Company: ATHE
Filing Date: 2025-08-29
Form Type: 20-F
Source: 0001213900-25-082027
Chunk: 43

Company: ALTERITY THERAPEUTICS LTD
Filing Date: 2025-08-29
Form: 20-F
Item: Item 4
Chunk 43
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 well characterized, Alterity conducted a natural history study called “Biomarkers of progression in Multiple System Atrophy (bioMUSE)” to track the progression of patients with MSA. The study was conducted in collaboration with Vanderbilt University Medical Center in the U.S. under the direction of Daniel Claassen, MD, Professor of Neurology and Principal Investigator. Natural history studies are important for characterizing disease progression in selected patient populations. The study provided vital information on early stage MSA patients, enabling the selection of biomarkers suitable for evaluation of target engagement and preliminary efficacy of drug candidates, and clinical data to characterize disease progression in patients that mirrored those enrolled in Alterity’s ATH434-201 Phase 2 clinical trial. To date, the study has provided rich data for optimizing the design of Alterity’s clinical program (see below).

Alterity’s lead candidate, ATH434, is a small molecule drug candidate designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration. ATH434 has been shown preclinically to reduce α-synuclein pathology and preserve nerve cells by restoring normal iron balance in the brain. In this way, it has potential to treat Parkinson’s disease and related disorders such as MSA.

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A comprehensive nonclinical program to evaluate ATH434’s profile to support clinical development is ongoing. ATH434 has also been profiled in mouse models of Parkinsonian disorders, including MSA. In one animal model, ATH434 prevented α-synuclein aggregation and preserved neurons in the substantia nigra and decreased the number of glial cell inclusions in the brains of treated animals. Glial cell inclusions are the pathological hallmark of MSA and contain abundant aggregated α-synuclein that is associated with neurodegeneration. The benefits shown on pathological examination were associated with improved motor function in treated animals.

Nonclinical safety pharmacology and toxicology studies of ATH434 that have been reviewed by regulatory authorities support clinical administration at doses predicted to provide efficacy in MSA.

We successfully completed Phase 1 clinical studies with ATH434 demonstrating that it is well tolerated, orally bioavailable, and achieved brain levels comparable to efficacious levels in animal models of MSA. During FY 2025 we also successfully completed two Phase 2 clinical trials with ATH434 (see below). ATH434 has been granted Orphan designation by the FDA and the European Commission and has received a Fast Track designation from the FDA for the treatment of MSA. 

Parkinson’s Disease

Parkinson’s disease, a neurodegenerative disease