Safety and Proof of Concept Study of ANXV (Annexin A5) in Patients With Retinal Vein Occlusion

Inclusion Criteria:

1. Must have given written informed consent (signed and dated), and any authorizationsrequired by local law and be able to comply with all study requirements

2. Male or female, ≥18 years of age at the time of informed consent

3. Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., ≥6 weeks post bilateral salpingectomy, bilateral oophorectomy with or withouthysterectomy) or post-menopausal (12 months of spontaneous amenorrhea in females > 55years of age or, in females ≤55 years, or 12 months of spontaneous amenorrheawithout an alternative medical, or 12 months with an elevated Follicle StimulatingHormone (FSH) level Males must either be surgically sterile or abstinent*, or ifengaged in sexual relations with a female of child-bearing potential, the subject orthe subject's non-pregnant female partner must use a highly effective contraceptionmethod from the time of signing the Informed Consent Form (ICF) until at least 30days after the last dose of study drug; Refer to Section 10.3 for acceptable methods

*Abstinence is only acceptable as true abstinence, i.e., when this is in line withthe preferred and usual lifestyle of the subject; periodic abstinence (e.g.,calendar, ovulation, symptothermal, post-ovulation methods). Declaration ofabstinence for the duration of a trial and withdrawal are not acceptable methods ofcontraception (Section 10.3).

4. Onset of symptoms of Retinal Vein Occlusion within 23 days prior to informed consent

5. The criterion has been removed

6. The criterion has been removed

7. Clear ocular media and adequate pupillary dilation in the Study Eye to permit highquality retinal imaging

8. Willing to refrain from strenuous exercise/activity (for example heavy lifting,weight training, intense aerobics classes etc.) for at least 72 hours prior to studyvisits

9. A negative rapid SARS-CoV-2 (COVID) test on Day 1 prior to initiation of study druginfusion

Exclusion Criteria:

Subjects will not be eligible if they have any of the following criteria:

Study Eye only:

1. A severe (≥0.9 log, Grade 3+ or worse) Relative Afferent Pupillary Defect (RAPD)

2. Evidence of deep intraretinal hemorrhage involving the center 1mm of the macula

3. Evidence of neovascularization

4. Ocular disorders/additional eye disease, which in the opinion of the Investigatormay confound interpretation of study results, compromise protocol assessments or arelikely to require intervention during the study, including, but not limited to,atrophy of the retinal pigment epithelium, sub-retinal fibrosis, organized hardexudate plaque, clinically significant diabetic macular edema, retinal detachment,macular hole, vitreomacular traction, macular epiretinal membrane, clinicallysignificant cataract, vitreal opacities or hemorrhage, glaucoma with documentedvisual field loss, ischemic optic neuropathy, retinitis pigmentosa or choroidalneovascularization of any cause (e.g., Age-related Macular Degeneration (AMD),ocular histoplasmosis, toxoplasmosis, or pathologic myopia)

5. Laser photocoagulation in the study eye within the preceding 6 months prior to theScreening Visit

6. Receipt within the past 6 months prior to the Screening Visit of any intraocularsurgery (including refractive surgery, cataract surgery), or intravitreal (IVT)injection, or planned intraocular surgery or procedure during the study, unlessapproved by Medical Monitor or Sponsor

7. Recent (6 months) history, or current evidence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus), unlessapproved by Medical Monitor or Sponsor Fellow Eye:

8. BCVA in the Fellow eye of ≤70 ETDRS letters (approximately 20/40 or less), unlessapproved by the Medical Monitor or the Sponsor Both Eyes:

9. Within 6 months prior to the Screening Visit, use of medications known to be toxicto the retina, lens, or optic nerve (e.g., desferoxamine,chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, andethambutol)

10. Known hypersensitivity or allergy to fluorescein (e.g., bronchospasm, rash, etc.) orto any component of the study products or a contraindication to dilation of thepupil or fixed pupils; mild allergies without angio-edema or treatment need may beacceptable if deemed not to be of clinical significance (including but not limitedto allergy to animals or mild seasonal hay fever)

11. An IOP greater than 24 mmHg that is not controlled with medication or surgery at thetime of the Screening Visit

12. Recent (6 months) history of, or presence of uveitis, presence of intraocularinflammation (history of blepharitis is not exclusionary), current ocular infection General:

13. Unwillingness or inability to attend all study visits and/or perform allprocedures/tests/examinations, including follow-up, as specified by this protocol,or unwillingness to cooperate fully with the Investigator

14. Any medical or surgical procedure or trauma within 4 weeks prior to the day ofTreatment 1 (study drug administration), or planned major surgery within theduration of the study through Day 120, unless approved by Medical Monitor or Sponsor

15. History of any clinically significant disease or disorder which, in the opinion ofthe Investigator, may either put the subject at risk because of participation in thestudy, or influence the results or the subject's ability to participate in the study

16. Prior exposure to a recombinant Annexin A5

17. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, asjudged by the Investigator, or history of hypersensitivity to biologics (for examplesystemically administered recombinant proteins/peptides; a similar drug class toANXV)

18. Uncontrolled hypertension (systolic > 180 mmHg or diastolic > 110 mmHg)

19. Current use of any systemically administered anti-angiogenic agent (e.g.,bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib) or corticosteroids,approved or 5 half-lives of investigational agent

20. Diagnosed untreated systemic metastasis malignancy

21. A current systemic infection or inflammation that may require antiviral orantimicrobial therapy that will not be completed prior to Screening Visit, or thatin the opinion of the Investigator and with concurrence of the Medical Monitor mayeither put the subject at risk or may influence the results of the study, or thesubject's ability to participate in the study

22. Treatment with another investigational drug, biological agent, or device within 3months of Screening Visit, or 5 half-lives of investigational agent, whichever islonger or planned participation in an investigational trial from signing ICF throughDay 120

23. History of thromboembolic events or deep venous thrombosis within 3 months ofScreening Visit

24. Current use of anticoagulant medication (any medications that might have effect oncoagulation, hemostasis, and platelets); low dose aspirin allowed prior to informedconsent but must be stopped at the time of consent; may begin again 1 day postTreatment 5 infusion

25. Current daily use of benzodiazepines (intermittent use permissible with MedicalMonitor or Sponsor approval)

26. Clinically significant abnormal coagulation parameters at baseline

27. The criterion has been removed from the protocol

28. History of autoimmune disease with anticipated presence of persistent Annexin A5antibodies, e.g., antiphospholipid syndrome, systemic lupus erythematosus,rheumatoid arthritis, Behcet disease or systemic sclerosis

29. Inherited blood disorder (e.g. sickle cell disease, thalassemia)

30. History of unstable coronary artery disease or cerebrovascular accident within thelast 3 months

31. GFR below 70 mL/min at baseline

32. Current drug or alcohol abuse, current excessive smoking (i.e., ≥ 20/day)

33. Known history of or positive test for hepatitis C or chronic hepatitis B

34. Class III obesity (Body Mass Index ≥ 40kg/m2), at the time of informed consent (Sponsor may accept eligibility for a subject with higher Body Mass Index