Artiva Biotherapeutics’ NK Cell Therapy AlloNK Cleared for Trial in Systemic Lupus Erythematosus

Artiva Biotherapeutics’ AlloNK (AB-101), an investigational allogeneic natural killer (NK) cell therapy, has received clearance of an investigational new drug (IND) application from the FDA to be evaluated in a clinical trial as part of a combination therapy with antiCD20 monoclonal antibody rituximab in patients with systemic lupus erythematosus (SLE) and active lupus nephritis (LN).¹

AlloNK, which is intended to heighten the effect of rituximab via antibody-dependent cellular cytotoxicity (ADCC), is unengineered and derived from cord blood units selected for the high affinity variant of the CD16 receptor and the KIR-B haplotype. Artiva noted that no allogeneic NK or chimeric antigen receptor T-cell (CAR-T) therapy has previously received IND clearance for evaluation in an autoimmune disease indication.

AlloNK is already being evaluated in 2 separate clinical trials for lymphoma indications: a multicenter phase 1/2 clinical trial (NCT04673617) both alone and in combination with rituximab for the treatment of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma and the multicenter, open-label phase 2 LuminICE-203 clinical trial (NCT05883449) in combination with innate cell engager AFM13 in patients with r/r CD30-positive lymphomas. Efficacy and safety data from the phase 1/2 clinical trial were presented in a poster at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois.²

According to a summary of the safety data in a press release from May 2023, AlloNK was well-tolerated at doses of 1 billion and 4 billion cells per dose at the time of the data cutoff.² Among 24 patients evaluable for safety, including 15 patients treated with the monotherapy and 9 patients treated with the combination therapy, the most common grade 3 or higher adverse event (AE) was myelosuppression. Artiva noted that this AE is consistent with standard lymphodepletion regimens and that the cases were manageable with the standard of care treatment. Grade 1 cases of cytokine release syndrome occurred in 2 patients. No patients experienced cases of neurotoxicity, graft versus host disease, or AEs leading to discontinuation of treatment with the cell therapy. Among the patients who were treated with the monotherapy, 2 patients experienced grade 3 or higher cases of febrile neutropenia, 2 patients experienced grade 3 or higher cases of malignant neoplasm progression, and 1 patient experienced a grade 1-2 case of malignant neoplasm progression; these were the most common serious AEs in the monotherapy cohort. A serious grade 3 case of pyrexia occurred in 1 patient who received the combination therapy.

“Although rituximab has been used off-label in the treatment of SLE, rituximab alone has been shown to give incomplete B-cell depletion,” Kenneth Kalunian, MD, a clinician andprofessor of Medicine at University of California, San Diego, and new member of Artiva’s advisory board, said in a statment.¹ “The addition of allogeneic NK cells as an ADCC-enhancing therapy could significantly enhance rituximab’s ability to drive deeper levels of B-cell depletion. Furthermore, SLE patients may have lower levels of NK cells than healthy subjects, and these cells may be functionally impaired. An effective off-the-shelf cell therapy that can be administered and managed in the community setting could be well received by lupus patients and physicians.”

AlloNK joins several autologous cell therapies currently under evaluation for the treatment of SLE and/or LN. Among these are ImmPACT Bio’s IMPT-514, an investigational bispecific CD19/CD20-directed CAR-T; Kyverna Therapeutics’ KYV-101, an investigational CD19-directed CAR-T; and Cabaletta Bio’s CABA-201, an investigational CD19-directed CAR-T.^3-6

“Seminal clinical data has been generated using autologous CAR-T cells suggesting that a deeper B-cell depletion can induce complete and long-lasting responses in patients with LN,” Fred Aslan, MD, the chief executive officer of Artiva, added to the statement.¹ “However, the use of autologous CAR-T cells requires apheresis, likely hospitalization, and the potential for serious side effects. AlloNK given in combination with rituximab, an antiCD20 antibody that targets B-cells, is already driving complete responses in late line B-NHL patients in an ongoing phase 1 study by enhancing the activity of rituximab. Our hypothesis is that AlloNK plus rituximab also has the potential to drive deep B-cell depletion in LN patients with an off-the-shelf therapy that could be administered and managed in an outpatient setting.”

REFERENCES
1. Artiva Biotherapeutics announces FDA clearance of IND for AlloNK cell therapy candidate in combination with rituximab in lupus nephritis. News release. Artiva Biotherapeutics, Inc. August 16, 2023. Accessed August 18, 2023. https://www.artivabio.com/artiva-biotherapeutics-announces-fda-clearance-of-ind-for-allonk-cell-therapy-candidate-in-combination-with-rituximab-in-lupus-nephritis/
2. Artiva Biotherapeutics presents initial data from first-in-human phase 1/2 clinical trial of AB-101 at the 2023 ASCO annual meeting. News release. Artiva Biotherapeutics, Inc. May 25, 2023. Accessed August 18, 2023. https://www.artivabio.com/artiva-biotherapeutics-presents-initial-data-from-first-in-human-phase-1-2-clinical-trial-of-ab-101-at-the-2023-asco-annual-meeting/
3. ImmPACT Bio announces FDA clearance of IND application for bispecific CD19/CD20 CAR T therapy IMPT-514 for the treatment of refractory systemic lupus erythematosus. News release. ImmPACT Bio USA, Inc. August 15, 2023. Accessed August 18, 2023. https://immpact-bio.com/news-and-events/immpact-bio-announces-fda-clearance-of-ind-application-for-bispecific-cd19-cd20-car-t-therapy-impt-514-for-the-treatment-of-refractory-systemic-lupus-erythematosus/
4. Kyverna Therapeutics announces FDA clearance of IND for KYV-101, a novel fully human CD19 CAR T-cell therapy to treat lupus nephritis. News release. Kyverna Therapeutics. November 11, 2022. Accessed August 18, 2023. https://kyvernatx.com/press-releases/kyverna-therapeutics-announces-fda-clearance-of-ind-for-kyv-101-a-novel-fully-human-cd19-car-t-cell-therapy-to-treat-lupus-nephritis/
5. Cabaletta Bio receives FDA clearance of IND application for CABA-201 for treatment of systemic lupus erythematosus. News release. Cabaletta Bio, Inc. March 31, 2023. Accessed August 18, 2023. https://www.cabalettabio.com/news-media/press-releases/detail/81/cabaletta-bio-receives-fda-clearance-of-ind-application-for