Phase 1 Study to Evaluate the Safety of ATA188 in Subjects With Progressive and Relapsing-Remitting Multiple Sclerosis

This is a multicenter, open-label, two-population, single-arm study with a sequential,
interpatient dose-escalation and dose expansion in adult subjects with progressive forms of
MS (Population A) and in adult subjects with RRMS (Population B).

This study will evaluate the safety of ATA188 administered by intravenous (IV) infusion.
ATA188 will be selected for each subject based on matching at least 2 human leukocyte antigen
(HLA) alleles shared between ATA188 and the subject including at least 1 HLA-restricting
allele.

Beginning 28 days after the last infusion, subjects will enter a follow-up period with 12
monthly (every 28 ±5 days) visits and an end-of-study (EOS) visit at 24 months. Together,
subjects will be observed for 2 years after the first dose of ATA188.

Inclusion Criteria:

A subject will be considered eligible to participate in this study if all of the following
are satisfied:

1. History of MS, with progressive forms of MS or RRMS as defined by the 2010 Revised
McDonald criteria for the diagnosis of MS.

a. Subjects with RRMS must have failed a health authority approved treatment

2. Positive EBV serology

3. Males and females of the following ages:

1. 18 to 65 years of age for subjects with progressive forms of MS

2. 18 to 45 years of age for subjects with RRMS

4. EDSS scores as follows:

1. 3.0 to 7.0 for subjects with progressive forms of MS. Subjects with EDSS scores
of 6.5 to 7.0 must retain measurable upper limb function as assessed by the
9-Hole Peg Test.

2. 2.0 to 5.5 for subjects with RRMS

5. Willing and able to provide written informed consent

Exclusion Criteria:

A subject will not be eligible to participate in the study if any of the following criteria
are met:

1. Active clinical relapse between providing informed consent and enrollment (ie, date of
the first dose of ATA188)

2. Concurrent serious uncontrolled or unresolved medical condition, such as infection,
limiting protocol compliance or exposing the subject to unacceptable risk

3. Positive serology and/or nucleic acid testing (NAT) for human immunodeficiency virus
(HIV)

4. Serology and/or NAT indicating active hepatitis B virus (HBV) infection or carrier
status for HBV (Note: A positive serology for HBV indicating a previous but cleared
infection with HBV is not an exclusion criterion)

5. Serology and/or NAT indicating active hepatitis C virus (HCV) infection

6. Positive serology for syphilis or human T cell lymphotrophic virus I/II (HTLV)

7. Significant non-malignant disease (eg, severe cardiac or respiratory dysfunction)

8. Uncontrolled psychosis, uncontrolled depression or suicide risk, substance dependence,
or any other psychiatric condition that may compromise the ability to participate in
this trial

9. Clinically significant abnormalities of full blood count, renal function, or hepatic
function:

- Elevated liver function tests, including total bilirubin (TBILI) > 1.5× the upper
limit of normal (ULN; unless subject has documented Gilbert's disease), aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0×ULN

- Subjects with both a creatinine > 1.5×ULN and an estimated creatinine clearance
of < 60 mL/min (using the Cockcroft-Gault equation)

- Hemoglobin < 10 g/dL; platelet < 100×109/L; absolute neutrophil count < 1.5×109/L

10. Any contraindication to MRI and/or Gd, eg, any object that is reactive to strong
static magnetic, pulsed-gradient fields including any metallic fragments or foreign
body (eg, aneurysm clip(s), pacemakers, electronic implants, shunts)

11. Prior cancers, except successfully treated non-melanoma skin cancer or carcinoma in
situ of the cervix, with a ≥ 5% chance of recurrence within 12 months of providing
informed consent

12. Prior MS therapy (in order of increasing washout period prior to the first dose of
investigational product [ie, Cycle 1 Day 1]) as follows:

1. 2 weeks: corticosteroids

2. 6 half-lives or 30 days (whichever is longer): glatiramer acetate, interferon
(IFN)β, dimethyl fumarate, B-cell depleting agent, methotrexate, azathioprine,
cyclosporine, fingolimod, natalizumab, teriflunomide (or within 2 weeks of Cycle
1 Day 1 if the subject has completed an accelerated clearance of teriflunomide
with cholestyramine), mitoxantrone, cyclophosphamide, cladribine, or any other
immunosuppressant or cytotoxic therapy (other than steroids), antithymocyte
globulin or similar anti-T cell antibody therapy

3. Any previous treatment: alemtuzumab, stem cell transplant, or EBV T-cell therapy

13. Unresolved reactions from previous MS therapies that may, in the investigator's
opinion, impact the safety of the subject or the conduct of this study

14. Female of childbearing potential unwilling to use a highly effective method of
contraception (ie, one that results in pregnancy less than 1% per year when used
consistently and correctly), eg, implants, injectables, combined oral contraceptives,
some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner,
and/or unwilling to refrain from donating eggs while undergoing treatment with ATA188
and for 3 months after the last dose OR Men with a female partner of childbearing
potential unwilling to use a highly effective contraceptive measure and/or unwilling
to refrain from donating sperm while undergoing treatment with ATA188 and for 3 months
after the last dose

15. Women who are breastfeeding

16. Pregnancy

17. Inability to comply with study procedures