Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

This will be a non-randomized, open-label, Phase 1/2 dose escalation study.

Approximately 15 participants will be enrolled. Each participant will receive the study agent
by subretinal injection in one eye on a single occasion. Enrollment will begin with the
lowest dose and will proceed to higher doses only after review of safety data by a Data and
Safety Monitoring Committee (DSMC). Participants in the dose escalation phase will be ≥ 18
years of age. After the maximum tolerated dose is identified individuals ≥ 6 years of age
will be enrolled.

Safety will be measured by the number and proportion of participants experiencing ocular and
non-ocular adverse events or abnormal clinically relevant hematology or clinical chemistry
parameters. Efficacy will be measured by evaluation of changes in visual structure, function,
and quality of life.

Inclusion Criteria:

- Male subjects with the clinical diagnosis of X-linked retinitis pigmentosa (XLRP) and
a documented molecular diagnosis from a CLIA-certified laboratory of mutations within
exons 1-14 and/or ORF15 of the RPGR gene;

- Best-corrected visual acuity not better than 78 ETDRS letters (20/32) in the study
eye;

- Ability to perform tests of visual and retinal function and structure and ability to
comply with other research procedures;

- Detectable remaining vision at the intended bleb region;

- Good general health based on a complete physical examination and hematology and
clinical chemistry studies performed at a pre-treatment evaluation;

- At least 18 years of age for Groups 1, 2 and 3 and at least 6 years of age for Group
4;

- Has a parent or caregiver able to follow study instructions, comply with the protocol
and attend study visits with the subject as required;

- Signed informed consent and assent (if necessary) obtained before screening.

Exclusion Criteria:

- Pre-existing eye conditions that would preclude the planned surgery or interfere with
the interpretation of study endpoints or increase the risk of surgical complications
(for example, glaucoma, corneal or lenticular opacities, diabetic retinopathy, retinal
vasculitis);

- Complicating systemic diseases (such as medical conditions causing immunosuppression
or known sensitivity or allergy to medications planned for use in the peri-operative
period) that would preclude the gene transfer or ocular surgery;

- Use of anti-coagulant agents that may alter coagulation within 7 days prior to study
agent administration;

- Use of systemic corticosteroids or other immunosuppressive medications within 3 months
prior to enrollment;

- Males who are unwilling to use barrier contraception for 3 months following agent
administration;

- Any other condition that would prevent a subject from completing follow-up
examinations during the course of the study;

- Any other condition that, in the opinion of the investigator, makes the subject
unsuitable for the study;

- Current, or recent (the longer of 90 days or 10 half-lives of the drug) participation,
in any other research protocol involving investigational agents or therapies;

- Previous receipt of any AAV gene therapy product;

- Study personnel or family members of the study personnel;

- Monocular or having BCVA less than 20/800 in the fellow eye.