NXNL1

SparingVision Reports Positive Initial Safety Data from the first cohort treated in its PRODYGY Phase I/II Gene Therapy Trial Lead gene therapy asset, SPVN06, reported to be well-tolerated in first dosed cohort at low dose with a favorable safety profilePositive recommendation received from Data Safety Monitoring Board (DSMB) to dose second cohort at the medium dose Paris, August 30, 2023 – SparingVision (“the Company”), a clinical-stage genomic medicine company developing vision-saving treatments for ocular diseases, today announced positive initial safety data from the Phase I/II clinical trial (‘PRODYGY’, NCT05748873) of SPVN06, the Company’s lead gene-agnostic gene therapy for the treatment of retinitis pigmentosa (RP). SPVN06 is a breakthrough gene therapy approach aimed at stopping or slowing disease progression in patients affected by rod-cone dystrophy, (RCD), regardless of their genetic background. SparingVision is initially focusing on mid-stage RP, one of the leading inherited causes of blindness globally. Safety data collected on the first three patients (cohort 1) treated with a low dose showed that SPVN06 has been well tolerated with a favorable safety profile. The patients were each injected at the 15-20 National Hospital in Paris, France. Following review of the data, the Data Safety Monitoring Board (DSMB) concluded that it is safe to initiate the second cohort at a medium dose. Stéphane Boissel, President and Chief Executive Officer of SparingVision, said: “We are committed to saving sight with pioneering genomics and firmly believe that SPVN06 has the potential to make a meaningful impact in patients' lives and bring hope to those affected by retinitis pigmentosa. This trial is just the beginning; we have a broad pipeline of vision-saving treatments that leverage cutting edge genomic technologies that will transform current treatment of retinal disease. We look forward to reporting on the progress of SPVN06 and our other programs as we rapidly move our portfolio through development.” Avril Daly, Chief Executive Officer of Retina International, a patient advocacy group, commented: “The positive initial safety data with SPVN06 is an important step forward for all those living with retinitis pigmentosa. As a community, we have highlighted the need for a therapy that addresses the wide range of genetic backgrounds that can cause RP for many years now. SparingVision's approach with SPVN06 offers hope for those of us who have been impacted by this degenerative blinding disease. We are eagerly awaiting the results of this Phase I/II trial and the potential for this therapy to slow or stop the progression of RP." The primary endpoint of the PRODYGY Phase I/II trial is expected to be reached in 2025 and preliminary efficacy results are expected within the same year. PRODYGY trial PRODYGY is a multicentric Phase I/II trial to assess the safety, tolerability as well as preliminary efficacy and quality-of-life following a single subretinal injection of SPVN06 in the worst-seeing eye of adult patients with RCD due to a mutation in the RHO, PDE6A, or PDE6B gene. The study will recruit a total of 33 patients, in two steps: Step 1: open-label, dose-escalation phase including three cohorts of three patients with severe advanced RCD, to determine two recommended best-tolerated doses for Step Two.Step 2: controlled, double-masked, randomized extension phase including 24 patients with intermediate advanced RP, divided into three cohorts: six untreated subjects and 18 patients receiving one of the two Recommended Doses determined in Step One. The principal investigators of the trial are Pr. Isabelle Audo at the 15-20 National Hospital in Paris, France and Dr. Joseph Martel at the Eye Center of the University of Pittsburgh Medical Center, Pittsburgh, USA. Further details of the trial can be found on clinicaltrials.gov under the identifier NCT05748873. SPVN06SPVN06 is a proprietary, mutation-agnostic, AAV gene therapy approach comprised of one neurotrophic factor (Rod derived Cone Viability Factor, RdCVF) and one enzyme reducing oxidative stress (Rod derived Cone Viability Factor Long form, RdCVFL). Acting synergistically, RdCVF and RdCVFL aim at slowing or stopping the degeneration of cone photoreceptors, which inevitably leads to blindness in patients with rod-cone dystrophies (RCD). SparingVision’s primary disease targets are retinitis pigmentosa (RP), one of the most common inherited retinal diseases that affects an estimated two million patients worldwide and dry Age-related Macular Degeneration (AMD). There is currently no treatment approved to treat RP patients independently of their