Inclusion Criteria:
1. Signed written informed consent
a. Participants must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written ICF in accordance with regulatory, local, and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
2. Age 18 to 60 inclusive
3. Diagnosis of anti-AQP4 antibody positive NMOSD by 2015 Wingerchuk IPND criteria
4. No relapses within last 12 months
5. Stable ravulizumab or satralizumab dosing for at least 6 months
6. Up to date on meningococcal vaccines and enrolled in any required REMS program
7. EDSS score of 6.5 or less
8. At least one eye best visual acuity 20/200 or better
9. Peripheral B cell count by flow cytometry of \>5%
10. Positive anti-AQP4 antibody test on cell based assay at screening
11. Patient has adequate vascular access for leukapheresis
12. ALT and AST \<1.5x upper limit of normal
Exclusion Criteria:
1. History of active meningococcal disease
2. Presence of active, clinically significant concomitant CNS pathology, other than NMOSD, that may confound the ability to interpret study results, including but not limited to, seizure disorder, traumatic brain injuries, delirium, Parkinson's disease, psychosis, Neuro-Behcet's disease, Guillain-Barré syndrome, metabolic or infectious cause of myelopathy, genetically-inherited progressive CNS disorder, ischemic cerebrovascular disorders, including, but not limited to, transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage; CNS sarcoidosis; history of anti- myelin oligodendrocyte glycoprotein antibody-associated disorder or a diagnosis of progressive multifocal leukoencephalopathy (PML) or history of PML; or of infectious or autoimmune encephalitis or meningitis under prior DMT.
3. Any significant medical condition, laboratory test abnormality or psychiatric Active infection requiring treatment
4. Hypersensitivity or allergy to fludarabine, cyclophosphamide, excipients of CC- 97540, ravulizumab, tocilizumab or satralizumab.
5. condition that would pose a risk the participant's safety from participating in the study.
6. Active autoimmune condition other than NMOSD that requires immunotherapy
7. History of any one of the following cardiovascular conditions within the 6 months prior to screening: Class III or IV heart failure as defined by the New York Heart Association, myocardial infarction, unstable angina, angioplasty or stenting, or other clinically significant cardiac disease.
8. Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the investigator; or unwillingness or inability to follow the procedures required in the protocol.
9. Prior history of malignancies or lymphoproliferative disease, unless the participant has been free of the disease for ≥ 2 years. The following are allowed:
1. Basal or squamous cell carcinoma of the skin.
2. Carcinoma in situ of the cervix or breast.
3. Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis clinical staging system) or prostate cancer that is curative.
4. Other completely resected Stage I solid tumor with low risk for recurrence.
10. Active syphilis, any human immunodeficiency virus, human lymphocytic T-cell virus type 1 and/or type 2, or active or latent tuberculosis infection.
11. Known chronic, active hepatitis B or C virus (HBV/HCV) infection or untreated prior HCV infection (positive HCV IgG result). Participants who had HCV but have received an antiviral treatment and show no detectable HCV viral RNA for 6 months are eligible. Participants with no active hepatitis B infection (eg, hepatitis B surface antigen \[HBsAg\] negative, anti-hepatitis B core antibody \[HBcAb\]positive) who are under adequate prophylaxis against HBV re-activation may be eligible; such participants must be screened using real-time polymerase chain reaction (PCR) measurement of HBV DNA levels or viral load; those who are PCR positive will be excluded. Participants who have received HBV vaccine and are hepatitis B surface antibody (HBsAb) positive, HBcAb negative, and HBsAg negative are eligible for study entry.
12. Uncontrolled or active systemic fungal, bacterial, viral, or other infection despite appropriate anti-infective treatment at the time of leukapheresis, or within 72hours before LD chemotherapy, or 5 days before CC-97540 (BMS-986353) administration.
13. Use of any live vaccines against infectious disease within 6 weeks prior to the start of lymphodepleting therapy, during CC-97540 (BMS-986353) infusion, and until immune recovery.
14. Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to leukapheresis or initiation of LD chemotherapy. Acute symptoms must have resolved and based on investigator assessment there are no sequelae that would place the participant at a higher risk of receiving study treatment.
15. Any condition that confounds the ability to interpret data from the study.
16. Participants who are not up to date on all recommended vaccinations per local/national Health Authority (eg, Centers for Disease Control and Prevention) or institutional guidelines for immunocompromised individuals. For vaccines requiring more than one dose, the full series (eg, both doses of a 2-dose series) should be completed prior to leukapheresis or initiation of LD chemotherapy when feasible and when a delay in leukapheresis or initiation of LD chemotherapy would not put the study participant at risk.
17. An answer of "yes" to items 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening (for the past 6-months interval).
18. Pregnancy or nursing women
19. Prior CAR T therapy
20. Stem cell transplantation within one year of screening
21. Positive Quantiferon test
22. Prisoners or participants who are involuntarily incarcerated.
23. Contraindications against MRI imaging, including non-MRI compatible metal implants, cardiac pacemakers, cochlear implants, ventricular shunt systems; metal particles in the body that pose a risk to the participant, including large tattoos in regions affected by cranial/neck MRI scanning, and severe claustrophobia. Contraindications against gadolinium-based contrast agents, including known hypersensitivity to gadolinium-based contrast agents.
