SPVN06 / SparingVision - LARVOL DELTA

Characterization of retinal degeneration in patients with rod-cone dystrophy to inform on potential efficacy endpoint of gene therapy (ESGCT 2024) - P=N/A, P1/2 | "After one year of prospective follow-up, markers of retinal degeneration showed a significant change in a majority of patients with RCD, although with high heterogeneity. This analysis allowed the identification of subjects whose disease is progressing more rapidly, and who can be of interest for their participation in the ongoing first-in-human trial of SPVN06, PRODYGY (NCT05748873)."

Clinical • Gene therapy • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • PDE6A

PRODYGY: A first-in-human trial of rod-derived cone viability factor (RdCVF) gene therapy in subjects with rod-cone dystrophy (ESGCT 2024) - P1/2 | "First administration of SPVN06 to patients has shown a favorable safety profile at the low and medium doses so far, with no significant immune response. Treatment of Cohort 3 is currently ongoing."

Clinical • First-in-human • Gene therapy • P1 data • Gene Therapies • Inflammation • Inherited Retinal Dystrophy • Macular Edema • Retinal Disorders • Retinitis Pigmentosa • PDE6A

PRODYGY: Promising ROd-cone DYstrophy Gene therapY (clinicaltrials.gov) - P1/2 | N=33 | Recruiting | Sponsor: SparingVision | Trial completion date: Mar 2029 ➔ Sep 2030 | Trial primary completion date: Mar 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • PDE6A • TNFA

Genetic Therapies for Retinitis Pigmentosa: Current Breakthroughs and Future Directions. (PubMed, J Clin Med) - "Luxturna (voretigene neparvovec-rzyl), the first FDA-approved gene therapy targeting RPE65 mutations, represents a milestone in precision ophthalmology, while OCU400 is a gene-independent therapy that uses a modified NR2E3 construct to modulate retinal homeostasis across different RP genotypes...Moreover, QR-1123, a mutation-specific antisense oligonucleotide targeting the P23H variant in the RHO gene, is under clinical investigation for autosomal dominant RP and has shown encouraging preclinical results in reducing toxic protein accumulation and preserving photoreceptors. SPVN06, another promising candidate, is a mutation-agnostic gene therapy delivering RdCVF and RdCVFL via AAV to support cone viability and delay degeneration, currently being evaluated in a multicenter Phase I/II trial for patients with various rod-cone dystrophies. Collectively, these advances illustrate the transition from symptom management toward targeted, mutation-specific therapies, marking a..."

Journal • Review • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • NR2E3 • PRPF31 • USH2A

Preclinical safety and biodistribution of SPVN06, a novel gene- and mutation-independent gene therapy for rod-cone dystrophies. (PubMed, Gene Ther) - P1/2 | "In NHPs, SPVN06 was well-tolerated up to 6.0 × 1010 vg/eye, with high and stable RdCVF and RdCVFL mRNA expression levels in the retina and retinal pigment epithelium. These results supported the initiation of the ongoing Phase I/II PRODYGY trial with RCD (NCT05748873)."

Journal • Preclinical • Gene Therapies • Inherited Retinal Dystrophy • Retinitis Pigmentosa

PRODYGY: A First-in-Human Trial of Rod-Derived Cone Viability Factor (RdCVF) Gene Therapy in Subjects with Rod-Cone Dystrophy (ASGCT 2025) - P1/2 | "First administration of SPVN06 to nine subjects with severe advanced RCD showed a favorable safety profile at all 3 doses tested, with no significant immune response. After data review, the DSMB recommended to assess the medium and high doses of SPVN06 in Step 2 of PRODYGY, and to continue the trial without modification. The controlled, double-masked, randomized extension phase of PRODYGY was initiated, and SPVN06 was administered to the two sentinel subjects with intermediate advanced RCD."

