Company plans to move ‘swiftly’ into efficacy studies of non-viral therapy that targets iron dysregulation as a driver of retinal degeneration.
French ophthalmology biotech PulseSight Therapeutics has initiated the first-in-human clinical trial of its lead gene therapy candidate for the treatment of dry age-related macular degeneration and its advanced form, geographic atrophy. The Paris-based company, which emerged from stealth last year, announced the first patient has been dosed in its Phase I trial, seeking to establish the safety and tolerability of its therapy, called PST-611.
Dry AMD, the leading cause of central vision loss among older adults, develops gradually and painlessly with age, progressing to GA, which results in irreversible vision loss and severely impairs quality of life. According to PulseSight, while there has been progress in the treatment of the neovascular, or “wet,” form of the disease, dry AMD continues to represent a significant unmet medical need, with existing therapies only showing modest benefit and requiring monthly injections.
PST-611 is a first-in-class non-viral gene therapy targeting iron dysregulation – a key driver of retinal degeneration – offering a mechanistically distinct approach that PulseSight believes may provide broader and more durable protection. The treatment encodes human transferrin, a protein responsible for regulating iron levels in the eye. Iron is essential to retinal metabolism but, in excess, becomes toxic, triggering inflammation, oxidative stress and, ultimately, cell death, a process known as ferroptosis. These mechanisms are central to the pathogenesis of dry AMD and GA.
By restoring iron balance, PST-611 aims to reduce retinal damage and preserve vision. The therapy leverages PulseSight’s proprietary electro-transfection delivery platform, which introduces therapeutic DNA into the ciliary muscle. The muscle cells then act as biofactories, continuously producing therapeutic proteins that reach the retina. This method offers a minimally invasive, long-acting alternative to frequent intraocular injections, with potential re-treatment intervals of four to six months.
The Phase 1 trial is structured as a single ascending dose study, enrolling between six and twelve patients with dry AMD or GA to determine the safety profile and maximum tolerated dose of PST-611. The trial lays the foundation for a Phase 2 study designed to assess efficacy in preserving retinal structure and function.
“Supported by the previous clinical demonstration of the safety profile of our innovative delivery technology and a solid pre-clinical package, we believe PST-611 holds the potential to improve both anatomical and functional features of dry AMD/GA,” said PulseSight CEO Judith Greciet. “Moreover, the sustained and long-lasting expression of transferrin should help reduce the need for frequent reinjections, strongly improving patients’ compliance to the treatment. Once the safety and the maximal dose are confirmed, our goal is to swiftly move into a Phase 2a proof-of-concept study, to demonstrate the ability of transferrin to protect retinal cells from atrophy and preserve vision.”
The study is being conducted in Paris and Grenoble under the leadership of Professors Francine Behar-Cohen and Christophe Chiquet, with results expected in early 2026.
“Having pioneered the development of the electro-transfection technology that delivers DNA plasmids encoding therapeutic proteins into the ciliary muscle of the eye, I am very excited to move PST-611, expressing transferrin, into its first clinical trial,” said Behar-Cohen, PulseSight’s scientific founder. “Late-stage dry AMD/ GA is a progressing disease that leads to vision loss and for which we have no therapeutic options for our patients. Based on its mechanism of action and thanks to the innovative delivery technology, PST-611 has potential to become a major treatment option for these patients.”
