An Open-label Study to Assess the Safety, Efficacy, and Cellular Kinetics of YTB323 in Relapsing Multiple Sclerosis

Inclusion Criteria:

• Signed informed consent, and able to communicate well with the investigator andcomply with the requirements of the study

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

• Male or female participants, ≥18 years to ≤60 years at screening, with diagnosis ofRMS according to the 2017 McDonald diagnostic criteria Evidence of recent (i.e.within 1 year) breakthrough disease activity while at least 6 months on a highlyefficacious therapy (any of the following): rituximab (Rituxan®), ocrelizumab (Ocrevus®), natalizumab (Tysabri®), ofatumumab (Kesimpta®), ublituximab (Briumvi®)or evidence of breakthrough disease activity within 2 years after the latestalemtuzumab infusion (Lemtrada®).

Evidence of breakthrough disease activity is defined as one or more of the following:

1. Confirmed Clinical MS relapse

2. Persistent radiological activity defined by one of the following:

• ≥2 T1 gadolinium-enhancing lesions on a single MRI scan

• ≥1 T1 gadolinium-enhancing lesions on two or more separate MRI scans

• ≥2 new T2 lesions compared to a previous scan within a period ≤1 year

• Ambulatory patients (EDSS of 3 to 6 points, inclusive assessed outside ofrelapse)

• Disease duration less than 15 years

• Participants must receive or be current on all recommended vaccinationsaccording to institutional, local, or global guidelines forimmunocompromised patients at least 6-weeks prior to lymphodepletion

Exclusion Criteria:

• Diagnosis of primary progressive multiple sclerosis (PPMS) according to the 2017revision of the McDonald diagnostic criteria at screening

• History of or current clinically significant CNS disease (e.g. stroke, traumaticbrain or spinal injury, history or presence of myelopathy) or neurological disorderswhich may mimic MS or ICANS at screening

• Evidence of clinically significant cardiovascular (such as but not limited tomyocardial infarction, unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolledhypertension within 6 months prior to screening), neurological disorders other thanMS (including seizure disorders even when well controlled), psychiatric, pulmonary (including, history of or active severe respiratory disease, including ChronicObstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis),renal, hepatic, endocrine, metabolic (e.g. severe hypoproteinemia due to nephroticsyndrome), hematological disorders or gastrointestinal disease that, in theinvestigator's opinion, would compromise the safety of the participant, interferewith the interpretation of the study results or otherwise preclude participation orprotocol adherence of the participant, prior to screening

• Have donated blood or experienced a loss of blood > 400 mL within 3 months priorscreening, or longer if required by local regulations

• Any prior stem cell therapy or organ transplantation or gene therapy

• Any contraindications to LP, including but not limited to:

• Known or suspected structural abnormality of the lumbar spine that, in theopinion of the Investigator, may interfere with the performance of the LP, orincrease the risk of the procedure for the participant

• Presence of risk for increased or uncontrolled bleeding including, but notlimited to, vascular abnormalities or neoplasms at or near the LP site,disorders of the coagulation cascade, platelet function, or platelet count

• Participants on anticoagulants (e.g., warfarin) or antiplatelets [except forlow-dose aspirin (100 mg/day or lower) and low-dose ibuprofen (600 mg/day orlower) which are allowable], are not eligible to participate

• Participants not willing or able to take MRI scans as per protocol. Unable toundergo MRI due to for example claustrophobia, or presents absolutecontraindications to MRI (e.g., metallic implants, metallic foreign bodies,pacemaker, defibrillator)

Other protocol-defined inclusion/exclusion criteria may apply