Key Takeaways

  • In the phase 1/2 LUCE-1 study, no serious adverse events or dose-limiting toxicities had been reported among 15 participants treated with AAVB-081, while preliminary visual function improvements were observed in the low- and mid-dose cohorts
  • AAVB-039, a dual-AAV gene therapy targeting ABCA4 in Stargardt disease, demonstrated full-length ABCA4 expression, reduced lipofuscin accumulation, and generally favorable ocular safety findings in preclinical models

AAVantgarde Bio reported updated clinical findings for its investigational gene therapy AAVB-081 in Usher syndrome type 1B (USH1B), along with preclinical and development updates for AAVB-039 in Stargardt disease type 1 (STGD1), at the 26th European Society of Retina Specialists (Euretina) Annual Congress in Vienna, Austria.

The company's investigational therapies use a dual adeno-associated virus (AAV) strategy designed to address inherited retinal diseases involving genes that are too large to fit within a conventional single AAV vector.

Francesca Simonelli, MD, presented preliminary findings from LUCE-1 (NCT06591793), an open-label phase 1/2 study evaluating subretinal administration of AAVB-081, a dual AAV8.MYO7A gene therapy that uses a DNA-splicing approach in adults with retinitis pigmentosa associated with USH1B.

Enrollment was completed in January 2026, with 15 participants treated across 3 dose cohorts. The latest presentation included safety findings from all treated participants and efficacy assessments from participants with at least 6 months of follow-up.

As of the August 3, 2026, data cutoff, no serious adverse events or dose-limiting toxicities had been reported, and no participants had discontinued the study, according to AAVantgarde.The company characterized ocular inflammation as limited and consistent with expectations, with cases responding to corticosteroid treatment.

Among 12 participants in the low- and mid-dose cohorts who had at least 6 months of follow-up, 7 achieved an improvement of at least 1 line in best-corrected visual acuity (BCVA), including 4 who improved by at least 2 lines.Six participants achieved an improvement of at least 1 line in low-luminance visual acuity (LLVA), including 4 who demonstrated gains of at least 3 lines. Exploratory evaluations also identified signals of improvement in fixation stability and microperimetry in several participants, according to the company.

Because LUCE-1 is an early-stage, open-label study without a control group, the findings represent preliminary efficacy signals and will require longer follow-up and additional clinical evaluation to determine the magnitude and durability of any treatment effect.

The company said the findings support continued development of AAVB-081 and further evaluation of visual function outcomes with longer follow-up.

AAVB-039 targets ABCA4 in Stargardt disease

Paulo Eduardo Stanga, MD, presented preclinical findings supporting the clinical development of AAVB-039, AAVantgarde's dual AAV8.ABCA4 gene therapy for STGD1.

AAVB-039 uses 2 AAV vectors and an intein-mediated protein trans-splicing approach designed to produce full-length ABCA4 protein in photoreceptors.

According to the company, studies in mouse, pig, and nonhuman primate models demonstrated reconstitution of full-length ABCA4 protein and reductions in lipofuscin accumulation, along with a favorable ocular safety profile.In a pig model of STGD1, treatment resulted in full-length ABCA4 expression exceeding 100% of endogenous ABCA4 levels in the reported analysis. Investigators also observed reduced lipofuscin accumulation in treated retinal areas compared with sham-injected knockout eyes.

In nonhuman primates, the 2 vector components co-transduced 76% to 99% of photoreceptors across approximately 60% of the analyzed retinal section, according to AAVantgarde. Ocular findings were characterized as mild and transient. Electroretinography changes were temporary and dose related, while histologic findings were described as minimal, localized, and improving over time.

Clinical development of AAVB-039 includes the STELLA natural history study and CELESTE, a first-in-human phase 1/2 trial.

STELLA has completed enrollment of 150 patients. CELESTE is evaluating the safety and preliminary efficacy of AAVB-039 in participants with STGD1 caused by biallelic pathogenic variants in ABCA4. The study is recruiting participants in the United States, United Kingdom, and Europe.

“The data presented at Euretina 2026 provide important updates across both of our lead programs,” Jayashree Sahni, MD, chief medical officer of AAVantgarde, said in a statement. “In LUCE-1, the continued absence of serious adverse events or dose-limiting toxicities, together with early signals of improved visual function in the low- and mid-dose cohorts, support the continued development of AAVB-081 in Usher syndrome type 1B,” Sahni said.

She added that the preclinical findings for AAVB-039 demonstrated ABCA4 expression, reductions in lipofuscin, and favorable ocular safety findings across relevant large-animal models, supporting continued clinical development of the company's dual-AAV approach in Stargardt disease.