Nkarta Enters the Lupus Nephritis CAR Cell Therapy Race With NKX019 IND Clearance


Nkarta intends to evaluate NKX019 in an open-label, multicenter, dose escalation clinical trial that will recruit up to 12 patients with refractory LN.

Nkarta’s NKX019, an investigational allogeneic chimeric antigen receptor (CAR) natural killer (NK) cell therapy, has received clearance of an investigational new drug (IND) application enabling its evaluation in a clinical trial for patients with lupus nephritis (LN).1

In light of the IND clearance, Nkarta intends to evaluate NKX019 in an open-label, multicenter, dose escalation clinical trial that will recruit up to 12 patients with refractory LN. The trial, which is expected to enroll its first participant in the first half of next year, will administer the NK cell therapy over the course of 3 doses set at either 1 billion or 1.5 billion cells per dose. The doses will be given on days 0, 7, and 14 after lymphodepletion, which will be conducted with the use of cyclophosphamide.

“The potential of cell therapy to reset the immune system and provide long-term, drug-free remissions for patients with severe autoimmune disease may represent the biggest medical breakthrough in the last 50 years of rheumatology,” Roberto Caricchio, MD, the Myles J. McDonough Chair in Rheumatology, a professor of medicine, and the chief of the Division of Rheumatology in the Department of Medicine at the University of Massachusetts Chan Medical School, said in statement.1 “Patients with LN have limited treatment options, and the early results with cell therapy suggest that we may be defining a new era of treatment.”

NKX019 consists of NK cells from the peripheral blood of healthy adult donors that have been genetically modified to target CD19 in order to eliminate B-cells. The NK cell therapy product is also modified to express a proprietary, membrane-bound form of interleukin-15 that is expected to allow for improved persistence and activity in the absence of outside cytokine support. NKX019 is also currently being evaluated for the treatment of relapsed/refractory nonHodgkin lymphoma in a phase 1 clinical trial (NCT05020678). Alongside the announcement of the IND clearance, Nkarta noted that it would be adding a compressed dosing cohort to the nonHodgkin lymphoma trial.

NKX019 is part of an ongoing trend among cell therapy developers repurposing CD19-directed CAR therapy, a modality which has previously shown success in hematological cancers, for the treatment of autoimmune indications like systemic lupus erythematosus (SLE) and LN. Many, though not all, other examples of CAR therapies in this space are autologous CAR T-cell therapies. Examples of such cell therapies include ImmPACT Bio’s IMPT-514, an investigational bispecific CD19/CD20-directed CAR-T; Artiva Biotherapeutics’ AlloNK (AB-101), an investigational allogeneic NK cell therapy; Cabaletta Bio’s CABA-201, an investigational CD19-directed CAR-T; and Kyverna Therapeutics’ KYV-101, an investigational autologous CD19-directed CAR-T.2-5 Notably, KYV-101, which is being evaluated in a phase 1 clinical trial (NCT05938725) for the treatment of LN, also recently received clearance of an IND for evaluation in patients with diffuse cutaneous systemic sclerosis.6

“We believe that NKX019, as an NK cell-based approach, has the potential to distinguish itself in the growing field of cell therapy for autoimmune diseases through improved access and tolerability,” David R. Shook, MD, the chief medical officer of Nkarta, added to the statement.1 “Off-the-shelf availability reduces patient burden and eliminates the need for costly infrastructure and treatment delays required for autologous cell therapies. Our proprietary engineering may also improve safety through a reduced need for lymphodepletion. NKX019 is active immediately and is self-sustaining, without the need for large cytokine surges from preparative chemotherapy. Patients with severe autoimmune diseases such as lupus nephritis need safe and novel therapies. We will continue to work closely with leading investigators to bring the promise of cell therapy to patients in need to explore this potentially transformative therapeutic approach.”

1. Nkarta receives FDA clearance of IND application for NKX019 in lupus nephritis. News release. Nkarta Inc. October 17, 2023. Accessed October 17, 2023. https://ir.nkartatx.com/news-releases/news-release-details/nkarta-receives-fda-clearance-ind-application-nkx019-lupus
2. 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 October 17, 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/
3. ArtivaBiotherapeutics announces FDA clearance of IND for AlloNK cell therapy candidate in combination with rituximab in lupus nephritis. News release. ArtivaBiotherapeutics, Inc. August 16, 2023. Accessed October 17, 2023. https://www.artivabio.com/artiva-biotherapeutics-announces-fda-clearance-of-ind-for-allonk-cell-therapy-candidate-in-combination-with-rituximab-in-lupus-nephritis/
4. 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 October 17, 2023. https://www.cabalettabio.com/news-media/press-releases/detail/81/cabaletta-bio-receives-fda-clearance-of-ind-application-for
5. Kyverna Therapeutics announces achievement of 28-day post-infusion milestone for first U.S. patient dosed in phase 1 clinical trial of CD19 CAR t-cell therapy for lupus nephritis. News release. Kyverna Therapeutics. September 13, 2023. Accessed October 17, 2023. https://kyvernatx.com/press-releases/kyverna-therapeutics-announces-achievement-of-28-day-post-infusion-milestone-for-first-u-s-patient-dosed-in-phase-1-clinical-trial-of-cd19-car-t-cell-therapy-for-lupus-nephritis/
6. Kyverna Therapeutics announces FDA clearance of IND for KYV-101, a novel fully human CD19 CAR T-cell therapy to treat scleroderma. News release. Kyverna Therapeutics. October 11, 2023. Accessed October 17, 2023. https://www.prnewswire.com/news-releases/kyverna-therapeutics-announces-fda-clearance-of-ind-for-kyv-101-a-novel-fully-human-cd19-car-t-cell-therapy-to-treat-scleroderma-301953561.html
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