Inclusion Criteria:
1. Age ≥18 and ≤70. 2. For participants taking corticosteroids, the prednisone (or equivalent) dose must be
≤40 mg/day at 6 weeks prior to Screening and stable for ≥ 14 days before start of
Screening. 3. For subjects on immunosuppressives or immunomodulators (other than corticosteroids),
all doses must be stable for ≥ 4 weeks prior to Screening.SSc:
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:
1. 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:
- - An increase in mRSS of ≥ 3 units.
- - Involvement of 1 new body area with ≥ 2 mRSS units.
- - 2 new body areas with ≥ 1 mRSS unit.
2. 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:
- - 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.IIM:
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 and Clinician Global Assessment ≥ 2 cm
with at least one of the following:
1. Evidence on magnetic resonance imaging (MRI) of active myositis within the last
6 months. 2. Electromyography (EMG) with active myositis within the last 6 months. 3. Muscle Biopsy of active myositis within last 6 months. 5. Refractory disease defined as ≥ 6 months failure (or intolerance) to at least 2
immunosuppressive therapies (including glucocorticoids)
AAV:
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.
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. Patients 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) ≤ 40%
of predicted at screening (per Investigator or Sponsor judgement)
8. 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. 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. 16. 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. 17. Prior cellular therapy. 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. 19. Immunosuppressive / immunomodulatory therapies for disease under study within 14
days or 5 half-lives of the drug (whichever is shorter), prior to LD, with notable
exceptions a. For those participants on B-cell-depleting or B-cell-modulating drugs
(eg, rituximab, belimumab), the participants must have received first dose ≥6 months
prior to LD.SSc
Exclusion Criteria:
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. Anti-centromere Ab positive. 4. Renal crisis or Pericardial tamponade within 6 months prior to enrollment. 5. Current gangrene of a digit.IIM
Exclusion Criteria:
1. Severe proximal muscle atrophy of upper or lower extremity on Magnetic Resonance
Imaging (MRI) or clinical exam. 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.AAV
Exclusion Criteria:
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
