Atsena Therapeutics completes dosing in Part A of Phase I/II clinical trial evaluating ATSN-201 to treat X-linked retinoschisis

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Atsena Therapeutics has announced dosing has been completed in Part A of the LIGHTHOUSE study, a Phase I/II clinical trial evaluating subretinal injection of ATSN-201 for the treatment of X-linked retinoschisis (XLRS).

According to the company, ATSN-201, a gene therapy product candidate, leverages AAV.SPR, the company’s novel spreading capsid, to achieve therapeutic levels of gene expression in photoreceptors of the central retina while avoiding the surgical risks of foveal detachment.¹

The LIGHTHOUSE study (NCT05878860) is a Phase I/II, open-label, dose-escalation and dose-expansion clinical trial evaluating the safety and tolerability of ATSN-201 in male patients ages six and older with a clinical diagnosis of XLRS caused by pathogenic or likely pathogenic mutations in RS1. Enrollment for this study is ongoing. ATSN-201 has received Orphan Drug and Rare Pediatric Disease designations from the U.S. Food and Drug Administration.

Understanding X-Linked retinoschisis

XLRS is a monogenic X-linked retinal disorder caused by mutations in the RS1 gene, which encodes retinoschisin, a protein secreted predominantly by photoreceptors. This protein localizes to the extracellular surface of rods, cones, and bipolar cells. XLRS is characterized by schisis—abnormal splitting of retinal layers—that results in impaired visual acuity uncorrectable with glasses, progressing ultimately to blindness.

The condition primarily affects males and is typically diagnosed in early childhood. In the United States and European Union, approximately 30,000 males are affected by XLRS. Unfortunately, there are currently no approved treatments for this debilitating condition.

AAV.SPR: A novel gene therapy approach for XLRS

Atsena Therapeutics’ AAV.SPR is an innovative capsid designed to achieve lateral spread beyond the subretinal injection site, allowing safe and efficient transduction of the central retina. This is particularly beneficial for XLRS patients, as schisis cavities are most prominent in the macula.

In preclinical studies involving non-human primates, AAV.SPR demonstrated transgene expression far beyond the subretinal injection bleb margins, unlike standard AAV vectors, which are confined to these boundaries. At clinically relevant doses, AAV.SPR efficiently transduces foveal cones without requiring surgical retinal detachment and does not induce inflammation, marking a significant advancement in gene therapy for retinal diseases.¹

Kenji Fujita, MD, Atsena’s chief medical officer, said in a statement that 9 adults have been treated in Part A of the study in which three dose levels of ATSN-201 are being evaluated for safety and efficacy.

“We have seen both structural and functional benefits in patients treated at all dose levels,” Fujita said.

The company also reported that no serious adverse events related to treatment have been reported.

“Collecting data from Part A of the trial is an important breakthrough for Atsena because it validates the use of our novel capsid to effectively treat inherited retinal disease and it informs the safest and most effective path forward for Part B,” Fujita said. “We look forward to providing further updates from those patients early next year.”

Currently, there are no approved treatments for XLRS which is typically diagnosed in early childhood and primarily affects males. XLRS is characterized by schisis, or abnormal splitting of retinal layers, which causes impaired visual acuity that is not correctable with glasses and ultimately leads to blindness. Approximately 30,000 males in the U.S. and EU have this inherited retinal disease.

Patrick Ritschel, CEO of Atsena Therapeutics, said the company has started to hear positive anecdotes from those involved in the study.

“This marks a significant milestone for patients with XLRS as we push to bring a therapeutic option to individuals that otherwise have no approved treatment,” Ritschel said. “It also represents potential for individuals living with other inherited retinal diseases that could benefit from our novel capsid.”

Reference

1. Haserick B. Atsena Therapeutics – Atsena Therapeutics Announces Dosing Completed in Part A of Phase I/II Clinical Trial Evaluating Gene Therapy ATSN-201 to Treat X-linked Retinoschisis. Atsena Therapeutics. Published December 16, 2024. Accessed December 16, 2024. https://atsenatx.com/press-release/atsena-therapeutics-announces-dosing-completed-in-part-a-of-phase-i-ii-clinical-trial-evaluating-gene-therapy-atsn-201-to-treat-x-linked-retinoschisis/