ATSENA is developing ATSN-401, an investigational gene therapy for Stargardt disease (STGD), the most common inherited macular dystrophy. ATSN-401 is currently being evaluated in IND-enabling studies. Approximately 60,000 patients in the U.S., Canada, and EU have Stargardt disease.
Disease Background
Stargardt disease is a juvenile form of macular degeneration caused by mutations in the ABCA4 gene, which encodes a transporter expressed in photoreceptors. Loss of functional ABCA4 leads to accumulation of toxic bisretinoid compounds in the retinal pigment epithelium, driving progressive photoreceptor and RPE cell death and bilateral central vision loss that typically begins in the first decade of life. More than 1,200 pathogenic mutations in ABCA4 have been identified; the ATSN-401 gene replacement approach allows for testing in all STGD patients, regardless of their underlying pathogenic mutations.
Our Approach
ATSN-401 leverages two of Atsena’s proprietary technologies. ATSN-401 employs AAV.SPR, Atsena’s laterally spreading capsid, which has been evaluated in patients with XLRS, where it demonstrated the ability to spread beyond the subretinal injection site and deliver gene therapy to the fovea — avoiding surgical detachment of the dystrophic macula required with conventional capsids. Because the ABCA4 coding sequence exceeds the packaging capacity of a single AAV vector, ATSN-401 also uses Atsena’s dual vector DNA recombination platform to split the gene across two vectors that recombine at the DNA level upon co-delivery, producing full-length ABCA4 mRNA and protein and directly targeting the root cause of bisretinoid accumulation.
Preclinical Data
Preclinical studies of ATSN-401 in mouse and non-human primate models demonstrated robust, properly localized ABCA4 expression, meaningful reduction of toxic bisretinoid compounds, and a manageable safety profile with no expression of truncated products, supporting the program’s best-in-class potential. Atsena has selected a lead clinical candidate for ATSN-401 based on expression, efficacy, and safety criteria evaluated across both model systems.
