Alterity Therapeutics to Present New ATH434 Neuroprotection Data at Neuroscience Meeting

Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE), a biotechnology company focused on developing treatments for neurodegenerative diseases, unveiled new promising data on their lead candidate ATH434 at the Society for Neuroscience 2024 in Chicago, USA. The presentation titled “Potent Antioxidant and Mitochondrial-protectant Effects of ATH434, a Novel Inhibitor of α-Synuclein Aggregation with Moderate Iron-binding Affinity” highlighted the neuroprotective and mitochondrial protective effects of ATH434. This compound demonstrated significant reduction in lipid damage across two distinct neuronal injury models relevant to disease.

Under the guidance of Dr. Daniel J. Kosman, Distinguished Professor of Biochemistry at the State University of New York at Buffalo, the study explored ATH434's antioxidant properties and its benefits in cellular energy utilization. Notably, ATH434’s antioxidant capabilities were differentiated from another iron-binding agent approved for iron overload treatment.

David Stamler, CEO of Alterity, emphasized the importance of ATH434’s intrinsic antioxidant activity, stating that the data enhances understanding of its potential as a disease-modifying treatment for neurodegenerative disorders such as Parkinson’s disease. He highlighted oxidative injury as a significant factor in neurodegeneration pathology, and ATH434’s dual approach of addressing oxidative injury directly and redistributing excess labile iron shows promise in treating these conditions. Furthermore, ATH434’s ability to reduce lipid membrane damage under oxidative stress may contribute to slowing disease progression.

The research, led by Dr. Danielle Bailey, assessed the efficacy of ATH434 and other agents as protectants against lipid peroxidation using menadione-induced and hemin-induced oxidative stress models in neuronal cells. Findings indicated that in unstressed cells, ATH434 promoted an energy production pathway in mitochondria less likely to cause oxidative stress. In-solution assays provided insights into ATH434’s direct antioxidant capacity in handling potentially damaging charged molecules, suggesting it can protect mitochondria vulnerable in neurodegenerative diseases.

ATH434, Alterity’s leading candidate, is an oral agent designed to inhibit the aggregation of pathological proteins linked to neurodegeneration. Preclinical studies have shown it can reduce α-synuclein pathology and maintain neuronal function by restoring normal brain iron balance. As an iron chaperone, ATH434 holds significant potential for treating Parkinson’s disease and Parkinsonian disorders such as Multiple System Atrophy (MSA). The compound has completed Phase 1 studies, demonstrating good tolerance and achieving brain levels comparable to effective levels in animal models of MSA. It is currently under evaluation in two clinical trials: a randomized, double-blind, placebo-controlled Phase 2 study in early-stage MSA patients (Study ATH434-201), and an open-label Phase 2 Biomarker trial in more advanced MSA patients (Study ATH434-202). The U.S. FDA and European Commission have granted Orphan drug designation to ATH434 for MSA treatment.

Alterity Therapeutics, with operations in Melbourne, Australia, and San Francisco, California, is a clinical-stage biotechnology company aiming to create novel treatments for neurodegenerative diseases. Besides ATH434, the company's drug discovery platform is generating patentable chemical compounds targeting the underlying pathology of neurological diseases.