A Phase 1/2 Study of NKX019 in Subjects With Autoimmune Disease (Ntrust-1)

Exclusion Criteria30

• eGFR \< 45 ml/min/1.73 m\^2
• Currently requiring renal dialysis or expected to require dialysis during the study period
• Previous solid organ or hematopoietic cell transplant or planned transplant within study treatment period
• Congenital or acquired immunodeficiency resulting in severe infection or those receiving chronic immunoglobulin replacement therapy
• Liver disease or dysfunction, including cirrhosis and/or aspartate aminotransferase, alanine aminotransferase, or bilirubin ≥ 3 times the upper limit of normal
• 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
• White blood cell count \< 3,000/mm\^3; hemoglobin levels \< 9 gm/dL absolute neutrophil count \< 2,000/mm\^3; platelet count \< 100,000/mm\^3
• Major cardiac disease, abnormalities, or interventions as defined by, but not limited to:
• Uncontrolled angina or unstable life-threatening arrhythmias
• History of myocardial infarction within 12 weeks prior to the first dose of NKX019
• Any prior coronary artery bypass graft surgery
• ≥ Class III New York Heart Association (NYHA) congestive heart failure (CHF), significantly decreased ejection fraction (EF ≤ 40%), or severe cardiac insufficiency.
• Prolongation of the QT interval corrected for heart rate (QTc) (Fridericia) interval of \> 480 msec
• 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
• Uncontrolled hypertension (systolic blood pressure \> 160mmHg and diastolic \> 90mmHg) despite therapy
• Active bleeding disorders
• Any overlapping autoimmune condition for which the condition itself or the treatment of that condition may affect the study assessments or outcomes; clinically significant conditions that could cause a secondary nephropathy; or kidney biopsy-confirmed significant renal disease other than disease under study
• Pregnancy, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions
• Current infection requiring active systemic anti-infective therapy or recent acute infection requiring systemic therapy within 30 days of planned LD
• 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
• Major surgery within 28 days prior to the first dose of NKX019
• 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
• Prior cellular therapy
• 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 active CNS lupus within 1 year prior to screening
• Any other acute or chronic medical or psychiatric condition, or known laboratory abnormality that, in the Investigator's opinion, is expected to interfere or impact study participation
• Disease-modifying therapies for disease under study or investigational agents within 14 days or 5 half-lives of the drug (whichever is shorter), prior to LD.
• a. For those subjects on B-cell-depleting or -modulating drugs (ie, rituximab, belimumab), the subject must have received first dose ≥ 6 months prior to LD
• Currently taking or known need for any of the medications prohibited in the study protocol
• Known hypersensitivity or contraindications to the study treatment including LD; or other components such as human serum albumin or dimethyl sulfoxide
• \. Known clinically active antiphospholipid antibody syndrome (APS); or high-risk profile