Safety, Tolerability and Efficacy of Intravitreal KIO-104 in Patients With Macular Edema

Inclusion Criteria:

Participants must meet all the following criteria:

1. Be aged 18 to 85 years inclusive at the time of consent.

2. Provide informed consent prior to any study procedures, as stipulated by local laws,Ethics Committee (EC) and Regulatory Authority (RA) guidelines.

3. Be willing and able to follow all study instructions, attend all study visits, andcomplete all study assessments.

4. Have a clinical diagnosis of ME in the study eye secondary to non-infectiousuveitis, retinal vein occlusion, diabetic retinopathy or cataract surgery.

5. If currently receiving systemic corticosteroid therapy or immunosuppressive therapy (or any combination thereof), be on a stable dose of therapy for at least 3 monthsprior to Screening and during the study.

6. Have a Central Subfield Thickness (CST) of ≥ 350 µm.

7. Have a Best Corrected Visual Acuity (BCVA) in the study eye of:

8. ≤ 20/32 (Feet); logMAR ≥ 0.2

9. ≥ 20/800 (Feet); log MAR ≤ 1.6

10. Have media clarity and pupillary dilation sufficient for adequate visualization andassessment of the study eye.

11. Be willing to avoid disallowed medications and treatments for the duration of thestudy.

12. Agree to follow appropriate contraception requirements from screening until 3 monthsafter the last dose of the study drug.

13. Participants assigned female at birth who are of child-bearing potential (OCBP)must agree to a pregnancy test at Screening and prior to each dose ofinvestigational medicinal product (IMP) and use an acceptable method of birthcontrol including oral, transdermal, injectable, or implantable hormonalcontraception, intrauterine device, abstinence from intercourse with partnerassigned male at birth, or surgical sterilisation of partner assigned male atbirth.

14. Participants assigned female at birth are not OCBP if they have had ahysterectomy, bilateral oophorectomy, bilateral tubal ligation, or arepost-menopausal by at least 12 months. Post-menopausal status of amenorrheicfemale participants should be confirmed at Screening through testing offollicle-stimulating hormone (FSH) as per analysing laboratory threshold.

15. Participants assigned male at birth with a partner OCBP must be surgicallysterile for at least 3 months prior to starting study drug, or ensure theirpartner uses contraception as outlined above, and must use a male condom.Participants assigned male at birth must not donate sperm from Screening until 3 months after the last dose of IMP.

16. Participants who have practiced true abstinence for at least 1 year due tousual and preferred lifestyle choice are exempt from contraceptiverequirements. If a participant who is abstinent becomes sexually active, theymust agree to use appropriate contraception as described above.

Exclusion Criteria:

Participants must not meet any of the following criteria:

1. Have media opacities (cornea, anterior or posterior synechia, cataract, vitreoushaze and others) of either eye that preclude investigation and documentation of theposterior pole and intravenous fluorescein angiography, or optical coherencetomography evaluation in the study eye.

2. Receive local or systemic biologicals (i.e. tumour necrosis factor [TNF]-blockers,B-cell blockers, cytokines, cytokine-blockers, receptor antagonists) 90 days priorto Day 1 or planned during the study.

3. Receive treatment with cyclophosphamide or chlorambucil during the study.

4. Receive intravitreal injections (including but not limited to anti-vascularendothelial growth factors) 90 days prior to Day 1 or planned during the study.

5. Receive a posterior subtenon's or orbital floor injection of steroids 90 days priorto Day 1 or planned during the study.

6. Have any implantable corticosteroid-eluting device (Ozurdex, Iluvien, Retisert,triamcinolone intravitreal implant, fluocinolone intravitreal implant) in the studyeye, with the following exceptions:

7. If the device had been removed more than 90 days prior to Day 1 of the study.

8. If Ozurdex® had been implanted at least 6 months before Day 1 of the study.

9. If Iluvien® or Retisert® had been implanted at least 3 years before Day 1 ofthe study.

10. Use of topical steroids are permissible provided the participant is receiving astable dose for at least 3 months prior to Screening and during the study.

11. Have ocular surgery (including cataract extraction, vitreoretinal or scleralbuckling surgery) in the study eye, within 90 days prior to Day 1, or planned duringthe study.

12. Have a capsulotomy in the study eye, within 30 days prior to Day 1, and during thestudy.

13. Have Intraocular pressure (IOP) ≥ 25 mmHg in the study eye (glaucoma patientsmaintained on no more than one topical medication with IOP < 25 mmHg are allowed toparticipate).

14. Have ocular hypotony (IOP < 6 mmHg).

15. Have aphakia or anterior chamber lens in the study eye.

16. Have visible scleral thinning, scleral ectasia or keratoconus in the study eye.

17. Have presence of any ocular malignancy in either eye.

18. Have evidence of any other clinically significant ocular disease that mightinterfere with the study assessments.

19. Have ocular or periocular (either eye) or systemic infection and/or a temperaturegreater than 38.0°C, or the use of systemic or topical ocular antibiotics within 14days of Day 1.

20. Have a psychiatric condition that, in the investigator's opinion, precludescompliance with the protocol; past or present psychoses; past or present bipolardisorder; disorder requiring lithium; or within five years prior to screening, ahistory of suicide plan.

21. Have any clinically significant abnormality at screening determined by medical andophthalmic history, vital signs, clinical biochemistry, hematology, urinalysis, or a 12-lead electrocardiogram (ECG), as assessed by the investigator, which mightinterfere with the study assessments or the ability of the participant to completethe study.

22. Have any other medical condition or significant co-morbidities, or any findingduring screening, which in the view of the investigator is likely to interfere withthe study or put the participant at risk, confound study data, or interferesignificantly with study participation.

23. Have participated in any other investigational drug or device clinical trial within 90 days prior to Day 1 or planning to participate in other investigational drug ordevice clinical trials during the study and within 90 days following Day 1. Thisincludes both ocular and non-ocular clinical trials.

24. Receive any anticoagulant or thrombocyte aggregation inhibiting agent (marcumar,warfarin, heparin, enoxaparin, apixaban, rivaroxaban, pentosanpolysulfate,dabigatran, aspirin and others) within 14 days prior to Day 1 or planned during thestudy.

25. Have a known allergy or hypersensitivity to the study medication, any component ofthe delivery vehicle, any corticosteroids, any diagnostic agents used during thestudy (e.g., fluorescein, dilation drops), or any other standard of care medicationslikely to be used during the study (e.g., antibiotic drops, povidone, rescuemedications).

26. Be pregnant or breast-feeding, or plan to become pregnant during the study.