genetic background. This approach is potentially applicable to many more diseases, where the loss of rods is known to be an early signal of the disease. SPVN06 is the result of decades of world-leading ophthalmology research by SparingVision founders José-Alain Sahel and Thierry Léveillard at the Paris Vision Institute.DISCLAIMER Dr. Jose-Alain Sahel and UPMC have financial interests in the study sponsor, SparingVision. These financial interests mean it is possible that the results of this research could lead to personal profit for Dr. Sahel and to institutional profit for UPMC. The conflicts of interest presented by these relationships are being managed by the University and UPMC. **ENDS** Contacts: SparingVisionStéphane BoisselPresident and CEONathalie TrepoInvestor Relations nathalie.trepo@sparingvision.comConsilium Strategic CommunicationsAmber Fennell, Namrata Taak, Davide Salvi+44 (0)20 3709 5700sparingvision@consilium-comms.com NOTES TO EDITORS: About SparingVisionSparingVision is a clinical-stage genomic medicines company with a mission to translate pioneering science into vision saving treatments. Leveraging its unparalleled understanding of retinal diseases, SparingVision has built the world’s most compelling portfolio of synergistic cutting-edge gene therapy and genome editing treatments for inherited retinal diseases (IRDs). Both of its most advanced products, SPVN06 and SPVN20 look to go beyond single gene correction therapies to deliver new gene-independent treatments for Retinitis Pigmentosa (RP), a group of IRDs which are the leading cause of blindness globally. The Company also has a strategic collaboration with Intellia Therapeutics (NASDAQ: NTLA) to develop novel genome editing-based treatments for ocular diseases utilizing CRISPR-Cas9 technology. SparingVision is a spin-off from the Paris Vision Institute and is backed by high-quality international investors including 4BIO Capital, AdBio Partners, Bpifrance, Fondation Voir & Entendre, Intellia Therapeutics, Jeito Capital, RD Fund (US), UPMC Enterprises, and Ysios Capital. Visit www.sparingvision.com for more and follow us on LinkedIn and Twitter @SparingVision. About Inherited Retinal DiseasesInherited retinal diseases are a group of progressive eye conditions that can cause severe vision loss and, in certain cases, lead to total blindness. One of the most common examples is Retinitis Pigmentosa, a type of retinal dystrophy that involves a breakdown and loss of cells in the retina. Retinal dystrophies are caused by mutations in any one of more than 270 genes identified to date (over 80 genes for RP alone) and have become a target for novel genomic medicines.

Paris, December 1, 2022 – SparingVision (“the Company”), a genomic medicine company developing vision-saving treatments for ocular diseases, today announces that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug application (IND) for SPVN06, its lead gene independent therapy for the treatment of retinitis pigmentosa (RP), a form of rod-cone dystrophy (RCD) and the most prevalent inherited retinal disease (IRD). SparingVision has also submitted a clinical trial authorisation (CTA) application to the French regulator (ANSM), which is currently under review. This approval paves the way for the initiation of Promising Rod-cone Dystrophy Gene therapy (PRODYGY), a first-in-human (FIH) Phase I/II clinical trial. First safety data are anticipated in 2023 and the primary endpoint is expected to be reached in 2025. PRODYGY Trial Design PRODYGY is a Phase I/II study to assess the safety, tolerability, efficacy and quality of life following a single subretinal injection of SPVN06 in the worst-seeing eye of adult patients with RP due to a mutation in the RHO, PDE6A, or PDE6B gene. The study will recruit up to a total of 33 patients, in two steps: Step One: open-label, dose-escalation phase including three cohorts of three subjects with advanced forms of RP, to determine two recommended highest tolerated doses for Step Two. The decision to initiate cohorts 2 and 3 will be based on the review by a Data Safety Monitoring Board (DSMB) of all available safety data from all subjects of the previous cohort(s). Step Two: controlled, double-masked randomized phase including 24 patients with advanced intermediate RP, divided into three cohorts: six untreated patients and 18 patients receiving either the low or high dose determined through Step One. The primary endpoint of PRODYGY is the safety and tolerability of SPVN06, 12 months after administration of a single injection of the gene therapy. Secondary objectives include notably preliminary efficacy and quality of life data. In addition, the