Nkarta goes back to basics

Nkarta, like its competitor Fate Therapeutics, found an initial NK cell therapy breakthrough to have been short-lived. And today the company lifted the lid on the disappointment that had prompted it to go back to the drawing board, redesigning its chemo conditioning regimen to give a product that, it hopes, will be more efficacious and longer-lasting.

First results of this new approach, pertaining to Nkarta’s lead pipeline asset, NKX101, are promising: four of six late-line acute myelogenous leukaemia patients have been put into remission, the company said today. But investors might sense echoes of last year’s illusory success, and could well come away saying: show me more data.

This is especially pertinent given Nkarta’s valuation, which at $225m refuses resolutely to approach that of Fate – in spite of Fate’s 60% collapse in January as that group purged its NK cell therapy pipeline, cut jobs and revealed the loss of Johnson & Johnson as a deal partner.

Short-lived

Just over a year ago Nkarta had boasted of a major clinical success with NKX101, an allogeneic NK cell therapy expressing a Car against NKG2D ligands, reporting five remissions among 17 AML patients, and raising $230m on the strength of the data.

This might have been respectable enough given the aggressive and intractable nature of AML, but Nkarta talked up five subjects given the highest NKX101 doses, 1-1.5 billion cells spread over three infusions. Three of these five had gone into compete remission, and the company moved to treat more patients with this dosing regimen.

However, things then went quiet, and today investors found out why: an additional 13 high-dose patients have yielded just one new response (a complete remission with residual thrombocytopenia). Not only that, but NKX101 had no durability: of the three initial responders, two relapsed within a couple of months, while the third was transplanted.

If this makes it clear that the initial promise of high doses was illusory, Nkarta has moved quickly to avoid the fate of Fate. A new lymphodepletion regimen has been investigated, substituting fludarabine/cyclophosphamide with fludarabine/cytarabine; cytarabine is a chemotherapy that Nkarta claims upregulates NKG2D ligands on blast cells.

And, alongside the postmortem on the initial dataset, today brought the first clinical efficacy data of such flu/cytarabine preconditioning with NKX101, given as 1.5 billion cells over three doses: results with six patients show three going into full remission, and a fourth reporting complete response with residual thrombocytopenia.

Flu/cytarabine is now “the go-forward lymphodepletion approach” for NKX101, Nkarta told Evaluate Vantage. “We believe cytarabine is particularly well suited ... in the AML setting.” For the time being it will only be used with NKX101.

Nkarta also highlighted the fact the new approach resulted in no cytokine release or neurotoxicity of any grade, though half the patients reported grade 3 sepsis. Dosing NKX101 with flu/cyclophosphamide lymphodepletion had yielded 12% mild cytokine release, and 60%, 53% and 43% respective rates of severe thrombocytopenia, anaemia and neutropenia.

However promising the new data look, there is a caveat. Most importantly, Nkarta cautions that follow-up from the six patients is limited, and only one of the four responders appears to have been in remission without transplant for over a month. Like the April 2022 data, the latest update might be a false dawn.

Fate’s experience suggested that NK cells do not expand like T cells, meaning that it might be impossible to dose a product high enough, and this will weigh heavy. Nkarta will not update the fludarabine/cytarabine NKX101 cohort until the first half of 2024, by which time it expects to have treated another 12-20 patients; until then investors are being asked to keep the faith.