Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Geographic Atrophy Associated With Age-Related Macular Degeneration

• INCLUSION CRITERIA:

Participant Eligibility Criteria:

To be eligible, the following inclusion criteria must be met, where applicable.

• Participant must be 55 years of age or older.

• Participant must have a diagnosis of dry AMD, defined as presence (or history, asdocumented in available color fundus photographs) of at least one medium or largedruse (greater than or equal to 63 micrometer diameter) in the macula in at leastone eye; AND presence of GA in at least one eye.

• Participant must understand and sign the protocol s informed consent document.

• Any participant of childbearing potential must have a negative pregnancy test atscreening and must be willing to undergo pregnancy testing prior to RPEtransplantation.

• Any participant of childbearing potential and any participant able to fatherchildren who has a partner of childbearing potential must have (or have a partnerwho has) had a hysterectomy or vasectomy, be completely abstinent from intercourse,or must agree to practice an effective method of contraception through Month 12 inthe study. Acceptable methods of contraception include:

• Hormonal contraception (i.e., birth control pills, injected hormones, dermalpatch or vaginal ring),

• Intrauterine device,

• Barrier methods (diaphragm, condom) with spermicide, or

• Surgical sterilization (tubal ligation).

• Participant must be medically able to comply with the study treatment (includingability to safely receive anesthesia for surgery), study testing and procedures, andfollow-up visits.

Study Eye/Fellow Eye Eligibility Criteria

The participant must have at least one eye meeting all inclusion criteria and none of the exclusion criteria listed below. The fellow eye must also meet the relevant eligibility criteria listed below.

Study Eye Inclusion Criteria:

• The study eye must have one or more regions of geographic atrophy with total area of 1 disc area or more. A region of geographic atrophy is defined as an area of uniformhypofluorescence on fundus autofluorescence (FAF) imaging, with greatest lineardimension at least 500 micrometer, with a border within 500 micrometer of the fovealcenter, not compatible with pigmentary changes, drusen, RPE detachment, drusenoidRPE detachment, hemorrhage, or other lesion. (Note: If macular geographic atrophy iscontiguous with peripapillary atrophy, complicating calculation of total area, onlyatrophy temporal to a vertical line placed a half disc diameter temporal to thetemporal border of the disc will be included in the total area of geographic atrophycalculated for eligibility purposes.)

• For participants in the first cohort, the study eye must have an ETDRSbest-corrected visual acuity (BCVA) letter score of <= 53 and >= CF (i.e., Snellenequivalent between 20/100 and CF), and the fellow eye must have a letter score nomore than five letters worse than the study eye using Electronic Visual Acuity (EVA)testing. If the study eye is CF vision, then the fellow eye must be both (1) CF orbetter vision and (2) subjectively as good or better than the study eye according tothe subject s perception. (Note: Letter scores within five or fewer letters of eachother are accordingly considered equal for eligibility determination, and otherfactors may be used to select the study eye if both are eligible by BCVA.

• For participants in the second cohort, the study eye must have an ETDRSbest-corrected visual acuity (BCVA) letter score of <= 58 and >= CF (i.e., Snellenequivalent between 20/80 and CF), and the fellow eye must have a letter score nomore than five letters worse than the study eye using Electronic Visual Acuity (EVA)testing. If the study eye is CF vision, then the fellow eye must be both (1) CF orbetter vision and (2) subjectively as good or better than the study eye according tothe subject s perception. (Note: Letter scores within five or fewer letters of eachother are accordingly considered equal for eligibility determination, and otherfactors may be used to select the study eye if both are eligible by BCVA.

• The compromise in visual acuity for the study eye must be judged predominantlysecondary to dry AMD, in the judgment of the investigator.

• The study eye must have clarity of ocular media and degree of pupil dilationsufficient to permit adequate fundus photography and safe vitrectomy surgery.

• The study eye must be either pseudophakic or aphakic.

