Paul Hastings. Nkarta

Nkar­ta maps out clin­i­cal, man­u­fac­tur­ing plans for CAR-NK fol­low­ing $114M round led by Sam­sara

Back in 2015 NEA Ven­tures, SR One and No­vo Hold­ings pulled to­geth­er $11 mil­lion to kick­start the lat­est ven­ture to come out of Dario Cam­pana’s lab — which has al­so birthed Unum and Me­diS­ix — fo­cused on nat­ur­al killer (NK) cells. Four stealthy years lat­er, Nkar­ta is poised for the clin­ic with a $114 mil­lion Se­ries B to fu­el the big leap.

While the cur­rent buzz on cell ther­a­pies for can­cer has gen­er­al­ly cen­tered around some vari­a­tion of T cells from the ap­proved CAR-T to TCR, Nkar­ta be­lieves NK cells of­fer ad­van­tages that T cells lack. Since they are part of the in­nate im­mune sys­tem, NK cells can iden­ti­fy and hit a broad­er range of tar­gets pre­sent­ed on tu­mor cells.

“Rather than re­act to anti­gens that are be­ing pre­sent­ed by for­eign in­vaders of the sys­tem, NK cells are there to make sure your own cells are be­hav­ing the way that they should,” said Nadir Mah­mood, SVP of cor­po­rate de­vel­op­ment.

Nadir Mah­mood

Click on the im­age to see the full-sized ver­sion

But they al­so make up a small por­tion of the im­mune cell pop­u­la­tion and their po­ten­cy could wane quick­ly. Cam­pana’s break­through is de­vis­ing ways to grow NK cells from healthy donors quick­ly by co-cul­tur­ing them with co-stim­u­la­to­ry cell lines, while en­gi­neer­ing them to ex­press a mem­brane bound form of IL-15, en­hanc­ing their per­sis­tence, Mah­mood added.

Build­ing on those foun­da­tion­al tech­nolo­gies, the Nkar­ta team has ze­roed in on NKX101, which they call fourth-gen­er­a­tion CAR-NK cells. Un­like the chimeric anti­gen re­cep­tor pro­grammed in­to T cells — which typ­i­cal­ly cor­re­sponds to one anti­gen — their CAR is de­signed to hit a tar­get called NKG2D as­so­ci­at­ed with up to eight lig­ands that can be found on tu­mor cells.

“The CAR for­mat makes it a more po­tent sig­naler of the cy­to­tox­ic ac­tiv­i­ty in the NK cell,” Mah­mood said of their ”su­per­charged” prod­uct.

Dario Cam­pana

It promis­es to be much more pow­er­ful than the NK en­gager ap­proach tak­en by Drag­on­fly and Af­fimed, which has gen­er­at­ed con­sid­er­able in­ter­est­ed from big play­ers like Mer­ck, Cel­gene and Genen­tech. Giv­en that NK cells from tu­mor pa­tients are im­paired and ex­haust­ed, Mah­mood said, an en­gager is es­sen­tial­ly re­cruit­ing a weak­er at­tack­er than what Nkar­ta of­fers.

With an IND planned for lat­er this year, Nkar­ta will fo­cus on re­lapsed, re­frac­to­ry cas­es of acute myeloid leukemia as their first hema­to­log­ic in­di­ca­tion. As for sol­id tu­mors, they will test a lo­cal de­liv­ery aimed at tam­ing liv­er as­so­ci­at­ed metas­tases.

A sec­ond CAR-NK pro­gram tar­get­ing CD19 in B-cell ma­lig­nan­cies is be­ing shep­herd­ed through pre­clin­i­cal stud­ies.

The tri­als will al­so rep­re­sent a test for Nkar­ta’s man­u­fac­tur­ing abil­i­ties. On top of clin­i­cal moves, in­vestors in the fi­nanc­ing — with Sam­sara Bio­Cap­i­tal lead­ing Am­gen Ven­tures, Deer­field Man­age­ment, Life Sci­ence Part­ners, Lo­gos Cap­i­tal and RA Cap­i­tal Man­age­ment — are al­so bankrolling a clin­i­cal GMP fa­cil­i­ty just a lev­el above Nkar­ta’s South San Fran­cis­co of­fices.

It’s not ex­pen­sive — Nkar­ta is pen­cilling in “sin­gle-dig­it mil­lions” in the bud­get — but mov­ing man­u­fac­tur­ing op­er­a­tions from aca­d­e­m­ic fa­cil­i­ties to their own would be cru­cial for main­tain­ing con­trol to the know-how, CEO Paul Hast­ings said.

“As you know in cell ther­a­py, the process is the prod­uct,” he said.

Matt Plun­kett

And it’s a process they are clear­ly proud of. CFO Matt Plun­kett added that each man­u­fac­tur­ing run yields hun­dreds if not low thou­sands of dos­es, low­er­ing the cost of goods to “two or­ders of mag­ni­tude be­low that of” Kym­ri­ah and Yescar­ta.

Nkar­ta is un­veil­ing its plans just as Fate Ther­a­peu­tics, a fel­low NK cell ther­a­py play­er that Hast­ings “has a lot of re­spect for,” an­nounced their first IND has been cleared. In­stead of healthy donors, Fate de­rives its NK cells from in­duced pluripo­tent stem cells (iP­SC).

The bat­tle for sec­ond-gen NK cell ther­a­peu­tics is just get­ting start­ed.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

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 on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

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.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

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.

What were End­points read­ers tun­ing in­to this year? Here’s a look at our 15 most pop­u­lar re­ports of the year (so far)

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.

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Iain McGill, Quell CEO

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.

Rogerio Vivaldi, Sigilon CEO (Sigilon via website)

Bob Langer biotech's lead cell ther­a­py re­mains on FDA hold, but re­searchers now may know the cause

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.

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Like the flu vac­cine every year, the FDA could move quick­ly on a vari­ant-tar­get­ed Covid vac­cine

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.

Jonathan Montagu (L) and Gerry Harriman, HotSpot co-founders

HotSpot gets hot­ter with $100M raise to push to­ward clin­ic

HotSpot Therapeutics, the allostery-focused biotech that works on what it calls “natural hotspots” — hence the name — is getting a bit hotter in its valuation from investors. And to that end they’ve raised $100 million.

The four-year-old AI computational biotech started by two former Nimbus execs announced this morning that it closed its Series C round right at the line of a 9-figure investment, courtesy of some big investors.

Thanks­giv­ing edi­tion: Top 15 End­points sto­ries of 2021; Can you name that vac­cine?; Mer­ck­'s Covid an­tivi­ral dis­ap­points; FDA nom­i­nee's in­dus­try ties; 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.

Happy Thanksgiving to all those who are celebrating it — although, if we are being honest, this week’s abbreviated edition is really for those who are not. Wherever you’re tuning in from, we appreciate your support, hope you find this recap helpful and we wish you a wonderful weekend.

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