Artiva Biotherapeutics, Inc., a clinical-stage company whose mission is to deliver highly effective, off-the-shelf, allogeneic natural killer (NK) cell-based therapies, announced today that the first patient has been dosed in its Phase 1 trial of AlloNK® (also known as AB-101) in combination with monoclonal antibodies for the treatment of lupus nephritis (LN) (ClinicalTrials.gov Identifier: NCT06265220). AlloNK is a non-genetically modified, allogeneic, cryopreserved NK cell therapy candidate being developed to enhance the activity of B-cell targeting monoclonal antibodies to drive B-cell depletion.

Seminal reports with autologous CAR-T cells have demonstrated that cell therapy can deeply and temporarily deplete B-cells with the potential to reset the immune system and provide complete and long-lasting responses in patients with LN. Artiva has analyzed blood samples from patients treated with AlloNK in combination with rituximab, an anti-CD20 antibody that targets B-cells, in a Phase 1/2 multi-center clinical trial in patients with relapsed or refractory B-cell-non-Hodgkin lymphoma (B-NHL) (ClinicalTrials.gov Identifier: NCT04673617). In all 29 patients with samples analyzed, as of March 26, 2024, all patients achieved non-quantifiable peripheral B-cell levels by Day 8 (except for one patient who achieved such B-cell depletion by Day 15) following the start of therapy, regardless of B-cell levels at baseline. Artiva believes this data provides support for the B-cell depleting mechanism of action. AlloNK has also demonstrated complete responses in B-NHL patients as measured by imaging of tumor lesions. Because of the common tissues of interest, principally the lymphoid tissues, in B-NHL and autoimmune diseases, Artiva believes data in these B-NHL patients provides supporting evidence for the therapeutic mechanism of action in autoimmune disease.

“We are excited to bring AlloNK to patients with autoimmune disease. To our knowledge, this is the first time a patient has received an allogeneic NK cell therapy candidate in a U.S. clinical trial for treatment of an autoimmune disease. We are encouraged by the activity of AlloNK in our NHL trial, demonstrating AlloNK’s ability to drive B-cell depletion and helping validate the therapy’s potential mechanism of action,” said Fred Aslan, M.D., Chief Executive Officer of Artiva. “Furthermore, our ability to combine AlloNK with CD20, CD19, or CD38 directed monoclonal antibodies gives AlloNK the versatility to target distinct B-cell subpopulations across different autoimmune diseases.”

The multi-center, open label clinical trial will assess the safety and clinical activity of AlloNK in combination with rituximab or obinutuzumab in patients with class III or class IV LN who have relapsed or did not respond to previous standard of care treatment approaches. Patients will receive a treatment composed of lymphodepletion with cyclophosphamide and fludarabine, three-doses of AlloNK, and two doses of monoclonal antibody.

“Lupus nephritis is among the most severe manifestations of systemic lupus erythematosus. Many patients do not respond to standard therapies. Examining new treatments could provide more novel options for this patient demographic,” said Kenneth Kalunian, M.D., Professor of Medicine and Director of the Lupus Center of Excellence at UC San Diego School of Medicine.

Artiva is collaborating with Lupus Therapeutics, the clinical research affiliate of the Lupus Research Alliance, to support the evaluation of AlloNK for LN. Lupus Therapeutics has provided advisory services and clinical operations support for the Artiva early development program through sites of the Lupus Clinical Investigators Network (LuCIN). The Network, overseen by Lupus Therapeutics, is comprised of leading research centers throughout North America with the purpose of accelerating and optimizing lupus clinical trials.