Safety and Efficacy Study of OpRegen for Treatment of Advanced Dry-Form Age-Related Macular Degeneration

OpRegen® is a cell-based product composed of retinal pigment epithelial (RPE) cells, derived
from human embryonic stem cells (hESC) and administered as a cell suspension in ophthalmic
Balanced Salt Solution Plus (BSS Plus).

This is a Phase I/IIa, dose-escalation, evaluating safety and tolerability of OpRegen
transplantation to patients with progressive dry-AMD. The study includes also initial
exploration of efficacy.

A total of approximately 24 subjects will be enrolled. The subjects should be 50 years of age
and older, with non-neovascular (dry) AMD, who have funduscopic findings of GA in the macula,
with absence of additional concomitant ocular disorders.

The subjects will be divided into four cohorts, according to their best corrected visual
acuity (BCVA) and administered OpRegen dose.

Inclusion Criteria:

1. Age 50 and older;

2. Diagnosis of dry (non-neovascular) age related macular degeneration in both eyes;

3. Funduscopic findings of dry AMD with progressive geographic atrophy in the macula;

4. Best corrected central visual acuity equal or less than 20/200 in cohorts 1-3 and
20/64-20/250 in cohort 4 in the study eye by ETDRS vision testing;

5. Vision in the non-operated eye must be better than or equal to that in the operated
eye;

6. Subjects with sufficiently good health to allow participation in all study-related
procedures and complete the study follow up period (medical records);

7. Ability to undergo a vitreoretinal surgical procedure under monitored anesthesia care;

8. Blood counts, blood chemistry, coagulation and urinalysis without abnormal
significance;

9. Negative for TB (cohort 4), HIV, HBC, and HCV, negative for CMV IgM and EBV IgM;

10. Patients with no history of malignancy (other than a non-melanoma skin cancer). For
cancers in remission for more then 5 years enrollment is allowed with concurred
documented approval of principal investigator and oncologist prior to enrollment;

11. Willing to defer all future blood and tissue donation;

12. Able to understand and willing to sign informed consent.

Exclusion Criteria:

1. Evidence of neovascular AMD by history, as well as by clinical exam, fluorescein
angiography (FA), or ocular coherence tomography (OCT) at baseline in either eye;

2. History or presence of diabetic retinopathy, vascular occlusions, uveitis, Coat's
disease, glaucoma, cataract or media opacity preventing posterior pole visualization
or any significant ocular disease other than AMD that has compromised or could
compromise vision in the study eye and confound analysis of the primary outcome;

3. History of retinal detachment repair in the study eye;

4. Axial myopia greater than -6 diopters;

5. At least 2 months following cataract removal in the study eye and Yttrium Aluminum
Garnet (YAG) laser capsulotomy in the study eye in the past 4 weeks and any other
ocular surgery in the study eye in the past 3 months prior to implantation;

6. History of cognitive impairments or dementia;

7. Contraindication for systemic immunosuppression;

8. History of any condition other than AMD associated with choroidal neovascularization
in the study eye (e.g. pathologic myopia or presumed ocular histoplasmosis);

9. Any type of systemic disease or its treatment, in the opinion of the Investigator,
including any medical condition (controlled or uncontrolled) that could be expected to
progress, recur, or change to such an extent that it may bias the assessment of the
clinical status of the patient to a significant degree or put the patient at special
risk.

10. Female; pregnancy or breastfeeding;

11. Current participation in another clinical study. Past participation (within 6 months)
in any clinical study of a drug administered systemically or to the eye.

12. Currently receiving aspirin, aspirin containing products and/or any other coagulation
modifying drugs which cannot be discontinued 7 days prior to surgery;

13. History of cancer (other than a non-melanoma skin cancer). For cancers cured more than
five years ago, enrollment is allowed with concurred documented approval of principal
investigator and oncologist prior to enrollment.