Atsena Therapeutics Announces Dosing Completed in Part A of Phase 1/2 Clinical Trial Evaluating Gene Therapy to Treat X-linked Retinoschisis

Atsena Therapeutics recently announced dosing has been completed in Part A of the LIGHTHOUSE study, a Phase 1/2 clinical trial evaluating subretinal injection of ATSN-201 for the treatment of X-linked retinoschisis (XLRS). ATSN-201, a best-in-class 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.

“Nine 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. Additionally, no serious adverse events related to treatment have been reported,” said Kenji Fujita, MD, Atsena’s Chief Medical Officer. “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. 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 US and EU have this inherited retinal disease.

“We are thrilled that dosing is complete in Part A of the LIGHTHOUSE study for ATSN-201 and that we’ve begun hearing positive anecdotes from those involved. 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,” said Patrick Ritschel, Chief Executive Officer of Atsena Therapeutics. “It also represents potential for individuals living with other inherited retinal diseases that could benefit from our novel capsid. We look forward to the insights gained from this trial as we pioneer new approaches to ocular gene therapy.”

The LIGHTHOUSE study is a Phase 1/2, 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. For more information, visit ClinicalTrials.gov (Identifier: NCT05878860). ATSN-201 has received Orphan Drug and Rare Pediatric Disease designations from the US FDA.

XLRS is a monogenic X-linked disease caused by mutations in the RS1 gene which encodes retinoschisin, a protein secreted primarily by photoreceptors. RS1 is localized to the extracellular surface of rods, cones, and bipolar cells. XLRS is characterized by schisis, or abnormal splitting of retinal layers, which causes impaired visual acuity that is not correctable with glasses and, ultimately, blindness. XLRS primarily affects males and is typically diagnosed in early childhood. Approximately 30,000 males in the US and EU have XLRS, for which there are currently no approved treatments.

AAV.SPR, one of Atsena’s novel capsids, spreads laterally beyond the subretinal injection site to enable safe and efficient transduction of the central retina (where schisis cavities predominate in XLRS patient retinas) when injected into areas outside the macula. A preclinical study in non-human primates demonstrated that AAV.SPR promotes transgene expression well beyond subretinal injection bleb margins. This is in stark contrast to benchmark AAV vectors, which remain confined to the original bleb margins. At clinically relevant doses, AAV.SPR efficiently transduces foveal cones without the need for surgical detachment and does not cause inflammation. For more information about the preclinical study and how AAV.SPR works, visit https://atsenatx.com/our-approach/laterally-spreading-aav/.

Atsena Therapeutics is a clinical-stage gene therapy company developing best-in-class treatments for the reversal or prevention of blindness from inherited retinal diseases. The company’s lead program is evaluating ATSN-201 in an ongoing Phase I/II clinical trial for X-linked retinoschisis (XLRS), a genetic condition that is typically diagnosed in childhood and leads to blindness later in life. ATSN-101, Atsena’s program for Leber congenital amaurosis type 1 (LCA1), one of the most common causes of blindness in children, has completed a Phase 1 / 2 trial with positive results (https://doi.org/10.1016/s0140-6736(24)01447-8) and is moving towards initiation of a pivotal trial. Atsena’s pipeline is powered by novel adeno-associated virus (AAV) technology tailored to overcome the hurdles presented by inherited retinal diseases. Founded by pioneers in ocular gene therapy, Atsena is led by an experienced team dedicated to addressing the needs of patients with vision loss. For more information, visit  https://atsenatx.com/.