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.

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

Hesaam Esfandyarpour holds what looks like a mini-cooler up to the computer screen in his California office.

Esfandyarpour is in his late-30s, with crows feet creeping up against a youthful face. He wears a gray polo and the device in his hand — with its hard plastic-looking shell, blue-and-white pattern, and a white plastic paddle resembling a handle jutting out the front — might contain diced strawberries and peanut-butter sandwiches to meet mom and the kids at a SoCal park. Instead, Esfandyarpour tells me it’s going to change medicine and biopharma research.

Almost two years after leaving GSK to launch Brii Bio with a whopping $260 million in funding, Zhi Hong is seeing the trans-Pacific infectious disease specialist he set out to build take shape.

“Our pipeline is coming together,” he told Endpoints News, with 12 partnered assets plus some internal programs.

As its latest partner, AN2 Therapeutics, comes into the limelight for the first time with a $12 million seed round, so is Brii’s plans in the antibiotics space. Brii has obtained China rights to AN2’s antibacterial targeting mycobacterium tuberculosis for multi-drug resistant TB, which it says is in the clinical stage.

Nearly a century passed between the first proto-immunotherapy attempts in cancer — crude and obscure but nonetheless with some scientific basis — and Jim Allison’s first T cell paper. Thirty-plus years flipped between the discovery of CTLA-4 as an off-switch and the approval of Yervoy. Twenty-two rolled between PD-1’s isolation and Opdiva and Keytruda. 

Longwood co-founder Lea Hachigian is betting she can hasten that. It’s a bet on newly established single-cell genomic analysis tech and the ability to crunch endless troves of data at a rate few others can, and investors including Leaps by Bayer and Novartis Venture Fund just put $39 million behind it. They call it Immunitas.