Nkarta's blood cancer CAR stalls again, with falling response rate forcing it out of the race

Nkarta’s CAR NK blood cancer candidate has again stalled after making a speedy start. The response rate fell away sharply in the latest update, mirroring what happened in an earlier cohort and driving the cell therapy developer to mothball the program.

The off-the-shelf candidate, NKX101, consists of CAR NK cells engineered to express a NKG2D receptor. Through the engineering, Nkarta tried to boost the longevity, potency and activity of NK cells and create a cell therapy that is effective in a range of blood cancers and solid tumors. The drug candidate has failed to live up to those ambitions, despite twice showing promise in small numbers of patients. 

Nkarta reported four complete responses in six acute myeloid leukemia (AML) last year, encouraging it to push ahead. Yet, the next 14 patients only included one complete response. The crumbling response rate, which fell from 67% to 25%, has prompted Nkarta to deprioritize NKX101.

The biotech is yet to completely give up on the asset, with CEO Paul Hastings saying in a statement that the team will “evaluate options for optimizing future study design, dosing schedule and manufacturing.” But Nkarta sees its autoimmune candidate as a better use of the $250.9 million it had at the end of last year. The biotech still expects its cash to last into 2026, a runway made possible by layoffs last year.

William Blair analysts said they view the pipeline reprioritization “positively” in a research note, telling inventors that they believe the shift “accurately reflects increased investor enthusiasm for the potential of allogeneic cell therapies for autoimmune diseases and waning interest in NKX101, particularly in light of the disappointing efficacy in AML.”

The falling response rate echoes what happened in an earlier cohort. In 2022, Nkarta said that three of the first five AML patients to receive the highest doses of NKX101 had complete responses and raised $230 million on the back of the news. However, the biotech only saw one more complete response in the next 13 high-dose patients. 

Nkarta responded to the first collapse of its response rate by switching its focus to a cohort that received a different conditioning regimen. We now know the 67% response rate seen in that cohort was another mirage, not a sign that Nkarta had cracked the CAR NK puzzle by giving cytarabine, a chemotherapy drug, before the cell therapy.

The failure to find a path forward for the cancer candidate leaves Nkarta’s hopes resting on NKX019, the CD19-directed CAR NK prospect that the FDA cleared for testing in lupus nephritis last year. Developers of CD19 cell therapies have surged into lupus over the past 18 months, attracted by data that suggest the treatments may cure the autoimmune disease.