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

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 ofScreening

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 ofAssociations for Rheumatology (EULAR) classification criteria for SSc

2. Meet criteria a and/or b:

3. Severe skin involvement defined as mRSS ≥ 30 or active skin disease defined asmRSS ≥ 15 at screening and one or more of the following within the prior 6months 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 ILDon High-resolution computed tomography (HRCT) and FVC < 70% of predicted orDLCO (hemoglobin or alveolar volume corrected) < 70% of predicted or ILD onHRCT and progressive ILD meeting at least 2 of the following 3 criteria withinthe 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, includingcyclophosphamide, methotrexate, MMF/mycophenolic acid, nintedanib, rituximab, ortocilizumab

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 cmwith at least one of the following:

5. Evidence on magnetic resonance imaging (MRI) of active myositis within the last 6 months

6. Electromyography (EMG) with active myositis within the last 6 months

7. Muscle Biopsy of active myositis within last 6 months

8. Refractory disease defined as ≥ 6 months failure (or intolerance) to at least 2immunosuppressive therapies (including glucocorticoids)

AAV:

1. Meets the 2022 ACR/EULAR classification criteria for Granulomatosis withPolyangiitis (GPA) (Robson 2022) or Microscopic Polyangiitis (MPA) (Suppiah 2022)

2. Relapsed or refractory AAV despite repeated treatment with immunosuppressive agentsor requiring prolonged and/or repeated courses of unacceptable doses ofglucocorticoids to maintain disease control

3. Positive test for anti-proteinase-3 (PR3-ANCA) or anti-myeloperoxidase (MPO-ANCA) atscreening

4. Have at least one "major" item, or at least 3 other items, or at least 2 renal itemson 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 studyperiod

3. Previous solid organ or hematopoietic cell transplant or planned transplant withinstudy treatment period

4. Congenital or acquired immunodeficiency resulting in severe infection or thosereceiving chronic immunoglobulin replacement therapy

5. Liver disease or dysfunction, including cirrhosis and/or bilirubin ≥ 3 times theupper limit of normal

6. Pulmonary comorbidity including chronic obstructive pulmonary disease or asthmarequiring daily oral steroids, resting hypoxemia (<92% oxygen saturation via pulseoximetry) on room air, or significant smoking history (i.e. >10 pack/year) withactive pulmonary disease

7. Patients with ILD with any of the following:

8. Requires supplemental oxygen therapy

9. FVC <=45% of predicted

10. Diffusing capacity of the lung (DLCO) corrected for alveolar volume (AV) ≤ 40%of predicted at screening (per Investigator or Sponsor judgement)

11. White blood cell count < 3,000/mm^3; hemoglobin levels ≤ 9 g/dL; absolute neutrophilcount (ANC) ≤ 2,000/mm^3; platelet count ≤ 100,000/mm^3, and blood transfusionwithin 60 days prior to LD

12. Major cardiac disease, abnormalities, or interventions as defined by, but notlimited to:

13. Uncontrolled angina or unstable life-threatening arrhythmias

14. History of myocardial infarction within 12 weeks prior to the first dose ofNKX019

15. Any prior coronary artery bypass graft surgery

16. ≥ Class III New York Heart Association (NYHA) congestive heart failure (CHF),significantly decreased ejection fraction (EF ≤ 40%), or severe cardiacinsufficiency

17. Prolongation of the QT interval corrected for heart rate (QTc) (Fridericia)interval of > 480 msec

18. Peripheral artery bypass graft surgery, pulmonary embolism, or other ≥ Grade 2thrombotic or embolic events within 12 weeks prior to the first dose of NKX019

19. Active bleeding disorders

20. Any overlapping autoimmune condition for which the condition or the treatment of thecondition may affect the study assessments or outcomes (eg, anti-GBM antibodyglomerulonephritis 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 significantrenal disease other than disease under study (eg, diabetic nephropathy, hypertensivenephropathy). Overlapping conditions for which the condition or treatment is notexpected to affect assessments or outcomes (eg, Sjögren's syndrome, rheumatoidarthritis) are not excluded

21. Pregnancy, breast feeding or, if of childbearing potential, not using adequatecontraceptive precautions

22. Current infection requiring active systemic anti-infective therapy or recent acuteinfection requiring systemic therapy within 30 days of planned LD

23. History of positive HIV test at screening, Hepatitis B or C positive at screening,active tuberculosis (TB) or latent TB requiring suppressive therapy

24. Major surgery within 28 days prior to the first dose of NKX019

25. Malignancy within 5 years of screening, with the exception of basal and squamouscell carcinomas treated by complete excision. Subjects with cervical dysplasia thatis cervical intraepithelial neoplasia but have been treated with conization or loopelectrosurgical excision procedure and have had a normal repeat Papanicolaou testare allowed

26. Prior cellular therapy

27. Central nervous system (CNS) comorbidity or any autoimmune disease with CNSinvolvement within 90 days prior to the first dose of NKX019 as well as evidence ofCNS related autoimmune manifestations within 1 year prior to screening

28. Immunosuppressive / immunomodulatory therapies for disease under study within 14days or 5 half-lives of the drug (whichever is shorter), prior to LD, with notableexceptions a. For those participants on B-cell-depleting or B-cell-modulating drugs (eg, rituximab, belimumab), the participants must have received first dose ≥6 monthsprior to LD

SSc Exclusion Criteria:

1. Moderate-to-severe Pulmonary arterial hypertension (PAH) on right heartcatheterization requiring PAH specific treatment. Those participants with mild PAH (as defined by the 2022 ECS/ERS Guidelines, [Humbert 2023]) well controlled ontherapy 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 ResonanceImaging (MRI) or clinical exam

2. MMT-8 of ≤ 80

3. Findings of muscular inflammation or myopathy due to another cause, such asinclusion body myositis, cancer-associated myositis (myositis diagnosed within 2years of cancer), amyloid myopathy, muscular dystrophy, metabolic myopathies, ormyositis in the context of significant overlap with another systemic IIMrheumatologic 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 includingeosinophilic GPA (Churg-Strauss), anti-glomerular basement membrane, systemic lupuserythematosus, IgA vasculitis (Henoch Schönlein), rheumatoid vasculitis, orcryoglobulinemic vasculitis