PulseSight Reports Positive Phase 1 Results for PST-611 in Geographic Atrophy

PulseSight Therapeutics SAS has reported encouraging Phase 1 clinical trial results for PST-611 in patients with late-stage dry age-related macular degeneration (AMD), also known as geographic atrophy (GA).

The findings were presented at the ARVO 2026 Annual Meeting and mark an important early milestone for a novel non-viral gene therapy platform targeting retinal disease.

A New Approach to Geographic Atrophy

Geographic atrophy is an advanced form of dry AMD that causes irreversible retinal degeneration and progressive central vision loss.

Unlike existing approaches that mainly slow disease progression, PST-611 targets a different biological pathway: iron homeostasis.

The therapy encodes transferrin, a naturally occurring protein responsible for regulating iron balance in retinal tissues.

Researchers believe excess free iron contributes to:

• Oxidative stress
• Retinal inflammation
• Lipid peroxidation
• Ferroptosis-driven cell death

By restoring physiological iron regulation, PST-611 aims to address an underlying disease mechanism rather than only treating symptoms.

Inside the Phase 1 Trial

The first-in-human study, PST-611-CT1, evaluated safety and tolerability across two dose levels.

Trial Design

• Single ascending dose study
• Six patients with late-stage GA
• Low-dose and high-dose cohorts
• 16-week follow-up period
• Conducted in Paris and Grenoble, France

The study was led by investigators from:

• Assistance Publique-Hôpitaux de Paris
• CHU Grenoble Alpes

Safety Results Met Primary Objectives

According to PulseSight, PST-611 demonstrated:

• Excellent safety and tolerability
• No intraocular inflammation
• No serious adverse events (SAEs)
• No suspected unexpected serious adverse reactions (SUSARs)

Most ocular adverse events were mild, while two were classified as moderate. Importantly, best corrected visual acuity (BCVA) remained stable throughout the study period.

For retinal gene therapies, achieving strong early safety data is critical given the sensitivity of ocular tissues and the chronic nature of AMD.

Early Efficacy Signals Draw Attention

Although the trial was not designed to evaluate efficacy, investigators reported encouraging early signals.

Functional Signals

Several patients spontaneously reported:

• Noticeable vision improvements
• Functional visual benefits after treatment

Anatomical Signals

Researchers also observed:

• Inflections in geographic atrophy lesion growth
• Potential slowing of disease progression

In one patient, the observed effect persisted beyond the official follow-up period. These findings remain preliminary, but they are notable for a small Phase 1 safety study.

Why PST-611 Stands Out?

Most retinal gene therapies rely on viral vectors delivered directly into the eye through invasive procedures. PulseSight is taking a different approach.

Non-Viral Delivery Platform

The company’s platform:

• Uses DNA plasmids instead of viral vectors
• Delivers therapy into the ciliary muscle
• Employs electro-transfection technology
• Enables minimally invasive administration

The ciliary muscle then acts as a “biofactory,” producing therapeutic proteins that reach retinal tissues.

Potential advantages include:

• Improved safety profile
• Reduced immune response risk
• Long-acting protein expression
• Less invasive delivery compared with subretinal injections

Moving Into Phase 2a

Following the positive Phase 1 readout, PulseSight Therapeutics SAS plans to initiate a repeat-dose Phase 2a trial.

Planned Phase 2a Study

Key details include:

• Three administrations of high-dose PST-611
• Up to 20 patients
• 52-week treatment period
• Three clinical trial sites in France

The company has already submitted a Clinical Trial Authorization (CTA) application to the French regulator:

• Agence Nationale de Sécurité du Médicament et des produits de santé

If approved:

• Enrollment is expected to begin in H2 2026
• Results are anticipated in 2028

The Growing Geographic Atrophy Market

AMD affects roughly 200 million people globally, while geographic atrophy impacts more than 5 million patients worldwide. Key challenges include:

• Irreversible vision loss
• Limited therapeutic options
• Major quality-of-life decline

Patients often lose the ability to:

• Read
• Recognize faces
• Drive
• Perform daily tasks independently

The market opportunity is substantial, with AMD therapies projected to reach approximately $27.5 billion by 2031.

The Bigger Picture for Retinal Gene Therapy

PST-611 reflects a broader industry shift toward:

• Durable ophthalmic therapies
• Disease-modifying mechanisms
• Non-viral delivery systems
• Less invasive retinal treatment approaches

If future studies confirm the early signals seen in Phase 1, PST-611 could emerge as a differentiated treatment candidate in geographic atrophy, particularly because it targets iron dysregulation rather than complement inhibition pathways used by current therapies.

Conclusion

The Phase 1 results for PST-611 provide an encouraging early look at a novel therapeutic strategy for geographic atrophy.

For PulseSight Therapeutics SAS, the combination of strong safety findings and preliminary efficacy signals supports advancement into mid-stage clinical development.

The upcoming Phase 2a trial will now determine whether these early observations can translate into meaningful long-term protection against vision loss in patients with dry AMD.