A Study of NKX019, a CD19 CAR NK Cell Therapy, in Subjects With Systemic Lupus Erythematosus

Inclusion Criteria:

• Age: 18-65 years old at the time of informed consent

• Signed informed consent form, able to adhere to the study visit schedule, and complywith other requirements of the study as specified in the protocol

• Score of 8 or more points on the Hybrid-SLEDAI with at least 6 points from clinicalitems and at least one BILAG A or 2 B

• If SLE and LN: Active nephritis Class III or IV with or without Class V using the 2018 International Society of Nephrology and Renal Pathology Society (ISN/RPS)criteria as evidenced on kidney biopsy during screening or within 12 months beforestudy enrollment. Per NIH indices, subjects must have at least activity score ≥ 2and no more than moderate chronicity index. Subjects must have urinaryprotein:creatinine ratio (UPCR) ≥ 1.5 g/g or proteinuria ≥ 1.5 g/day, however,subjects must have ≤7g/ day of proteinuria.

• For patients with biopsies older than 6 months we will include an adjudicationcommittee to review clinical data and decide on appropriateness of including thepatient (see section 7.3). Additionally, all patients with active LN maximallytolerated doses of renin angiotensin aldosterone system (RAAS) blockade agents,except for patients with contraindications or intolerance to RAAS.

• Women of childbearing potential must have a negative serum pregnancy test atscreening and agree to complete abstinence from intercourse from 2 weeks prior toadministration of the first dose of study agent until 1 year after the last dose ofstudy agents OR consistent and correct use of acceptable birth control (e.g.levonorgestrel implants, ethinyl estradiol/etonogestrel vaginal ring; injectableprogesterone, intrauterine device [IUD] with failure rate < 1% per year, oralcontraceptives, double barrier method, transdermal contraceptive patch) OR malepartner sterilization with documentation of azoospermia prior to subject's entryinto the study.

• Male patients must agree to always use a latex or other synthetic condom during anysexual activity with women of childbearing potential. Male participants must agreeto continue to use a condom during the intervention period and for at least 1 yearfollowing last treatment with investigational product. Female partners of maleparticipants should be advised to use a highly effective method of contraceptionduring treatment period and at least 12 months following treatment.

• One of the following: positive antinuclear antibodies (ANA) ≥ 1:80 at screening ORpositive anti-dsDNA OR positive anti-Smith (anti-Sm) as determined by the locallaboratory.

• Refractory SLE defined as having received ≥ 2 prior therapies for SLE (oneimmunosuppressant and one biologic/advanced therapy) and had an inadequate responseto therapy despite being on a therapeutic dose for ≥ 90 days.

• For subjects taking chronic corticosteroids for SLE/LN management, the dose must bestable for ≥ 14 days before screening and cannot exceed 20 mg prednisone/day orequivalent at LD start with planned taper to ≤ 5 mg prednisone by the time of LDstart with planned taper to ≤ 5 mg prednisone by the time of the first NKX019infusion.

• Negative SARS-CoV-2 test.

Exclusion Criteria:

• Estimated glomerular filtration rate (eGFR) as calculated by the Chronic KidneyDisease Epidemiology Collaboration (CKD-EPI) equation of < 45 mL/min/1.73 m2 atscreening.

• Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expectedto require dialysis during the study period

• More than 7 g/ day of proteinuria.

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

• Congenital or acquired immunodeficiency resulting in severe infection or thosereceiving 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 asthmarequiring daily oral steroids or resting hypoxemia (< 90% oxygen saturation viapulse oximetry) on room air.

• >10 pack years of smoking.

• Exacerbation of COPD/asthma requiring systemic steroid therapy within the past 6months.

• Bone marrow insufficiency unrelated to active SLE (according to Investigatorjudgment) with white blood cell count < 1,500/mm3; hemoglobin levels < 9 g/dLabsolute neutrophil count (ANC) < 1,000/mm3; absolute lymphocyte count </=500 mm3,or platelet count ≤ 75,000/mm3

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

1. Uncontrolled angina or unstable life-threatening arrhythmias

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

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 ≤ 45%), or severe cardiacinsufficiency

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 2thrombotic or embolic events within 12 weeks prior to the first dose of NKX019

7. Active CNS SLE . 13. Active bleeding disorders.

• Any overlapping autoimmune condition for which the condition or the treatment of thecondition may affect the study assessments or outcomes (e.g. scleroderma withsignificant pulmonary hypertension; any condition for which additionalimmunosuppression is indicated). Overlapping conditions for which the condition ortreatment is not expected to affect assessments or outcomes (e.g. Sjögren'ssyndrome) are not excluded.

• Pregnancy, breast feeding or, if of childbearing potential, not using adequatecontraceptive precautions or planned oocyte and sperm donation.

• Current/active infection, and any infection requiring systemic antimicrobial therapywithin the past 30 days of planned LD.

• History of positive HIV antibody or test positive at screening. Hepatitis B or Cpositive at screening, active tuberculosis (TB) or latent TB requiring suppressivetherapy.

• Major surgery within 28 days prior to the first dose of NKX019 or any surgery fromwhich the subject has not recovered or has ongoing complications.

• 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.

• Prior cellular therapy, including mesenchymal, CAR-T or CAR-NK cells.

• Prior cerebrovascular ischemia/hemorrhage including transient ischemic attack within 90 days prior to the first dose of NKX019.

• Any other acute or chronic medical or psychiatric condition, or known laboratoryabnormality that, in the Investigator's opinion is expected to:

1. Increase the risk associated with study participation or NKX019 administration

2. Interfere with the informed consent process, compliance with the studyrequirements, or interpretation of the study results

3. Make the subject inappropriate for entry into this study

4. Require concomitant use of any medication that is listed as prohibited while onstudy

5. In the opinion of the Investigator, clinically significant drug or alcoholabuse within 2 years prior to screening

• Prior therapies for SLE, including investigational agents, within 4 weeks or 5half-lives of the drug (whichever is longer) prior to lymphodepletion.

• Currently taking or known need for any of the medications prohibited in the studyprotocol.

• Known hypersensitivity or contraindications to the study treatment including LD; orother components such as human serum albumin or dimethyl sulfoxide.