Company: ATHE
Filing Date: 2025-08-29
Form Type: 20-F
Source: 0001213900-25-082027
Chunk: 44

Company: ALTERITY THERAPEUTICS LTD
Filing Date: 2025-08-29
Form: 20-F
Item: Item 4
Chunk 44
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 of the aging population, causes a progressive slowing of movement, tremors and the loss of fine motor control due to the death of substantia nigra cells in the brain. These cells produce the neurotransmitter dopamine in the brain, which is required for normal motor control. Existing therapies, such as dopaminergic agents, may provide symptomatic relief, but do not address the underlying pathology of the disease.

During 2009 and 2010, our lead Parkinson’s disease treatment candidate emerged, ATH434 (described below), based on significant improvement in motor function and coordination in both models. Importantly, ATH434 demonstrated improved relevant indices when administered after toxins had destroyed significant amounts of substantia nigra nerve cells, indicating that the compound can preserve normal neuronal function. Mechanistic work during this period demonstrated that ATH434 reduced the aggregation of toxic α-synuclein species as well as markers of oxidative stress.

Since 2011, we have continually progressed our understanding of the mechanism of action of ATH434 and its potential to treat other movement disorders characterized by the aggregation of α-synuclein. Our non-clinical research and development activities in Parkinson’s disease were supported by a USD $206,000 grant from the New York-based Michael J. Fox Foundation entitled, ‘ATH434, a Novel Neuroprotective Drug For Parkinson’s Disease; Completion of Pre-Clinical Studies to Enable Human Clinical Trials.’

In 2017, Doctors Finkelstein, Cherny and colleagues published data indicating that ATH434 prevented cell death in the substantia nigra in a dose-dependent manner. The data also demonstrated the therapeutic potential of ATH434 to slow neurodegeneration with results in multiple Parkinson’s disease models, including a transgenic model of Parkinson’s disease (A53T) in which mice over-expressed the α-synuclein protein. In A53T mice, animals treated with ATH434 exhibited significantly increased numbers of s. nigra neurons and a significant reduction in insoluble α-synuclein and incidence of clasping behavior. Encouragingly, these results showed that ATH434 lowered α-synuclein, preserved neurons and simultaneously improved motor performance. The paper was entitled, “The novel compound ATH434 prevents iron mediated neurodegeneration and α -synuclein toxicity in multiple models of Parkinson’s disease” and was published in Acta Neuropathol Comm.

In February 2021, the Michael J. Fox Foundation awarded Alterity a second grant, entitled “Pharmacologic Evaluation of ATH434 in a