Amlogenyx’s AM805 Gene Therapy Significantly Reduces Amyloid In Preclinical Alzheimer’s Studies

Amlogenyx Inc., a biotechnology company focused on developing gene therapies for Alzheimer’s disease and other neurodegenerative disorders, has announced encouraging results from a series of preclinical studies of AM805, an investigational AAV9-based gene therapy for Alzheimer’s disease. The therapy is designed to deliver protective protein cathepsin A (PPCA), a potent lysosomal enzyme, to the brain in order to reduce the buildup of amyloid, a key factor in the progression of Alzheimer’s disease.

The preclinical studies showed that AM805 successfully reduced amyloid in both young and aged mice, across models of moderate and severe Alzheimer’s disease. The therapy was effective in clearing amyloid both inside cells and in plaques outside of cells, suggesting it may address multiple aspects of the disease. The results will be presented at the AD/PDTM 2026 International Conference on Alzheimer’s and Parkinson’s Diseases, taking place from March 19 to 21 in Copenhagen, Denmark, as well as online via an ePoster.

Arjun Natesan, head of early research and development at Amlogenyx, explained that although amyloid is clearly implicated in Alzheimer’s and other neurodegenerative diseases, treatments capable of halting or reversing disease progression have remained elusive. 

He noted that Amlogenyx was established to pursue a novel approach aimed at reducing amyloid burden in the brain by delivering a lysosomal enzyme that can remove both intracellular amyloid and extracellular plaques. He stated that the preclinical data demonstrate that AM805 can achieve substantial amyloid reduction in the central nervous system, even in advanced stages of the disease, highlighting its potential as a preventive and therapeutic option.

Amyloid accumulation in the central nervous system disrupts normal cell function, impairs synaptic communication, activates microglia, and triggers chronic neuroinflammation. In collaboration with St. Jude Children's Research Hospital, Amlogenyx researchers identified PPCA as a lysosomal enzyme capable of efficiently degrading amyloid. To leverage this activity, the team developed AM805, an AAV9-PPCA vector engineered to deliver PPCA to the brain and reduce amyloid levels.

Study results showed that AM805 increased PPCA activity and reduced amyloid-positive brain regions in a dose-dependent manner in mouse models of both moderate and severe Alzheimer’s disease. The reductions achieved were comparable to or exceeded those reported for approved Alzheimer’s monoclonal antibodies. 

Both intracellular and extracellular amyloid, measured by Aβ peptide (4G8 positive signal), were lowered. Importantly, the therapy demonstrated effectiveness across multiple delivery routes, indicating that the enzyme can provide therapeutic benefits regardless of how it is administered. Safety studies in non-human primates showed that AM805 could be delivered to the brain without adverse effects, achieving enzyme expression levels similar to those producing therapeutic effects in mice.

These findings will be presented in Poster #3157, Shift #2, at the AD/PD 2026 conference, along with an accompanying ePoster and audio presentation available on the meeting platform. AM805 is currently undergoing IND-enabling studies, and Amlogenyx plans to submit an Investigational New Drug application to the U.S. Food and Drug Administration in 2027.