New data have revealed the potential of a DNA plasmid expressing human transferrin for the treatment of dry age-related macular degeneration (AMD) and geographic atrophy (GA).

PulseSight Therapeutics shared the data on its lead programme PST-611 at the European Association for Vision and Eye Research (EVER) Congress 2024.

AMD is the leading cause of central vision loss in the elderly, affecting 200 million people worldwide. AMD’s pathogenesis is complicated and involves the disruption of iron homeostasis, leading to an excess of free iron, which results in inflammation, oxidative stress, and cell death.

In advanced stages, dry AMD progresses into geographic atrophy (GA), characterised by atrophy of the retinal pigment epithelium (RPE), photoreceptors, and choriocapillaris, responsible for a progressive vision loss.

PST-611 is a non-viral vectorised therapy for the treatment of dry AMD/GA coding for human transferrin, a highly potent iron chelator, thus restoring normal iron homeostasis.

Restoring normal iron homeostasis

During his oral presentation, Dr Thierry Bordet, CSO of PulseSight, showed data from a retrospective study in a large cohort of dry AMD patients confirming a higher level of free iron and increased transferrin saturation in AMD patients versus control patients.

Additionally, he presented data showing that transferrin supplementation in iRPE (human iPSC-derived retinal pigment epithelial) cells exposed to high concentration of iron, restores iron homeostasis and rescued RPE cells from oxidative stress, mitochondrial damage, inflammation, complement activation, and ferroptosis, preserving their integrity.

The development of novel treatments for retinal diseases is often hindered by the challenge of delivering the drug to the back of the eye. At EVER, Dr Karine Bigot, Head Pharmacology & Toxicology at PulseSight, presented a poster demonstrating the safety of PST-611, administered to the ciliary muscle using a minimally invasive electrotransfection system.

Thierry Bordet, CSO of PulseSight Therapeutics said: “Excess iron is known to be highly toxic to retinal cells, leading to oxidative stress, inflammation, and ferroptosis. By restoring normal iron homeostasis, transferrin mitigates these toxic effects and protects retinal cells, offering the potential to slow GA lesions’ growth and improve patients’ visual function. As a novel non-viral vectorised gene therapy delivered through electroporation, PST-611 benefits from a very good safety profile. We are convinced that PST-611 could become a major treating option for dry AMD patients who are progressively losing sight and for which the medical need is huge.”

PulseSight plans to submit a Phase I clinical trial authorisation (CTA) by the end the year, to be followed by a Phase II proof-of-concept to demonstrate the efficacy and the safety of PST-611 by the end 2027.

Diana Spencer, Senior Digital Content Editor, DDW