PulseSight Therapeutics SAS has announced the initiation of its clinical plan for PST-611, a first-in-class non-viral vectorized therapy targeting dry age-related macular degeneration (AMD) and geographic atrophy (GA). The company has submitted a Clinical Trial Authorization (CTA) to the Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM) in France for a Phase I trial (PST-611-CT1) to evaluate the safety and tolerability of PST-611 in humans. This study marks a significant step forward in addressing the unmet needs of patients suffering from these progressive and debilitating eye conditions.
The PST-611-CT1 trial is designed as a first-in-human, single ascending dose study. It aims to confirm the favorable safety profile of PST-611 and determine the optimal dose for a subsequent Phase II proof-of-concept study. The trial will enroll six to twelve patients with dry AMD/GA, with the study expected to commence in early Q2 2025 and a readout anticipated by the end of 2025 or early 2026.
Addressing Iron Homeostasis in AMD
AMD is a leading cause of central vision loss in the elderly, affecting approximately 200 million people worldwide. The pathogenesis of AMD is complex, involving the dysregulation of iron homeostasis, which leads to an excess of free iron, resulting in inflammation, oxidative stress, and cell death. PST-611 is designed to counteract this process by expressing human transferrin, a potent iron regulator, to restore normal iron homeostasis in the retina.
Judith Greciet, CEO of PulseSight Therapeutics, stated, "This first in human study is a significant milestone for the clinical development of PST-611, which we believe holds the potential to become a major new treatment option for patients with dry AMD/GA. Our goal is to confirm the safety of our drug candidate to then rapidly move into a Phase II proof-of-concept study, to demonstrate transferrin’s ability to protect retinal cells from atrophy and preserve vision."
Building on Preclinical Success
The Phase I trial builds upon PulseSight’s previous clinical demonstration of the favorable safety profile of its electrotransfection delivery system and plasmid technology. Preclinical experiments have demonstrated that PST-611 reduces oxidative stress and inflammation and preserves the integrity of the retinal pigment epithelium, potentially preventing retinal degeneration and vision loss.
Dirk Sauer, Chairman of the Board of PulseSight Therapeutics, commented, "This is a pivotal moment as we progress towards clinical studies with our lead program PST-611. PST-611 has shown unique features in terms of efficacy, safety and durability of effect in a robust preclinical plan. This program is the first milestone in the validation of our candidate’s potential to be truly life-changing for dry AMD/GA patients."
Financial Support and Future Development
PulseSight Therapeutics has secured the first close of its Series A financing, with existing investor Pureos BioVentures committing new funds to support the Phase I study of PST-611 and enable preparation for a Phase IIa clinical trial. The Series A financing remains open to new investors, to provide funds to support PST-611 Phase IIa clinical trial preparation and implementation, as well as the development of PulseSight’s wider portfolio of non-viral vectorized therapies, including PST-809 for wet AMD.
Dominik Escher, board director of PulseSight and Partner at Pureos Bioventures, said, “PST-611 is developed in GA, a blinding disease with no treatments approved in Europe. PST-611 has a completely new mode of action with the potential to stop the progression of the disease, a truly high unmet medical need."
