An Open-label, Study to Assess Safety, Efficacy and Cellular Kinetics of YTB323 in Severe, Refractory Systemic Lupus Erythematosus

Inclusion Criteria:

• Signed informed consent

• Adequate renal, hepatic, cardiac, hematological and pulmonary function

• Men and women with SLE, aged ≥18 years and ≤65 years at screening, fulfilling the 2019 European League Against Rheumatism EULAR/ACR classification criteria for SLE.

• Patient must be positive for at least one of the following autoantibodies atscreening: antinuclear antibodies (ANA) at a titer of ≥1:80, or anti dsDNA (abovethe ULN); or anti-Sm (above the ULN)

• Active (severe) disease as defined by SLEDAI-2K ≥ 8 (not including the SLEDAI-2Kdomains of lupus headache, cerebrovascular accident, organic brain syndrome) and atleast one of the following significant SLE related organ involvements:

• Renal

• At least moderate or severe peri/myocarditis

• At least moderate or severe pleuritis or other lung involvement

• Vasculitis

• Failure to respond to two or more standard immunosuppressive therapies (includingone of mycophenolate or cyclophosphamide), unless contraindicated or havingexperienced documented adverse events or intolerance related to suchimmunosuppressive drugs not allowing their further use, in combination withglucocorticoids and failure to respond to at least one biological agent (unlesscontraindicated, the patient deemed ineligible by the Investigator or not availablein a country).

Exclusion Criteria:

• Clinically significant active, opportunistic, chronic or recurrent infectionconfirmed by clinical evidence, imaging, or positive laboratory tests (e.g., bloodcultures, PCR for DNA/RNA, such as COVID-19 etc.) one month prior to or duringscreening. Patients who have had at least one severe infection that requiredprolonged hospitalization in the intensive care setting within 5 years prior toscreening and/or at least one severe infection that required prolongedhospitalization within one year prior to screening.

• Uncontrolled diabetes mellitus, lung diseases or any other illness that are notrelated to SLE that in the opinion of the Investigator would jeopardize the abilityof the patient to tolerate lymphodepletion and CD19 CAR-T cell therapy

• Prior history of malignancy except for localized basal cell or squamous skin cancer.Other malignancies for which the patient is judged to be cured by local surgicaltherapy, such as head and neck cancer, or stage I breast cancer will be consideredon an individual basis

• Any patients requiring medications prohibited by the protocol

• Any psychiatric condition or disability making compliance with treatment or informedconsent impossible

• Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior genetherapy product (e.g. CAR-T cell therapy)

• History of bone marrow/hematopoietic stem cell or solid organ transplantation

• Female participants who are pregnant or breastfeeding, or intending to conceiveduring the course of the study

• Women of childbearing potential, defined as all women physiologically capable ofbecoming pregnant, unless they are using a highly effective method of contraceptionstarting from the time of enrollment to at least 12 months after the YTB323 infusion (or longer if required as per local regulations) and until CAR-T cells are no longerpresent by qPCR on two consecutive tests

• Sexually active males unwilling to use a condom during intercourse from the timeenrollment for at least 12 months after the YTB323 infusion and until CAR-T cellsare no longer present by qPCR on two consecutive tests

• Any acute, severe lupus related flare during screening that needs immediatetreatment and/or makes the immunosuppressive washout impossible; thus, makes thepatient ineligible for CD19 CAR-T therapy as judged by the Investigator, such asacute central nervous system (CNS) lupus (e.g. psychosis, epilepsy) or catastrophicantiphospholipid syndrome

• Significant, likely irreversible organ damage related to SLE, e.g. end stage renaldisease, that in the opinion of the Investigator renders CD19 CAR-T cell therapywould be unlikely to benefit the patient

• B cell aplasia