ATSN-401, Atsena Therapeutics’ investigational gene therapy for Stargardt disease, has been selected as the company’s lead clinical candidate and will now advance into IND-enabling studies.

The treatment is being developed for Stargardt disease, the most common inherited macular dystrophy, which affects around 60,000 people across the USA, Canada and the European Union. The condition is caused by mutations in the ABCA4 gene, leading to progressive central vision loss that often begins during childhood. There are currently no approved treatments that address the underlying genetic cause of the disease.

ATSN-401 is designed to deliver a full-length, functional copy of the ABCA4 gene to photoreceptor cells in the central retina. Because the gene is too large to fit inside a conventional adeno-associated virus (AAV) vector, Atsena has developed a proprietary dual-vector DNA recombination platform that splits the gene across two vectors. Once inside retinal cells, the DNA recombines to produce full-length ABCA4 messenger RNA and protein.

The programme also uses the company’s AAV.SPR capsid, which is designed to spread laterally through the retina following a peripheral injection. According to Atsena, this approach could allow surgeons to avoid detaching the central retina during treatment, potentially reducing surgical risk compared with conventional delivery methods.

Patrick Ritschel, chief executive officer of Atsena, said: “For patients with Stargardt disease, there is no approved treatment that addresses the underlying cause, and we believe ATSN-401 has the potential to change that.”

He added that the programme combines the company’s AAV.SPR capsid technology with its dual-vector platform, alongside experience gained from other inherited retinal disease programmes currently in clinical development.

The company selected ATSN-401 following preclinical evaluation in mouse and non-human primate models. Atsena said the candidate demonstrated robust expression of ABCA4 in the retina, reduced levels of toxic bisretinoid compounds associated with Stargardt disease and showed a manageable safety profile.

Shannon Boye, chief scientific officer of Atsena, said the candidate met the company’s criteria for expression, efficacy and safety.

She said: “We saw robust, properly localized ABCA4 expression, meaningful bisretinoid reduction at well-tolerated doses, and spreading behavior from AAV.SPR that confirms the capsid reaches the central retina from a peripheral injection site.”

The company believes this ability to reach the central retina without directly detaching the diseased macula could become an important feature of the therapy if it progresses through clinical development.

The AAV.SPR capsid is also being evaluated in the ongoing LightHouse Phase 1/2/3 trial of ATSN-201 for X-linked retinoschisis, while Atsena is developing additional gene therapy programmes for inherited retinal diseases including Usher syndrome type 1B and Leber congenital amaurosis type 1.

Advancing ATSN-401 into IND-enabling studies marks the next step towards first-in-human clinical testing, although further preclinical work and regulatory review will be required before clinical trials can begin.