Nkarta Therapeutics

Nkarta thinks it has answers to the problems that have made natural killer cells a bit-part player in the story of cell therapies to date. (Nkarta Therapeutics)

Taking natural killer cell therapies into the mainstream.

CEO: Paul Hastings
Founded: 2015
Based: South San Francisco
Clinical focus: Anti-cancer natural killer cell therapies

The scoop: CAR-T therapies have validated the potential of engineering immune cells to treat cancer. However, the therapeutic power and commercial potential of approved CAR-Ts are constrained by a range of issues, from logistics to safety. Nkarta Therapeutics thinks engineered natural killer (NK) cells can eliminate those constraints, resulting in better therapies that are equipped to go mainstream.

What makes Nkarta fierce: Nkarta thinks it has answers to the problems that have made NK cells a bit-part player in the story of cell therapies to date. If successful, Nkarta stands to tap into the natural advantages of NK cells over T cells to create anti-cancer therapies that are safer, more effective and simpler to manufacture than the current crop of CAR-Ts.

“You can take NK cells from one individual and put them into another individual and not see graft-versus-host disease,” Nadir Mahmood, Ph.D., Nkarta’s chief business officer, said. "Further, you don't see the cytokine storm and neurotoxicity. Their biology is different. Their ability to expand is going to be different."

As Nkarta sees it, there are two main reasons why work on NK cells has lagged behind. Firstly, NK cells are found in relatively low numbers in the body, making it hard to get enough of them to deliver a therapeutic dose. Secondly, NK cells have short half-lives.

Dario Campana, M.D., Ph.D., now at the National University of Singapore, came up with fixes for both problems. Campana developed an expansion technology to increase NK numbers and engineered the cells to express a membrane-bound form of IL-15, a cytokine growth factor. Those advances attracted NEA, Novo Holdings and SR One, leading to the foundation of Nkarta.

Four years on from its founding, Nkarta has $114 million in series B funding to draw on as it takes its co-lead candidates into human testing and up to clinical proof of concept.

NKX101, an anti-NKG2D NK cell therapy, is one of the two assets. NKG2D is normally expressed on the surface of NK cells and recognizes eight ligands that are upregulated in a range of hematological cancers and solid tumors. Other groups have leveraged these natural anti-cancer capabilities to show the raw potential of unmodified NK cells. Nkarta wants to go several steps further.

“The beauty of the system is this is one of the primary drivers in the way that NK cells recognize and differentiate a tumor cell from a healthy cell,” Mahmood said. “We're taking this native system and native biology that is how the NKs surveil our system and keep us healthy and sort of supercharging it by putting it into a chimeric antigen receptor format.”

Nkarta plans to test NKX101 in acute myeloid leukemia and liver-associated solid tumors. In parallel, Nkarta will work to get its other lead candidate through IND-enabling studies and into the clinic.

The other lead candidate is a CAR-NK program targeting CD19 in B-cell malignancies. That focus puts Nkarta squarely on the turf of approved and experimental CAR-T therapies, including Kite’s Yescarta and Novartis’ Kymriah. Those pioneering CAR-Ts have a big head start on Nkarta’s program but have struggled to capitalize on their first-mover advantage.

With neither Yescarta nor Kymriah setting the world alight commercially, Nkarta thinks there is a gap for a drug with a similar mechanism of action that is easier and cheaper to produce. Off-the-shelf cell therapy startups such as Allogene Therapeutics have identified the same gap, but they must engineer T cells to use allogeneic starting materials. Nkarta’s use of NK cells renders that step unnecessary.

That could give Nkarta an advantage. While Mahmood thinks most allogeneic CAR-T startups would love to achieve 100 to 150 doses per manufacturing run, Nkarta has aspirations to produce 1,000 or more doses per run.

The value of that potential advantage will only come into play if Nkarta’s cells work as expected. With two programs due to enter the clinic by the end of next year, Nkarta will soon start to learn whether that is the case.

Investors: NEA, Novo Holdings, SR One, Samsara BioCapital, Amgen Ventures, Deerfield Management, Life Science Partners, Logos Capital and RA Capital Management

Nkarta Therapeutics