RPE stem cells may address the cause of AMD

May open a new opportunity for treating retinal diseases

Dr. Keith E. Dionne (Chief Executive Officer), Dr. Sally Temple (Founder, Chief Scientific Officer), Dr. Jeffrey Stern (Founder, Co-CEO)

“Added 2 clinical sites recently, and is aiming to complete Phase 1/2a trial by the fourth quarter of this year"

What if damaged human tissues and organs could be “restored”?

 

If severed spinal cords could be reconnected, and eyes that have lost their sight could once again detect light on their own.

 

The technology to revive human tissues that have lost their function has been a long-standing aspiration of humanity.

 

Tissue regeneration using stem cells is considered the key to opening this new frontier in treatment.

 

Stem cells are cells that possess both self-replication and differentiation capabilities.

 

They can not only replicate themselves infinitely but also transform into various types of cells in the body as needed, making them a focal point in regenerative medicine.

 

However, despite the high expectations for stem cells, there is prevalent skepticism both within and outside the academic community.

 

This is due to the limited number of cases where its therapeutic efficacy has been clearly demonstrated, as well as unresolved challenges such as long-term safety and the potential for tumor formation.

 

In Korea, stem cell technology has often been labeled as the “technology of doubt” since the 2005 scandal involving the fabrication of research papers by Woo Suk Hwang.

 

Despite this, some companies continue to believe in the potential of this technology and are actively pursuing its development.

 

One such company is Biotechnology.

 

Luxa is a U.S.

 

joint venture established in 2019 by Y2 Solution and Neural Stem Cell Institute (NSCI), the first independent stem cell research institute in the U.S.

 

Luxa is currently developing “RPESC-RPE-4W,” a candidate drug for the treatment of dry age-related macular degeneration using retinal pigment epithelial stem cell (RPESC).

 

Luxa's Chief Scientific Officer is Dr.

 

Sally Temple, co-founder of Luxa and co-founder of NSCI.

 

Dr.

 

Temple is a world-renowned authority in the field of stem cells, having first identified neural stem cells in the adult central nervous system.

 

Dr.

 

Jeffrey Stern is Dr.

 

Temple's spouse and a retina specialist ophthalmologist who co-founded NSCI with her, and is jointly leading the development of stem cell-based therapies.

 

Dr.

 

Keith Dionne is also a key member of Luxa's executive team.

 

Dr.

 

Dion is a seasoned executive with over 20 years of experience in the biotechnology industry, having served as CEO of four biotechnology companies, including Alantos Pharmaceuticals, Surface Logix, Constellation Pharmaceuticals, and Casma Therapeutics, where he led the growth and mergers and acquisitions (M&A) of these companies.

 

Dr.

 

Dion currently leads the company as co-CEO.

 

Dailypharm met with Dr.

 

Temple, Dr.

 

Stern, and Dr.

 

Dionne at the 2025 annual meeting of the Association for Research in Vision and Ophthalmology held in Salt Lake City.

 

Utah, to hear about the competitiveness of RPESC-RPE-4W, the latest clinical results, and the company’s future development strategies.

 

(from the left) Dr.

 

Keith E.

 

Dionne, Dr.

 

Sally Temple, Dr.

 

Jeffrey Stern

- What kind of treatment is Luxa’s RPESC-RPE-4W? Dr.

 

Temple: RPESC-RPE-4W is a cell therapy candidate for dry age-related macular degeneration (AMD) based on adult retinal pigment epithelial stem cells (RPESC).

 

Dry AMD is caused by the degeneration of RPE cells located in the central part of the retina, ultimately leading to central vision loss.

 

This candidate aims to improve the damaged retinal environment and help restore vision by culturing RPE cells externally and transplanting them into the patient's retinal layer.

 

It is currently in Phase 1/2a clinical trials.

 

- I understand that NSCI has begun preclinical research on RPESC-RPE-4W.

 

What prompted the development of a treatment for dry AMD? Dr.

 

Temple: The discovery of RPE cells in 2012 opened up new opportunities for treating retinal diseases.

 

At the time, my husband, Dr.

 

Stern, was treating many patients with macular degeneration, including my mother.

 

It was then that I learned there was no effective treatment for dry AMD.

 

After realizing that RPE cells could potentially address the underlying cause of AMD, we conducted animal experiments and observed significant recovery of vision loss.

 

Dr.

 

Temple: Central nervous system tissue was long considered incapable of regeneration, but this perception is changing as recent research suggests that some regeneration is possible.

 

The discovery of how certain levels of recovery can occur after disease or injury has raised the possibility that stem cells or progenitor cells responsible for regeneration may exist within the CNS.

 

-There is still skepticism within the academic community regarding stem cell therapy.

