Study of SAR421869 in Patients With Retinitis Pigmentosa Associated With Usher Syndrome Type 1B

Following screening procedures the gene transfer agent will be injected once only under the
retina by an opthalmic surgeon under anesthesia. Patients will then have regular follow up
visits where general health examinations, blood tests and ophthalmic examinations including
best corrected visual acuity, slit lamp examination, intraocular pressure, fundoscopy,
autofluorescence, optical coherence tomography, perimetry and electroretinogram will be
undertaken.

At the end of the study, the patient will be invited to enter in an open-label safety study
and long-term follow-up visits (at least once every six months) including ophthalmological
examinations and recording of adverse events will continue for 5 years; then the Investigator
will follow the patient by telephone for a subsequent 10 years at a minimum interval of once
a year to monitor delayed adverse events.

Inclusion Criteria:

- Clinical and molecular diagnosis of Retinitis Pigmentosa associated with Usher
Syndrome type 1B, caused by at least one pathogenic MYO7A mutation on both alleles,
confirmed by direct sequencing and co-segregation analysis within the patient's
family.

- Suitable verbal/auditory and/or tactile sign language communication (in the opinion of
the investigator) as to allow written informed consent to be obtained.

- Women of childbearing potential must have a negative pregnancy test at screening and
at baseline, and agree to use an effective form of contraception such as the
contraceptive pill or intra uterine device for at least three months following
SAR421869 administration, or be surgically sterile or postmenopausal, with the last
menstrual period being over two years prior to enrolment.

- Males of reproductive potential must agree with their partner to use two forms of
contraception, including one barrier method for at least three months following
SAR421869 administration if their partner is of childbearing capacity, or must be
surgically sterile.

- Patients must agree to not donate blood, organs, tissues or cells for at least three
months following SAR421869 administration.

Exclusion Criteria:

- Presence of significant ocular abnormalities in the study eye that in the opinion of
the investigator would preclude the planned surgery, effective safety follow-up, or
interfere with the interpretation of study endpoints (eg, glaucoma, corneal or
significant lens opacities, pre-existing uveitis, intraocular infection, choroidal
neovascularization).

- Any pre-existing factor or past history of eye disease in children that may predispose
to an increased risk of surgical complications in the study eye (eg, trauma, previous
surgery, uveitis, congenital, developmental or structural abnormalities).

- Concomitant systemic diseases including those in which the disease itself, or the
treatment for the disease, can alter ocular function (eg, malignancies, diabetes,
juvenile rheumatoid arthritis or sickle cell disease).

- Any contraindication to pupil dilation in either eye.

- Contraindications to use of anesthesia (local or general, as appropriate).

- Treatment with intravitreal, subtenon, or periocular steroid within 4 months of the
screening visit.

- Any known allergy to any component of the delivery vehicle or diagnostic agents used
during the study (eg, fluorescein, dilation drops), or medications planned for use
during the peri-operative period, particularly topical, injected or systemic
corticosteroids.

- Life-threatening illness.

- Alcohol or other substance abuse.

- History of malignancy within a five year period or have had a positive cancer
screening test within a one year period of the screening visit.

- Laboratory test abnormalities or abnormalities in electrocardiogram or chest X-ray,
that in the opinion of the principal investigator, are clinically significant and
would make the patient unsuitable for participation in the study.

- Intercurrent illness or infection 28 days prior to SAR421869 administration.

- Concurrent anti-retroviral therapy that would inactivate the investigational agent.

- Current treatment with immunosuppressant therapies.

- Pre-menopausal or non-surgically sterile women who are unwilling to use an effective
form of contraception such as the contraceptive pill or intrauterine device.

- Men or women who do not agree to use barrier contraception as specified in the
inclusion criteria.

- Pregnant or breastfeeding women.

- History of any investigational agent within 28 days prior to SAR421869 administration.

- Participation in a prior gene transfer therapy study.

- Enrolment in any other clinical study, for any condition, including those relating to
Usher syndrome Type 1B, throughout the duration of the SAR421869 study.

- Current or anticipated treatment with anticoagulant therapy or the use of
anticoagulation therapy within the four weeks prior to surgery.

- Past medical history of HIV, or hepatitis A, B or C.

- Inability to comply with the study protocol.

- Any ocular surgery including laser and cataract surgery with intraocular lens
implantation, aphakia or prior vitrectomy, in the study eye within 6 months of
screening.