Shots:
- PulseSight Therapeutics is advancing a novel approach to Geographic Atrophy (GA) with PST-611, a first-in-class non-viral gene therapy designed to restore iron homeostasis by targeting transferrin biology—an upstream driver of retinal degeneration.
- At ARVO 2026, PST-611 delivered encouraging Phase I results, demonstrating an excellent safety and tolerability profile, stable visual acuity, and early signals of potential functional and anatomical benefit in patients with dry AMD-associated GA.
- PharmaShots welcomes Judith Greciet, PharmD, Chief Executive Officer of PulseSight Therapeutics, to discuss the promise of targeting iron dysregulation in retinal disease, the advantages of PulseSight’s non-viral gene therapy platform, and the company’s strategy to advance next-generation treatments for GA and other retinal disorders.
Saurabh: PulseSight recently presented positive Phase I data for PST-611 at ARVO 2026. Could you highlight the key findings and their significance for patients with dry AMD/Geographic Atrophy (GA)?
Judith: The PST-611 Phase 1 clinical trial (PST-611-CT1) was a single ascending dose first-in-human trial that evaluated the safety and tolerability of in two successive dose groups, in a total of six patients, with a 16-week follow-up in patients with Geographic Atrophy (GA).
PST‑611’s Phase I study delivered a highly encouraging early clinical profile for patients with GA, an area where therapeutic progress has historically been slow. This first‑in‑human, single‑ascending‑dose trial, aimed to assess the safety and tolerability of PST-11 in a total of six GA patients, with a 16-week follow-up. The study met all primary and secondary endpoints, demonstrating excellent safety and tolerability across both dose levels. Most reported ocular adverse events were mild, with two assessed as moderate. There were no observations of intraocular inflammation, and no treatment emergent serious adverse events (SAE) or suspected unexpected serious adverse reactions (SUSAR) were reported. The Best Corrected Visual Acuity (BCVA) was stable over the entire follow-up period.
Importantly, although not designed to assess efficacy, early functional and anatomical signals were observed, including spontaneous patient reports of vision improvement and inflections in GA lesion growth, with one patient showing a response that persisted beyond the 16‑week follow‑up.
For patients with GA, where progression is relentless and treatment options remain limited, these findings underscore the potential of PST‑611 as a new therapeutic modality with the potential to improve both functional and anatomical outcomes.
Saurabh: PST-611 utilizes a non-viral gene therapy approach targeting iron dysregulation in GA. What led PulseSight to focus on transferrin biology and iron homeostasis as a therapeutic strategy?
Judith: GA is a multifactorial disease involving a dysregulation of iron homeostasis. PST-611 is a first-in-class gene therapy candidate encoding transferrin, a natural iron transporter playing a key role in iron homeostasis.
Abnormal iron deposits were first documented in the retinas of dry AMD patients over two decades ago. Since then, multiple lines of evidence, have pointed toward iron overload as a driver of retinal degeneration. Today, iron dysregulation is increasingly recognized as a therapeutic target, alongside a deeper understanding of iron-related cascades — most notably ferroptosis.
Transferrin is a glycoprotein responsible for binding and transporting iron thus maintaining normal iron homeostasis. Iron is needed to ensure proper cell and visual cascade function but excess of non-bound iron triggers highly toxic cascades leading to ferroptosis, an iron mediated cell death mechanism.
Containing a plasmid coding for human transferrin, PST-611 restores normal iron homeostasis and prevents the iron-induced toxic cascade.
PST-611 represents a firstinclass, upstream approach that addresses a root cause rather than a downstream inflammatory consequence.
Saurabh: Geographic Atrophy remains an area of high unmet need despite recent approvals. How does PST-611 differentiate itself from existing and emerging therapies in the retinal disease landscape?
Judith: Complement inhibitors have opened the door for GA treatment, with their recent approval in the US. However, these drugs target the complement cascade, one of the multiple pathways involved downstream in GA. Their modest slowing of lesion growth, lack of demonstrated functional benefit, and frequent intravitreal dosing have limited adoption. They have not been approved in Europe.
PST‑611 differentiates itself in three key ways:
- Upstream mechanism: It targets iron dysregulation, involved upstream in the disease and triggering many of toxic pathways including ferroptosis, leading to retinal atrophy and vision loss.
- Nonviral gene therapy: Enables sustained protein expression without the risks associated with viral vectors, nor the cost and allowing a long acting although transient efficacy.
- Reduced injection frequency: Thanks to the innovative administration technology
On top of these attributes, PST-611 has demonstrated an excellent safety and tolerability profile, in its first-in-human Phase 1 study.
All these differentiating advantages position PST‑611 as a next‑generation therapeutic with the potential for deeper and more durable impact.
Saurabh: PulseSight’s electro-transfection delivery platform represents a novel approach in ophthalmology. Could you elaborate on the technology and the advantages it may offer over conventional viral gene therapies?
Judith: The administration system consists of a dedicated ocular device linkedto a pulse generator delivering controlled electrical pulses that transiently increase cell membrane permeability, enabling plasmid penetration into the ciliary muscle cells. Once transfected, these cells act as a biofactory, producing therapeutic proteins that distribute into the vitreous and the retina in a sustained manner.
