A Phase 1b Dose Escalation Evaluation of Safety and Tolerability and a Phase 2 Proof of Concept Investigation of Efficacy and Safety of ASP7317 for Atrophy Secondary to Age-related Macular Degeneration

This is a two stage study followed by an extension stage. Stage 1 is a Phase 1b dose
escalation evaluation of 3 doses of ASP7317; Stage 2 is Phase 2 Proof of Concept (PoC)
investigation and Stage 3 is the extension stage which offers treatment options for
participants randomized to the untreated control group in Stage 2.

During the dose escalation stage participants will be treated in each of the 3 dose cohorts
(low cells/dose; medium cells/dose; high cells/dose). Doses will be administered to the study
eye via a subretinal injection. Four weeks after the last participant in each dose cohort is
treated, the independent Data Safety Monitoring Board (DSMB) will review data and images.
Depending on the safety data there will be a recommendation to continue enrollment in the
current cohort, or open enrollment for the next higher dose; stop dose escalation;
investigate a lower dose or repeat a dose level.

The PoC stage will begin immediately following the decision of the Dose Escalation Committee
(DEC) on the selected dose. Participants will be randomized in a 1:1:1 ratio to either the
low cells/dose; the selected cells/dose or an untreated control group. Doses will be
administered to the study eye via a subretinal injection for the low cells/dose and the
selected cells/dose.

All participants treated with ASP7317 in the Dose Escalation and PoC stage will receive 13
weeks of immunosuppressive therapy (IMT) starting 1 week prior to day of transplant and
continuing for 12 weeks post-transplant. If the primary outcome for PoC is demonstrated for
the low cells/dose and the selected cells/dose then participants in the untreated control
group who completed the 26 week visit are allowed to cross over to treatment with ASP7317
provided the participants remain suitable for immunosuppression therapy and ASP7317.

At the last study visit or time of withdrawal participants receiving ASP7317 will be
consented to participate in the safety surveillance period of the study (under a separate
protocol 7316-CL-0007), which will continue to monitor the participants for long-term safety
via an annual questionnaire.

General Inclusion Criteria:

- Subject must be willing to take immunosuppressive therapy (IMT) and willing to
discontinue any medication that has a known strong interaction with Prograf or MMF.

- Subject should be in sufficiently good mental and physical health to reasonably be
expected to complete the study to the week 26 visit.

- Subject must have a score of ≤ 9 on the patient health questionnaire depression scale
(PHQ-9) at the screening visit (criterion not applicable for subjects in dose
escalation stage).

- Subject who is taking an antidepressant must be on a stable and effective dosage and
must be willing to take it reliably for as long as it is required.

- Subject must be willing and medically suitable to undergo monitored anesthesia care
during the transplant.

- Subject is medically suitable to undergo vitrectomy and subretinal injection.

- Subject agrees not to participate in another interventional study until the 26-week
visit has been completed.

- Pregnancy, breastfeeding, effective forms of birth control and ova/sperm donation
criteria are specified in the clinical protocol and will be discussed with potential
study subjects during the informed consent process.

Ocular Inclusion Criteria:

- Subject has atrophy secondary to AMD in the study eye.

- Subject has the border of the area of definite decreased autofluorescence (DDAF) in
the study eye, within the vascular arcades (criterion not applicable for subjects in
dose escalation stage).

- Subject has a best corrected visual acuity (BCVA) score ≤37 early treatment diabetic
retinopathy study (ETDRS) letters, in the study eye, at the second assessment during
the screening visit between 4 and 23 ETDRS letters. In the dose escalation stage for
the first dose cohort only, the study eye must be between light perception and ≤ 23
ETDRS letters at the second assessment during the screening visit.

- Subject has stable BCVA, in the study eye, to ensure stability of the visual acuity
measures for study analyses (criterion not applicable for subjects in dose escalation
stage).

- Subject has spectral domain-optical coherence tomography (SD-OCT) scans obtained of
the study eye at the screening visit of suitable quality for grading retinal
microstructures.

- Subject, at the screening visit, must have in the study eye an area with reduced
retinal function and evidence of structural retinal preservation between the border of
the area of atrophy and the vascular arcades, as determined by the subject selection
committee (SSC) (criterion not applicable for subjects in dose escalation stage).

- Subject is recommended by the SSC for trial participation.

Inclusion Criteria for Extension Stage 3:

- Subject was previously enrolled as an untreated control subject in the PoC stage and
completed the 26-week visit.

- Subject is suitable to receive IMT and ASP7317 as determined by the SSC.

