Nkarta Launches Trial for CAR-NK Therapy NKX019 in Lupus and Gains Clearance for Separate Trial in Other Autoimmune Diseases

Paul J. Hastings, BS
Credit: Nkarta

The first patient has entered screening for Nkarta’s Ntrust-1 clinical trial (NCT identifier pending) evaluating NKX019, an investigational allogeneic chimeric antigen receptor natural killer (NK) cell therapy, for the treatment of lupus nephritis (LN); the company has also received clearance from the FDA for a separate clinical trial (Ntrust-2) for NKX019 in systemic sclerosis (SSc, scleroderma), idiopathic inflammatory myopathy (myositis), and ANCA-associated vasculitis.¹

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. Both Ntrust-1 and Ntrust-2 are open-label, multicenter, dose escalation clinical trials that will seek to recruit up to 12 patients each. The trials will both 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 alone. Additional cycles may be added for patients in Ntrust-1 to restore responses if necessary.

“The initiation of Ntrust-1 in LN and the investigational new drug (IND) application clearance for 3 additional indications are critical milestones in our mission to improve the accessibility and safety of cell therapy,” Paul J. Hastings, BS, the president & CEO of Nkarta, said in a statement.¹ “NKX019 is unencumbered by many of the safety, infrastructure, and logistical challenges associated with existing cell therapy approaches. Many people living with lupus are historically underserved, and our aim is to develop treatments that are broadly accessible and easier to tolerate and administer. Our vision goes beyond LN, as the unmet need in autoimmune disease is substantial. The clearance of our second IND in autoimmune disease broadens the development of NKX019 and enables us to evaluate 3 additional B-cell mediated diseases in parallel. We have selected a contract research organization to support Ntrust-2, and trial activation activities are underway. Meanwhile, we are also exploring other opportunities to positively impact the treatment of different populations with autoimmune disease through collaborations with leading investigators.”

Nkarta stated that it expects to announce initial data from the 2 clinical trials in 2025. Notably, NKX019 was originally developed for oncology indications and is also being evaluated in an ongoing phase 1 clinical trial (NCT05020678) for relapsed/refractory nonHodgkin lymphoma. The IND clearance for LN was obtained in October 2023.²

“People living with SSc have limited treatment options, especially treatments that target the whole patient and not just 1 organ system,” Elizabeth Volkmann, MD, MS, the director of the UCLA Scleroderma Program and the founder and co-director of the UCLA Connective Tissue Disease-Related Interstitial Lung Disease Program, added to the statement.¹ “The early results of studies using cell therapy in autoimmune diseases such as SSc are encouraging, and I look forward to seeing how these treatments affect outcomes for people living with this condition.”

According to Nkarta, NKX019 is the first engineered NK cell therapy to enter clinical trials for LN. Although, earlier this year Artiva Biotherapeutics dosed the first patient in its phase 1 clinical trial (NCT06265220) evaluating AlloNK (AB-101), an unengineered allogeneic NK cell therapy, for the treatment of systemic lupus erythematosus (SLE) and active LN.³ AlloNK is being administered in the trial alone or alongside 1 of 2 antiCD20 monoclonal antibodies: rituximab or obinutuzumab. The NK cell therapy, which is intended to heighten the B-cell depleting effect of the monoclonal antibodies via antibody-dependent cellular cytotoxicity, is derived from cord blood units selected for the high affinity variant of the CD16 receptor and the KIR-B haplotype.⁴

REFERENCES
1. Nkarta initiates clinical trial of NKX019 in lupus nephritis with first patient in screening and announces pipeline expansion to additional autoimmune indications. News release. Nkarta, Inc. June 27, 2024. Accessed July 9, 2024. https://ir.nkartatx.com/news-releases/news-release-details/nkarta-initiates-clinical-trial-nkx019-lupus-nephritis-first
2. Nkarta receives FDA clearance of IND application for NKX019 in lupus nephritis. News release. Nkarta Inc. October 17, 2023. Accessed July 9, 2024. https://ir.nkartatx.com/news-releases/news-release-details/nkarta-receives-fda-clearance-ind-application-nkx019-lupus
3. Artiva Biotherapeutics announces first patient dosed in phase 1 trial of AlloNK® cell therapy candidate in lupus nephritis. News release. Artiva Biotherapeutics, Inc. April 17, 2024. Accessed July 9, 2024. https://www.artivabio.com/artiva-biotherapeutics-announces-first-patient-dosed-in-phase-1-trial-of-allonk-cell-therapy-candidate-in-lupus-nephritis/
4. 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 July 9, 2024. https://www.artivabio.com/artiva-biotherapeutics-announces-fda-clearance-of-ind-for-allonk-cell-therapy-candidate-in-combination-with-rituximab-in-lupus-nephritis/