Ascidian to Launch Clinical Trial for Stargardt Disease RNA Editing Therapy

Ascidian Therapeutics has received authorization from the US Food & Drug Administration to launch a Phase 1/2 clinical trial for ACDN-01, the company’s RNA editing therapy for people with Stargardt disease, an inherited form of macular degeneration caused by mutations in the ABCA4 gene. The company plans to begin enrollment for the clinical trial, known as STELLAR, during the first half of 2024.

Unlike genetic therapies that deliver an entire healthy gene (DNA) to replace the mutated gene, or which edit DNA, ACDN-01 re-writes RNA, the genetic message derived from DNA that cells read to make proteins. Healthy proteins are essential to the survival and function of all cells in the body, including those of the retina. ACDN-01 specifically re-writes RNA exons, the regions where mutations are most likely to occur for the ABCA4 gene. Ascidian estimates that ACDN-01 can address mutations in ABCA4 for a significant percentage of people with Stargardt disease because the editing replaces a large number of exons, all at once.

By targeting Stargardt disease at the RNA level, ACDN-01 overcomes two limitations with therapeutic approaches that replace or edit DNA. First, it circumvents the challenge of delivering the large ABCA4 gene which exceeds the capacity of the viral delivery systems known as adeno-associated viruses (AAVs) that are typically used in retinal gene therapies. Also, RNA editing avoids permanent, off-target DNA editing which is a potential risk with gene editing.

ACDN-01 is delivered by a one-time, subretinal injection.

The emerging treatment is the first RNA exon editor to enter clinical development for any disease and the only clinical-stage therapeutic targeting the genetic cause of Stargardt disease.

ACDN-01 has demonstrated efficient and durable RNA exon editing in a large animal model and in human retinal explants.

The Foundation and Ascidian collaborate closely. The Foundation provided data from its ProgSTAR natural history study on how Stargardt disease progresses for affected patients.

Stargardt disease affects approximately 30,000 people in the US. It is characterized by the accumulation of toxic byproducts from vitamin A metabolism in the retina, ultimately leading to retinal cell death and central vision loss. People with Stargardt disease can lose the ability to read, drive, and recognize faces. The condition is usually diagnosed in children or young adults, but age of onset, severity, and rate of progression can vary.