Exclusion Criteria:

- Subject is an employee of Astellas.

Ophthalmic Disease/Conditions:

The following conditions are exclusionary if present in the study eye, unless otherwise
specified.

- Subject has foveal sparing as determined by either of the following methods (criterion
not applicable for subjects in dose escalation stage):

- Any of the 9 loci in central square of the macula test grid with ≥ 0 dB
sensitivity based on microperimetry testing at the prescreening or screening
visit assessments.

- Presence of potentially viable photoreceptors, as evidenced by presence of
ellipsoid zone (EZ), ≤ 250.

- Subject has evidence of prior or active choroidal neovascularization (CNV). Evidence
of CNV will be assessed by the image reading center through review of the screening
fundus photographs, fluorescein angiography (FA) and SD-OCT images. Evidence of CNV
seen on 1 or more imaging modality is exclusionary.

- Subject has macular atrophy due to causes other than AMD.

- Subject has pathologic myopia defined as a spherical equivalent of > 8.00 diopters or
axial length > 28 mm at the prescreening or screening visit, or myopic macular
degeneration.

- Subject has a contraindication to pupil dilation.

- Subject has any other current sight-threatening ocular disease.

- Subject has presence of a posterior staphyloma.

- Subject has a current or prior history of optic neuropathy.

- Subject has presence of a macular hole.

- Subject has presence of macular schisis.

- Subject has a current or prior history of retinal dystrophy, retinitis pigmentosa,
chorioretinitis, central serous choroidopathy, diabetic retinopathy, diabetic macular
edema, vasoocclusive disease or other retinal vascular disease (e.g., compromised
blood-retinal barrier) or retinal degenerative disease other than AMD.

- Subject has a prior history of retinal detachment within the vascular arcades.

- Subject has nevus of Ota (oculodermal melanocytosis), a choroidal pigmented lesion
showing characteristics associated with high risk of malignancy (e.g., orange
pigmented or elevated lesions) or a choroidal nevus within the macula.

- Subject has presence of submacular scarring.

- Subject has presence of an ocular toxoplasmosis scar or suspected active infection (or
presence of elevated immunoglobulin M [IgM] toxoplasmosis titer).

- Subject has an abnormality of vitreoretinal interface (i.e., vitreomacular traction,
epiretinal membranes, etc.) which can interfere with measurement of macular thickness
or with the potential for macular structural damage.

- Subject has an intraocular pressure (IOP) of < 6 mmHg at the screening or first
baseline (day -21) visits.

- Subject has presence of glaucomatous optic atrophy or uncontrolled intraocular
pressure (IOP), or is using more than 2 agents to control IOP.

- Subject has active or history of uveitis.

- Subject has obscured ocular media opacity (e.g., corneal scars, lens opacities,
vitreous abnormalities, etc.) at the screening or first baseline (day -21) visits such
that reliable evaluations of the posterior segment cannot be performed.

- Subject has any other current ocular condition that can interfere with the assessment
of disease progression including but not limited to accumulation of intraretinal
fluid, subretinal fluid, sub-retinal pigment epithelial/epithelium (RPE) fluid or
cyctoid macular edema.

- Subject has monocular vision.

- Subject has a history of ocular cancer in either eye.

Other Medical Conditions:

- Subject has a history of severe allergic reaction to fluorescein (e.g., hives or
anaphylaxis) or inadequate venous access for FA.

- Subject has a history of recurrent varicella-zoster virus (VZV) infection or a
clinical diagnosis of VZV infection within 4 weeks of the baseline day -21 visit.

- Subject has a history of recurrent cytomegalovirus (CMV) infection or a clinical
diagnosis of CMV infection within 4 weeks of the baseline day -21 visit.

- Subject has received a solid organ or bone marrow transplant.

- Subject has an active, extraocular infection requiring the prolonged or chronic use of
antimicrobial or antiinfective agents.

- Subject has a current malignancy or is being treated for malignancy. Subject with a
history of malignancy that has been treated successfully may be included.

- Subject has a history of familial adenomatous polyposis.

- Subject has a history of myocardial infarction in previous 12 months and whom disease
is either unstable and/or symptomatic (e.g., angina, dyspnea, etc.).

- Subject has any abnormality in Electrocardiogram (ECG) results that is clinically
significant and could either jeopardize the safety of the subject, impact the
subject's ability to comply with study visit schedule or impact the validity of the
study results. Note: Subjects with a mean Fridericia-corrected QT interval (QTcF) of >
430 ms (for males) and > 450 ms (for females) at screening must be cleared by a
cardiologist prior to the first baseline visit (day -21).

