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 at
screening: antinuclear antibodies (ANA) at a titer of ≥1:80, or anti dsDNA (above
the ULN); or anti-Sm (above the ULN)

- Active (severe) disease as defined by SLEDAI-2K ≥ 8 (not including the SLEDAI-2K
domains of lupus headache, cerebrovascular accident, organic brain syndrome) and at
least 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 (including
one of mycophenolate or cyclophosphamide), unless contraindicated or having
experienced documented adverse events or intolerance related to such
immunosuppressive drugs not allowing their further use, in combination with
glucocorticoids and failure to respond to at least one biological agent (unless
contraindicated, the patient deemed ineligible by the Investigator or not available
in a country).

Exclusion Criteria:

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

- Uncontrolled diabetes mellitus, lung diseases or any other illness that are not
related to SLE that in the opinion of the Investigator would jeopardize the ability
of 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 surgical
therapy, such as head and neck cancer, or stage I breast cancer will be considered
on an individual basis

- Any patients requiring medications prohibited by the protocol

- Any psychiatric condition or disability making compliance with treatment or informed
consent impossible

- Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene
therapy 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 conceive
during the course of the study

- Women of childbearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using a highly effective method of contraception
starting 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 longer
present by qPCR on two consecutive tests

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

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

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

- B cell aplasia