May 13, 2026 —
Amlogenyx announced new preclinical data for AM805, also known as AAV9-PPCA, an investigational AAV9-mediated gene therapy being developed for Alzheimer’s disease. The data, highlighted in an oral presentation at the 2026 American Society of Gene & Cell Therapy Annual Meeting, showed that AM805 substantially reduced both intracellular and extracellular amyloid-β (Aβ42) across multiple Alzheimer’s disease models.
AM805 uses an AAV9 vector to deliver protective protein/cathepsin A (PPCA), a lysosomal enzyme designed to degrade amyloid and restore lysosomal function. This strategy differs from antibody-based Alzheimer’s therapies, which primarily target extracellular amyloid plaques. By targeting amyloid accumulation inside neurons as well as outside cells, Amlogenyx aims to address a broader component of Alzheimer’s disease biology, including intraneuronal Aβ42, which may contribute to neurotoxicity and neuronal dysfunction.
In preclinical studies using 5xFAD and Tg2576 mouse models, AM805 reduced intraneuronal Aβ42 accumulation in neuronal cell bodies and axons, while also decreasing the size and number of extracellular amyloid plaques. Higher PPCA expression was associated with up to 60–80% reductions in amyloid burden, with effects observed across multiple routes of administration and in animals that already had established pathology at the time of dosing.
Amlogenyx also reported that intrathecal administration of AM805 was well tolerated at therapeutically relevant doses, with no significant adverse findings. The company highlighted a potential cross-correction mechanism, in which PPCA secreted from transduced cells can be taken up by neighboring cells, enabling broader amyloid clearance even in regions with lower direct transduction. This feature may support therapeutic activity at relatively low gene therapy doses.
The company plans to submit an Investigational New Drug application to the FDA later this year and initiate a Phase 1/2 clinical study in 2027. If successfully translated, AM805 could represent a novel one-time AAV gene therapy approach for Alzheimer’s disease, focused on lysosomal amyloid clearance and neuronal functional restoration rather than plaque reduction alone.