- Subject has a study day diastolic blood pressure > 95 mmHg, at either the screening or
first baseline (day -21) visit.

- Subject has any condition that would prohibit the use of systemic immunosuppression
with Prograf and MMF.

- Subject has inflammatory bowel disease (e.g., clinically diagnosed irritable bowel
syndrome, Crohn's disease, ulcerative colitis).

- Subject has a positive tuberculosis (TB) test during the screening period by an
interferon gamma release assay (e.g., QuantiFERON). If a subject has tested negative
for TB within the 6 months prior to the screening visit, retesting is not required
unless clinically indicated.

- Subject has a history of or current condition that will interfere with the subject's
ability to comply with the protocol, compromise subject safety or interfere with the
interpretation of the study results (e.g., cognitive impairment, dementia, active
substance abuse, uncontrolled psychiatric disorder or elective treatment).

Prior and Concomitant Ocular Therapies:

The following conditions are exclusionary if present in the study eye, if applicable.

- Subject has received prior treatment with anti-vascular endothelial growth factor
(VEGF) (for any indication) within 12 weeks prior to the screening visit or
anticipated use at any point during the study.

- Subject has received prior intravitreal treatment other than anti-VEGF treatment.

- Subject has undergone intraocular surgery or refractive surgery within 12 weeks prior
to the screening visit.

- Subject is anticipated to require ocular surgery prior to completing the 26-week visit
or any ocular treatment, which could confound the efficacy results or affect subject
compliance with the visit schedule.

- Subject has any history of an ocular implant, with the exception of an intraocular
lens.

- Subject has undergone prior retinal surgery involving the macula, vitrectomy, macular
laser photocoagulation, external-beam radiation therapy, transpupillary thermotherapy,
glaucoma filtration surgery or corneal surgery (except cataract surgery).

Prior and Concomitant Therapy:

- Subject has received gene transfer or cell transplant therapy in a prior clinical
trial.

- Subject has participated within 12 weeks prior to the screening visit in any clinical
trial of a drug by ocular or systemic administration and/or has not recovered from any
reversible effects or side effects of a prior investigational agent.

- Subject is receiving or has received any IMT (other than topical, inhaled or low-dose
systemic corticosteroid use not exceeding 7.5 mg of prednisone daily [or equivalent])
within 6 weeks or 5 plasma half-lifes, whichever is longer, prior to the
administration of adjunct study medication.

- Subject is unwilling to discontinue or avoid any CYP3A4 inducers (e.g., rifampin,
rifabutin, phenytoin, carbamazepine, phenobarbital, St. John's wort) or subject is
unwilling to discontinue or avoid protease inhibitors (e.g., nelfinavir, telaprevir,
boceprevir), direct Factor Xa inhibitors, direct thrombin inhibitors, verapamil,
diltiazem or erythromycin while taking Prograf.

- Subject is unwilling to discontinue cholestyramine and azathioprine while the subject
is taking MMF.

Clinical Laboratory Tests:

The following are exclusionary if observed at the screening visit.

- Subject has any abnormality in blood chemistry, urinalysis or hematology results that
is clinically significant and prohibits participation in the study.

- Subject has an estimated glomerular filtration rate (eGRF) of ≤ 45 mL/min, calculated
by the chronic kidney disease epidemiology collaboration (CKD-EPI) equation.

- Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or
gamma-glutamyltransferase (GGT) and total bilirubin (TBL) ≥ 2 times the upper limit of
normal (ULN).

- Subject has severe anemia (hemoglobin < 9 g/dL [male] or hemoglobin < 8 g/dL
[female]), leucopenia (white blood cell count < 2500/mm3), thrombocytopenia (platelet
count < 80000/mm3) or polycythemia (hematocrit > 54% [male] or hematocrit > 49%
[female]).

- Subject has a hemoglobin A1c > 8.5%.

- Subject has a clinically significant coagulopathy (i.e., activated partial
thromboplastin time [aPTT] ≥ 1.5 times the ULN and/or prothrombin time adjusted for
the international normalized ratio [PT-INR] ≥ 2.0).

- Subject has serology result indicative of having syphilis, Lyme disease, human
immunodeficiency virus (HIV) infection or active infection with hepatitis A, B or C
virus (HAV, HBV or HCV, respectively).

- Subject has a positive urine screen for drugs of abuse (amphetamines, barbiturates,
benzodiazepines, opiates, cocaine, phencyclidine and methadone), unless the drug is
taken for a documented medical condition and under the supervision of a physician.