For many children, inherited retinal diseases begin early in life, slowly taking away vision with no approved drug therapies available to slow or stop the damage. PolyActiva and RareSight are now working together to address that, collaborating on the development of first-in-class pharmacologic treatments for rare pediatric inherited retinal diseases (IRDs).
The partnership centers on PolyActiva’s PREZIA drug delivery platform, which uses covalent bonding to attach therapeutic agents to a polymer backbone, enabling sustained, zero-order drug release directly to retinal tissue following intravitreal administration. RareSight is contributing disease-area expertise and target validation in pediatric IRDs, where conventional systemic or topical approaches often fail to deliver sufficient drug levels to the back of the eye.
According to the companies, the goal is to advance new chemical entity (NCE)–eligible pro-drug candidates that can maintain consistent therapeutic exposure over extended periods without the need for daily dosing.
Addressing discovery-stage constraints in pediatric IRDs
Jerry St. Peter, CEO and board director of PolyActiva, said that several features of the PREZIA platform motivated its application to pediatric IRDs, where adherence and delivery remain persistent challenges.
“Key aspects of PREZIA for IRD indications are zero-order release of drug over a long period of time, drug delivery directly to the relevant tissue, enhanced compliance in populations where daily dosing is challenging, and versatility of using different molecules to address the disease in the platform,” St. Peter told DDN.
He added that these attributes are particularly relevant in children, where frequent eye drops or repeated injections are often impractical. The platform’s flexibility, he said, also allows PolyActiva and RareSight to “explore multiple therapeutic approaches within the same delivery framework.”
From a chemistry and pharmacokinetics standpoint, St. Peter told DDN that PREZIA enables NCE-eligible candidates because the active molecule is chemically synthesized into the polymer platform itself, rather than being passively embedded in a matrix that erodes over time. This distinction, he said, differentiates PREZIA from other ocular implant technologies. While the collaboration has not disclosed specific targets or pathways, St. Peter noted that PolyActiva has generated extensive internal data supporting the platform’s use across a range of molecular classes.
Biological and translational hurdles in pediatric retinal disease
David Eveleth, PhD, executive chairman of RareSight, told DDN that pediatric IRDs present unique biological challenges that limit the effectiveness of conventional treatment modalities.
“These diseases arise early in development, involve highly specialized retinal cell layers, and occur in very small, rapidly changing eyes,” Eveleth told DDN. He added that systemic and topical therapies rarely achieve therapeutic concentrations in the posterior segment, while frequent dosing is especially burdensome for children and caregivers.
Eveleth told DDN that a targeted, sustained-release implant could bypass the blood–retina barrier and provide continuous, precise drug exposure while minimizing systemic effects. He said RareSight believes this approach increases the likelihood of achieving meaningful structural and functional benefit in a patient population that has historically been difficult to treat pharmacologically.
RareSight’s target and mechanism of action have already been clinically validated by multiple investigators, Eveleth told DDN, but current methods of modulating that target are limited. The collaboration, he said, aims to improve the effectiveness of this mechanism through more consistent tissue exposure rather than by introducing a new biological target.
Bridging discovery and early clinical development
St. Peter added that the preclinical milestones required to advance PREZIA-based candidates toward first-in-human testing are similar to those for traditional small molecules, including toxicology and pharmacology studies to support an investigational new drug application.
From a clinician-scientist perspective, Sandeep Grover, professor of ophthalmology and director of inherited retinal diseases and electrophysiology at the University of Florida, told DDN that IRD development is complicated by uncertainty around disease prevalence, genetic heterogeneity, and natural history.
“There is limited clarity on how rare the condition actually is and whether the patient population is genetically or phenotypically heterogeneous,” Grover told DDN, noting that these factors directly affect trial feasibility, endpoint selection, and expected treatment variability.
Grover also pointed to gaps in understanding disease pathology and a lack of predictive preclinical models as major barriers to translation. He told DDN that early-phase pediatric trials often rely on objective measures — such as optical coherence tomography, electroretinography, and visual evoked potentials — because subjective visual function tests may not be feasible in young children.
Together, Grover said, imaging, electrophysiology, and genetic data can help generate early safety and efficacy signals that support progression into phase 1/2 studies, while accounting for pediatric-specific constraints on trial design.
