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.

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.

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.

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.

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.