Atsena Reports Positive Phase I/II Data on ATSN-201 for XLRS

Atsena Therapeutics, a clinical-stage gene therapy company dedicated to combating blindness through genetic medicine, has announced encouraging preliminary results from the first cohort of its ongoing LIGHTHOUSE study. This Phase I/II clinical trial is investigating the efficacy of ATSN-201, administered via subretinal injection, for the treatment of X-linked retinoschisis (XLRS). XLRS is a genetic condition caused by mutations in the RS1 gene, leading to schisis, or abnormal splitting of the retinal layers, which significantly impairs vision and can progress to blindness. Affecting approximately 30,000 males in the U.S. and EU, XLRS currently has no approved treatments.

The LIGHTHOUSE study focuses on male patients aged six and older who have been clinically diagnosed with XLRS. ATSN-201 employs a novel spreading capsid, AAV.SPR, designed to achieve therapeutic gene expression in the central retina's photoreceptors without necessitating foveal detachment surgery. This innovative approach aims to mitigate the surgical risks associated with treating retinal conditions.

In the first, low-dose cohort of the study, three patients received the ATSN-201 treatment. Results showed considerable promise, with two out of three patients exhibiting significant resolution of schisis starting at 8 weeks post-dosing and continuing to improve through the 24-week mark—the latest timepoint assessed. Remarkably, resolution of schisis cavities was noted both within and beyond the subretinal injection blebs, indicating that AAV.SPR effectively spreads laterally from the injection site. This lateral spread aligns with the intended design of the novel capsid.

Early efficacy was also demonstrated through microperimetry, which revealed functional improvements in the areas showing structural recovery. One patient experienced enhancements of up to 14 decibels (dB), with 38 loci showing improvements exceeding 7 dB. According to the U.S. Food and Drug Administration (FDA), a gain of at least 7 dB at five or more pre-specified loci is considered clinically meaningful.

ATSN-201 was well tolerated by all three patients in the first cohort, with no serious adverse events reported. These findings underscore the potential of subretinal injections of ATSN-201 as a safe treatment for patients with extensive retinal schisis.

Kenji Fujita, MD, Chief Medical Officer of Atsena Therapeutics, expressed optimism about the preliminary results. He highlighted the significance of the clinical validation of AAV.SPR's ability to spread laterally beyond the injection sites. As the study progresses to the mid-dose cohort, there is hope for accelerated development of ATSN-201, providing a potential therapeutic option for XLRS patients who currently have no approved treatments.

Safety data from the first cohort of the LIGHTHOUSE study will be presented at the Retinal Cell and Gene Therapy Innovation Summit 2024 in Seattle. The presentation, titled "Preliminary safety of ATSN-201 subretinal gene therapy in patients with X-linked retinoschisis," will be delivered by Dr. Christine Kay, Clinical Ophthalmology Advisor at Atsena Therapeutics.

In addition to ATSN-201, Atsena Therapeutics is also conducting a Phase I/II clinical trial for ATSN-101, targeting Leber congenital amaurosis type 1 (LCA1), a prevalent cause of childhood blindness. Atsena's pipeline leverages advanced adeno-associated virus (AAV) technology to address the unique challenges of inherited retinal diseases. Founded by leaders in ocular gene therapy, the company is driven by a mission to develop transformative treatments for patients suffering from vision loss.