• First oral presentation on SPVN20 in a major scientific and medical conference
• SPVN20 is a gene therapy product uniquely positioned to restore visual acuity and color vision in patients with late-stage retinitis pigmentosa and other inherited retinal diseases (IRDs)
• The product is currently undergoing IND-enabling studies with a clinical trial submission expected in early 2024

Paris, May 22, 2023 – SparingVision (“the Company”), a clinical-stage genomic medicine company developing vision-saving treatments for ocular diseases, announces today that it has presented progress of its pioneering gene-agnostic gene therapy program, SPVN20, at the ASGCT 26^th Annual Meeting this week in Los Angeles.

In an oral presentation titled, ‘Development of a mutation-independent gene therapy for cone reactivation in the treatment of Retinitis Pigmentosa’, Hanen Khabou, Ph.D., Senior Scientist at SparingVision, presented in vitro and in vivo data supporting the potential of SPVN20, its second lead gene therapy program. SPVN20 is an AAV gene therapy based on an IVT-permissive capsid, which aims to restore visual acuity and color vision in late-stage retinitis pigmentosa (RP) patients with dormant cones, independently of the causative genetic mutation. SPVN20’s mode of action is to reactivate opsin signalling in dormant cones by introducing a G-Protein Coupled Inwardly Rectifying Potassium (GIRK) channel, not normally expressed in the retina.

Florence Lorget, Chief Development Sciences Officer of SparingVision, said:

“ASGCT 2023 provided the perfect platform to provide greater insight and data around our second lead program, SPVN20, which is addressing a new patient subgroup to that of our lead program, SPVN06. For the first time, we’ve shared proof of concept data highlighting visual restoration via GIRK channel activation in a mouse model of retinitis pigmentosa, as well as strong GIRK expression following intravitreal injection with SPVN20 in the non-human primate fovea– an important study as the majority of cones are located in the fovea, and responsible for high acuity vision. These data are fundamental as we move towards IND with SPVN20, highlighting the rationale and scientific basis behind our clinical candidate selection.”

Dr. Khabou first presented in vitro data demonstrating responses to light stimuli in HEK cells co-expressing opsin and GIRK channels, as measured by current. Analysis of cones of RP patients showed cone opsin and cone arrestin are co-expressed in dormant cones, with the expression of opsin providing a target to reactivate cone activity.

Dr. Khabou then presented in vivo proof of concept (POC) data in a rd10 mouse model. The data demonstrated vision restoration upon a single bilateral subretinal AAV administration with GIRK1(F137S), the GIRK variant selected in in vitro experiments as the most efficient at generating a light response. The data showed significant improvements in visual function (optokinetic reflex (OKT)) and retinal electrical activity (electroretinograms (ERG)). Visualization of GIRK expression in cones of rd10 mice was consistent with OKT and ERG data, detecting GIRK1(F137S)-positive cones at the higher, but not lower dose levels.

 In vivo data in a 3-month non-human primate (NHP) study showed GIRK1(F137S) expression in the foveal cones following intravitreal injection of SPVN20 (AAVi-PR1.7-hGIRK1(F137S)) at 7e10 vg/eye. Intravitreal delivery is the preferred method as it is less invasive to the fragile retina of late-stage RP patients.

IND-enabling studies for SPVN20 are underway with regulatory submission planned for early 2024.