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DURHAM, NC, May 1, 2024 – Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced positive preliminary data from the first cohort of the ongoing LIGHTHOUSE study, a Phase I/II clinical trial evaluating subretinal injection of ATSN-201 for the treatment of X-linked retinoschisis (XLRS). ATSN-201 utilizes 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.

The LIGHTHOUSE study is evaluating ATSN-201 in male patients ages 6 and older with a clinical diagnosis of XLRS caused by mutations in the RS1 gene. XLRS is characterized by schisis, or abnormal splitting of retinal layers, which causes impaired visual acuity that is not correctable with glasses and leads to progressive vision loss and ultimately blindness. XLRS impacts approximately 30,000 males in the U.S. and EU and there are no approved treatments.

In the first (low-dose) cohort of the LIGHTHOUSE study, two of the three patients showed extensive resolution of schisis beginning at 8 weeks after dosing. Additional and continued resolution of schisis was observed through week 24, the latest time point available. Notably, areas of schisis cavity resolution were found both inside and well outside of the subretinal injection blebs, indicating that AAV.SPR is spreading laterally from the injection blebs, consistent with expectations of this novel, laterally spreading capsid.

Early efficacy was also observed using microperimetry, with functional improvements seen in the same locations as structural improvements. Improvements of up to 14 dB were seen in one patient, with 38 loci showing an improvement of greater than 7 dB. The U.S. Food and Drug Administration considers an improvement of at least 7 dB at 5 or more prespecified loci to be clinically meaningful.

ATSN-201 was well tolerated in all three XLRS patients in the first cohort and no serious adverse events were reported. These results demonstrate, for the first time, the ability to safely administer subretinal injections in patients with extensive retinal schisis.

“The favorable safety profile and early efficacy observed in patients treated with ATSN-201 in the low- dose cohort of the LIGHTHOUSE study are very encouraging,” said Kenji Fujita, MD, Chief Medical Officer of Atsena Therapeutics. “We’re particularly pleased to have clinical validation of AAV.SPR’s ability to spread laterally well beyond the subretinal injection blebs. With dosing of patients in the mid-dose cohort underway, we look forward to the swift progression of this first clinical trial utilizing our novel spreading capsid and to the continued development of our best-in-class gene therapy candidate for XLRS patients who currently lack an approved treatment option.”

Safety data from the first cohort of the LIGHTHOUSE study will be presented at the Retinal Cell and Gene Therapy Innovation Summit 2024 being held Friday, May 3, 2024, in Seattle. Details are as follows:

Title: Preliminary safety of ATSN-201 subretinal gene therapy in patients with X-linked retinoschisis

Presenter: Christine Kay, MD, Clinical Ophthalmology Advisor, Atsena Therapeutics

Time: 11:05-11:20 a.m. PT

For more information about the Phase I/II open-label, dose-escalation, and dose-expansion clinical trial with four active study sites, visit ClinicalTrials.gov (Identifier: NCT05878860).

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 leads to progressive vision loss and ultimately blindness. XLRS primarily affects males and is typically diagnosed in early childhood. Approximately 30,000 males in the U.S. 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://atsena.wpenginepowered.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 progressive genetic condition affecting boys and men that is typically diagnosed in childhood. Another ongoing Phase I/II clinical trial is evaluating ATSN-101 for Leber congenital amaurosis type 1 (LCA1), one of the most common causes of blindness in children. 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, please visit  https://atsena.wpenginepowered.com/.

Tony Plohoros

6 Degrees

(908) 591-2839

tplohoros@6degreespr.com

info@atsenatx.com