EXCLUSION CRITERIA:

A participant is not eligible if any of the following exclusion criteria are present:

• Participant is actively receiving another study medication / investigational product (IP).

• Participant has any condition that significantly increases risk of systemiccorticosteroids or systemic steroid-sparing immuno-modulatory agents, such asuncontrolled diabetes mellitus, chronic hepatitis or liver failure, chronic renalfailure, or present infection with HIV, syphilis, tuberculosis, hepatitis B, orhepatitis C (past infection now resolved, where applicable, is not exclusionary; butpersistent infection, even if latent, is exclusionary).

• Participant has diagnosis of a malignancy expected to affect two-year survival.

• Participant is pregnant, breast-feeding, or planning to become pregnant through thefirst 12 months of the study.

• Participant has a family history of a retinal degeneration other than AMD suspectedto play a role in the ocular phenotype of the participant in the judgment of theinvestigator, based on disease features and mode of inheritance, such as in a caseof autosomal dominant retinal degeneration in a parent or child.

• Participant is taking, or has taken within the previous year, medication with knownpotential toxicity to the retina, optic nerve, or lens (such as chloroquine,hydroxychloroquine, ethambutol).

• Participant is taking any form of systemic anticoagulation which cannot be stoppedfor an indefinite period of time without significant risk. The determination ofsignificant risk to the participant must be at the discretion of the studyinvestigators and prescribing physician (or qualified alternative).

• Participant is unable or unwilling to give informed consent that includes use ofmedical records and clinical samples for current and future research.

Study Eye Exclusion Criteria:

• The study eye has macular, subretinal or choroidal neovascularization, as assessedby FA and OCT; or any history of such neovascularization (as assessed by pastavailable records or images).

• The study eye has serous or hemorrhagic pigment epithelial detachment, as assessedby FA and OCT, that is clinically significant in the judgment of the investigator.

• The study eye has a history of photodynamic therapy (PDT) or macular thermal laserphotocoagulation, or history of intravitreal injection of anti-vascular endothelialgrowth factor (VEGF) agents or corticosteroids (excepting medications usedperi-operatively at prior cataract surgery). The study eye has had intravitrealinjections (anti-complement therapy) for treatment of dry AMD in the previous 12weeks before enrollment. Any intravitreal injections with anti-complement therapyprior to 12 weeks are not exclusionary.

• The study eye has an axial length > 25.0 mm.

• The study eye has had surgery in the previous 12 weeks, or laser capsulotomy in theprevious four weeks.

• The study eye has chronic glaucoma; OR significant ocular hypertension, defined asdocumented intraocular pressure of >= 26 mmHg on at least two occasions in theabsence of self-limited acute glaucoma; OR history of probable or definite steroidresponse manifesting as acute glaucoma or ocular hypertension, even if self-limitedand no longer present; and the fellow eye has evidence for present or past glaucomaor ocular hypertension judged to significantly impact the risk of glaucoma in thestudy eye (including history of probable or definite steroid response). (Note:History of self-limited acute glaucoma in a study or fellow eye, if not secondary tosteroid response, and if now resolved and not expected to recur (e.g., history ofelevated intraocular pressure from retained visco-elastic after cataract surgery),is not exclusionary. History of glaucoma or ocular hypertension in the fellow eye,if not felt to significantly impact risk of glaucoma in the study eye, is notexclusionary.)

• The study eye has a condition materially increasing the risks of surgery orpotentially affecting visual function over the next two years in the judgment of theinvestigator, such as chronic uveitis, diabetic retinopathy, keratitis, scleritis,optic neuropathy, untreated retinal detachment, macular edema from prior veinocclusion or other cause, proliferative vitreoretinopathy (PVR), vitreoushemorrhage, pathologic myopia, etc. A history of such conditions is notexclusionary, if judged to not materially increase risks of surgery or topotentially affect vision in the next two years in the opinion of the investigator.