First time patients with LCA1 have been treated with gene therapy ATSN-101 demonstrated durable, clinically significant improvements in vision at the high dose and was well-tolerated 12 months post-treatment in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D DURHAM, N.C., Sept. 05, 2024 (GLOBE NEWSWIRE) — 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 that 12-month safety and efficacy data from Atsena’s Phase I/II clinical trial evaluating the investigational gene therapy ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1) were published in The Lancet. ATSN-101 was originally developed by Atsena’s founders, Shannon and Sanford Boye at the University of Florida, and is the first gene therapy being studied to treat patients with LCA1. “There are no approved treatments for LCA1, an inherited retinal disease that affects the retina and causes severe vision impairment or blindness in infancy,” said Artur Cideciyan, PhD, Research Professor of Ophthalmology at the Scheie Eye Institute of the University of Pennsylvania and senior author of the paper. “The improvements in visual function and tolerability we saw at the high dose of ATSN-101 at 12 months post-treatment in the ongoing Phase I/II trial support a future randomized, controlled Phase III trial to further evaluate this subretinal gene therapy in patients with LCA1. ATSN-101 represents a significant advancement in the reversal of blindness that begins in childhood.” All 15 enrolled patients with genetically confirmed LCA1 received unilateral subretinal injections to determine the safety and preliminary efficacy of ascending doses of ATSN-101. Thirteen of the patients were treated at the Scheie Eye Institute. Two were treated at the Oregon Health & Science University (OHSU) Casey Eye Institute, under the guidance of Paul Yang, MD, PhD, and Andreas Lauer, MD. In the dose escalation phase, three adult cohorts (n=3 each) were treated with three ascending doses: 1.0E10 vg/eye (low dose), 3.0E10 vg/eye (mid dose), and 1.0E11 vg/eye (high dose). In the dose expansion phase, one adult and one pediatric cohort (n=3 each) were treated at the high dose. The primary endpoint of the Phase I/II clinical trial is the incidence of treatment-emergent adverse events (TEAEs), and secondary endpoints include full-field stimulus test (FST) and best-corrected visual acuity (BCVA). A multi-luminance mobility test (MLMT) was also performed. “This is the first time patients with LCA1 have been treated with gene therapy, making this promising treatment potentially the first-ever gene therapy for this inherited retinal disease,” said Paul Yang, MD, PhD, Associate Professor of Ophthalmology in the OHSU School of Medicine and lead author of the paper. “We are excited to have these results published in The Lancet, a top-tier medical journal, which helps broaden the reach of the important work underway at Atsena to the wider medical community.” For high-dose subjects, mean change in dark-adapted FST was 20.3 decibels, representing a 100-fold improvement for treated eyes. Improvements were first observed at day 28 and persisted over 12 months (p = 0.012). Modest improvements in BCVA were also observed with an average improvement of -0.16 logMAR or 8 letters 12 months post-treatment for high-dose subjects (p = 0.10). Three of six high-dose subjects that performed MLMT achieved the maximum score in the treated eye at Month 12. All adverse events were either mild (91%) or moderate (9%) in severity, and TEAEs (including serious adverse events) were similar to those reported in previous subretinal gene therapy studies. No serious TEAEs were related to ATSN-101, and the majority of TEAEs were related to the surgical procedure. Ocular inflammation was mild and reversible with steroid treatment. “The preliminary efficacy and robust safety data from our ongoing Phase I/II trial underscore the potential of ATSN-101 to be a first-in-class gene therapy for LCA1. It is encouraging that improvements in retinal sensitivity were observed as early as 28 days post-treatment and persisted over at least 12 months, highlighting the durability of our investigational gene therapy,” said Kenji Fujita, MD, Chief Medical Officer of Atsena Therapeutics and co-author of the paper. “We are thrilled that the 12-month data have been published for the first time in this prestigious medical journal.” The published manuscript, titled “Safety and Efficacy of ATSN-101 in Patients with Leber Congenital Amaurosis caused by Biallelic Mutations in GUCY2D: A Phase 1/2, Multi-Center, Open-Label, Unilateral Dose Escalation Study,” is available online and will appear in the print issue of The Lancet at a later date. About GUCY2D-associated Leber congenital amaurosis (LCA1)LCA1 is a monogenic eye disease that disrupts the function of the retina. It is caused by mutations in the GUCY2D gene and results in early and severe vision impairment or blindness. GUCY2D-LCA1 is one of the most common forms of LCA, affecting roughly 20 percent of patients who live with this group of inherited retinal diseases. There are currently no approved treatments for LCA1. About ATSN-101ATSN-101 is an investigational, subretinal AAV5 gene therapy being evaluated in an ongoing Phase I/II clinical trial for Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1). ATSN-101 was originally developed at the University of Florida and introduces functional human GUCY2D to photoreceptors. At 12 months post-treatment, ATSN-101 has demonstrated durable, clinically meaningful improvements in vision at the high dose and is well-tolerated. Atsena has received Rare Pediatric Disease designation, Regenerative Medicine Advanced Therapy designation, and Orphan Drug designation from the U.S. Food and Drug Administration for ATSN-101 for the treatment of GUCY2D-associated LCA1. About Atsena TherapeuticsAtsena 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://atsenatx.com/. Media Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com Business Contact:info@atsenatx.com