SparingVision’s first AAV-based gene therapy, SPVN06, is a breakthrough gene-agnostic therapy approach targeting inherited retinal diseases (IRDs).

SPVN06 has the potential to preserve visual function and slow the degeneration of cone photoreceptors, which ultimately leads to blindness. The initial disease target for SPVN06 is retinitis pigmentosa (RP), one of the most common inherited retinal diseases that affects two million patients worldwide.

SPVN06 treatment is gene-agnostic, and, therefore potentially capable of addressing more than 80 known genetic mutations of RP. SPVN06 expresses proprietary neurotrophic factors (Rod derived Cone Viability Factor, RdCVF) and one enzyme reducing oxidative stress (Rod derived Cone Viability Factor Long form, RdCVFL). It aims to maintain cone metabolism by delivering RdCVF through a single subretinal delivery via AAV vector.

SPVN06’s comprehensive and unique mechanism of action is also “disease agnostic” meaning its cone preservation properties can be applied to other retinal diseases – including geographic atrophy (GA) secondary to dry age related macular degeneration (AMD) – affecting photoreceptors by targeting a shared metabolic pathway implicated in cone degeneration. This approach is designed to extend the functional phase of the disease and help protect the cellular substrate needed for later restoration.

SPVN06 represents the preservation arm addressing diseases at any given time in in their evolution, where vision can still be maintained and complementing the restorative focus of SPVN20 in patients who retain partially structurally intact cones.

What are photoreceptors?

Photoreceptors are cells in the retina that begin the process of seeing, essential for producing the sharpest vision. They absorb and convert light into electrical signals. These signals are sent to other cells in the retina and then through the optic nerve to the brain where they are processed into the images we see.

There are two general types of photoreceptors: rods and cones. Rods are in the outer regions of the retina and allow us to see in dim and dark light. Cones reside mostly in the central portion of the retina and allow us to perceive fine visual details and color.

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SPV06 in Retinitis Pigmentosa

Description

Unlike traditional gene therapies which replace a specific defective or missing gene in a cell, SPVN06, our lead investigational drug product, acts independently of the causative gene mutation. SPVN06 counteracts the degeneration of cone photoreceptors by restoring RdCVF, a neurotrophic factor naturally produced by functioning rods in the retina; and by promoting RdCVFL, a potent antioxidant which protects cones against oxidative stress. The DNA of the two distinct isoforms (RdCVF and RdCVFL) of the NXNL1 gene are supplied via an adeno-associated virus (AAV), a viral vector classically used in gene therapy.

SPVN06 is delivered via the subretinal route to the cones and retinal pigmented epithelium (RPE). Such route of administration has already been proven as safe and efficacious for the delivery of gene therapies. Upon delivery of SPVN06, the transgenes are mainly expressed in the RPE cells for RdCVF and in the cones for RdCVFL. SPVN06 is expected to provide a long-lasting neuroprotective effect to prevent the progression of RP in patients with moderate to severe pathology.

Development plan

SPVN06 has recently completed the enrollment of PRODYGY (NCT05748873), a Phase I/II clinical trial, aimed at testing the safety, tolerability, preliminary efficacy and quality of life of SPVN06 in patients with RP. A total of 33 participants were enrolled in the PRODYGY study, including 27 participants dosed and 6 randomized a control arm.

RCD is a rare disease, and only limited information is available about its natural history, with no published prospective or retrospective natural history studies focused on patients with advanced RCD. Therefore, SparingVision has conducted two large proprietary natural history studies, one retrospective (PHENOROD 1, NCT03975543) and one prospective (PHENOROD 2, NCT04285398), with circa 200 participants enrolled in total. These natural history studies will inform about patients characteristics and endpoints for ongoing trials.

SparingVision will also leverage data collected from these proprietary natural history studies, using cutting-edge AI-powered machine learning tools in parallel with statistical analyses, to generate a comprehensive understanding of data from the PRODYGY study.

Beyond RP, SparingVision will explore opportunities to evaluate SPVN06 in other blinding retinal diseases, such as dAMD, where its mechanism of action could be particularly relevant.

Disclaimer

This investigational gene therapy has not been approved by any regulatory authority and is not available for commercial sale. The information presented on this page relates to an investigational product currently under clinical evaluation. Statements regarding its potential safety, efficacy, mechanism of action, or therapeutic benefit are based on non-clinical data and/or ongoing clinical research and should not be interpreted as established clinical outcomes.