Manufacture and release testing of CellThRPE1 for treatment of dry age-related macular degeneration

Abstract

Purpose : The major cause of blindness in the aged population in developed countries has been dry-age related macular degeneration (dAMD) accounting for more than 200 million patients worldwide. Now, there is no treatment or intervention to stop the progression of dAMD, even less, to cure it. We explore if cell replacement therapies can substitute the retinal pigment epithelium (RPE) slowing down the progressive vision loss in dAMD patients.

Methods : Embryonic stem cell were differentiated 63 days and cryostored as mature RPE cells with our GMP suite in the Karolinska Cell Therapy Center. We developed and validated purity, impurity, viability and functional in-vitro assays to identify lingering pluripotent cells and show RPE-specific function. In addition we have initiated 5-year stability testing as well as in use stability and dose delivery accuracy. Toxicology preclinical studies were performed by Charles River in nude rats, efficiency and feasibility studies by Pharmacon in Royal College of Surgeons (RCS) rat or nude rats, respectively.

Results : We manufactured and cryopreserved one engineering and one GMP clinical batch, fulfilling our quality control criteria. We found that the cells maintain these properties during cryopreservation and that our delivery device performs well with sufficient dose accuracy.
The toxicology study results showed no major clinical ophthalmologic and biodistribution concerns. For efficiency studies, ONL thickness, OKR and ERG were evaluated and the results concluded that the rats injected with RPEs showed less degeneration of the retina that is normally observed in the RCS rat model. The feasibility studies showed the cells to be viable and able to be delivered through transvitreous subretinal injection via pars plana into the subretinal space without major complications.

Conclusions : Our new RPE cell product shows promising data relating to feasibility, functionality and safety, supporting further clinical development aiming towards FIH trial within St. Erik Eye Hospital, Stockholm.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.