Our delivery technology has demonstrated a favourable safety profile in both preclinical and clinical studies. The same administration procedure and device is applicable across all drugs of our platform.
Key advantages include:
- Non‑viral delivery, avoiding immunogenicity and cargo‑size limitations and viral related toxicity and regulatory burden.
- Repeat‑dose feasibility, which is challenging for viral vectors.
- Manufacturing simplicity reduces cost and complexity compared with AAV‑based therapies.
- Broader payload flexibility enables delivery of larger or multiple genes not compatible with AAV capsid size limits.
- Platform scalability, with the same device and procedure applicable across multiple programs.
This positions PulseSight as a leader in next‑generation ocular gene therapy modalities.
Saurabh: Treatment burden continues to be a major challenge in retinal disorders. How meaningful is PST-611’s potential for sustained protein expression with only limited annual dosing?
Judith: Treatment burden is a defining challenge in retinal disease. PST‑611’s ability to achieve sustained intraocular protein expression for up to six months in preclinical models offers a meaningful advantage.
Unlike intravitreal injections required monthly or bimonthly, PST‑611’s ciliary muscle delivery is designed for durability and convenience.
This could translate into better adherence, fewer clinic visits, and a more manageable long‑term treatment experience for elderly patients.
Saurabh: Safety and tolerability were primary endpoints in the Phase I study. What insights did the trial generate regarding PST-611’s safety profile and clinical feasibility?
Judith: The Phase I study confirmed that PST‑611 has an excellent safety and tolerability profile, with no intraocular inflammation, no SAEs, and stable BCVA throughout the 16‑week follow‑up. The absence of inflammation is particularly notable given the challenges seen with some viral gene therapies. These findings support advancing to repeat‑dose studies and reinforce the safety of the electro‑transfection platform.
Saurabh: Following the encouraging Phase I results, what are the key objectives and anticipated milestones for the upcoming Phase IIa development program?
Judith: PulseSight plans to initiate a repeatdose Phase IIa trial evaluating three administrations of high‑dose PST‑611 over 52 weeks. The goals are to:
- Further characterize safety under repeat dosing.
- Explore efficacy signals across functional and anatomical endpoints.
- Inform dose selection and design for subsequent pivotal studies.
This Phase IIa program represents the next major inflection point for PST‑611’s clinical development.
Saurabh: Beyond PST-611, how scalable is PulseSight’s non-viral gene therapy platform across other ophthalmic or retinal disease indications?
Judith: Our platform is inherently modular. Because it relies on plasmid DNA rather than viral vectors, we can rapidly adapt it to encode different therapeutic proteins relevant to other retinal diseases — including inherited retinal dystrophies, diabetic retinopathy, and macular edema etc. The ability to re‑dose safely is particularly attractive for chronic or progressive conditions requiring long‑term modulation of biological pathways.
The absence of cargo size limitation allows large transgene including transgene coding for two proteins, as it is the case with PST-809 coding for aflibercept and decorine.
Saurabh: The ophthalmology space is rapidly evolving with innovations in gene therapy, complement inhibition, and regenerative medicine. How does PulseSight position itself within this competitive ecosystem?
Judith: PulseSight occupies a unique position at the intersection of gene therapy innovation and practical clinical applicability.
While many competitors focus on complement inhibition, viral vectors, or cell‑based regeneration, PulseSight is pioneering a repeatdose, nonviral, multicargo gene therapy platform with broad applicability. This positions the company as a potential partner of choice for next‑generation retinal therapeutics.
The administration procedure is minimally invasive, therefore suitable for chronic diseases and fitting normal ophthalmology practices (like IVTs).
Saurabh: Looking ahead, what are PulseSight Therapeutics’ strategic priorities over the next 12–24 months as the company advances its retinal disease pipeline and partnership opportunities?
Judith: PulseSight’s near‑term priorities are clear:
- Advance PST‑611 into its Phase IIa repeat‑dose study.
- Secure the funding required to execute this trial and progress additional pipeline assets.
- Continue development of PST‑809 and other platform‑enabled programs.
- Build strategic partnerships to accelerate clinical and commercial pathways.
About Judith Greciet, PharmD
Chief Executive Officer
Judith brings over three decades of experience in the pharma and biotech industries. Since 2022, she has been providing consulting and advisory services to healthtech companies, particularly start-ups focusing on innovative and unique healthcare projects. She was previously CEO at Onxeo, a publicly listed French Biotech company for 12 years and, during her time there, she successfully completed global registrations and licensing agreements with commercial partners, while reshaping the company’s strategic direction towards breakthrough innovations, especially in oncology. She also executed two M&A transactions, including a cross-border deal with a Danish-listed company and the acquisition of DNA Therapeutics, a spin-off from the Institut Curie, which positioned the company in the promising field of Tumoral DNA Damage Response (DDR) inhibition. Previous experience included 15 years in international pharma companies, including roles in sales, marketing, and strategy (Pharmacia, Zeneca, LFB, Wyeth France – now Pfizer), and was appointed President of Eisai France in 2007. She is a Doctor of Pharmacy and holds a postgraduate degree in Pharmaceutical Management and Marketing.
