Initial data from trial of AAV therapy NKX019 expected this year
Nkarta testing several doses in adults with autoimmune diseases
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Nkarta said it expects initial data from a clinical trial testing its cell therapy candidate NKX019 in adults with ANCA-associated vasculitis (AAV) and other autoimmune diseases to be presented later this year.
The Phase 1/2 Ntrust-2 trial (NCT06733935) is testing several doses of NKX019 in up to 144 people with AAV, idiopathic inflammatory myopathy, or systemic sclerosis (SSc). Enrollment of 12 participants per dose level per disease is ongoing at sites in several U.S. states and Puerto Rico.
Designed to kill the immune B-cells that produce antibodies, including those that drive autoimmune diseases, the therapy is also being tested in a parallel Phase 1/2 study, called Ntrust-1 (NCT06557265). That study is enrolling adults with autoimmune disorders affecting the kidneys, including lupus nephritis and primary membranous nephropathy.
“Thoughtfully leveraging our safety data, we are now dosing patients at 4 billion cells in a three-dose cycle for a total of 12 billion cells as we look to maximize the depth and durability of B-cell depletion and clinical response, positioning us to unlock the full potential of NKX019 for people living with autoimmune disease,” Paul J. Hastings, CEO of Nkarta, said in a company press release. “We look forward to sharing a comprehensive clinical update from Ntrust-1 and Ntrust-2 later this year with the aim of presenting a meaningful data set at a medical conference.”
AAV is caused by self-reactive antibodies called ANCAs, which are made by immune B-cells. The disease inflames and damages small blood vessels.
Off-the-shelf therapy shows promise in preclinical studies
NKX019 is designed to reduce harmful immune responses by eliminating B-cells. It is made from natural killer (NK) cells, a type of immune cell that can kill other cells, collected from healthy donors and engineered in the lab to recognize CD19, a protein found on the surface of B-cells. The modified cells also include IL-15, a signaling molecule intended to help the NK cells survive and remain active for longer in the body.
Because these engineered NK cells can be manufactured in advance and stored, NKX019 is being developed as an off-the-shelf therapy that can be infused directly into the bloodstream when needed. By lowering B-cell levels, the treatment is expected to reduce ANCA production and help relieve AAV symptoms.
In preclinical studies using blood samples from people with autoimmune diseases, NKX019 consistently lowered B-cell counts, supporting the therapy’s potential across B-cell-driven conditions such as AAV.
Ntrust-2, which began enrolling patients in late 2024, is focused on people with difficult-to-treat granulomatosis with polyangiitis or microscopic polyangiitis — the two most common types of AAV — who test positive for ANCAs against the PR3 or MPO proteins, the two most common targets of AAV-driving antibodies.
Participants are receiving increasing doses of NKX019 to help researchers determine the most appropriate dose to take forward into the trial’s next phase, where more patients will be treated at the optimal dose.
Before receiving NKX019, participants undergo lymphodepletion, using the chemotherapy drugs fludarabine and cyclophosphamide, to reduce existing immune cells and help the infused NK cells grow and persist in the body. For patients with pre-existing low blood cell counts, cyclophosphamide alone may be used instead.
After lymphodepletion, participants receive a three-dose NKX019 treatment cycle on days 0, 3, and 7. Nkarta has said no immunotherapies are used in the study, allowing NKX019 to be evaluated as a single agent and potentially helping streamline development.
Ntrust-2 is primarily assessing the therapy’s safety and tolerability. It is also tracking whether treatment can support lasting disease control — including sustained remission and reduced disease activity — measured with tools such as the Birmingham Vasculitis Activity Score, over a follow-up of as long as two years.
Both Ntrust-2 and Ntrust-1 are testing a second dose of NKX019, 4 billion cells per infusion. Dose escalation followed clearance from an independent data safety monitoring board, which gave its approval after reviewing safety results from the first, lower dose of NKX019 in both trials.
Nkarta also noted that enrollment is ongoing in investigator-sponsored trials of NKX019 in other autoimmune diseases, such as generalized myasthenia gravis and systemic lupus erythematosus.