long-term follow-up of the study will focus on safety and tolerability for a total of five years after treatment administration. Dr Daniel Chung, Chief Medical Officer of SparingVision, said: “RP is a highly prevalent eye disease leading inevitably to blindness with no treatment available for the vast majority of patients. The unique neuroprotective mechanism of action of SPVN06 has the potential to change the course of the natural history of the disease, independently of the genetic background of patients and of the time of disease diagnosis. With this Phase I/II trial we will be looking to demonstrate SPVN06’s safety and tolerability as well as identify preliminary signs of efficacy through several structural, functional and quality of life endpoints.” SPVN06 is a breakthrough gene therapy approach aimed at stopping or slowing disease progression in patients affected by IRDs and dry age-related macular degeneration (AMD), regardless of their genetic background. SparingVision is initially focused on mid-stage RP, one of the leading causes of blindness globally that affects two million patients.1 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), the viral vector of choice for retinal gene therapy. The treatment is delivered by subretinal injection, a route of administration that has already been proven safe and efficacious for the delivery of gene therapy. Stéphane Boissel, President and Chief Executive Officer of SparingVision, said: “Receiving IND clearance is a testament to the incredible efforts of everyone at SparingVision, but also to the strength of our science, which encompasses more than 20 years of leading research by our scientific founders, including Professor José Sahel, Chair of the Ophthalmology Department at the University of Pittsburgh Medical Center. With over 80 genes involved in RP, each with numerous causative mutations, we need to go beyond the gene-by-gene treatment approach. SPVN06 has the potential to become the universal therapeutic solution that patients need, and we are excited for the next phase of development.” About SparingVision SparingVision is a clinical stage genomic medicines company with a mission to translate pioneering science into vision saving treatments. Leveraging its unparalleled understanding of retinal diseases, SparingVision has built the world’s most compelling portfolio of synergistic cutting-edge gene therapy and genome editing treatments for inherited retinal diseases (IRDs). Both of its most advanced products, SPVN06 and SPVN20 look to go beyond single gene correction therapies to deliver new mutation agnostic treatments for Retinitis Pigmentosa (RP), a group of IRDs which are the leading cause of blindness globally. The Company also has a strategic collaboration with Intellia Therapeutics (NASDAQ: NTLA) to develop novel genome editing-based treatments for ocular diseases utilizing CRISPR-Cas9 technology. SparingVision was spun out from the Paris Vision Institute and is backed by high-quality international investors including 4BIO Capital, AdBio Partners, Bpifrance, Fondation Voir & Entendre, Intellia Therapeutics, Jeito Capital, RD Fund (US), UPMC Enterprises, and Ysios Capital. Visit www.sparingvision.com for more and follow us on LinkedIn and Twitter @SparingVision. About SPVN06 SPVN06 is a proprietary, mutation-agnostic, AAV gene therapy approach comprised of one neurotrophic factor (Rod derived Cone Viability Factor, RdCVF) and one enzyme reducing oxidative stress (Rod derived Cone Viability Factor Long form, RdCVFL) which, acting synergistically, aim at slowing or stopping the degeneration of cone photoreceptors, which inevitably leads to blindness in patients with rod-cone dystrophies (RCD). SparingVision’s primary disease targets are Retinitis Pigmentosa (RP), one of the most common inherited retinal diseases that affects two million patients worldwide and dry Age-related Macular Degeneration (AMD). There is currently no treatment approved to treat RP patients independently of their genetic background. This approach is potentially applicable to many more diseases where the loss of rods is known to be an early signal of the disease. About Inherited Retinal Diseases Inherited retinal diseases are a group of progressive eye conditions that can cause severe vision loss and, in certain cases, lead to total blindness. One of the most common examples is Retinitis Pigmentosa, a type of retinal dystrophy that involves a breakdown and loss of cells in the retina. Retinal dystrophies are caused by mutations in any one of more than 270 genes identified to date (over 80 genes for RP alone) and have become a target for novel genomic medicines.