ABCA4

Pictured: FDA signage outside its headquarters/iStock, JHVEPhoto Ascidian Therapeutics has received IND clearance from the FDA and has been granted Fast Track Designation for its asset to treat Stargardt disease, a genetic eye disease that can cause blindness in children and young adults, the company announced Monday. Ascidian’s asset, known as ACDN-01, had been given clearance from the agency and is expected to start enrollment in Phase I/II study of the drug in Stargardt and other ABCA4 retinopathies sometime in the first half of 2024. The asset itself is a clinical-stage RNA exon editor and, according to Ascidian, is the only therapeutic going after the “genetic cause” of Stargardt. “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,” Ascidian Interim CEO Michael Ehlers said in a statement. “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 expand the reach of genetic medicine dramatically,” Ehlers added. The open-label study, known as Stellar, will investigate the safety and efficacy of a single dose of the asset and will be administered by a subretinal injection. “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 look forward to this promising approach's clinical evaluation." Byron Lam, the Mark J. Daily Inherited Retinal Disease Research Center director at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, said in a statement. Ascidian launched in 2022 and was named to BioSpace’s NextGen Class of 2024’s top life science companies to watch. The company is differentiating itself from other gene therapy companies by using the exon swaps in RNA transcripts that encode proteins. When the company launched, it had $50 million in funding total with backing from Apple Tree Partners. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

ACDN-01 is the first RNA exon editor to enter clinical development and the only clinical-stage therapeutic targeting the genetic cause of Stargardt disease Ascidian expects to initiate enrollment in Phase 1/2 STELLAR study in the first half of 2024 ACDN-01 also granted Fast Track designation by FDA BOSTON, Jan. 29, 2024 /PRNewswire/ -- Ascidian Therapeutics, a biotechnology company aspiring to treat human diseases by rewriting RNA, today announced that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application and granted Fast Track designation for ACDN-01. ACDN-01 is the first-ever clinical-stage RNA exon editor and the only clinical-stage therapeutic 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, M.D., Ph.D., President and Interim Chief Executive Officer 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." "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 L. Lam, M.D., 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. Stargardt patients deserve treatment options, and I am looking forward to the clinical evaluation of this promising approach." 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. Ascidian also announced that the FDA has granted Fast Track designation for ACDN-01. 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. About Stargardt Disease and ACDN-01 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. 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. About Ascidian Therapeutics Ascidian Therapeutics, an ATP company, is redefining the treatment of disease by rewriting RNA. By editing exons at the RNA level, Ascidian therapies enable precise post-transcriptional editing of genes, resulting in full-length, functional proteins at the right levels, in the right cells, at the right time. With discovery, preclinical, and clinical programs in retinal, neurological, neuromuscular, and genetically defined diseases, Ascidian's approach has the potential to treat patients with one dose of an RNA exon editor, opening new therapeutic possibilities for patients and their families who are seeking breakthroughs. For more information, visit . SOURCE Ascidian Therapeutics

The FDA has given the all-clear for Ascidian Therapeutics to begin evaluating its experimental RNA exon editor in clinical trials, a first for this treatment modality. The company expects to begin recruiting patients in the Phase I/II STELLAR study of its lead ACDN-01 programme in Stargardt disease and other ABCA4 retinopathies in the first half.The move comes a little over a year after the ATP-incubated startup launched with $50 million in Series A funding and a platform that it says can sidestep drawbacks of conventional approaches. It took in another $40 million in an extended round late last year.The company's name is a tip of the hat to a group of marine organisms, also known as sea squirts, that undergo RNA trans-splicing and alternative splicing to modify their transcriptome as they transition from larvae to adults. Ascidian says its approach of "rewriting" RNA by editing and replacing human exons is inspired by this process."We have conviction in the rigour of our data, and that by editing RNA and not DNA, the Ascidian approach brings unique advantages," said interim CEO Michael Ehlers. These advantages include durability of gene therapy while reducing risks associated with DNA editing and manipulation.Last year, Ascidian presented six-month data from its lead programme demonstrating the "efficient and durable" production of full-length ABCA4 protein with a single AAV-delivery of ACDN-01 in the retina of non-human primates.The company notes that diseases caused by ABCA4 loss of function are examples of genetic disorders that cannot be addressed by standard gene replacement or base editing, either due to the large size of the gene or the extensive mutational variability within the affected gene itself. Stargardt disease has more than 1000 mutations across the ABCA4 gene.