NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Participants With Immune-Mediated Diseases (Ntrust-2)

Eligibility Criteria

• 1. Age ≥18 and ≤65
• 1. Meets the 2013 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for SSc
• 2. Active disease as defined by mRSS ≥ 15 at screening and one or more of the following within the prior 6 months of screening:
• 1. An increase in mRSS of ≥ 3 units
• 2. Involvement of 1 new body area with ≥ 2 mRSS units
• 3. 2 new body areas with ≥ 1 mRSS unit
• 4. Evidence of Interstitial Lung Disease (ILD) on High-resolution computed tomography (HRCT) and progressive ILD meeting at least two of the following 3 criteria:
• * Worsening respiratory symptoms
• * Evidence of progression on HRCT, or
• * Evidence of absolute decline in FVC ≥ 5% (Raghu et al 2022)
• 3. Presence of anti-nuclear antibody ≥ 2 x upper limit of normal (ULN)
• 4. 10 years or less since the first non-Raynaud's sign or symptom
• 5. Inadequate response or intolerance to at least one treatment, including cyclophosphamide, methotrexate, MMF/mycophenolic acid, nintedanib, rituximab, or tocilizumab
• 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 \<136/150
• 4. Creatinine kinase or aldolase ≥ 1.5 x ULN (except for DM) and Clinician Global Assessment ≥ 2 cm with at least one of the following:
• 1. Evidence on magnetic resonance imaging (MRI), electromyography (EMG), Muscle Biopsy of active myositis within last 6 months
• 2. Global extramuscular activity score ≥ 2 cm per Clinician Visual Analog Scale (VAS) (0-10 cm)
• 5. Refractory disease defined as ≥ 6 months failure (or intolerance) to at least two immunosuppressive therapies (including glucocorticoids)
• 1. Meets the 2022 ACR/EULAR classification criteria for Granulomatosis with Polyangiitis (GPA) (Robson 2022) or Microscopic Polyangiitis (MPA) (Suppiah 2022)
• 2. Relapsed or refractory AAV despite repeated treatment with immunosuppressive agents or requiring prolonged and/or repeated courses of unacceptable doses of glucocorticoids to maintain disease control
• 3. Positive test for anti-proteinase-3 (PR3-ANCA) or anti-myeloperoxidase (MPO-ANCA) at screening
• 4. Have at least one "major" item, or at least 3 other items, or at least 2 renal items on the BVAS version 3
• 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 (\<92% oxygen saturation via pulse oximetry) on room air, or significant smoking history (i.e. \>10 pack/year)
• 7. White blood cell count \< 3,000/mm\^3; hemoglobin levels ≤ 9 g/dL; absolute neutrophil count (ANC) ≤ 2,000/mm\^3; platelet count ≤ 100,000/mm\^3, and blood transfusion within 60 days prior to LD
• 8. Major cardiac disease, abnormalities, or interventions as defined by, but not limited to:
• 1. Uncontrolled angina or unstable life-threatening arrhythmias
• 2. History of myocardial infarction within 12 weeks prior to the first dose of NKX019
• 3. Any prior coronary artery bypass graft surgery
• 4. ≥ Class III New York Heart Association (NYHA) congestive heart failure (CHF), significantly decreased ejection fraction (EF ≤ 40%), or severe cardiac insufficiency
• 5. Prolongation of the QT interval corrected for heart rate (QTc) (Fridericia) interval of \> 480 msec
• 6. Peripheral artery bypass graft surgery, pulmonary embolism, or other ≥ Grade 2 thrombotic or embolic events within 12 weeks prior to the first dose of NKX019
• 9. Active bleeding disorders
• 10. Pregnancy, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions
• 11. Current infection requiring active systemic anti-infective therapy or recent acute infection requiring systemic therapy within 30 days of planned LD
• 12. History of positive HIV antibody or test positive at screening, Hepatitis B or C positive at screening, active tuberculosis (TB) or latent TB requiring suppressive therapy
• 13. Major surgery within 28 days prior to the first dose of NKX019
• 14. Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects with cervical dysplasia that is cervical intraepithelial neoplasia but have been treated with conization or loop electrosurgical excision procedure and have had a normal repeat Papanicolaou test are allowed
• 15. Prior cellular therapy
• 16. Central nervous system (CNS) comorbidity or any autoimmune disease with CNS involvement within 90 days prior to the first dose of NKX019 as well as evidence of CNS related autoimmune manifestations within 1 year prior to screening