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

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 (\<92% oxygen saturation via pulse oximetry) on room air, or significant smoking history (i.e. \>10 pack/year) with active pulmonary disease
• •7. Participants with ILD with any of the following:
• •1. Requires supplemental oxygen therapy
• •2. FVC \<45% of predicted
• •3. Diffusing capacity of the lung (DLCO) corrected for alveolar volume (AV) or Hemoglobin (Hgb) ≤ 40% of predicted at screening (per Investigator or Sponsor judgement)
• •i. If the participant has a historical FVC value within the last year that exceeds the 45% threshold, discuss with the Medical Monitor should the Screening FVC be \<45% predicted
• •8. Bone marrow insufficiency unrelated to active underlying autoimmune disease with white blood cell count \< 3,000/mm\^3; hemoglobin levels ≤ 9 g/dL; absolute neutrophil count (ANC) ≤ 1500/mm\^3; platelet count ≤ 100,000/mm\^3, and blood transfusion within 60 days prior to LD
• •9. 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
• •10. Active bleeding disorders
• •11. Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes (eg, anti-GBM antibody glomerulonephritis or any condition for additional immunosuppression is indicated); clinically significant conditions that could cause a secondary nephropathy (eg, infections, liver disease, tumors or drugs); or kidney biopsy-confirmed significant renal disease other than disease under study (eg, diabetic nephropathy, hypertensive nephropathy). Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes (eg, Sjögren's syndrome, rheumatoid arthritis) are not excluded
• •12. Pregnancy, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions
• •13. Current infection requiring active systemic anti-infective therapy or recent acute infection requiring systemic therapy within 30 days of planned LD
• •14. History of positive HIV test at screening, Hepatitis B or C positive at screening, active tuberculosis (TB) or latent TB requiring suppressive therapy
• •15. Major surgery within 28 days prior to the first dose of NKX019 or any surgery from which the participant has not recovered or has ongoing complications
• •16. Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Participants 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
• •17. Prior cellular therapy including mesenchymal, CAR-T or CAR-NK cells
• •18. 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
• •1. Moderate-to-severe Pulmonary arterial hypertension (PAH) on right heart catheterization requiring PAH specific treatment. Those participants with mild PAH (as defined by the 2022 ECS/ERS Guidelines, \[Humbert 2023\]) well controlled on therapy can be enrolled
• •2. Gastrointestinal (GI) dysmotility requiring total parenteral nutrition (TPN)
• •3. Renal crisis or Pericardial tamponade within 6 months prior to enrollment
• •4. Current gangrene of a digit
• •1. Evidence of severe chronic proximal muscle involvement of upper or lower extremities, based on Magnetic Resonance Imaging (MRI) defined as:
• •1. ≥15% fibro-fatty replacement in core muscle groups (including gluteus and vastus musculature), and/or
• •2. ≥15% muscle atrophy in these regions Participants will also be excluded if the combined extent of fibro-fatty replacement and muscle atrophy exceeds 30% in aggregate
• •2. MMT-8 of ≤ 80
• •3. Findings of muscular inflammation or myopathy due to another cause, such as inclusion body myositis, cancer-associated myositis (myositis diagnosed within 2 years of cancer), amyloid myopathy, muscular dystrophy, metabolic myopathies, or myositis in the context of significant overlap with another systemic IIM rheumatologic disease (overlap myositis), except with Sjögren's syndrome
• •4. Generalized severe musculoskeletal or neuro-muscular conditions other than IIM
• •5. Immune-mediated necrotizing myopathy
• •1. Alveolar hemorrhage requiring invasive pulmonary ventilation support
• •2. Required dialysis or plasma exchange within 12 weeks prior to screening
• •3. Any other known disease that may interfere with the assessments including eosinophilic GPA (Churg-Strauss), anti-glomerular basement membrane, systemic lupus erythematosus, IgA vasculitis (Henoch Schönlein), rheumatoid vasculitis, or cryoglobulinemic vasculitis