Company: ATHE
Filing Date: 2025-08-29
Form Type: 20-F
Source: 0001213900-25-082027
Chunk: 52

Company: ALTERITY THERAPEUTICS LTD
Filing Date: 2025-08-29
Form: 20-F
Item: Item 4
Chunk 52
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 marker of axonal injury, when compared to participants who declined.

In September 2024, we presented positive interim data from the ATH434-202 trial as both a late-breaking oral presentation and poster session entitled “Preliminary Efficacy and Safety of ATH434 in Multiple System Atrophy” at the MDS meeting.

In March 2025, we announced that the last patient in the ATH434-202 Phase 2 trial completed the study. Subsequent to the end of the period, in July 2025, we reported positive topline data that showed ATH434 conferred a clinical benefit on areas of impairment in MSA and stabilized key biomarkers that underpin the pathology of the disease. Based on the observed clinical and neuroimaging data, ATH434 improved overall neurological symptoms and slowed disease progression compared to historical data.

Over the 12-month treatment period, disease progression as assessed with UMSARS I was reduced by approximately half as compared to historical controls. The mean (SD) UMSARS scores increased from baseline to 12 months by 3.5 (4.7) points. These study data compare favorably to historical data in a similar MSA population, where an increase (worsening) of 6.5 (6.0) points over 12 months was observed. 43% (3/7) of participants who completed the study had stable UMSARS scores. In addition, 30% of participants reported stable neurological symptoms over the course of the study. On the important symptom of orthostatic hypotension, ATH434 on average stabilized low blood pressure symptoms in study participants.

Biomarker endpoints were used to evaluate potential drug effect and target engagement. Neuroimaging outcomes indicate that ATH434 slowed brain atrophy in MSA affected areas, as measured by the MSA Atrophy Index (MSA-AI), when compared to placebo-treated participants in Study 201. Moreover, the effects on brain volume were comparable to those observed in participants in the 75 mg dose group in Study 201. In addition, ATH434 led to lower iron accumulation in the putamen and globus pallidus as compared to placebo treated patients in Study 201, providing further evidence of target engagement.

ATH434 was well tolerated with no serious adverse events related to ATH434 reported, and most adverse events were mild to moderate in severity.

Importantly, the aggregate data indicates that ATH434 has similar clinical efficacy in this advanced MSA population as was observed in the earlier stage patients in Study ATH