 

What is your perspective on this? During my PhD, I studied progenitor cells in single-cell culture, which was a highly suitable approach for investigating stem cells in the brain or retina.

 

During the research, Dr.

 

Stern provided significant assistance in developing a time-lapse video system that enabled us to track and observe brain cells in culture.

 

Using this system, we identified a rare but actual population of stem cells within the central nervous system.

 

The next question was how these central nervous system stem cells are regulated.

 

Through our research, we discovered that whether stem cells remain in a quiescent state or actively divide to regenerate brain tissue depends on how closely they are in contact with blood vessels.

 

Based on this finding, NSCI was established in 2005.

 

In recent years, we have observed patients with age-related macular degeneration who have shown improvements in vision following RPE stem cell transplantation therapy, which has brought us great joy in seeing that our research is benefiting.

 

- What is the current status and outlook for the dry AMD treatment market?

 

Dr.

 

Dionne: Dry AMD affects approximately 200 million people worldwide, and this number is expected to increase with the aging population.

 

It is one of the leading causes of blindness in adults, and there is currently no fundamental cure.

 

The current best treatment is complement inhibitors, with FDA-approved drugs such as Syfovre and Izervey.

 

However, these treatments require monthly or bimonthly injections into the back of the eye and only slow disease progression without improving vision.

 

Luxa's RPESC-RPE-4W has demonstrated the potential to replace damaged RPE cells and improve vision.

 

Additionally, recent reports indicate that global pharmaceutical giants like Merck in the U.S.

 

are acquiring ophthalmic biotech companies targeting smaller markets than dry AMD for billions of dollars.

 

This demonstrates that the size of the market is not the key factor, but rather how quickly we can respond to it.

 

-Dry AMD treatments are being developed by several companies besides Luxa.

 

Various therapeutic agents with different mechanisms, such as induced pluripotent stem cells (iPSCs), embryonic stem cells, and gene therapies, are under development.

 

What makes RPESC-RPE-4W unique? Dr.

 

Temple: The biggest difference between Luxa's clinical trial and others is the type of RPE cells being transplanted.

 

We use “adult RPE stem cells” that are specialized to develop into RPE cells.

 

In contrast, other therapies first create pluripotent stem cells, such as iPSCs or embryonic stem cells, which can differentiate into various cell types, and then artificially differentiate them into RPE cells for transplantation.

 

This approach involves a complex differentiation process and carries the risk of unwanted cells being mixed in.

 

Luxa eliminates the risk of generating abnormal cells by directly using adult RPE stem cells.

 

Additionally, adult RPE stem cells are highly stable, do not induce tumors, and effectively differentiate into the desired RPE cells, making them more suitable for treatment.

 

-Please tell us about the interim results of the RPESC-RPE-4W Phase 1/2a trial presented at ARVO 2025. Dr.

 

Stern: Luxa is conducting the RPESC-RPE-4W Phase 1/2a clinical trial, and at this conference, we presented data from the low-dose Cohort 1, which involved administering 50,000 cells to six patients.

 

The interim results showed no serious adverse events (SAEs), tumorigenicity, inflammatory responses, or retinal detachment associated with the investigational drug.

 

As a result, the company is now able to proceed to the next phase, which involves increasing the dose to 150,000 and 250,000 cells.

 

ETDRS chart (Source: Luxa)

Early signs of vision recovery were also observed in the trial.

 

Luxa measured changes in vision after RPESC-RPE-4W administration using the ETDRS (Early Treatment Diabetic Retinopathy Study) chart.

 

Each line contains five letters.

 

Being able to read 15 more letters means being able to read 3 more lines.

 

Interim results of the Phase 1/2a clinical trial showed that patients with the poorest vision were able to read approximately 21 more letters or 3 more lines on the ETDRS chart.

 

Before treatment, patients could only read the largest letters, but after treatment, they were able to read the fourth line on the ETDRS chart due to an improvement of three lines in visual acuity.

 

Visual acuity improved within approximately one month after administration, and the effect was maintained stably throughout the one-year clinical period.

 

-What is your outlook for the RPESC-RPE-4W clinical trial, and how do you plan to develop it in the future? Dr.

 

Stern: I believe that the current results are most likely to continue.

 

While there is a possibility that the eight patients treated so far are exceptional cases, the probability is very low.

 

To confirm this, we need to analyze all 18 patients who participated in the clinical trial.

 

Since initial safety and tolerability have already been established, we have added two new clinical sites to accelerate the clinical trial.

 

One is the Byers Eye Institute at Stanford University in the United States, and the other is LA Retina, a large private hospital located in Los Angeles, California, United States.

 

The ongoing Phase 1/2a clinical trial is scheduled to be completed by the fourth quarter of this year.

 

Following this, the company plans to seek business partners to conduct large-scale clinical trials and obtain FDA approval for RPESC-RPE-4W.