PulseSight Therapeutics Presents New Data on PST-611 Transferrin Vectorized Therapy for Geographic Atrophy at EVER Congress 2024
Paris, France, 6th November 2024 – PulseSight Therapeutics SAS, an ophthalmology biotech company developing disruptive non-viral vectorized therapies with minimally-invasive delivery technology, has presented new data on its lead program PST-611, a DNA plasmid expressing human transferrin, in dry age-related macular degeneration (AMD)/geographic atrophy (GA) at the European Association for Vision and Eye Research 27th 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), characterized by atrophy of the retinal pigment epithelium (RPE), photoreceptors, and choriocapillaris, responsible for a progressive vision loss.
PST-611 is a first in class non-viral vectorized therapy for the treatment of dry AMD/GA coding for human transferrin, a highly potent iron chelator, thus 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 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.
Whilst PulseSight has confirmed transferrin as a drug candidate for the treatment of GA and dry AMD, the development of novel treatments for retinal diseases is often hindered by the challenge of delivering the drug to the back of the eye. To address these limitations, 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.
These data support the continued clinical development of PST-611 for dry AMD/GA patients.
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 patient’s visual function. As a novel non-viral vectorized 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. We look very much forward to demonstrating the value of our candidate in the soon to start clinical plan.”
PulseSight plans to submit a phase I clinical trial authorization (CTA) by the end the year, to be closely followed by a phase II proof-of-concept to demonstrate the efficacy and the safety of its drug candidate PST-611 by the end 2027.
References
- Oral and Poster Presentation by Dr Thierry Bordet (CSO): Transferrin is a drug candidate for the treatment of geographic atrophy (GA)/dry age-related macular degeneration (AMD)
Presentation 09:20- 10:35 CET
Poster 11:05-12:05 CET (ID# T.129)
Bordet T, Youale J, Bigot K, Jaworski T, Lebon C, Françon C, Delaunay K, Bénard R, De Bastard T, Kaddour N, Behar-Cohen F, Picard E
PulseSight Therapeutics, Paris, France,
Université Paris Cité; Sorbonne Université; INSERM, Paris, France
AP-HP, Paris, France
- Poster Presentation by Dr Karine Bigot (Head Pharmacology & Toxicology): Non-clinical safety of PST-611, non-viral vectorized human transferrin, for the treatment of geographic atrophy (GA)
Presentation 11:05-12:05 CET (ID# T.063)
Karine Bigot, Romain Bénard, Pauline Gondouin, Marie Piazza, Elise Orhan1, Elodie Touchard, Francine Béhar-cohen, Thierry Bordet
PulseSight Therapeutics, Paris, France,
Université Paris Cité; Sorbonne Université; INSERM, Paris, France
AP-HP, Paris, France
