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.
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.
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.
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.