Company: ATHE
Filing Date: 2025-08-29
Form Type: 20-F
Source: 0001213900-25-082027
Chunk: 51

Company: ALTERITY THERAPEUTICS LTD
Filing Date: 2025-08-29
Form: 20-F
Item: Item 4
Chunk 51
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: “A Phase 2 Study
            of ATH434, a Novel Inhibitor of α-Synuclein Aggregation, for the Treatment of Multiple System Atrophy”       
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●   April 2024 – American Academy of Neurology (AAN), Title: “A Phase 2 Study of ATH434, a Novel Inhibitor of α-Synuclein
                                  Aggregation, for the Treatment of Multiple System Atrophy”                             
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30

ATH434-202 Phase 2 Clinical Trial

In May 2023, we initiated a second Phase 2 clinical trial entitled, “A Biomarker Study of ATH434 in Participants with MSA”, known as ATH434-202. The Biomarker trial is a single arm open label study that will enroll up to 15 individuals with advanced MSA. ATH434-202 study participants received treatment with ATH434 for 12-months. The study was designed to assess the effect of ATH434 treatment on clinical and biomarker endpoints, safety, and pharmacokinetics. The selected biomarkers include brain iron which is an important contributor to MSA pathology. The primary objective of this study is to evaluate the impact of 12 months treatment with ATH434 on brain iron by MRI (QSM/R2*).

The 202 study gives us the opportunity to evaluate the effects of ATH434 treatment in an MSA population more advanced than individuals enrolled in the ATH434-201 study. Individuals with more advanced disease face severe challenges due to the stage of their illness. Data from this study will help Alterity guide the MSA development program given the differences between the open-label 202 study and the double-blind trial.

In July 2024, we reported positive interim data from the ATH434-202 trial in participants with advanced MSA. The interim analysis included clinical and biomarker data on 7 participants treated with ATH434 for 6 months and neuroimaging data on 3 participants who were treated for 12 months. After 6 months of treatment, 43% of participants showed improvement on the UMSARS, indicating reduced disability on activities of daily living. Over the same period, 29% of participants had stable or improved neurological symptoms (clinical responders) as assessed by the global impression of change by both the treating physician and the patient. The clinical responders on average had reduced accumulation of iron on MRI in the substantia nigra, putamen and globus pallidus and stable levels of Neurofilament Light Chain (NFL), a