Atsena Therapeutics select lead clinical candidate for Stargardt gene therapy
Atsena Therapeutics, a clinical-stage gene therapy company, has completed an important but early milestone by selecting the version of ATSN-401 that they will develop as a potential treatment for Stargardt disease, known as the lead clinical candidate.
In a nutshell:
Atsena Therapeutics has selected the lead clinical candidate for ATSN-401, an investigational gene therapy being developed for Stargardt disease. This announcement means that they have finished the research stage where several versions of the therapy were tested and a specific version has been chosen to move forward with into clinical development. The therapy uses an innovative dual-vector approach to deliver the large ABCA4 gene, together with Atsena's novel AAV.SPR technology to target the central retina more effectively. This marks an important early milestone, as the chosen candidate showed encouraging safety and efficacy in preclinical studies and will now move into investigative new drug-enabling studies before the company can apply to begin human clinical trials.
What is Stargardt Disease?
Stargardt disease is a progressive inherited retinal condition in which vision loss is caused by the death of photoreceptor cells (light-sensing cells) in the central portion of the retina called the macula. It is the most common form of juvenile macular dystrophy.
The condition is most commonly caused by mutations in the ABCA4 gene, which provides the instructions needed to make a protein found in the photoreceptor cells. This protein is responsible for transporting toxic byproducts, made by the regular visual cycle, away from photoreceptor cells. Without this protein, these toxins can accumulate over time on the macula, which we use for seeing fine detail in high definition, destroying light-sensing cells and central vision.
There are currently no treatments available for the condition, however, there are several therapeutic approaches in development, including ATSN-401 by Atsena Therapeutics.
What is ATSN-401?
ATSN-401 is a dual adeno-associated viral vector gene therapy. This means that a small virus, that doesn’t cause illness in humans, is used as a delivery system to introduce or alter genetic material within cells. Most gene therapies for IRDs work on the premise of delivering an entire new gene to replace the mutated one. However, the whole ABCA4 gene is too large to deliver in one viral vector. Atsena look to overcome this problem by delivering the ABCA4 gene in two halves, using two viral vectors, through a one-time injection into the eye. Once in the cells, the halves recombine at the DNA level to produce full length ABCA4 mRNA and protein.
Atsena will also use their novel spreading capsid technology, called AAV.SPR, to ensure ATSN-401 is delivered to photoreceptors in the central retina. AAV.SPR allows the gene therapy to reach more photoreceptors by spreading beyond the margins of the injection bleb which is the small, localised pocket of fluid that forms in the retina where the treatment is initially delivered. AAV.SPR has demonstrated its unique capabilities in the ongoing LIGHTHOUSE trial for X-linked retinoschisis.
What does this update mean?
By announcing the selection of a lead clinical candidate for ATSN-401, Atsena has completed an important but early milestone. This announcement means that they have finished the research stage where several versions of the therapy were tested and a specific version has been chosen to move forward with into clinical development.
In early drug development stages, researchers often create several candidate therapies which they then compare in laboratory and animal studies to investigate how well they work, how safe they are and whether manufacturing can be completed consistently. The lead clinical candidate is the version that performed best overall. The chosen ATSN-401 candidate demonstrated robust, properly localized ABCA4 expression, bisretinoid reduction and a manageable safety profile, supporting the program’s best-in-class potential in mouse and non-human primate models.
“Our clinical candidate for ATSN-401 stood out clearly across our criteria of expression, efficacy, and safety in both mouse and primate models. We saw robust, properly localized ABCA4 expression, meaningful bisretinoid reduction at well-tolerated doses, and spreading behaviour from AAV.SPR that confirms the capsid reaches the central retina from a peripheral injection site. That last point is critical for Stargardt patients: the ability to avoid injecting into a dystrophic macula is not just a surgical convenience, it is a potential safety advantage that we believe will be an important differentiator for ATSN-401.” – Shannon Boye, Ph.D., Chief Scientific Officer of Atsena.
This is an exciting early step in the development of ATSN-401, but it does not mean that human clinical trials have started yet. Atsena are now preparing the required data to file an Investigational New Drug (IND) application which could potentially lead to the authorisation to begin testing in human trials. We look forward to hearing an update from Atsena Therapeutics soon.
If you’d like to read more about Atsena Therapeutics or ATSN-401, please visit their website here.