Novel and potent catalytic approach that directly clears amyloid on the inside of neurons as well as reduces amyloid plaques with the potential to be superior to monoclonal antibodies and restore neuronal function while halting or reversing disease progression
NOVATO, Calif., March 16, 2026 (GLOBE NEWSWIRE) -- Amlogenyx Inc., a biotechnology company focused on developing gene therapies for Alzheimer’s disease and other neurodegenerative diseases, today announced multiple positive results from a broad series of preclinical studies of AM805, an investigational AAV9 gene therapy for the treatment of Alzheimer’s disease. The results demonstrate that delivery of the carboxypeptidase called protective protein cathepsin A (PPCA), a potent lysosomal enzyme, was successful in reducing amyloid in the brain of both severe and moderate animal models of Alzheimer’s disease in both young and aged mice. The data will be presented in a poster session, taking place March 19-21, and in an ePoster at the AD/PDTM 2026 International Conference on Alzheimer’s and Parkinson’s Diseases in Copenhagen, Denmark and online.
Arjun Natesan, the head of early R&D at Amlogenyx, said: “Despite clear biology implicating amyloid in Alzheimer’s and other neurodegenerative diseases, treatments that can halt, or possibly even reverse, disease progression have eluded researchers to date. Amlogenyx was founded to pursue an entirely novel approach of reducing amyloid burden in the brain by delivering a potent lysosomal enzyme which would enable clearance of the intracellular burden as well as enable clearance of plaque outside of cells. We are extremely pleased to present preclinical data demonstrating that AM805 can achieve robust amyloid reduction in the CNS and reduce both intracellular and extracellular amyloid, even in advanced disease, underscoring its strong potential to prevent and treat this devastating and intractable disease.”
In the central nervous system, amyloid is a key driver of Alzheimer’s disease, disrupting cellular homeostasis by impairing synaptic function, activating microglia, and triggering chronic neuroinflammation. In the data presented at AD/PD 2026, researchers from Amlogenyx and St. Jude Children's Research Hospital identified a specific lysosomal enzyme – PPCA – that degrades amyloid efficiently. To address this, researchers engineered AM805, an AAV9-PPCA vector, to deliver PPCA to the CNS and reduce amyloid burden.
Study results showed that all routes of dosing resulted in increased PPCA activity and reduced amyloid-positive brain area in a dose-dependent manner in mouse models of both severe and moderate Alzheimer’s disease. The magnitude of reduction achieved was comparable to, and in some cases exceeded, that reported for approved Alzheimer’s disease monoclonal antibodies. Aβ peptide levels (4G8 positive signal) were lowered in both intracellular and extracellular compartments. Importantly, PPCA produced these reductions across multiple routes of administration, demonstrating that regardless of how the enzyme reaches the brain, it is therapeutically effective. The data also show that the enzyme can be delivered safely to the brain in non-human primates and achieve levels of enzyme expression consistent with the therapeutic effect in the AD mouse models.
These data are being presented at the AD/PD Conference in Poster #3157, Shift #2, from March 19–21. The ePoster and associated audio presentation will also be available on the meeting platform.
AM805 is currently being tested in IND-enabling studies and the Company plans to pursue an Investigational New Drug (IND) application submission to the U.S. Food and Drug Administration for AM805 in 2027.
About Alzheimer’s Disease
Alzheimer’s disease is a progressive, degenerative brain disorder and the most common cause of dementia, gradually affecting memory, thinking, behavior, and the ability to carry out daily activities. It is characterized by changes in the brain that begin years before symptoms appear and worsen over time. A hallmark of the disease is the abnormal accumulation of amyloid in the brain, which is believed to play an important role in the development and progression of Alzheimer’s. Alzheimer’s affects millions of individuals and families worldwide, underscoring the urgent need for continued research, earlier detection, improved treatments, and comprehensive support for patients and caregivers.
About AM805
AM805 is a novel protease delivered via AAV9 gene therapy for the treatment of Alzheimer’s disease that functions to reduce amyloid, a biomarker that helps predict progression of Alzheimer's disease. AM805 utilizes an AAV9 gene therapy vector to deliver protective protein cathepsin A (PPCA), a lysosomal carboxypeptidase that degrades amyloid, directly to the brain. AM805 has been shown to substantially reduce amyloid (Aβ42) in preclinical models of Alzheimer’s disease – beyond the capabilities of traditional monoclonal antibody treatments. This investigational one-time gene therapy for Alzheimer’s disease has the potential to significantly alter the course of the disease by preventing and reversing amyloid plaque build-up and promoting neuronal health.
About Amlogenyx
Amlogenyx is dedicated to the development of a novel gene therapy strategy to reduce amyloid accumulation in the brain in order to prevent and treat diseases such as Alzheimer’s disease. Treatment with monoclonal antibodies to reduce amyloid has been shown to potentially slow the disease but not stop or reverse it, underscoring the need for improved treatment options. The Company is developing AM805, a novel protease therapy shown to reduce amyloid (Aβ42) accumulation in preclinical models of Alzheimer’s disease. Amlogenyx is a subsidiary of Ultragenyx. For more information on Amlogenyx, please visit the company’s website at: https://www.amlogenyx.com/.
Amlogenyx Contacts
Investors and Media:
info@amlogenyx.com
