Artiva Biotherapeutics announced it would discontinue AlloNK, its allogeneic NK cell therapy given with rituximab in rheumatoid arthritis and other B-cell-driven autoimmune diseases. B-cell depletion and clinical activity were consistent with earlier data, but longer follow-up did not show the durability of response the company needed.
Two patients died. One developed fatal leukoencephalopathy after lymphodepletion with cyclophosphamide and fludarabine, assessed as likely fludarabine neurotoxicity. The second died suddenly about two months after treatment, assessed as unrelated to the regimen. Artiva is cutting about 94% of its staff and reviewing strategic alternatives.
My thoughts are with the patients and families, and with the Artiva team. They did serious work in a hard field, and they are sharing the fludarabine case so others can learn from it. That is to their credit.
The treatment-related death was not caused by the NK cells. It was caused by the chemotherapy given to make room for them. Lymphodepletion is standard across most cell therapies, autologous and allogeneic alike. In oncology that risk is often accepted. In autoimmune disease, where patients are not facing a fatal cancer, the tolerance is far lower. This death joins other recent safety reports that are tempering enthusiasm for cell therapy in autoimmunity.
SUPLEXA is given without lymphodepleting chemotherapy and without cytokine support after infusion. In SUPLEXA-101, 35 patients with metastatic solid tumors received more than 209 doses with no drug-related serious adverse events (SITC 2023, Poster 727). These were heavily pretreated patients, dosed repeatedly. SUPLEXA was made from 50 mL of whole blood, with no apheresis, and more than 60 clinical batches have been manufactured without a failure.
- SUPLEXA-101 at a glance
- 35 patients with metastatic solid tumors
- More than 209 doses
- No drug-related serious adverse events
- More than 60 clinical batches manufactured without a failure
Allogeneic cells are recognized as foreign and cleared by the immunocompetent host, unless they are genetically modified to mask their allogeneic nature. Short persistence is a known property of allogeneic NK products, and in my view it is the most likely reason AlloNK’s responses did not last. Artiva itself described the shortfall as durability of clinical response.
SUPLEXA is autologous: the patient’s own cells, returned to the patient, with no host rejection to overcome. SUPLEXA cells also express CD25, the high-affinity IL-2 receptor. Like regulatory T cells, they should be able to sustain themselves on the low levels of IL-2 the body makes on its own. That is why SUPLEXA needs no IL-2 cytokine support after infusion, unlike IL-2-dependent products such as TILs.
How long SUPLEXA cells persist in patients is a question that can only be addressed in clinical trials, but the literature supports the notion that NK cells with a memory phenotype can persist for over a decade.
SUPLEXA cells traffic to the bone marrow. Our lead program takes advantage of this endogenous trafficking pattern, and hematologic malignancies are now a priority: medium/higher-risk myelodysplastic syndromes and relapsed/refractory AML, with a U.S. IND planned for the first quarter of 2027.
Artiva’s experience is a reminder that in cell therapy, safety is not a slogan. It decides which therapies ultimately reach patients.
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