IND Cleared for First RNA Exon Editor Therapy, Trial to Initiate in Stargardt Disease


Ascidian Therapeutics presented positive preclinical data at the 2023 ASGCT meeting.

Byron L. Lam, MD

Byron L. Lam, MD

Credit: University of Miami

The FDA has cleared Ascidian Therapeutics’ investigational new drug application for ACDN-01, permitting evaluation of the RNA exon editor therapy in a phase 1 trial in people with Stargardt disease.1

"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," Michael Ehlers, MD, PhD, President and Interim Chief Executive Officer, Ascidian Therapeutics, said in a statement.1 "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."

With the clearance, ACDN-01 becomes the first RNA exon editortherapy to reach the clinical stage as well as the only investigational therapeutic to target the specific genetic cause of Stargardt disease. The company plans to initiate enrollment in the phase 1/2 STELLAR trial that will evaluate ACDN-01 for Stargardt and other ABCA4 retinopathies in the first half of 2024. The FDA also granted fast track designation to the therapy at the same time as the IND clearance.

"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," Byron L. Lam, MD, Director, Mark J. Daily Inherited Retinal Disease Research Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, added.1 "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. Stargardt patients deserve treatment options, and I am looking forward to the clinical evaluation of this promising approach."

READ MORE: Ocugen Doses First Patient With Stargardt Disease With Gene Modifier Therapy

STELLAR will evaluate the safety and efficacy of a single dose of ACDN-01 administered via subretinal injection. ACDN-01 is an in vivo RNA exon editor delivered by a single vector. Ascidian previously presented preclinical data supporting the IND submission at the American Society of Gene and Cell Therapy (ASGCT) meeting in May 2023. The data demonstrated the production of full-length ABCA4 protein following administration to the non-human primate retina. In non-human primates, RNA exon editing durability and efficiency was demonstrated for up to 6 months of follow-up. The data also highlighted the first successful RNA exon editing via trans-splicing in both human photoreceptors ex vivo and in large animals.2

“These data could have therapeutically meaningful implications for patients with Stargardt disease, the most common form of inherited macular degeneration, as well as other diseases that are not addressable by today’s gene therapy and gene editing technologies,” Romesh Subramanian, PhD, Ascidian’s former President and Chief Executive Officer, said in a statement at that time.2 “More than a quarter of a century has passed since the cause of Stargardt disease was discovered, and this is the first report quantifying and confirming therapeutically relevant levels of full-length ABCA4 protein produced after a single dose in a large animal. With durable editing now confirmed in non-human primates and replicated in human retinal explants, these findings add to the growing body of evidence supporting the potential of Ascidian’s proprietary exon editing platform to transform the treatment of genetically defined diseases.”

1. Ascidian Therapeutics Announces First-Ever IND for an RNA Exon Editor as FDA Approves Trial Plan and Fast Tracks ACDN-01 in Stargardt Disease and Other ABCA4 Retinopathies. News release. Ascidian Therapeutics. January 29, 2024.
2. Ascidian Therapeutics to Present New Data From Its Lead Program Targeting ABCA4 Retinopathies at the ASGCT 2023 Annual Meeting. News release. Ascidian Therapeutics. May 9, 2023. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/
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