Key Takeaways
- Atsena selected ATSN-401 as its lead clinical candidate for Stargardt disease and is advancing it in IND-enabling studies.
- ATSN-401 is designed to deliver full-length ABCA4 using a dual-vector DNA recombination platform.
- The therapy uses the AAV.SPR laterally spreading capsid, which is intended to reach the central retina from a peripheral injection site.
Atsena Therapeutics has selected a lead clinical candidate for ATSN-401, a gene therapy program for Stargardt disease, and is advancing the candidate into IND-enabling studies.
ATSN-401 is designed to deliver full-length, functional ABCA4 to photoreceptors in the central retina. Stargardt disease, the most common inherited macular dystrophy, is caused by mutations in the ABCA4 gene and is associated with progressive accumulation of toxic bisretinoid compounds in the RPE, photoreceptor and RPE cell death, and bilateral central vision loss. According to the company, no approved treatment currently addresses the underlying genetic cause.
Because the ABCA4 coding sequence exceeds the capacity of a single AAV vector, Atsena’s dual-vector DNA recombination platform splits the gene across two vectors. After cotransduction, the two halves recombine at the DNA level to produce full-length ABCA4 mRNA and protein, according to the company.
The therapy also uses Atsena’s AAV.SPR laterally spreading capsid, which is intended to allow peripheral subretinal delivery with spread to photoreceptors in the central retina. Atsena said this approach may allow retinal specialists to avoid surgical detachment of a dystrophic macula, a step required with conventional capsids.
In preclinical mouse and nonhuman primate studies, the ATSN-401 candidate demonstrated properly localized ABCA4 expression, bisretinoid reduction, and a manageable safety profile, according to Atsena. The AAV.SPR capsid is also being evaluated in the ongoing phase 1/2/3 LIGHTHOUSE clinical trial of ATSN-201 for X-linked retinoschisis.
