FDA Fast Tracks Ascidian’s RNA Exon Editor Stargardt Disease and Other ABCA4 Retinopathies

Rare Daily Staff    

Less than two years ago, Ascidian Therapeutics emerged from stealth aspiring to treat human disease by rewriting RNA. Now its lead candidate, RNA-exon editor ACDN-01, is poised to enter clinical development to target the genetic cause of Stargardt disease after the U.S. Food and Drug Administration cleared its investigational new drug (IND) application and granted Fast Track designation for ACDN-01.

ACDN-01 is the first and only clinical-stage RNA exon editor targeting the genetic cause of Stargardt disease. Ascidian 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.

“This 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,” said Michael Ehlers, president and interim CEO of Ascidian Therapeutics. “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.”

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 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.

Ascidian’s technology enables therapeutic targeting of large genes and genes with high mutational variance while maintaining native gene expression patterns and levels. This approach is designed to provide the durability of gene therapy while reducing risks associated with DNA editing and manipulation. 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.

“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,” said Byron 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. “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.”

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.

Fast Track designation is 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.

Photo: Michael Ehlers, president and interim CEO of Ascidian Therapeutics