• VG801 is the first FDA IND clearance for novel mRNA trans-splicing gene therapy, delivering the full-length functional ABCA4 gene to target the genetic root cause of retinal dystrophies associated with ABCA4 mutations
• VG801 IND clearance expands ViGeneron’s clinical-stage pipeline to two programs, utilizing its novel gene therapy delivery technology platforms vgAAV capsid and REVeRT
• Selected by FDA for the Rare Disease Endpoint Advancement (RDEA) Pilot Program

Munich, Germany, December 18, 2024 –– ViGeneron GmbH, a next-generation clinical-stage gene therapy company, today announced that the United States Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for the Phase I/II study of VG801, a potentially transformative gene therapy to treat Stargardt disease and other retinal dystrophies associated with mutations in the ABCA4 gene.
VG801 utilizes ViGeneron’s proprietary dual AAV vector technology REVeRT (REconstitution Via mRNA Trans-splicing), as the human ABCA4 coding sequence, approximately 6.7kb in size, is too large to be packaged into a single AAV vector (Nature Communications 2023, PMID: 37852949). REVeRT enables the reconstitution of the full-length ABCA4 messenger ribonucleic acid (mRNA) through transduction with dual AAV vectors. Each vector carries one half of the ABCA4 coding sequence, producing two separate pre-mRNAs that are trans-spliced to form a full-length mRNA, which is subsequently translated into the functional protein. VG801 utilizes a novel vgAAV capsid, derived from ViGeneron’s proprietary vgAAV technology and designed to enable widespread retinal transduction (EMBO Mol Med 2021, PMID: 33616280).
“By delivering full-length functional ABCA4 gene, VG801 has the therapeutic potential to address the genetic root cause of Stargardt disease and other ABCA4-linked retinal dystrophies,” commented Dr. Caroline Man Xu, ViGeneron’s Co-founder and CEO. “The VG801 IND clearance, together with our ongoing VG901 clinical trial for Retinitis Pigmentosa, expands our clinical-stage pipeline to two programs and underscores our commitment to advancing next-generation gene therapies with novel technologies to address significant unmet medical needs.”
The Phase I/II multicenter, open-label, dose-escalation clinical trial will evaluate the safety, tolerability and preliminary efficacy of VG801. The study will recruit patients globally as part of a global regulatory strategy for VG801’s clinical development, with a Clinical Trial Application (CTA) submission to the European Medicines Agency (EMA) planned in the coming months.
ViGeneron also proudly announced that the FDA has selected its proposal for the Rare Disease Endpoint Advancement (RDEA) pilot program. The RDEA program is designed to foster innovation and advance rare disease drug development programs. As part of the RDEA program, ViGeneron will collaborate with the FDA throughout the novel efficacy endpoint
development process and gain additional opportunities to meet with the FDA. Notably, the FDA accepts no more than three RDEA programs per year for fiscal years 2024 to 2027.

About Stargardt Disease and VG801

Stargardt disease, the most prevalent inherited retinal disease (IRD), affects approximately 1 in 8,000 to 10,000 individuals worldwide. Caused by mutations in the ABCA4 gene, Stargardt disease, along with other ABCA4-linked retinal dystrophies, leads to a gradual decline in visual acuity and, in some cases, legal blindness. Currently, there are no approved treatments to halt disease progression, highlighting a critical unmet medical need for effective therapies.
VG801 is a novel mRNA trans-splicing gene therapy using dual adeno-associated virus (AAV) vectors to deliver the full-length human native ABCA4 gene. By targeting the genetic root cause through gene supplementation, VG801 aims to treat patients with biallelic ABCA4 mutation-associated Stargardt disease and other ABCA4-linked retinal dystrophies. VG801 has demonstrated in vivo functionality and expression of the full-length ABCA4 gene in an animal model of Stargardt disease, as well as efficient, durable expression and safety in non-human primate retinas. Additionally, VG801 has efficiently reconstituted the full-length ABCA4 gene in human retinal organoids.

About ViGeneron GmbH

ViGeneron is dedicated to bringing gene therapy innovations to people in need. The company is advancing its proprietary, clinical-stage gene therapy pipeline to treat ophthalmic diseases, while partnering with leading biopharmaceutical players in retinal diseases, CNS, cardiovascular and other disease areas. ViGeneron’s three novel next-generation gene therapy platforms are geared towards addressing the limitations of existing adeno-associated virus (AAV)-based gene therapies. The first, the vgAAV vector platform, enables a superior transduction efficiency of target cells and is designed to overcome biological barriers, thus enabling novel, less invasive routes of administration such as intravitreal and systemic administration. The second, the REVeRT (REconstitution Via mRNA Trans-splicing) technology platform, allows for efficient reconstitution of large genes (>5kb) in any tissue which can be targeted with a given capsid. The third, the AAV Transactivation is a CRISPR-Cas–based AAV gene therapy platform that enables the regulation of one or multiple genes in vivo by increasing or inhibiting their expression. Privately-owned ViGeneron was founded in 2017 by a seasoned team with in-depth experience in AAV vector technology and clinical ophthalmic gene therapy programs and is located in Munich, Germany. For further information, please visit www.vigeneron.com.