MELBOURNE, Australia and SAN FRANCISCO, USA — October 5, 2026

Alterity Therapeutics Limited announced new analyses from its randomized, double-blind, placebo-controlled ATH434-201 Phase 2 trial in multiple system atrophy (MSA) presented at the 2026 International Congress of Parkinson’s Disease and Movement Disorders in Seoul, South Korea. After adjusting for baseline disease severity using cerebrospinal fluid neurofilament light chain (CSF NfL), ATH434 50 mg twice daily significantly slowed functional decline by approximately 52% versus placebo at Week 52 on the 11-item Unified Multiple System Atrophy Rating Scale (UMSARS) Part I. The analysis also found that baseline CSF NfL predicted the rate of functional decline, supporting its potential use as a severity covariate in future Phase 3 MSA studies.

ATH434 Demonstrates Slowing of Functional Decline

The CSF NfL-adjusted analysis showed a statistically significant treatment effect for ATH434 50 mg on functional decline in MSA. Using a mixed model for repeated measures in the modified intent-to-treat population of 61 patients, the 50 mg dose produced a −4.64-point difference versus placebo in change from baseline at Week 52 (p=0.032). The company said this effect represented approximately 52% slowing of functional decline compared with placebo and was roughly three times greater than the 1.5-point minimal clinically important difference. The 75 mg dose also showed a numerical slowing of decline, with a −2.81-point difference versus placebo at Week 52, although the result was not statistically significant. The new analysis was consistent with the previously reported Phase 2 finding showing a 46% slowing of decline with ATH434 50 mg

CSF NfL Supports Disease Severity Assessment

Baseline CSF NfL was identified as a predictor of subsequent functional decline in patients with MSA. Each 1,000 pg/mL increase in baseline CSF NfL was associated with approximately 0.9 additional points of worsening on UMSARS Part I at Week 52 (p=0.033). Alterity said the finding supports the use of CSF NfL as a covariate in future clinical trials because accounting for an established predictor of disease progression may improve the precision of treatment-effect measurements. The company plans to incorporate the learnings from the Phase 2 program into its planned Phase 3 pivotal trial of ATH434 in MSA.

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MRI Findings Support ATH434 Iron-Chaperone Mechanism

Additional quantitative susceptibility mapping (QSM) MRI analyses provided findings consistent with ATH434’s proposed mechanism as an iron chaperone. ATH434 is designed to redistribute reactive, labile iron believed to contribute to MSA pathology. Although the Phase 2 trial did not meet its primary endpoint for change in substantia nigra iron at Week 52, iron accumulation was numerically lower in the putamen and globus pallidus with ATH434 compared with placebo. In the dentate nucleus, iron signal increased relative to placebo at Week 52 in the 50 mg group, a finding the company said may reflect redistribution of mobilized iron through the brain’s glymphatic system. With the Phase 2 program demonstrating a clinically meaningful slowing of functional decline and supporting biomarker findings, Alterity is preparing ATH434 for Phase 3 development as a potential disease-modifying treatment for MSA.

Source: Alterity Therapeuticspress release