An Open-Label Safety Study of Retinal Gene Therapy for Choroideremia with Bilateral, Sequential Administration of Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1)

The objective of the study is to evaluate the safety of bilateral, sequential sub-retinal administration of a single dose of AAV2-REP1 in adult male subjects with choroideremia (CHM). Inclusion Criteria: During the Screening Period, subjects will be found eligible for study participation if they meet all of the following inclusion criteria.

1. Are willing and able to give informed consent for participation in the study to have both eyes treated
2. Are male and ≥18 years of age
3. Have documentation of a genetically-confirmed diagnosis of CHM
4. Have active disease clinically visible within the macular region of both eyes
5. Have a BCVA of ≥34 ETDRS letters (20/200 or better Snellen acuity) in both eyes, or in the untreated eye, if the other eye was previously treated with AAV2-REP1*
   1. *If previously treated with AAV2-REP1 in an antecedent study, subjects may be eligible for participation following Sponsor approval
6. For subjects who received treatment with AAV2-REP1 in an antecedent study, have biological samples available to complete an adequate immunology profile

Exclusion Criteria: At the Screening Visit, subjects will be found not eligible for study participation if they
meet any of the following exclusion criteria.

1. Have a history of amblyopia or inflammatory disorder in either eye.
2. Are unwilling to use barrier contraception methods, or abstain from sexual intercourse for a period of 3 months following treatment with AAV2-REP1 in either eye.
3. Have had previous intraocular surgery performed within 3 months of the Screening Visit in either eye.
4. Have any other significant ocular or non-ocular disease/disorder which, in the opinion of the investigator, may either put the subjects at risk because of participation in the study, or may influence the results of the study, or the subject’s ability to participate in the study. This includes but is not limited to a potential subject:
   1. with a contraindication to oral corticosteroid (e.g. prednisolone/prednisone).
   2. with clinically significant cataract in either eye.
   3. who, in the clinical opinion of the Investigator, is not an appropriate candidate for subretinal surgery.
5. Have participated in another research study involving an investigational product in the past 12 weeks or received a gene/cell-based therapy at any time previously, except if treated within in an antecedent study with AAV2-REP1.

IRB Approved: 9/9/2019

Study: NSR-REP-02 Site: 4004 Web Post Script Version 1.0 31 Jul 2019

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