AAVantgarde sees early efficacy signals in dual-AAV eye therapy
AAVantgarde Bio has presented updated clinical data from its LUCE-1 study and new preclinical findings for its Stargardt disease candidate at EURetina 2026 in Vienna, with both programmes reporting encouraging safety and early efficacy signals.
The Milan-based company's lead asset, AAVB-081, is a dual AAV8.MYO7A gene therapy designed to treat Usher syndrome type 1B (USH1B), a condition that leaves patients born deaf and causes progressive vision loss from childhood. Because the MYO7A therapeutic gene is 6.7 kilobases in length, it exceeds the packaging capacity of a standard single AAV vector, making the dual-vector splicing approach central to AAVantgarde's platform differentiation.
LUCE-1 clinical readout
Enrolment in the LUCE-1 Phase 1/2 study completed in January 2026, with 15 participants dosed across three cohorts. As of the 3 August data cut, no serious adverse events or dose-limiting toxicities had been recorded, and no participant had withdrawn. Ocular inflammation was described as limited and responsive to corticosteroid treatment.
Among the 12 participants in the low- and mid-dose cohorts with at least six months of follow-up, seven achieved a one-line or greater improvement in best-corrected visual acuity, including four who gained at least two lines. Six participants showed a one-line or greater gain in low-luminance visual acuity, with four achieving three or more lines. Exploratory measures including fixation stability and microperimetry also showed supportive signals in several participants.
Presenting the data, Prof. Francesca Simonelli said the findings support continued development in USH1B and longer follow-up to characterise the durability of visual function outcomes.
Stargardt preclinical package
AAVantgarde also presented its preclinical dataset for AAVB-039, a dual AAV8.ABCA4 candidate for Stargardt disease, the most common form of inherited macular degeneration. The ABCA4 gene, at 6.8 kilobases, similarly exceeds single-vector capacity. Across mouse, pig and non-human primate models, the dual-vector approach achieved full-length ABCA4 protein reconstitution and reduced lipofuscin accumulation, a key toxic byproduct that drives photoreceptor loss in Stargardt patients.
In a pig model, ABCA4 expression exceeded 100% of endogenous levels in treated areas, with lipofuscin reduced versus sham-injected controls. In non-human primates, 76 to 99% of photoreceptors were co-transduced across approximately 60% of the analysed retinal section. Ocular safety findings were described as mild, transient and dose-related, with histological signals that improved over time.
The CELESTE Phase 1/2 first-in-human study for AAVB-039 is currently recruiting in the US, UK and Europe, supported by the STELLA natural history study, which has completed enrolment of 150 Stargardt patients.
Market context
Inherited retinal diseases represent a concentrated but competitive area for gene therapy developers. Spark Therapeutics' Luxturna, approved for RPE65-associated retinal dystrophy, established the regulatory and commercial template for subretinal AAV delivery, but no approved therapy yet exists for either USH1B or Stargardt disease, leaving an estimated combined patient population of roughly 80,000 to 95,000 individuals in the US and EU without a treatment option.
AAVantgarde's dual-vector platform is not unique in the field; several academic groups and early-stage companies have explored dual-AAV approaches for large-gene retinal indications. What distinguishes the LUCE-1 readout is the combination of a clean safety profile and measurable visual gains at low and mid doses, data points that regulators will scrutinise carefully as the company seeks to advance to the high-dose cohort and eventually into a registrational study.
Chief executive Jayashree Sahni said the EURetina presentations provided "important updates across both of our lead programs" and confirmed the company's confidence in the dual AAV intein platform for both indications.