Atsena Therapeutics recently reported interim 6-month results from Part B of the phase 1/2/3 LIGHTHOUSE trial evaluating ATSN-201, an investigational gene therapy, in patients with X-linked retinoschisis (XLRS).
The data was presented at the Foundation Fighting Blindness Retinal Therapeutics Innovation Summit in Denver, Colorado.
We’ll begin with Atsena.
Atsena Therapeutics is a Durham, North Carolina-based clinical-stage gene therapy company developing next generation treatments for the reversal or prevention of blindness from inherited retinal diseases, such as:
- XLRS
- GUCY2D-associated Leber congenital amaurosis (LCA1)
- MYO7A-associated Usher syndrome (USH1B)
And its portfolio?
The company’s lead asset is ATSN-201, a subretinal gene therapy under development for both XLRS and USH1B that utilizes AAV.SPR, one of Atsena’s novel capsids that holds a key role in treating XLRS.
Note: ATSN-201 has received four FDA designations over the past 2 years, including:
- Regenerative Medicine Advanced Therapy (RMAT; April 2025)
- Fast Track (March 2025)
- Orphan Drug (September 2024)
- Rare Pediatric Disease (August 2024)
Plus: ATSN-101, a first-in-class, investigational gene therapy for Leber congenital amaurosis type 1 (LCA1) is also currently in development.
Any recent news from Atsena?
Indeed. In July 2025 the company announced that the FDA agreed to expand the ongoing LIGHTHOUSE clinical study of ATSN-201 for XLRS into a continuous phase 1/2/3 pivotal trial.
- Meaning: An additional cohort will be added to the study (Cohort #5) with an estimated 30 adult and pediatric patients randomized 1:1 between treatment and control groups.
Why: To allow its clinical data to be used to support an upcoming Biologics License Application (BLA) submission to the FDA.
Impressive! Give me a refresher on the technology behind ATSN-201.
The next-generation, adeno-associated virus (AAV) technologies feature novel, laterally-spreading capsids, dual vectors, and intravitreal capsids that deliver larger payloads for genetic mutations that are too large to treat with a single AAV vector.
In other words: The capsid spreads laterally beyond the subretinal injection site (bleb margins) to safely deliver retinoschisin (RS1) to photoreceptors within the central retina/fovea.
- Click here to learn more about the mechanism of action behind AAV.SPR.
Let’s move on to this LIGHTHOUSE trial.
Originally initiated in 2023 with plans to conclude in 2028, this open-label, dose-escalation, and dose-expansion trial (NCT05878860) consists of three parts (A, B and C) and six cohorts.
Note: The phase 1/2 portion includes cohorts 1-3 (Part A) and cohorts 4-5 (Part B), while cohort 6 (Part C) will serve as the phase 3 portion of the study.
- Click here for more information on the set up of the LIGHTHOUSE trial.
Didn’t the company release new findings a while back?
Yup, in May 2025. The data was based on Part A of the study—which involved just the first three cohorts (with three patients in each).
The crux of those results:ATSN-201 was found to be safe and well tolerated; demonstrated efficacy across all dose levels; and resulted in “statistically significant improvements” for both BCVA and LLVA.
And this new interim data?
Some highlights from the data on ATSN-201’s efficacy from the interim 6-month Part B data include:
- The kinetics of structural and functional responses in cohort 4 were consistent with those observed in cohorts 1-3
- Foveal schisis closure at Month 6 was confirmed in 4 of 6 treated adults (67%) in cohort 4.
- None of the three untreated control subjects and none of the six untreated contralateral eyes demonstrated foveal schisis closure
- Microperimetry response at Month 6 for Part B closely mirrored that observed for Part A at the same time point
- Foveal schisis closure at Month 6 was confirmed in 4 of 6 treated adults (67%) in cohort 4.
What about the findings on safety?
A favorable safety profile was observed across all Part B cohorts with no serious adverse events (SAEs), instances of macular hole formation or retinal detachment, and no subject discontinuations.
- Plus: Subretinal deposits observed in a subset of subjects in cohort 4 were resolved with transient steroid treatment.
A clean safety profile was observed in pediatric subjects (cohort 5, ages 8-12), with no SAEs, subretinal deposits, macular hole formation, retinal detachment, and discontinuations.
Any comments from Atsena about this new data?
Shannon Boye, PhD, co-founder and CSO of Atsena highlighted that “Part B of our LIGHTHOUSE study is delivering exactly as we expected—a favorable safety profile, schisis resolution, and functional improvements at 6 months that closely replicate what we observed at the same time point in Part A of the study.”
And what are the next steps for ATSN-201?
Kenji Fujita, MD, the CMO of Atsena noted that patient screening is underway in the pivotal Part C cohort, with enrollment expected to be completed by the end of Q1 2027.
He added that they remain on track to file a BLA in 2028 supported by data from the phase 3 cohort.
Anything else going on with Atsena?
As part of its exclusive strategic collaboration with Nippon Shinyaku Co., Ltd. ATSN-101 has completed a phase 1/2 trial (NCT03920007) with positive results, and Atsena expects to initiate a global pivotal phase 3 clinical trial evaluating ATSN-101 in H2 2026.