A Phase 1/2 Study of NKX019 in Subjects With Immune-Mediated Diseases (Ntrust-2)

This is a Phase 1/2, open-label, multi-center, multi-cohort, non-randomized dose escalation and dose expansion basket study to determine the safety and tolerability of NKX019 (allogeneic CAR NK cells targeting CD19) in participants with autoimmune diseases.

General Inclusion Criteria: 1. Age ≥18 and ≤75 2. Signed informed consent form and ability to adhere to the study visit schedule and comply with other protocol requirements 3. Women of childbearing potential must have negative pregnancy tests at screening and baseline, and agree to abstinence or acceptable birth control from 2 weeks prior to the first dose through 1 year after the last dose 4. For participants taking corticosteroids, the prednisone (or equivalent) dose must be ≤20 mg/day at 2 weeks prior to Screening and stable for ≥ 14 days before start of Screening 5. For participants on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to Screening 6. eGFR as calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of ≥45 mL/min/1.73 m2 at screening SSc Inclusion Criteria: 1. Meets the 2013 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for SSc 2. Meet criteria a and/or b: a. Severe skin involvement defined as mRSS ≥ 30 or active skin disease defined as mRSS ≥ 15 at screening and one or more of the following within the prior 6 months of screening: i. An increase in mRSS of ≥ 3 units ii. Involvement of 1 new body area with ≥ 2 mRSS units iii. 2 new body areas with ≥ 1 mRSS unit b. Moderate to severe Interstitial Lung Disease (ILD) defined by evidence of ILD on High-resolution computed tomography (HRCT) and FVC \< 70% of predicted or DLCO (hemoglobin or alveolar volume corrected) \< 70% of predicted or ILD on HRCT and progressive ILD meeting at least 2 of the following 3 criteria within the prior 6 months of screening: i. Worsening respiratory symptoms ii. Evidence of progression on HRCT, or iii. Evidence of absolute decline in FVC ≥ 5% 3. 10 years or less since the first non-Raynaud's sign or symptom 4. Inadequate response or intolerance to at least one treatment, including cyclophosphamide, methotrexate, MMF/mycophenolic acid, nintedanib, rituximab, or tocilizumab IIM Inclusion Criteria: 1. Diagnosis for IIM as per 2017 ACR/EULAR Classification Criteria 2. One positive myositis antibody 3. Activity defined as manual muscle testing (MMT-8) score \3.2\]) after at least 12 weeks of therapy with the following: 1. At least 1 conventional synthetic DMARD (csDMARD) (eg, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine) AND 2. Either of the following: i. At least 2 biologic (b) DMARDs (eg, TNF inhibitors, abatacept, anti-IL-6 or anti-IL-6R, rituximab) with distinct mechanisms of action (MoAs) OR ii. At least 1 bDMARD and at least 1 targeted synthetic DMARD (tsDMARD) (eg, JAK inhibitor) AND c. Have failed no more than 3 biologics or tsDMARDs with unique mechanisms of action 5. Minimum of 6 swollen joint counts (SJCs) and 6 tender joint counts (TJCs) according to joint assessment General Exclusion Criteria: 1. eGFR \< 45 ml/min/1.73m2 2. Currently requiring renal dialysis or expected to require dialysis during the study period 3. Previous solid organ or hematopoietic cell transplant or planned transplant within study treatment period 4. Congenital or acquired immunodeficiency resulting in severe infection or those receiving chronic immunoglobulin replacement therapy 5. Liver disease or dysfunction, including cirrhosis and/or bilirubin ≥ 3 times the upper limit of normal 6. Pulmonary comorbidity including chronic obstructive pulmonary disease or asthma requiring daily oral steroids, resting hypoxemia (\10 pack/year) with active pulmonary disease 7. Participants with ILD with any of the following: 1. Requires supplemental oxygen therapy 2. FVC \