Corneal Endothelial Cell Therapy Has Potential to Address Unmet Needs for Patients With Corneal Dystrophies

Arnaud Lacoste, PhD

Currently, the typical standard of care for patients with corneal dystrophies in the United States and Western Europe is corneal transplant. Although the procedure can improve vision for these patients, it is invasive, complex, and often yields imperfect outcomes, making it a less–than ideal option for patients and ophthalmic surgeons alike. Furthermore, many patients with corneal dystrophies in other parts of the world cannot receive treatment for their condition at all due to global shortages of donor corneal tissue. As such, a significant unmet need remains for the global patient community.

Arnaud Lacoste, PhD, the chief scientific officer of Aurion Biotech, co-authored a poster entitled, “AURN001, a Cell Therapy with Immunomodulatory Properties Required for Long-term Maintenance of the Immunological Homeostasis of the Eye,” which was presented at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, 2023, in New Orleans, Louisiana.¹ The poster described non-clinical research on the immunomodulatory properties of AURN001, a corneal endothelial cell therapy which was approved in Japan under the name Vyznova in March 2023 and is progressing towards clinical trials in the United States.^2,3

CGTLive™ spoke with Lacoste to learn more about AURN001 and how it could potentially provide an appealing new option for patients and treating surgeons alike.

CGTLive: Can you tell us about the current standard of care for patients affected by corneal dystrophies?

Arnaud Lacoste, PhD: If you are affected by corneal dystrophies, today—and by the way, it affects about 4% of the population over the age of 40, so it's a pretty large patient population—if you get affected by this kind of disease and you live in the US or most of Western Europe, the standard of care is typically a corneal transplant. So, you will receive a corneal transplant, meaning that part of the cornea or the whole cornea will be replaced by corneal tissue that is obtained from a deceased organ donor.

What unmet needs remain for patients who receive corneal transplants?

This standard of care will restore vision for several years, but it comes with a few issues. For patients, it requires that they lie on their back for several days after the surgery is performed for the graft to attach. And it often requires surgical adjustments in the operating room after the graft is put in place to readjust the graft. The quality of vision is also often not optimal. Because the interface between the graft and the recipient’s cornea is not perfect, there are some irregularities in the topology of the tissue. And that affects vision because that affects the path of light, and it can create halos that affect the quality of vision.

For ophthalmic surgeons, corneal transplant is actually a complicated procedure to perform and for many surgeons it is not really an attractive—or at least economically attractive—part of their practice. So,a standard of care exists, but many, many things can be improved there.

And that is just for the US and Western Europe. Outside of Western Europe and the US, if you get corneal dystrophy, you probably won't be treated because the supply of corneal tissue typically doesn't meet the demand. In fact, it is estimated that, worldwide, about 1 cornea is available for 70 needed. So, most patients outside of the US and Europe will most likely lose vision because of this disease.

What is AURN001? Can you describe its makeup?

AURN001—which we actually call corneal endothelial cell therapy—is an allogeneic cell therapy. It is “universal” and it aims at treating corneal dystrophies. The idea for creating this cell therapy originates from the fact that there is now considerable evidence, especially clinical evidence, showing that corneal dystrophy is because of the loss of pretty much only 1 cell type: a cell type called corneal endothelial cells. These cells normally form a monolayer on the posterior side of our cornea; that monolayer is called the corneal endothelium. That monolayer of cells is necessary and sufficient to restore vision. The rest of the cornea that is included in a corneal transplant actually does not drive efficacy—doesn’t contribute to restoring vision—only the corneal endothelial cells do.

How is AURN001 intended to address unmet needs for patients with corneal dystrophies?

It seems to us that a cell therapy is the much better option than typical corneal transplant for both patients and ophthalmic surgeons. For patients, the procedure required to deliver cells is much less invasive than a typical corneal transplantation and our clinical studies suggest that the cell therapy restores vision at least to the level that corneal transplants do currently. For ophthalmic surgeons, cell therapy is also very advantageous because the procedure is less complex to perform. This makes it much more likely that more ophthalmic surgeons will be able to provide the treatment and that improves, of course, patient access. 

Again, that is only for the US and the Western world. Worldwide, having a cell therapy as a replacement for corneal transplantation addresses the gap between the demand for treatment and tissue availability. As I mentioned earlier, we have about 1 cornea available for about 70 needed. With our cell therapy, we can take 1 tissue from 1 donor and generate many doses. And that will eventually enable us to bridge the gap between the demand for treatment and the supply. And because our cell therapy, again, is allogeneic—so it’s universal—from that 1 donor, we can treat any patients, regardless of their HLA type. This is very important because, again, it speaks to the impact that this cell therapy will have worldwide. And we've made good progress so far with this cell therapy. We received approval in Japan about 6 weeks ago and we are on track to bring it to patients in the US and Europe and eventually the rest of the world.

Transcript edited for clarity.

REFERENCES
1. Littlefield C, Berenshteyn F, Yasin J. AURN001, a cell therapy with immunomodulatory properties required for long-term maintenance of the immunological homeostasis of the eye. Presented at: Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting. April 23-27, 2023; New Orleans, LA. Abstract #779 – C0380
2. Aurion Biotech receives approval from Japan’s PMDA for new drug application. News release. Aurion Biotech. March 23, 2023. Accessed April 25, 2023. https://aurionbiotech.com/aurion-biotech-receives-approval-from-japans-pmda-for-new-drug-application/
3. Aurion Biotech. Products. Website. Accessed April 25, 2023. https://aurionbiotech.com/products/