Study to Evaluate Safety and Tolerability of QR-421a in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene

The purpose of this study is to evaluate the safety and tolerability of QR-421a administered
via IVT in subjects with RP due to mutations in exon 13 of the USH2A gene. Subjects will
receive one single IVT injection of QR-421a or sham-procedure in one eye (subject's worse
eye) and will be followed up for 48 weeks.

Three dose levels of QR-421a will be evaluated: 50, 100, and 200 µg. Additional dose levels
(eg, 25 or 400 µg) may be evaluated based on ongoing safety and efficacy data monitoring.

Per dose cohort, a minimum of 4 subjects will be treated with QR-421a and a minimum of 2
subjects will receive the sham-procedure. The first subject in a dose cohort will receive
QR-421a (open-label); subsequent subjects in the same dose cohort will be randomized to
either QR-421a or sham-procedure.

Inclusion Criteria:

1. Male or female, ≥ 18 years of age.

2. Clinical presentation consistent with RP with Usher syndrome type 2 or non-syndromic
RP (NSRP), based on ophthalmic, audiologic, and vestibular examinations.

3. An ERG result consistent with RP with Usher syndrome type 2 or NSRP.

4. A molecular diagnosis of homozygosity or compound heterozygosity for 1 or more
pathogenic exon 13 mutations in the USH2A gene, based on genetic analysis upon Sponsor
approval.

5. A BCVA less than or equal to Logarithm of the Minimum Angle of Resolution (LogMAR)
+0.2 in the worse eye.

6. Semi-Automated Kinetic VF V4e (Octopus 900): Continuous area of central field greater
than or equal to 10 degrees diameter (equivalent in area: 78.53981634 deg2) in both
eyes.

7. No limitations to OCT image collection that would prevent high quality, reliable
images from being obtained in both eyes (including outer segment [OS] thickness and
volume, outer nuclear layer [ONL] thickness, total receptor (TR) thickness, EZ
horizontal and vertical widths, apparent continuous EZ area, central macula thickness
[CMT], grading of cystic macular lesions [CML] if any), as determined by the reading
center.

8. Reliable perimetry measurements in both eyes, as described in the Study Reference
Manual and determined by the reading center.

9. Clear ocular media and adequate pupillary dilation to permit good quality retinal
imaging, as assessed by the Investigator.

Exclusion Criteria:

1. Presence of additional non-exon 13 USH2A pathogenic mutation(s) on the USH2A allele
carrying the exon 13 mutation in subjects who are compound heterozygous for mutations
in exon 13.

2. Presence of non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects
who are homozygous for mutations in exon 13.

3. Presence of pathogenic mutations in genes (other than the USH2A gene) associated with
Usher syndrome Type 2 or NSRP, or other inherited retinal degenerative diseases or
syndromes.

4. Any contraindication to IVT injection according to the Investigator's clinical
judgment and international guidelines.

5. Nystagmus or unstable fixation.

6. Amblyopia.

7. Prior receipt of intraocular surgery or procedure or IVT injection within 12 weeks
prior to study start or planned intraocular surgery or procedure during the course of
the study.

8. Any prior treatment with genetic therapy.