September 4 t h , 2024
To Whom It May Concern,Announcement of First Transplantation in the Domestic Phase II Clinical
Trial of the AE101 Regenerative Medicine Cell ProductWe are pleased to inform you that the first patient in our domestic Phase II clinical
trial of AE101, a regenerative medicine cell product under development byActualEyes Inc., has successfully received the transplantation. AE101 is designed forthe treatment of bullous keratopathy (see Note 1). We are also pleased to report thatthe necessary safety evaluations have been completed, allowing for the continuationof the trial with subsequent patients.
This study aims to investigate the safety and efficacy of AE101 transplantation inpatients with bullous keratopathy. The first transplantation was performed in July
2024, and the patient's post-transplant progress has been favorable. Following a safety
review by the independent Efficacy and Safety Evaluation Committee, the trial wasapproved to proceed with further patient recruitment and treatment.
Please see below for a summary of this clinical trial. We look forward to continuing
the evaluation of AE101 and further advancing this promising treatment for bullous
keratopathy.
Summary of the phase II clinical trial
Study design
Target numberof cases

6Evaluation

48 weeks after the implantation of the investigational productandMulticenter, open-label, uncontrolled trial.

observation
periodendpoint

The number and incidence of adverse events, including thosewith a non-negligible causal relationship to the investigational
product (%)

Secondary

1. Safety evaluation

Primaryendpoints

1) Observation and evaluation of safety endpoints
2) Number and incidence of serious adverse events (%)
2. Evaluation of effectiveness1) Improvement in visual acuity at 24 weeks post-implantationof the investigational product.
2) Changes in best-corrected visual acuity over time.
3) Changes in central corneal thickness over time.
4) Changes in corneal endothelial cell density over ti me.

AE101 is a cryopreserved formulation of cultured human corneal endothelial cells,
where human corneal endothelial cells are expanded in vitro and suspended in a
cryoprotectant solution containing a Rho kinase inhibitor. The product is injected
into the anterior chamber of the eye to promote regeneration of the corneal
endothelium.
To expedite the availability of AE101 as a treatment for patients, ActualEyes Inc.
will continue to advance this clinical trial, focusing on confirming both its efficacyand safety. D-Western Therapeutics Laboratories Co., Ltd. (see Note 2) iscollaborating with us in the development of AE101. Additionally, the production ofAE101 for this trial is being outsourced to Japan Tissue Engineering Co., Ltd. (seeNote 3), a company with extensive experience in the development, manufacturing,and commercialization of regenerative medicine products.
Terminology*1 Bullous keratopathy
A condition in which the corneal endothelial cells are damaged, leading to corneal
edema, whitening, and cloudiness, resulting in significant vision loss. Causes
include Fuchs endothelial corneal dystrophy, cataract surgery, glaucoma, and otherocular surgeries that damage the corneal endothelial cells. The current treatment iscorneal transplant surgery using donor corneas.
*2 D-Western Therapeutics Institute, Inc.
For details, please refer to the following website.
De Western Therapeutics Institute (dwti.co.jp)*3 Japan Tissue Engineering Co., Ltd.
For details, please refer to the following website.
Japan Tissue Engineering Co., Ltd. (jpte.co.jp)