Phase 2 study

Reproduced exactly, unedited. Written for researchers rather than for patients.

Inclusion Criteria:

1. Must give written informed consent before any study-related activity is carried out

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

3. Body mass index ≥18.0 and ≤35.0 kg/m2

4. Have a recent (within five years) genetic diagnosis of OPA1 mutation-associated (haploinsufficiency) ADOA and/or confirmed diagnosis during pre-screening or screening, as determined by the PI.

5. Treatment naïve participants with best-corrected visual acuity (BCVA) of between ≤20/40 (≤70 Early Treatment of Diabetic Retinopathy Study [ETDRS] letters) and ≥20/200 (≥35 ETDRS letters).

6. Treatment Naïve participants with mild to moderate visual field loss and retinal nerve fiber layer (RNFL) loss in the study eye only as determined by the Spectralis Glaucoma Module Premium Edition (GMPE) RNFL & visual field structure function data (map)

7. Medically healthy (in the opinion of the PI), as determined by pre-study medical history

8. Female participants must be of non-childbearing potential or if female participants are of childbearing potential, they must:

   1. Have a negative pregnancy test at the screening visit and on study Day -1;
   2. Agree not to attempt to become pregnant or donate ova from signing of the consent form until at least 130 days after final IVT dose administration of PYC-001;
   3. Agree to use adequate contraception

9. Male participants must:

   1. Agree not to donate sperm
   2. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception
   3. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom

10. Willing and able to comply with all study assessments and protocol schedule/ restrictions

Exclusion Criteria:

1. Participant has a known allergy to PYC-001 or any of its excipients;
2. Demonstrated clinically significant co-morbidities, which, in the opinion of the PI, would interfere with the participant's ability to participate in the study and/or confound study outcomes;
3. Females who are breastfeeding or planning to breastfeed;
4. Based on recent genetic testing, the participant has mutations in genes that cause ADOA, other than OPA1 (for example in case of dominant negative ADOA and ADOA Plus) or has other pathological variants that result in an ADOA-like optic atrophic phenotype or other pathologic genetic findings indicating presence of additional confounding ocular diseases based on comprehensive genetic screening.
5. Have received any prior cell or gene therapy for a retinal condition, excluding participation in study PYC-001-101;
6. Within three months prior to study Day -1, have undergone any vitreoretinal surgery or any other ocular surgery in the study eye.
7. Within three months prior to study Day -1, have placement of an Ozurdex® implant. T
8. Within three years prior to study Day -1, have placement of Retisert® of Iluvien® implants.
9. Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmic evaluation or photography, ;
10. Macular edema (intraretinal, sub-retinal or other fluid) in the study eye requiring treatment.
11. History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation;
12. Have used within 30 days of the Screening visit or is using any investigational drug or over-the-counter drug such as Idebenone, Vitamin B6, Vitamin B12, A decision will be made on a case-by-case basis by the PI in consultation with the Sponsor.
13. Over-the-counter drugs like CoQ10 and other Nutraceutical usage will require a washout by five half-lives prior to baseline visit.
14. Have a recent history (<6 months) of or current excessive recreational drug or alcohol use, in the opinion of the PI.
15. Positive alcohol breath test as assessed at screening, and on study Day -1 and study Day 1;
16. Positive urine drugs of abuse as assessed at screening and on study Day -1 and study Day 1;
17. Any retinal pathology other than ADOA or any other condition or prior therapy that in the opinion of the PI would make the volunteer unsuitable for this study
18. Presence of illness or pathology that, per investigator, include symptoms and/or the associated treatments that can alter visual function including current ocular infection.
19. Positive test for human immunodeficiency virus, hepatitis B or C virus;
20. Clinically significant findings in clinical chemistry, hematology, coagulation and urinalysis tests at screening