PulseSight Therapeutics has achieved a significant milestone by dosing the first patient in its Phase I clinical trial of PST-611, a novel non-viral vectorized therapy targeting dry age-related macular degeneration (AMD) and geographic atrophy (GA). The Paris-based ophthalmology biotech company announced that the first-in-human study (PST-611-CT1) has commenced, marking a crucial step forward in addressing a major unmet medical need affecting 200 million people worldwide.
Novel Approach to Iron Homeostasis
PST-611 represents a first-in-class therapeutic approach that expresses human transferrin, a highly potent iron regulator that plays a central role in restoring normal iron homeostasis. The therapy directly addresses the pathological mechanisms underlying dry AMD, where dysregulation of iron homeostasis leads to an excess of free iron causing highly toxic effects including inflammation, oxidative stress, and ultimately retinal cell death through ferroptosis.
"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," said Professor Francine Behar-Cohen, MD, PhD at the Department of Ophthalmology, Cochin – Assistance Publique-Hôpitaux de Paris (AP-HP), who pioneered the underlying electro-transfection technology. "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."
Clinical Trial Design and Timeline
The PST-611-CT1 study is designed as a first-in-human single ascending dose study that will establish the safety profile of the drug and validate the maximal tolerated dose in six to a maximum of 12 dry AMD/GA patients. The trial is being conducted at two sites in France: Paris under Professor Behar-Cohen's leadership and Grenoble under Professor Christophe Chiquet, MD, PhD at the Department of Ophthalmology, CHU Grenoble Alpes.
Preliminary results from the Phase I trial are anticipated in early 2026, subject to patient recruitment. The company plans to use these safety and dosing data to advance into a Phase IIa proof-of-concept study designed to demonstrate transferrin's ability to protect retinal cells from atrophy and preserve vision.
Innovative Delivery Technology
The therapy utilizes PulseSight's proprietary electro-transfection technology platform, which delivers DNA plasmids encoding therapeutic proteins into the ciliary muscle of the eye. The ciliary muscle cells function as biofactories, expressing therapeutic proteins that reach the retina with high distribution. This approach has already been clinically validated for its safety and sustained activity.
A key advantage of this delivery system is the potential for extended dosing intervals. According to the company, PST-611 may require retreatment only every four to six months, which could significantly improve patient compliance compared to more frequent injection regimens.
Market Opportunity and Unmet Need
AMD represents the leading cause of central vision loss in the elderly, with dry AMD being the most common form that progresses through successive stages into geographic atrophy. The disease causes progressive, painless loss of central vision with a strong burden on patients' everyday life, impacting their ability to read, recognize faces, and see objects, ultimately leading to irreversible central vision loss.
The AMD market represents a compelling opportunity, with estimates projecting it will reach $27.5 billion by 2031. Despite this large market, significant unmet medical needs remain, particularly for dry AMD/GA where therapeutic options are limited.
Company Perspective
Judith Greciet, CEO of PulseSight Therapeutics, emphasized the significance of this milestone: "The dosing of the first patient in our PST-611-CT1 trial is a very exciting milestone for the company. 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."
PulseSight Therapeutics is backed by investors including Pureos Bioventures, ND Capital, and Korea Investment Partners (KIP). The company focuses on developing disruptive non-viral vectorized therapies with minimally invasive delivery technology for retinal diseases, with particular emphasis on age-related macular degeneration including both wet AMD and geographic atrophy secondary to dry AMD.
