Polyclonal Regulatory T Cells (PolyTregs) for Pemphigus

Up to 12 adults between the ages of 18 and 75 years of age who have been diagnosed with
pemphigus and meet all other entry criteria will be enrolled to receive one infusion of their
own expanded Tregs at one of the following doses:

- 2.5 x 10^8 PolyTregs or

- 10 x 10^8 PolyTregs.

Safety, disease activity, and mechanism of action will be assessed over a three year period,
using biospecimens from blood and skin. Study therapy administration will occur during an
overnight stay, followed by 2 weekly visits, then monthly visits from Week 8 to Week 12, then
quarterly visits from Week 26 to Week 52, then twice a year visits until Week 156.

Inclusion Criteria:

- Ability to provide informed consent;

- Diagnosis of Pemphigus Vulgaris (PV) or Pemphigus Foliaceus (PF), defined by H&E
staining (e.g., Haemotoxylin and Eosin) and direct immunofluorescence staining of skin
biopsy at any time prior to enrollment;

- Pemphigus treated with systemic corticosteroids within the 2 years prior to screening
(historic or current);

- Presence of:

- anti-Dsg3 antibodies (>20.0 U/ml) at screening visit consistent with diagnosis of
pemphigus vulgaris or,

- anti-Dsg1 antibodies (>20.0U/ml) at screening visit consistent with diagnosis of
pemphigus foliaceus.

- Active of PV or PF as defined by Pemphigus Disease Area Index (PDAI) overall activity
score 3-10 at screening visit, and PDAI overall activity score 1-12 at baseline visit;

- Positive test for Epstein-Barr Virus (EBV) antibody; and

- Adequate venous access to support draw of 400 ml whole blood and infusion of
investigational therapy.

Exclusion Criteria:

- Initiation of systemic corticosteroid therapy, prednisone dose > 25 mg/d (or
equivalent) or change in prednisone dose within 4 weeks prior to screening;

- Addition of a new medication, or change in the dose of any background medication used
to treat any aspect of pemphigus within the timeframes listed below. Specifically:

- methotrexate, mycophenolate mofetil, mycophenolic acid, azathioprine,
cyclosporine or dapsone within the 6 weeks prior to screening or in the time
between screening and study drug infusion,

- intravenous Immunoglobulin (IVIG) within 12 weeks prior to screening or in the
time between screening and study drug infusion (subjects on IVIG must be on
stable dose for at least 12 weeks prior to screening),

- treatment with cyclophosphamide within 12 weeks prior to screening or in the time
between screening and study drug infusion.

- Doses of background medications at screening:

- methotrexate > 25 mg/week,

- mycophenolate mofetil > 3000 mg/d,

- mycophenolic acid > 1080 mg/bid,

- azathioprine > 200 mg/d,

- cyclosporine > 2 mg/kg/d,

- dapsone >250 mg/d,or

- intravenous immunoglobulin (IVIG) > 4mg/kg monthly.

- Use of rituximab within the 12 months prior to screening;

- Change in dosing frequency, concentration, or applied surface area of topical steroids
and/or topical calcineurin inhibitors within 2 weeks prior to screening;

- Paraneoplastic pemphigus;

- Pemphigus erythematosus;

- Pemphigus vegetans;

- Immunoglobulin A (IgA) pemphigus;

- Drug-induced pemphigus;

- Blood donation within 10 weeks prior to baseline visit (Day 0);

- Hemoglobin < 10 g/dL;

- White blood cell (WBC) count < 3,000/ mm^3 (equivalent to < 3 x10^9/L);

- Lymphocyte count < 800/mm^3 (equivalent to < 0.8 x10^9/L);

- Absolute neutrophil count < 1,500/mm^3 (equivalent to < 1.5 x10^9/L);

- Platelets < 100,000/mm^3 (equivalent to < 100 x 10^9/L);

- Liver function test [aspartate aminotransferase (AST)], alanine aminotransferase
(ALT), or alkaline phosphatase (ALK)] results that are ≥ 2 times the upper limit of
normal (ULN);

- Direct bilirubin > ULN;

- End stage renal disease [estimated glomerular filtration rate (eGFR) < 20
ml/min/1.73m^2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation];

- At or within three months of screening:

- a positive QuantiFERON(R)-TB Gold test or positive purified protein derivative
tuberculin skin test (PPD) [>5mm induration, regardless of Bacille Calmette
Guerin (BCG) vaccine administration] unless completion of treatment has been
documented for active Tuberculosis (TB),

- an indeterminate QuantiFERON (R)-TB Gold test unless followed by a subsequent
negative PPD or negative QuantiFERON(R)-TB Gold test as well as a consultation
with and clearance by local infectious disease (ID) department.

- Recent or ongoing active bacterial, viral, fungal, or opportunistic infections
requiring systemic anti-infective therapy;

- Evidence of current or prior infection with human immunodeficiency virus (HIV),
hepatitis B [as assessed by HBsAg and anti-hepatitis B core antigen (HBc) Ab] or
hepatitis C [as assessed by anti-Hepatitis C Virus (anti-HCV) Ab];

- Detectable circulating EBV or Cytomegalovirus (CMV) genomes or active infection;

- Chronic infection that is currently being treated with suppressive anti-infective
therapy, including but not limited to tuberculosis, pneumocystis, CMV, herpes zoster,
and atypical mycobacteria, with the exception of historical orolabial or localized
cutaneous herpes simplex infections treated with suppressive anti- viral therapy;

- Receipt of a live-attenuated vaccine within 12 months prior to screening;

- Concomitant malignancies or a history of malignancy, with the exception of completely
treated basal cell carcinoma of the skin;

- Pregnancy;

- Lactating or breastfeeding;

- Unwilling or unable to use reliable method(s) of contraception:

- For females of child-bearing potential, from four weeks prior to Day 0 through

1 year after Treg dosing;

- For males, from the day of Treg infusion (baseline visit) to three months after
Treg infusion.

- Use of an investigational therapeutic medication, or other biologic medications except
rituximab, within the past 90 days, or 5 half-lives prior to screening, whichever is
greater;

- Concomitant medical condition that places the subject at risk by participating in this
study, including but not limited to:

- another severe, systemic autoimmune disease or condition (besides pemphigus)
requiring systemic immunosuppressive therapy (e.g., rheumatoid arthritis,
Systemic Lupus Erythematosus (SLE), systemic sclerosis, primary Sjogren's
syndrome, primary vasculitis, psoriasis, multiple sclerosis, ankylosing
spondylitis, and inflammatory bowel disease), or

- severe, progressive, or poorly controlled renal, hepatic, hematological,
gastrointestinal, pulmonary, cardiac, or neurological disease, or

- history of significant infection or recurrent infection that, in the
investigator's opinion, places the subject at risk by participating in this
study, or

- any other concomitant medical condition that, in the investigator's opinion,
places the subject at risk by participating in this study.

- Comorbidities requiring glucocorticoid therapy, including those which have required
three or more courses of systemic glucocorticoids within the previous 12 months;

- Current or history within the past year of substance abuse; or

- Inability to comply with study and follow-up procedures.