Positive Early Results for ATSN-201 Gene Therapy in XLRS Phase I/II Study

Atsena Therapeutics, a company specializing in gene therapy for vision restoration, has reported promising initial findings from a Phase I/II clinical trial of ATSN-201. This treatment is designed to address X-linked retinoschisis (XLRS), a genetic disorder leading to progressive vision loss in males. The trial, known as LIGHTHOUSE, involves subretinal injections of ATSN-201, which utilizes the innovative AAV.SPR spreading capsid. This capsid is engineered to disperse laterally from the injection site, ensuring therapeutic gene expression in the central retina without risking foveal detachment.

The study focuses on male patients aged six and above diagnosed with XLRS due to mutations in the RS1 gene. XLRS is marked by schisis, an abnormal separation of the retinal layers, resulting in uncorrectable visual impairment and eventual blindness. This condition affects approximately 30,000 males in the U.S. and EU, with no current approved treatments available.

In the initial low-dose group of the LIGHTHOUSE study, two out of three patients exhibited significant schisis resolution as early as eight weeks post-injection, with continued improvements observed up to 24 weeks. The resolution was noted both within and beyond the injection areas, confirming the lateral spreading capability of AAV.SPR. Additionally, functional improvements were detected using microperimetry, with one patient showing a 14 dB improvement and 38 loci demonstrating a gain of over 7 dB, which is considered clinically significant by the FDA.

ATSN-201 was found to be well-tolerated, with no serious adverse events reported among the three XLRS patients in the first group. This marks the first time that subretinal injections have been safely administered to patients with extensive retinal schisis. The Chief Medical Officer of Atsena Therapeutics, Dr. Kenji Fujita, expressed optimism regarding the safety and early efficacy of ATSN-201. He highlighted the importance of the clinical validation of AAV.SPR's lateral spreading ability and the ongoing dosing in the mid-dose cohort.

The first cohort's safety data is scheduled to be presented at the Retinal Cell and Gene Therapy Innovation Summit 2024, with Christine Kay, MD, Clinical Ophthalmology Advisor at Atsena, as the presenter. The study, which has four active sites, is registered on ClinicalTrials.gov with the identifier NCT05878860.

XLRS is a monogenic X-linked disorder caused by RS1 gene mutations, which encodes retinoschisin, essential for retinal cell function. It is characterized by schisis and typically diagnosed in early childhood, predominantly affecting males.

AAV.SPR is a novel capsid developed by Atsena that spreads beyond the injection site, facilitating efficient transduction of the central retina. Preclinical studies in non-human primates have shown its effectiveness in promoting transgene expression beyond the injection bleb margins, unlike traditional AAV vectors that remain confined.

Atsena Therapeutics is a clinical-stage company developing treatments for inherited retinal diseases, with ongoing trials for XLRS and Leber congenital amaurosis type 1 (LCA1). The company's pipeline leverages novel AAV technology to overcome challenges in treating inherited retinal diseases. Atsena is led by a team with deep expertise in ocular gene therapy, committed to improving the lives of those with vision loss.