The goal of this clinical trial is to treat male and female participants with two types of Multiple Sclerosis (MS) called primary progressive or secondary progressive MS.

The main questions the trial aims to answer are the following:

• Is TRX319 safe when administered to patients with progressive forms of MS?
• At what dose does TRX319 work the best to treat participants with primary and or secondary progressive MS?
• Is pre-conditioning (with Bendamustine) needed to allow TRX319 to better treat participants with primary and/or secondary progressive MS?

Participants will be asked to be on study for up 1 year and may receive up to 3 total administrations of TRX319. While on study, participants will have blood tests and other assessments (MRI scans and lumbar punctures) done to understand the safety of TRX319 and how it may benefit their multiple sclerosis.

Inclusion Criteria:

1. Clinical diagnosis of MS with evidence of PPMS or SPMS according to 2025 McDonald criteria.
2. Expanded Disability Status Scale (EDSS) range ≥ 2.5 to ≤ 6.5.
3. Evidence of clinical disability progression within 2 years prior to enrollment.
4. Documented presence of CSF-restricted OCBs and/or elevated IgG index and/or κ free light chain.
5. Males and females ≥ 18 and ≤ 65 years of age at time of consent.
6. Evidence of adequate organ function
7. Women of child bearing potential have a negative pregnancy test at screening.
8. Contraceptive use by all participants while on study.
9. Participants must be able to understand, consent, and be willing and able to complete all specified procedures and visits.
10. Positive varicella zoster virus titer. Participants who test seronegative for varicella zoster virus IgG antibodies need to complete vaccination ≥ 4 weeks prior to TRX319 infusion.
11. Participants must be willing to refrain from donating blood for 1 year after TRX319 infusion.

Exclusion Criteria:

1. MS clinical stability on disease modifying therapy.
2. Clinical relapse of MS in the 1 year prior to study entry.
3. Diseases other than MS to explain the first demyelinating event, including aquaporin 4 IgG or myelin oligodendrocyte glycoprotein-IgG seropositivity.
4. Prior treatment with CAR-T or gene therapy product directed at any target.
5. Prior treatment with mitoxantrone, cladribine (or other chemotherapies), or alemtuzumab within 2 years prior to TRX319 dose.
6. Prior treatment with CD20-depleting antibodies within 3 months and prior treatment with Bruton's tyrosine kinase inhibitor (BTKi) and sphingosine 1 phosphate (S1P) modulators within 1 month of TRX319 dose.
7. Plan to or have received live, attenuated vaccines less than 4 weeks (28 days) prior to TRX319 infusion, and other vaccines less than 2 weeks (14 days) prior to TRX319 infusion.
8. Serologic status reflecting active hepatitis B or C infection.
9. Positive serology for human immunodeficiency virus (HIV).
10. History of progressive multifocal leukoencephalopathy.
11. Untreated active, or active with documented completed treatment but without a negative chest X-ray that shows no evidence of active tuberculosis, or latent tuberculosis.
12. Primary immunodeficiency as defined by a known genetic disorder.
13. History of splenectomy.
14. Impaired cardiac function or clinically significant cardiac disease.
15. Previous or concurrent malignancy.
16. Prior organ transplant, or allogeneic hematopoietic stem cell transplantation or recipient of peripheral blood products < 3 years prior to TRX319 infusion.
17. Major surgery within 4 weeks prior or planned within 4 weeks after TRX319 administration.
18. History of any other neurologic disorder or medical condition the Investigator considers would increase the risk for the participant, including seizure disorders.
19. Life-threatening allergies, hypersensitivity, or documented intolerance to TRX319 drug product excipients.
20. Subjects that are pregnant, breast feeding or aim to become pregnant during the study period (Subjects must agree to use a highly effective method of contraception).
21. Serious and/or uncontrolled medical condition that, in the Investigator's judgment, would cause unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol.