SAD of IVT PYC-001 in OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy (Sundew)

Inclusion Criteria:

1. Must have given written informed consent before any study-related activities arecarried out and must be able to understand the full nature and purpose of the trial,including possible risks and adverse effects;

2. Adult males and females, aged 18 years and above at screening;

3. Body mass index (BMI) ≥18.0 and ≤32.0 kg/m2, with a body weight ≤ 100kg atscreening;

4. Have a molecular (genetic) diagnosis of OPA1 mutation at screening;

5. Have a clinical diagnosis of OPA1 mutation-associated ADOA at screening;

6. Participants with BCVA of between 20/40 (70 ETDRS letters) and 20/160 (39-43 ETDRSletters). If both eyes meet this eligibility criteria, the eye with worse BCVA willbe selected as the study eye and the other eye will be designated as the "felloweye";

7. Medically healthy (in the opinion of the Investigator), as determined by pre-studymedical history, and without clinically significant abnormalities including:

8. Physical examination without any clinically relevant findings;

9. Systolic BP in the range of 90 to 160mmHg and diastolic BP in the range of 50to 95 mmHg after 5 minutes in supine of semi-supine position;

10. Heart rate in the range of 45 to 100 bpm after 5 minutes rest in supine orsemi-supine position;

11. Body temperature (tympanic), between 35.5°C and 37.7°C;

12. ECG without clinically significant abnormalities including QT intervalcorrected for Fredericia (QTcF) < 450 msec for male subjects and < 470 msec forfemale subjects;

13. No clinically significant findings in clinical chemistry, hematology,coagulation and urinalysis tests at screening.

14. Female volunteers must be of non-child-bearing potential, i.e., surgicallysterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6weeks before the screening visit) or postmenopausal (where postmenopausal is definedas no menses for 12 months without an alternative medical cause and a folliclestimulating hormone [FSH] level consistent with postmenopausal status, per locallaboratory guidelines). Females receiving hormone replacement therapy (HRT) may beconsidered for inclusion if the need for HRT is for no other medical reason than totreat symptoms associated with menopause. If female participants are ofchild-bearing potential, they must:

15. Have a negative pregnancy test at the screening visit, on study Day -1 andstudy Day 1 prior to dosing;

16. Agree not to attempt to become pregnant or donate ova from signing the consentform until at least 130 days after IVT administration of PYC-001 and at least 30 days after the final dose of ANX776;

17. Agree to use adequate contraception (defined as use of a condom by the malepartner combined with use of a highly effective method of contraception fromone month prior to screening until at least 30 days after the final dose ofANX776 (study Day 336), if not exclusively in a same-sex relationship orabstinent as a committed lifestyle.

18. Male volunteers must:

19. Agree not to donate sperm from signing the consent form until at least 190 daysafter IVT administration of PYC-001 and at least 90 days after the final doseof ANX776;

20. If engaging in sexual intercourse with a female partner who could becomepregnant, agree to use adequate contraception (defined as use of a condomcombined with use of a highly effective method of contraception) from signingthe consent form until at least 190 days after IVT administration of PYC-001and at least 90 days after the final dose of ANX776;

21. If engaging in sexual intercourse with a female partner who is not ofchild-bearing potential or a same-sex partner, agree to use a condom fromsigning the consent form until at least 190 days after IVT administration ofPYC-001 and at least 90 days after the final dose of ANX776;

22. Have suitable venous access for blood sampling

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

Exclusion Criteria:

1. Participants has a known allergy to PYC-001 or any of its excipients;

2. Demonstrated clinically significant co-morbidities, which, in the opinion of theInvestigator, would interfere with the volunteer's ability to participate in thetrial and/or confound study outcomes;

3. Females who are breastfeeding or planning to breastfeed;

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

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

6. Within 3 months prior to study Day -1, have undergone any vitreoretinal surgery (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;

7. Within 3 months prior to study Day -1, have placement of an Ozurdex® implant;

8. Within 3 months prior to study Day -1 have placement of Retisert® of Iluvien®implants;

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

10. Macular edema (intraretinal, sub-retinal or other fluid) requiring regular treatmentat a frequency of less than every 6 weeks; macular edema must be stable for at least 3 months prior to screening. Note, the above conditions will be permitted forinclusion if, in the opinion of the Investigator and in consultation with the SMM,they will not interfere with study evaluations, or have resolved by study Day -1prior to dose administration;

11. Have used any investigational drug or device within 90 days or 5 estimatedhalf-lives of the investigational drug or device (whichever is longer) prior tostudy Day -1, or plan to participate in another study of a drug or device during thestudy period. Participation in observational trials is allowed based on Investigatordiscretion and consultation with the Sponsor's Medical Representative;

12. 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;

13. Positive alcohol breath test as assessed at screening, and on study Day -1 and studyDay 1;

14. Positive urine drugs of abuse as assessed at screening and on study Day -1 and studyDay 1;

15. Any retinal pathology other than ADOA or any other condition or prior therapy thatin the opinion of the Investigator would make the volunteer unsuitable for thisstudy, including inability to cooperate fully with the requirements of the studyprotocol or likelihood of noncompliance with any study requirements.