Atsena Therapeutics’ Trial for X-Linked Retinoschisis Gene Therapy ATSN-201 Finishes Dosing Adult Patients in Part B

Atsena Therapeutics has finished dosing adult patients in Part B of its phase 1/2/3 LIGHTHOUSE clinical trial (NCT05878860) evaluating ATSN-201, an investigational adeno-associated virus (AAV) gene therapy, for the treatment of X-linked retinoschisis (XLRS) associated with mutations in the RS1 gene.¹

Part B of LIGHTHOUSE enrolled 9 patients and is expected to enroll 3 pediatric patients. Atsena expects to begin recruitment of pediatric patients in the final quarter of this year if the study’s data monitoring committee gives a green light. The adult patients participating in the trial were assigned to either a low volume group, a high volume group, or a control group. The patients in the control group may choose to receive ATSN-201 after 1 year of observation.

“Dosing of adult patients in all groups of Part B is now complete, and follow-up is ongoing,” Kenji Fujita, MD, the chief medical officer of Atsena Therapeutics, said in a statement.¹ “Preliminary safety data remain favorable, and early structural and functional readouts, including improvements in foveal schisis and retinal sensitivity, are consistent with the positive signals observed in Part A. These findings will enable initiation of pediatric dosing, a critical next step in assessing the full therapeutic potential of ATSN-201 across the XLRS patient population.”

Earlier this year, in July, Atsena announced that it had come into alignment with the FDA on the regulatory path for ATSN-201.² The agreement enabled the trial, originally a phase 1/2 study, to expand into a phase 1/2/3 study, thus paving the way for it to serve as a pivotal trial to support a future biologics license application (BLA).

The expanded trial design gets rid of the need for a separate phase 3 study and is expected to accelerate potential approval by at least 1.5 years. Enrollment in the new pivotal cohort, which will enroll around 30 adult and pediatric participants who will be randomly assigned to treatment or control groups in a 1:1 fashion, is expected to begin in the first quarter of 2026 and the BLA submission is anticipated in early 2028. Atsena also expects to provide a pivotal data readout in the second half of 2027. Patients who are assigned to the control group will be able to receive the gene therapy after 1 year.

ATSN-201 uses Atsena’s AAV.SPR capsid, which is intended to spread laterally beyond the site where the product is injected subretinally.¹ In May 2024, Atsena announced findings from LIGHTHOUSE's first, low-dose cohort.³ Notably, among the first 3 participants dosed, there were no serious adverse events. Furthermore, 2 of the 3 patients experienced extensive resolution of schisis beginning at 8 weeks after receiving ATSN-201 and continuing and deepening through week 24 of follow-up until data cut off. Lateral spread of the capsid was indicated by areas of schisis cavity resolution being observed by investigators both inside and well outside of the subretinal injection blebs.

“Data from the ongoing trial show that subretinal delivery of ATSN-201 has been well tolerated to date, including in patients with severe schisis cavities, and has led to encouraging improvements in both retinal structure and visual function,” Fujita said in a July 2025 statement.² “This program marks the first clinical use of our laterally spreading subretinal vector, offering important proof of principle for our ocular gene therapy platform. With the study’s expansion, we’re positioned to generate the pivotal data needed to potentially bring the first treatment for XLRS across the finish line.”

REFERENCES
1. Atsena Therapeutics Announces Dosing Complete for Adults in Part B of the Phase I/II/III LIGHTHOUSE Trial Evaluating ATSN-201 to Treat X-linked Retinoschisis. News release. Atsena Therapeutics. September 23, 2025. Accessed September 24, 2025. https://atsenatx.com/press-release/atsena-therapeutics-announces-dosing-complete-in-adults-in-part-b-of-the-phase-i-ii-iii-lighthouse-trial-evaluating-atsn-201-to-treat-x-linked-retinoschisis/
2. Atsena Therapeutics announces alignment with FDA on regulatory pathway to approval for ATSN-201 in x-linked retinoschisis (XLRS). News release. Atsena Therapeutics. July 9, 2025. Accessed September 24, 2025. https://atsenatx.com/press-release/atsena-therapeutics-announces-alignment-with-fda-on-regulatory-pathway-to-approval-for-atsn-201-in-x-linked-retinoschisis-xlrs/
3. Atsena Therapeutics announces positive clinical data from the first cohort of phase I/II trial evaluating ATSN-201 gene therapy for the treatment of X-linked retinoschisis (XLRS). News release. Atsena Therapeutics. May 1, 2024. Accessed September 24, 2025. https://atsenatx.com/press-release/atsena-therapeutics-announces-positive-clinical-data-from-the-first-cohort-of-phase-i-ii-trial-evaluating-atsn-201-gene-therapy-for-the-treatment-of-x-linked-retinoschisis-xlrs/