Clinical • Gene therapy • Late-breaking abstract • P1 data • Gene Therapies • Inherited Retinal Dystrophy • Retinal Disorders • Retinitis Pigmentosa • PDE6A

PRODYGY: A First-in-Human Trial of Rod-Derived Cone Viability Factor (RdCVF) Gene Therapy in Subjects with Rod-Cone Dystrophy (ARVO 2025) - P1/2 | "Purpose SPVN06 is a gene-independent investigational gene therapy allowing the expression of the neurotrophic rod-derived cone viability factor (RdCVF) and the thioredoxin RdCVF-Long (RdCVFL), that aims to slow down the progression of central vision loss in patients with rod-cone dystrophy, regardless of the underlying pathogenic variant(s)...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Gene therapy • P1 data • Inherited Retinal Dystrophy • Macular Edema • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • PDE6A

PRODYGY: A First-in-Human Trial of Rod-Derived Cone Viability Factor (RdCVF) Gene Therapy in Subjects with Rod-Cone Dystrophy (ASGCT 2024) - P1/2 | "First administration of SPVN06 to patients showed a favorable safety profile at low and medium doses, with no significant immune response. Plain Language Summary: Rod-cone dystrophy (RCD) is a rare inherited retinal disorder leading to significant vision loss, and for which no treatment is currently available to most patients. SPVN06 is a gene-independent investigational gene therapy expressing the neurotrophic rod-derived cone viability factor (RdCVF) and the thioredoxin RdCVF-Long (RdCVFL), that aims at slowing down the progression of central vision loss in patients with RCD, regardless of the underlying pathogenic variant(s)."

Clinical • Gene therapy • P1 data • Gene Therapies • Hematological Disorders • Inherited Retinal Dystrophy • Macular Edema • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • PDE6A

PRODYGY: A First-in-Human Trial of Rod-Derived Cone Viability Factor (RdCVF) Gene Therapy in Subjects with Rod-Cone Dystrophy (ARVO 2024) - P1/2 | "First administration of SPVN06 to patients at a low dose showed a favorable safety profile of the procedure and no significant immune response."

Clinical • Gene therapy • P1 data • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • PDE6A

Development of a Mutation Independent Gene Therapy for Cone Reactivation in the Treatment of Retinitis Pigmentosa (ASGCT 2023) - "Our lead product SPVN06, aiming to improve cone outer segment renewal and viability at intermediate stages of the disease, has recently been approved for human clinical studies...GIRK1 F137S expression was found in human cones by immunohistochemistry, at the cell membrane, as observed in rd10 mice. Altogether, these encouraging in vitro and in vivo findings in mouse and human tissue support exploring the potential of AAVi-GIRK1 F137S, with the aim of developing a noninvasive and restorative gene therapy product for late-stage RP patients."

Gene therapy • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

PRODYGY: Promising ROd-cone DYstrophy Gene therapY (clinicaltrials.gov) - P1/2 | N=33 | Recruiting | Sponsor: SparingVision | Not yet recruiting ➔ Recruiting

Enrollment open • Gene therapy • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • PDE6A • TNFA

Mouse model selection for pharmacological evaluation of AAV-based therapeutic agents for the treatment of Rod-Cone Dystrophies (RCD) (ARVO 2023) - "To assess SPVN06 pharmacological activity, an AAV-based therapy that aims at slowing down cone degeneration, we evaluated 2 mouse models of RCD characterized by a loss of rods followed by a loss of cones eventually causing blindness...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Preclinical • Inherited Retinal Dystrophy • Ophthalmology • Retinitis Pigmentosa • EIF4G1

Nonclinical safety and pharmacokinetic assessment of SPVN06, an AAV-based gene therapy for the treatment of rod-cone dystrophies. (ARVO 2023) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Gene therapy • PK/PD data • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

PRODYGY: Promising ROd-cone DYstrophy Gene therapY (clinicaltrials.gov) - P1/2 | N=33 | Not yet recruiting | Sponsor: SparingVision

Gene therapy • New P1/2 trial • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • PDE6A • TNFA