Adverum Biotechnologies, Inc. announced new nonclinical data supporting the use of ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022) at the American Society of Gene & Cell Therapy (ASGCT) 2023 Annual Meeting in Los Angeles, California. Ixo-vec is currently being evaluated in the Phase 2 LUNA trial in wet age-related macular degeneration (wet AMD). The data being presented at ASGCT are featured in an oral presentation on the identification of dose-dependent immune landscape signatures in nonhuman primates (NHPs), an oral presentation of nonclinical data that supports the potential for staggered, bilateral dosing of Ixo-vec and a poster presentation evaluating Ixo-vec per cell vector genome (vg)iodistribution and mRNA expression in NHPs.

Data Highlights: Ixo-vec aflibercept protein levels were consistent across 2x10^11 vg/eye (2E11) and 6x10^10 vg/eye (6E10) doses, suggesting lower doses may offer similarly robust levels of efficacy with improved inflammation profiles. Immune landscape signatures demonstrated a dose-dependent activation of innate and adaptive immune response consistent with AAV-associated inflammation. No evidence that harnessing ocular cells as biofactories to produce aflibercept leads to aflibercept expression-related toxicity/inflammation.

No evidence that ciliary body architecture was directly affected by Ixo-vec. In an encore to the company's recent presentation at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, Adverum presented data outlining the rationale for staggered, bilateral administration of Ixo-vec in patients with bilateral disease. Up to 42% of wet AMD patients experience neovascularization in the second eye in the first two to three years following diagnosis in the primary eye, indicative of an unmet need for many wet AMD patients globally.

Ixo-vec was administered to one eye and then two months later to the fellow eye of NHPs. Following the second, staggered administration of Ixo-vec, the fellow eye demonstrated aflibercept protein levels within the targeted therapeutic range.   Staggered, bilateral intravitreal (IVT) administration of Ixo-vec was well tolerated, with encouraging therapeutic activity as well as no increase in intraocular inflammation levels. These data demonstrate for the first time that the ocular humoral response in NHP is compartmentalized to the eye dosed with AAV capsid.

An evaluation of intraocular per cell biodistribution of Ixo-vec vg and aflibercept mRNA via in-situ hybridization in NHP eyes at the human equivalent dose of 2E11 and 6E10 revealed: Intraocular fluid convection together with anterior and posterior fluid outflow influence ubiquitous distribution of vgs from IVT-delivered ocular gene therapy products. Ixo-vec drives aflibercept mRNA expression in anterior and posterior tissues with most prominent expression in the macula and peripheral retina. Localization of aflibercept mRNA expression in retina is influenced by the internal limiting membrane (ILM) barrier.