Ascidian Therapeutics announces first-ever IND for an RNA exon editor as FDA approves trial plan and fast tracks ACDN-01 in Stargardt Disease

(Image credit: AdobeStock/Kitreel)

Ascidian Therapeutics today announced the FDA has cleared its investigational new drug (IND) application and granted Fast Track designation for ACDN-01.

According to a news release from the Boston-based biotechnology company, ACDN-01 is the first-ever clinical stage RNA exon editor and the only clinical-stage therapeutic targeting the genetic cause of Stargardt disease.The company said in its release today that it expects to initiate enrollment in the Phase 1/2 STELLAR study of ACDN-01 in Stargardt disease and other ABCA4 retinopathies in the first half of 2024.

ACDN-01 is an in vivo RNA exon editor delivered by a single vector. It has demonstrated efficient, durable in vivo RNA exon editing in non-human primate retina and ex vivo RNA exon editing in human retinal explants.

Michael Ehlers, MD, PhD, president and Interim CEO of Ascidian Therapeutics, noted in the news release the open IND for ACDN-01 by the FDA – the first regulator to have cleared ACDN-01 for clinical development – represents an important milestone for Ascidian and the broader field of RNA editing.

“We chose to go to the FDA first because we have conviction in the rigor of our data, and that by editing RNA and not DNA, the Ascidian approach brings unique advantages with potential to transform the lives of people living with Stargardt disease and, more broadly, to dramatically expand the reach of genetic medicine;” he said in the news release.

Moreover, Byron L. Lam, director of the Mark J. Daily Inherited Retinal Disease Research Center at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, pointed out the advancement of Ascidian’s first-of-its-kind RNA exon editor from the lab to the clinic is a unique and novel therapeutic approach targeting the genetic cause of Stargardt disease.

“This is a critical step toward overcoming the challenges of Stargardt disease, such as the size of the ABCA4 gene and large number of mutations within the patient population, that have long kept Stargardt out of reach for conventional gene therapies,” Lam said in the news release. “Stargardt patients deserve treatment options and I am looking forward to the clinical evaluation of this promising approach.”

According to the company, the open-label Phase 1/2 STELLAR study will evaluate the safety and efficacy of a single dose of ACDN-01, administered via subretinal injection in individuals with Stargardt disease and other ABCA4 retinopathies.

Further, the company also noted ACDN-01 will receive Fast Track designation, designed to facilitate the review of new medicines for serious conditions with high unmet need. This designation enables Ascidian to expedite development of ACDN-01 with regular feedback from FDA through the clinical development process.

Stargardt disease is the most common form of inherited macular degeneration and has no FDA-approved treatments. Affecting approximately 30,000 individuals in the U.S. alone, Stargardt disease is caused by mutations in the ABCA4 gene which lead to progressive retinal degeneration and vision loss, typically beginning in childhood and young adulthood.

More than 1,000 mutations across the ABCA4 gene have been found to cause Stargardt disease. Diseases caused by ABCA4 loss of function – including Stargardt disease – are examples of genetic disorders that cannot be addressed by standard gene replacement, given the large size of the gene, or by base editing, due to the high mutational variance of the affected gene.