Natural History of Autosomal Dominant Optic Atrophy (ADOA), Caused by OPA1 Mutation

Inclusion Criteria:

• Participants and/or their parent(s)/guardian(s) must have given written informedconsent before any study-related activities are carried out and must be able tounderstand the full nature and purpose of the trial, including possible risks andadverse effects. Assent, where appropriate, will be obtained according toinstitutional guidelines.

• Males and females, 8 years of age and above.

• Have a clinical diagnosis of OPA1 mutation (haploinsufficiency) associated ADOA.

• No other ocular pathology.

• Patients with best-corrected visual acuity (BCVA) of between 20/40 (70 EarlyTreatment of Diabetic Retinopathy Study [ETDRS] letters) and 20/160 (39-43 ETDRSletters)

• Willing and able to comply with all study assessments and adhere to the protocolschedule and restrictions.

• For sites performing the Detection of apoptosis in retinal cells (DARC) procedure,and in volunteers ≥ 12 years only:

1. Female volunteers must: I. Be of non-child-bearing potential at least 6 weeks before the screeningvisit or postmenopausal (where postmenopausal is defined as no menses for 12months without an alternative medical cause), or II. If of childbearing potential, must:

• Have a negative pregnancy test at the screening visit and prior to eachadministration of ANX776, and
• Agree not to attempt to become pregnant or donate ova from signing theconsent form until at least 30 days after the last dose of ANX776, and
• Agree to use adequate contraception (defined as the use of a condom by themale partner combined with the use of a highly effective method ofcontraception from one month prior to screening until at least 30 daysafter the last dose of ANX776, if not exclusively in a same-sexrelationship or abstinent as a committed lifestyle.

2. Male volunteers must:

• Agree not to donate sperm from signing the consent form until at least 90days after the last dose of ANX776, and
• If engaging in sexual intercourse with a female partner who could becomepregnant, agree to use adequate contraception (defined as the use of acondom combined with the use of a highly effective method ofcontraception) from signing the consent form until at least 90 days afterthe last dose of study drug.

Exclusion Criteria:

• Participant has a known allergy to ANX776 or any of its excipients.

• Have any uncontrolled systemic disease that, in the opinion of the Investigator,would preclude participation in the study, which includes but is not limited to,infection, uncontrolled elevated blood pressure, cardiovascular disease, or glycemiccontrol issues, or any other medical condition that may put the participant at riskdue to study procedures. Note: comorbidities relevant to the pathogenesis of OPA1associated ADOA (including hearing loss, peripheral neuropathy, myopathy, andataxia) are acceptable.

• Have mutations in genes that cause ADOA, other than OPA1 (for example in case ofdominant negative ADOA) and ADOA Plus.

• Within 3 months prior to Baseline (Visit 2), have undergone any vitreoretinalsurgery (scleral buckle, pars plana vitrectomy, retrieval of a dropped nucleus orintraocular lens, radial optic neurotomy, sheathotomy, cyclodestructive proceduresor multiple filtration surgeries [2 or more]) or any other ocular surgery.

• Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmicevaluation or photography, as assessed by the Investigator.

• Have used any investigational drug or device within 90 days or 5 estimatedhalf-lives of Visit 2, whichever is longer, or plan to participate in another studyof a drug or device during the study period. Participation in observational trialsis allowable based on Investigator discretion and consultation with the MedicalMonitor. It is assumed that the observational trial evaluations would not interferewith participation in this study.

• Have received any prior cell or gene therapy for a retinal condition.

• Have a recent history (<6 months) of or current excessive recreational drug oralcohol use, in the opinion of the Investigator. Note: excessive alcohol use isdefined as regular consumption of > 10 standard drinks per week or > 4 standarddrinks per day, where 1 standard drink is defined as 10 grams of pure alcohol.

• Any other condition or prior therapy that in the opinion of the Investigator wouldmake the volunteer unsuitable for this study, including inability to cooperate fullywith the requirements of the study protocol or likelihood of noncompliance with anystudy requirements.