"These data continue to strengthen the evidence that ATH434 has the potential to be the first disease-modifying treatment for MSA, a rare and devastating disease with no approved therapy," said David Stamler, M.D., CEO of Alterity Therapeutics. "Our Phase 2 trial showed statistically significant slowing of disease progression, and the use of advanced MRI methods gives us a powerful way to identify the right patients and measure how the drug is working. Together, these advances directly inform the design of our upcoming Phase 3 trial. By moving beyond traditional trial paradigms, we are focused on identifying and treating the right patients with greater precision, with the ultimate goal of delivering a meaningful therapeutic option for this devastating disease."
Presentation Highlights:
Quantitative Susceptibility Mapping Detects Progressive Iron Accumulation in Early MSA
- Author: Oral presentation delivered by Paula Trujillo, PhD, Research Assistant Professor, Department of Neurology, Vanderbilt University Medical Center
- Conference: The International Society for Magnetic Resonance in Medicine 2026 ISMRM and ISMRT Annual Meeting and Exhibition
- Summary: New research shows that Alterity's MRI imaging approach can detect MSA in its earliest stages and track brain iron changes over time, a methodology that could transform how MSA trials are run. Dr. Trujillo presented findings recently published in NeuroImage demonstrating that quantitative susceptibility mapping (QSM) detects progressive iron accumulation in MSA. The measure may serve as a biomarker for early diagnosis, monitoring, and trial enrichment. The evaluation utilizes longitudinal data generated through Alterity's Biomarkers of Progression in Multiple System Atrophy (bioMUSE) Natural History Study, together with additional cross-sectional MSA, Parkinson's Disease, and healthy control data. QSM provides the ability to: detect iron dysregulation early — even before clinical diagnosis, track progression over 12 months, provide individual-level, interpretable maps for monitoring, and it is standardizable across scanners which can provide a meaningful tool for multicenter trials.
Results from a Randomized, Double-Blind, Placebo-Controlled Study of ATH434 in MSA using CSF NfL as a Covariate
- Author: Poster presentation delivered by Daniel Claassen, M.D., M.S., Professor of Neurology at Vanderbilt University Medical Center and Chief Medical Advisor for Alterity
- Conference: Movement Disorder Society of Australia and New Zealand (MDSANZ) Scientific Meeting
- Summary: A new analysis of Alterity's Phase 2 trial brings together clinical, biomarker, and imaging evidence that support ATH434's impact on slowing MSA progression. Dr. Claassen's poster described outcomes from the ATH434-201 Phase 2 clinical trial in MSA. In particular, the poster evaluates CSF NfL1 which is an established prognostic biomarker of clinical decline in MSA and was prespecified as a disease-severity covariate in the trial. There were several key outcomes:
1) ATH434 slowed functional decline in MSA: Significant effect at 50 mg BID (−4.0 points, p=0.035; ~48% slowing) and a consistent directional trend at 75 mg BID. Combined active arms significantly slowed UMSARS2 I progression vs placebo (p=0.047).
2) CSF NfL is a meaningful prognostic covariate: Higher baseline CSF NfL predicted greater UMSARS-I worsening (β=0.90, p=0.033). Adjusting for it strengthened detection of treatment effects and supports CSF NfL for stratification in future trials.
3) Imaging supports the iron-chaperone mechanism: QSM trend of reduced iron accumulation in putamen and globus pallidus consistent with the iron-chaperone mechanism of action; the dentate signal increase is consistent with glymphatic iron redistribution rather than disease progression.
4) ATH434 is a promising potential disease-modifying therapy: Convergent clinical, biomarker, and imaging signals support continued development.
ATH434 Clinical Update and Phase 3 Planning
- Author: Oral presentation delivered by David Stamler, M.D., CEO of Alterity Therapeutics
- Conference: MSA Symposium (University College London) 2026
- Summary: New analyses of Alterity's Phase 2 trial were presented, bringing together clinical, biomarker, and imaging evidence that support ATH434's impact on slowing MSA progression. In particular, analyses of key clinical endpoints, including the Unified MSA rating scale Part I, were presented that include CSF NfL as a covariate. The biomarker data presented by Dr. Stamler included QSM MRI data from the ATH434-201, demonstrating that ATH434 decouples iron accumulation from clinical progression thus supporting its role as an iron chaperone. New data on the impact of ATH434 on swallowing were also presented, demonstrating that both doses of ATH434 reduce the progression of this key MSA symptom. Swallowing impairment was assessed with the 15-item Swallowing Disturbance Questionnaire (SDQ), a validated patient reported outcome. Over 52 weeks treatment, placebo patients worsened by a mean adjusted increase score of 8.5 points as compared to an increase of 1.2 and 5.0 points for the 50 mg and 75 mg groups, respectively, with the mean adjusted difference at 50 mg achieving statistical significance (p=0.003).