Open-label, Multi-center, Phase I/II Study to Assess Safety, Disease Progression and Cellular Kinetics Following YTB323 Administration in Participants With Non-active Progressive Multiple Sclerosis (PMS)

Key Inclusion Criteria:

1. Male or female participants 18 to 60 years (inclusive) at screening.

2. Signed informed consent must be obtained prior to participation in the study.

3. Able to communicate well with the investigator, to understand and comply with therequirements of the study including:

• Able to undergo lumbar puncture (LP), blood draws, tolerate brain and spinalMRI, and able to participate and tolerate all study procedures at study visits.

4. Diagnosis of SPMS or PPMS according to the 2017 McDonald diagnostic criteria (Thompson et al 2018) as confirmed at screening visit.

5. Less than 15 years (inclusive) from onset of first MS symptoms as determined by theinvestigator during screening.

6. Ambulatory Patients (EDSS 3 to 6.5 inclusive) at screening.

7. Evidence of recent (within 24 months) disease progression of ≥1.00 on the EDSSscale.

8. No relapse in the last 24 months at screening.

9. No Gd-enhancing lesion on brain or spinal cord MRI at screening.

10. Participants must receive or be current on all recommended vaccinations according toinstitutional, local, or global guidelines for immunocompromised patients at least 6weeks prior to lymphodepletion.

Key Exclusion Criteria:

1. Diagnosis of relapsing multiple sclerosis (RMS) or active PMS according to the 2017revision of the McDonald diagnostic criteria (Thompson et al 2018) at screening.

2. History of, or current, clinically significant CNS disease except MS (e.g. stroke,traumatic brain or spinal injury, history or presence of myelopathy, history ofseizures or epilepsy) or neurological disorders which may mimic MS at screening.

3. Evidence of clinically significant cardiovascular (such as but not limited tomyocardial infarction, unstable ischemic heart disease, New York Heart AssociationClass III/IV left ventricular failure, arrhythmia and uncontrolled hypertensionwithin 6 months prior to or during screening).

4. Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or neurological symptoms consistent with PML prior to or during screening.

5. Clinically significant, active, opportunistic, chronic or recurrent infection (including positive for hepatitis B or hepatitis C) confirmed by clinical evidence,imaging, or positive laboratory tests one month prior to leukapheresis.

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

7. Any prior stem cell therapy or organ transplantation or gene therapy.

8. 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 nonsteroidalanti-inflammatory drugs such as ibuprofen (600 mg/day or lower) which areallowed], are not eligible to participate.

9. Not willing or able to have MRI scans as per protocol e.g. due to claustrophobia, orabsolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies,pacemaker, defibrillator).

10. Pregnant or nursing (lactating) women.

11. Past surgical history of splenectomy.

12. Evidence of active or latent tuberculosis (TB) infection by QuantiFERON® TB-Goldassay (or equivalent) performed at Screening by central lab. In case of unclear orindeterminate test results, the Investigator should consult with an infectiousdisease expert to exclude the diagnosis of active or latent TB infection anddocument this in the source data. Participant should be excluded if they have anysigns of active TB observed in available lung imaging (e.g., X-ray or HRCT).

13. Any psychiatric, pulmonary (including, history of or active severe respiratorydisease, including Chronic Obstructive Pulmonary Disease, interstitial lung diseaseor pulmonary fibrosis), renal, hepatic, endocrine, metabolic (e.g. severehypoproteinemia due to nephrotic syndrome), hematological disorders orgastrointestinal disease that, in the investigator's opinion, would compromise thesafety of the participant, interfere with the interpretation of the study results orotherwise preclude participation or protocol adherence of the participant, prior toor during screening.

14. Grade 2 or higher thromboembolic event in the past 4 weeks prior to or duringScreening or evidence of disorders of coagulation or platelet function includingsubjects that require chronic use of anticoagulation or antiplatelet drugs (pleaserefer to the key exclusion criteria no. 8 for the exceptions).