Tern Therapeutics Presents Long-Term Data Showing Durable Preservation of Retinal Structure in CLN2 Batten Disease with One-Time TTX-381 Gene Therapy
One-time treatment with TTX-381 preserved photoreceptors throughout the macula, including at the fovea, through up to 24 months of follow-up, compared to rapidly progressive degeneration in untreated fellow eyes
No treatment-related serious adverse events observed in 18 patients treated with TTX-381 as of March 31, 2026
Findings are consistent with a potential disease-modifying effect and support the continued development of TTX-381 for vision loss in CLN2 disease
WASHINGTON, DC, May 8, 2026 – Tern Therapeutics, LLC (“Tern”), a biotechnology company developing one-time gene therapies for rare diseases, presented long-term safety and efficacy data for its investigational TTX-381 program at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting in Denver, Colorado on May 7, 2026. Robert Henderson, MD, Principal Investigator and Consultant Retinal Surgeon at Great Ormond Street Hospital in London, presented long-term data from the ongoing open-label Phase 1/2 study of TTX-381 demonstrating durable stabilization of retinal structure through up to 24 months after treatment with TTX-381, in contrast to progressive retinal degeneration observed in untreated fellow eyes.
“We are thrilled that the stabilized retinal health we observed at one year in these first participants is continuing to improve in longer term follow up,” said Christina Ohnsman, MD, Chief Medical Officer of Tern Therapeutics. “These encouraging results reaffirm our commitment to advance TTX-381 as quickly as possible.”
Dr. Henderson added, “In each of these patients, we have seen consistent evidence of stable visual behaviours in the treated eye; some patients are even covering their untreated eyes. It’s hugely exciting data and the families are universally both happy and adamant that trial participation has maintained quality of life for their children.”
Long-Term Follow-up Data from TTX-381 Clinical Trial
Study design
The ongoing open-label, dose-escalation Phase 1/2 study of TTX-381 is being conducted at clinical sites in the United Kingdom and Germany and evaluating two dose levels across multiple cohorts:
Cohort 1: 2.0 × 10¹⁰ genome copies (GC) / eye (n=3)
Cohort 2: 6.0 × 10¹⁰ GC / eye (n=3)
Expansion Cohort: 2.0 × 10¹⁰ GC / eye (up to n=16)
Both dose escalation cohorts are fully enrolled, and enrollment in the expansion cohort is ongoing.
Given the highly symmetric nature of photoreceptor degeneration in CLN2 disease, each patient’s untreated fellow eye serves as an internal control. Treated and untreated eyes are assessed longitudinally using spectral domain optical coherence tomography (SD-OCT).
Safety and Tolerability
As of the data cut-off on March 30, 2026, a total of 18 patients have been treated with TTX-381, including 14 patients in the ongoing clinical trial and 4 patients under an expanded access program. Safety analyses included all patients exposed to TTX-381 (n=18) through the data cut-off date. TTX-381 has been well-tolerated, with no serious adverse events (SAEs) related to the treatment or its subretinal administration procedure. Safety follow-up ranges from 5 months to up to 33 months.
Anatomic Data from Longitudinal SD-OCT Imaging
Anatomic analyses were reported for a subset of patients who received a full dose of TTX-381 and had ≥ 1 year available follow-up data (n=5).
At 12 months following treatment with TTX-381, all treated eyes in this subset showed stabilization or improvement in area of ellipsoid zone (EZ) loss and central photoreceptor layer thickness. In contrast, all untreated fellow eyes showed progressive retinal degeneration consistent with the known natural history of CLN2 disease. These differences were maintained in this subset through 12 to 24 months of follow-up (up to last available assessment):
Area of EZ Loss
Area of EZ loss was stable to improved in all 5 treated eyes at the last available timepoint (median change from baseline: -0.06 mm²; range: 0.00 to -0.53 mm² decrease), whereas all 5 untreated fellow eyes showed continued progression toward complete EZ loss within the macula (median change: 6.33 mm²; range: 1.46 to 38.99 change mm² increase). Two of 5 untreated fellow eyes reached maximal EZ loss area of 40.7 mm².Photoreceptor Layer Thickness
Central photoreceptor layer thickness remained stable or improved in treated eyes (median change from baseline: -2 μm; range -10 to +21 μm), whereas all untreated fellow eyes exhibited marked thinning (median change: -62 μm; range -83 to -48 μm).Foveal Integrity
All treated eyes maintained a substantially intact fovea – the centermost area of the retina responsible for sharpest visual acuity – through up to 24 months, whereas no untreated fellow eyes retained foveal integrity beyond 18 months.
These findings demonstrate the sustained preservation of retinal structure following administration of TTX-381 and are consistent with a potentially durable disease-modifying effect of TTX-381 on retinal degeneration in CLN2 disease. Preservation of foveal architecture is particularly notable, as it is closely associated with the maintenance of central vision. The data collectively suggest that early intervention with TTX-381 may help preserve meaningful vision in patients with CLN2 disease.
About TTX-381
TTX-381 is a novel one-time AAV gene therapy designed to deliver a working copy of the TPP1 gene directly to the retina to provide a durable source of TPP1 to maintain the health of the retina and address vision loss in people with CLN2 disease. Vision loss in CLN2 disease rapidly progresses to blindness, and there is currently no available treatment for the ocular manifestations of CLN2 disease. The open-label clinical trial to evaluate the safety and efficacy of TTX-381 is active and recruiting patients in an expansion cohort. Learn more at euclinicaltrials.eu (EUCT number: 2025-521175-31-00) and clinicaltrials.gov (NCT05791864).
About Tern Therapeutics
Tern is a privately held biotechnology company founded in 2023 with a new vision for speeding the development of transformative, one-time gene therapy medicines for rare diseases. Guided by a team of leading physicians, scientists, and business leaders and in collaboration with patient communities, we are driven to deliver transformative treatments with urgency to those living around the world with rare diseases. For more information about Tern, please visit www.terntx.com.
Contacts
Matthew Rosini
Tern Therapeutics, LLC
mrosini@terntx.com
