Safety and Feasibility of CALEC for LSCD

This is an open label, single center study to assess safety, feasibility, and efficacy of
Cultivated Autologous Limbal Epithelial Cell (CALEC) grafts in 24 patients with unilateral
limbal stem cell deficiency (LSCD). The first 3 participants enrolled will receive the study
treatment, CALEC, to assess for safety and feasibility. Subjects 4-24 will be randomized to
either the study treatment, CALEC, or to the standard treatment for LSCD, which is
conjunctival limbal autograft (CLAU) in a 2:1 ratio.

Participants receiving the study intervention will have a corneal biopsy in their
non-diseased eye, which will provide cells for the creation of the CALEC graft. The CALEC
will be made at the Good Manufacturing Practice (GMP) Laboratory, Dana Farber Cancer
Institute and transported to Mass. Eye and Ear Infirmary for application to the participant's
diseased eye during their standard corneal reconstruction procedure. Subjects randomized to
the standard treatment arm will undergo CLAU surgery, with the biopsy performed at the time
of surgery. Investigators, study personnel, and subjects will be aware of the study
assignment, given the different procedures required for each, during and after surgery.
Subjects will be monitored up to month 24 to assess for any delayed adverse events of the
product (CALEC) or procedure as well as assessment of the durability of the transplant.

Inclusion Criteria:

- Male or female participants age 18 to <80 years old at time of enrollment

- Ability of a subject or guardian/legal representative to provide written informed
consent and to comply with study assessments for the full duration of the study.

- Patients with unilateral limbal stem cell deficiency (LSCD) as determined by
conjunctivalization of the cornea defined by fibrovascular pannus more than 2 mm from
the limbus for greater than or equal to 6 clock hours.

- Additional optional criteria:

- Lack of limbal palisades of Vogt for greater than or equal to 9 clock hours

- Goblet cell presence as defined by impression cytologic criteria

Exclusion Criteria:

- Corneal or ocular surface infection within 30 days prior to study entry or CALEC
transplantation

- Ocular surface malignancy

- Uncontrolled diabetes with most recent HgA1c greater than 8.5%

- Renal Failure with eGFR below 60 mL/min per 1.73 m2

- Aspartate aminotransferase and alanine aminotransferase levels greater than 3 times
institutional upper limit of normal

- Total bilirubin greater than 2 times institutional upper limit of normal (except
patients with known Gilbert's syndrome)

- Platelet levels less than 100,000 or greater than 450,000 per microliter

- Hemoglobin levels of less than 11.0 g/dL in men or less than 10.0 g/dL in women

- Prothrombin time greater than 16 seconds and activated partial thromboplastin time
greater than 35 seconds in patients not taking warfarin and an international
normalized ratio greater than 3 in patients taking warfarin

- Inability to tolerate monitored anesthesia

- HIV infection or AIDS

- Active Hepatitis B or C

- Pregnancy (positive test) or lactation

- Participation in another simultaneous medical investigation or trial

- Severe cicatricial eye disease

- Severe dry eye disease as determined by Schirmer's test less than 1mm in at least one
eye.

- Any medical, psychiatric, debilitating disease/disorder or social condition that in
the judgment of the investigator would interfere with or serve as a contraindication
to adherence to the study protocol or ability to give informed consent.

- Signs of current infection, including fever and current treatment with antibiotics.

- History of allo-limbal transplantation

- Presence of allergy to the CALEC graft or any of the chemical components within its
formulation.

Exclusion Based on Donor Eye:

- Conjunctivalization of the cornea defined by fibrovascular pannus more than 2 mm from
the limbus for greater than or equal to 3 clock hours

- Lack of limbal palisades of Vogt for greater than or equal to 3 clock hours

- History of allo-limbal transplantation