Ascidian Therapeutics has received FDA clearance for its investigational new drug (IND) application for ACDN-01, a first-ever, clinical-stage ribonucleic acid (RNA) exon editor targeting Stargardt disease.
Give me the rundown on this company.
Founded in 2020 and based in Boston, Massachusetts, Ascidian is a biotechnology company focused on rewriting RNA in order to develop precise, post-transcriptional editing of genes that creates novel RNA exon editor molecules.
These molecules are intended to target inherited retinal diseases (IRDs) associated with mutations in the ATP-binding cassette subfamily A, member 4 (ABCA4) gene—including Stargardt disease (and to a lesser extent retinitis pigmentosa [RP] and cone-rod dystrophy [CRD]).
Explain the science of this.
The company has designed a gene editing platform that replaces (edits) mutated exons (which form into pre-mRNA molecules that then translate into protein) to develop therapies that could target large genes and those with a high mutational variance—all while maintaining the gene’s natural expression patterns and levels.
The intended result: to provide the durability associated with gene therapy and significantly reduce any potential risks typically linked with DNA editing, manipulation and gene replacement.
How does this compare to standard gene therapy?
Prior research has noted that gene therapy or gene editing processes involving the ABCA4 gene tend to be “too large to be delivered with a single AAV construct” and “too many patient mutations exist to feasibly address each mutation via mutation-specific base editing.”
So how is this editing done?
Per Ascidian, the company’s “first-of-its-kind RNA exon editing platform” uses molecular biology + “computational biology” to design novel RNA exon editor molecules.
Through this process, a single exon molecule can replace multiple mutated exons without modifying DNA or requiring the use of any foreign enzymes.
And its delivery?
Due to its small size—which would enable the exon to replace disease-causing exons in a gene—the exon editing molecule could then be able to fit in adeno-associated virus (AAV) or other viral / non-viral vector delivery vehicles.. “Ascidian’s platform is versatile, allowing the RNA exon editing therapeutics to be administered using a delivery vehicle targeted specifically to the location where post-transcriptional editing is needed to treat disease” the company explained.
Gotcha. That’s pretty in-depth… so what is ACDN-01?
Part of Ascidian’s lead program on ABCA4 retinal dystrophies, ACDN-01 is an in vivo RNA exon editor designed to target the genetic cause of Stargardt disease.
The investigational candidate is administered via subretinal injection.
And the FDA’s clinical update on it?
Aside from clearing ACDN-01’s IND application (more on that in a moment), the federal agency also granted Fast Track designation—enabling Ascidian to expedite its development through the regulatory clinical process.
So what’s next for ACDN-01?
Thanks to the FDA’s IND acceptance, the company will begin patient enrollment for the phase 1/2 STELLAR study on the exon editor.
A single subretinal injection of ACDN-01 will be evaluated for both its safety and efficacy in resting Stargardt disease and other ABCA4 retinopathies.
When will this trial commence?
Per Ascidian, enrollment will be initiated within the first half of 2024.
How significant is this update?
For patients with Stargardt disease and other ABCA4 retinal dystrophies, it could be considered a landmark moment.
The RNA exon gene editor would be the first and only clinical-stage therapeutic of its kind to manage patients with this IRD.
Lastly, any expert input?
And according to Ascidian’s Michael Ehlers, MD, PhD, president and interim CEO, ACDN-01’s IND clearance is both a milestone for the company and the field of RNA gene editing.
“This is a critical step toward overcoming the challenges of Stargardt disease,” stated Byron L. Lam, MD, director of the Mark J. Daily Inherited Retinal Disease Research Center at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, “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.”