has picked out de­sign com­po­nents that make its Tregs even stronger.

Tregs, McGill ex­plained, are a dou­ble-edged sword: They can flip from a sup­pres­sor phe­no­type in­to an at­tack­ing, ef­fec­tor phe­no­type. In a worst case sce­nario, this change can lead not on­ly to lack of ef­fi­ca­cy but a safe­ty con­cern where­by the CAR-Tregs turn out to de­stroy the very tis­sue they were in­tend­ed to pro­tect.

To pre­vent that, Quell trans­duces the cells with mul­ti­ple copies of FOXP3, which McGill called the ‘mas­ter tran­scrip­tion fac­tor’ for a Treg.

‘By hard­wiring the cells with mul­ti­ple copies of FOXP3, you sort of lock the cells in that phe­no­typ­ic sup­pres­sion mode,’ he said. ‘So you tran­scrip­tion­al­ly lock them as a Treg. And that gives them sta­bil­i­ty. What we found when we start­ed do­ing that, be­cause in ad­di­tion to giv­ing the cells phe­no­typ­ic sta­bil­i­ty, it al­so in­creased their sup­pres­sive po­ten­cy.’

The first pro­gram, which is de­signed to wean pa­tients off im­muno­sup­pres­sants fol­low­ing liv­er trans­plants, knocks in three ad­di­tion­al genes to ‘re­set the me­chan­ics of re­jec­tion.’ The UK has cleared a clin­i­cal tri­al and Quell is on track to re­cruit its first pa­tient by the end of this year.

Be­hind that it has lined up two pro­grams in dif­fer­ent di­rec­tions, one aimed at ALS and the oth­er for type 1 di­a­betes.

‘Here, we ex­pect ex­e­cu­tion to be a con­tin­u­ing, fo­cus­ing chal­lenge and a key dif­fer­en­tia­tor for suc­cess,’ said Rachel Mears, part­ner at Jeito Cap­i­tal, which co-led the round along­side Ridge­back Cap­i­tal In­vest­ments, SV Health In­vestors and Fi­deli­ty Man­age­ment & Re­search Com­pa­ny.

Mears is join­ing the board of di­rec­tors along­side Ridge­back man­ag­ing di­rec­tor Jef­frey Long-McGie and SV man­ag­ing part­ner Houman Ashrafi­an.

The round will al­so help fund the build out of man­u­fac­tur­ing ca­pa­bil­i­ties, which McGill not­ed is sim­i­lar to tra­di­tion­al CAR-T but dif­fer­ent in mean­ing­ful ways. For in­stance, the pa­tients they’re look­ing to treat are dif­fer­ent from the very sick can­cer pa­tients seek­ing au­tol­o­gous cell ther­a­pies, for whom vein-to-vein time is a life-or-death mat­ter.

Quell, on the oth­er hand, is work­ing with sta­ble pa­tients, such as those be­tween one and five years post-trans­plant:

We don’t have to in­ter­vene im­me­di­ate­ly for each of these pa­tients, which means that we can ware­house pa­tients, we can se­quence pa­tients, we can bring them in­to our man­u­fac­tur­ing cen­ter in a way that suits the sched­ul­ing of man­u­fac­tur­ing, rather than hav­ing to or­ga­nize man­u­fac­tur­ing around pro­vi­sion of the leuka­phere­sis to man­u­fac­ture a prod­uct, which is ex­act­ly what you have to do in on­col­o­gy. So we can use the fa­cil­i­ty in a more or­dered and struc­tured process, which I think brings great ben­e­fit in terms of sta­bil­i­ty and ro­bust­ness of the man­u­fac­tur­ing process go­ing for­ward.

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Tillman Gerngross (Adagio)

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Rogerio Vivaldi, Sigilon CEO (Sigilon via website)

Back in July, the FDA placed a clinical hold on the Bob Langer and Flagship-backed biotech Sigilon Therapeutics for its lead program to treat hemophilia A. On Monday, Sigilon reported what caused the pause.

After a patient in the three-person Phase I/II study reported a serious adverse event, Sigilon discovered the spheres used to deliver the cell therapy had fibrosed, the biotech announced Monday. As a result, the treatment contained within the spheres was no longer viable after the patient developed inhibitors to Factor VIII.

Unlock this story instantly and join 124,100+ biopharma pros reading Endpoints daily — and it’s free.

In the same way that the FDA signs off on flu vaccines every year without requiring large clinical trials to measure their efficacy, the FDA may employ a similar strategy in authorizing variant-focused versions of the mRNA vaccines.

As the world braces for more data on the latest variant Omicron, which may reduce vaccine efficacy, top vaccine developers like Moderna and Pfizer-BioNTech have promised they can pull together a new vaccine targeted against a specific Covid variant in about 100 days. Since Omicron emerged last week, Pfizer-BioNTech, Moderna and J&J have all said they’ve begun work on Omicron-specific vaccines, if needed.

Dutch VC Forbion is hopping on the ever-lengthening SPAC train.

To be led by Jasper Bos, who joined Forbion Growth as a general partner back in May just after the fund closed at $428 million, Forbion European Acquisition will target late-stage opportunities in the life sciences industry in Europe to merge with and bring onto Nasdaq.

Cyril Lesser, senior controller at Forbion, will be the CFO while Bos serves as CEO.

Jeff Albers, Blueprint Medicines CEO

J&J’s Rybrevant scored the first approval back in May for a small group of lung cancer patients with a rare EGFR mutation. Despite a swarm of other biopharma companies angling for a piece of that market, Blueprint Medicines is betting nearly $500 million on a candidate it thinks will stand out.

Blueprint is putting down $250 million in cash and another $215 million in biobucks for Lengo Therapeutics and its preclinical non-small cell lung cancer program LNG-451. Though it hasn’t been tested in humans, Blueprint says the candidate was ‘highly brain-penetrant’  in preclinical trials, and has the potential to inhibit all common EGFR exon 20 insertion variants — which are found in just 2% to 3% of NSCLC patients.

Unlock this story instantly and join 124,100+ biopharma pros reading Endpoints daily — and it’s free.

Shares of Fennec Pharmaceuticals stock were cut almost in half early Monday as the company said manufacturing issues caused another FDA rejection of its reformulated version of sodium thiosulfate, which is intended to help kids who lose hearing due to chemo treatment.

The biotech had resubmitted an NDA for the drug to treat platinum-based, chemo-related ototoxicity in young children earlier this year. The first NDA was denied by the FDA last year, with the agency citing manufacturing issues with the biotech’s supplier.

At the beginning of this year, I laid out a basic objective for Endpoints News as we headed to our 5th anniversary. We’ve long been doing a fine job covering the breaking news in R&D — if I do say so myself — but we needed to expand our horizons on industry coverage, increase the staff and go much, much deeper when the stories demanded it.

In a phrase: broader and deeper.

It’s safe to say, based on our daily web traffic, that you all seemed to like this idea. We’ve doubled the staff — thanks to a growing group of paid subscribers — ramped up the daily report and now publish a regular slate of in-depth articles. And traffic — those clicks you always read about — have gone up in volume too. Monthly sessions are up 43%, to close to 1.5 million. Unique readers are up 63%, to 874,480 in October, after setting a record of close to a million the month before. Page views are running at 3 million-plus a month. And the overall number of subscribers has surged to 124,000.

Unlock this story instantly and join 124,100+ biopharma pros reading Endpoints daily — and it’s free.
https://endpts.com/european-investors-pour-156m-to-beat-bluestone-third-rock-and-ra-capital-in-multibillion-dollar-race-to-the-clinic/