ATH434 / Alterity Therap - LARVOL DELTA

A Phase 1 Study to Evaluate a Tablet Formulation of PBT434 in Healthy Volunteers (ANZCTR) - P1 | N=42 | Completed | Sponsor: Alterity Therapeutics Limited | Recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease

A Study to Assess the Effect of Acid-Reducing Medicines on ATH434 in Healthy Volunteers (ANZCTR) - P1 | N=12 | Not yet recruiting | Sponsor: Alterity Therapeutics Limited

New P1 trial • CNS Disorders • Movement Disorders • Multiple System Atrophy

ATH434 Demonstrates Disease-Modifying Signal in Multiple System Atrophy Using the MuSyCA Composite Scale (AAN 2026) - No abstract available

Late-breaking abstract • CNS Disorders • Movement Disorders • Multiple System Atrophy

Advancing Toward Phase 3 and Potential Future Commercialization (The Manila Times) - "Following the successful Phase 2 program, we are now focused on aligning with the FDA on key clinical and regulatory considerations for Phase 3 and expect to hold our End-of-Phase 2 meeting in mid-2026. The goal of this meeting is to finalise the Phase 3 design, including patient selection, efficacy and safety endpoints, and the statistical framework for analyzing the results."

Clinical protocol • New P3 trial • Multiple System Atrophy

Alterity Therapeutics Presents Promising Impact of ATH434 on Orthostatic Hypotension and Disease Progression in MSA at the 36th International Symposium on the Autonomic Nervous System (GlobeNewswire) - "'These data are very important as we design our Phase 3 protocol and prepare for our upcoming FDA interactions.'....In the trial, severe OH is defined as a sustained decrease in systolic blood pressure > 30mm Hg after three minutes of standing. Baseline data from the trial revealed that severe OH was substantially higher in the 75 mg dose group at 29.2% of participants, versus 4% in the 50 mg arm and 4.5% in the placebo arm. When orthostatic blood pressure change was used as a covariate in the analysis of the UMSARS I at 52 weeks, the efficacy signal in 75 mg dose group strengthened from -2.4 to -2.8 points, improving the relative treatment effect from 30% to 35%. This baseline difference in severe OH largely explains the different responses in the 50 mg and 75 mg treatment groups."

New P3 trial • P2 data • Hypotension • Multiple System Atrophy

The novel antioxidant iron chaperone ATH434 suppresses heme-induced oxidative stress in glutamatergic HT22 neurons (Neuroscience 2025) - "In a menadione-induced oxidative stress model in HT22 neurons with mitochondrial superoxide production, ATH434 rescued deficits in mitochondrial membrane potential while deferiprone (DFP), a strong ferric iron chelator did not. Hemin-induced saturation of the labile iron pool was evident at 6 h. The dose-dependent susceptibility of neurons to hemin-induced lipid peroxidation support this as a cellular model for damage induced by intracranial hemorrhage or microbleeds. ATH434's novel iron chaperone and antioxidant activities show potential for neuroprotective therapeutic activity after neurovascular injury."

Oxidative stress • Cerebral Hemorrhage • CNS Disorders • HMOX1

Independent commercial assessment indicates USD $2.4 billion dollar potential worldwide peak sales opportunity in MSA for ATH434 (GlobeNewswire)

Sales projection • Multiple System Atrophy

The Fast Track Designation granted to ATH434 affords Alterity the opportunity to engage with the FDA in a series of Type C meetings related to the nonclinical and the chemistry, manufacturing, and controls (CMC) data necessary to support Phase 3. (GlobeNewswire) - "Following these meetings, an End-of-Phase 2 meeting will be held to align with the FDA on all elements of the Phase 3 program. Conducting these meetings in sequence allows Alterity to focus the End-of-Phase 2 meeting on the clinical development topics, including the Phase 3 protocol, and data requirements to commence the Phase 3 study. This series of meetings is expected to occur over the next several months with the End-of-Phase 2 meeting in mid-year 2026."

FDA event • Multiple System Atrophy

Relationship Between Alpha-Synuclein Aggregation Profiles, Imaging Biomarkers, and Disease Severity in a Phase 2 Study of ATH434 in MSA (MDS Congress 2025) - "In a clinically defined Phase 2 MSA population, approximately 80% of patients had concordant SAA data. Over 80% of MSA patients with a PD/DLB SAA profile had radiographic evidence of MSA. These findings confirm the need to combine α-syn SAA results in a multimodal approach including clinical and neuroimaging data to improve the diagnostic accuracy of MSA."

Biomarker • P2 data • CNS Disorders • Movement Disorders • Multiple System Atrophy

Differences Between Clinical and Imaging Phenotypes in Phase 2 Study of ATH434 in Multiple System Atrophy (MDS Congress 2025) - "MRI biomarkers offer an objective framework for MSA classification, potentially improving early diagnosis, refining subtype differentiation, and enhancing disease monitoring in clinical trials. Further validation is necessary to establish standardized imaging criteria."

Clinical • P2 data • CNS Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease

ATH434 Slowed Disease Progression in a Phase 2 Study in Multiple System Atrophy (MDS Congress 2025) - "Treatment with ATH434 50 mg and 75 mg bid for one year led to robust efficacy on the modified UMSARS I activities of daily living scale with a favorable safety profile. ATH434 demonstrated target engagement by stabilizing or reducing iron content in MSA affected areas. ATH434 is a potential disease modifying treatment based on its ability to redistribute excess labile iron, reduce α‑synuclein aggregation and reduce oxidative injury."

P2 data • CNS Disorders • Movement Disorders • Multiple System Atrophy • NEFL • Plasma NfL

Differences Between Clinical and Imaging Phenotypes in Phase 2 Study of ATH434 in Multiple System Atrophy (GlobeNewswire) - "Dr. Trujillo’s presentation assessed the two main clinical phenotypes of MSA in Alterity’s ATH434-201 trial: the parkinsonian (MSA-P, n=47) and cerebellar (MSA-C, n=25). The clinical subtypes were assigned by the site investigators and were compared with multiple neuroimaging assessments including MRI, quantitative susceptibility mapping (QSM) to measure brain iron, and automated segmentation to measure brain atrophy. The results show that quantitative MRI largely complements clinical classification (90% concordance), reinforcing its role as an objective biomarker. The observed discordance (10%) suggests MRI may capture underlying pathology not evident clinically, highlighting its value in refining diagnosis and tracking disease evolution."

P2 data • Multiple System Atrophy

Relationship Between Alpha-Synuclein Aggregation Profiles, Imaging Biomarkers, and Disease Severity in a Phase 2 Study of ATH434 in MSA (GlobeNewswire) - "In Dr. Bradbury’s presentation the imaging biomarkers utilized in the ATH434-201 trial presented supportive features of MSA in 96.1% of the 77 enrolled subjects as compared to 78.9% for α-synuclein aggregation profiles in cerebrospinal fluid (CSF) alone (60 of 76). Of the 11 participants with an α-synuclein aggregation profile consistent with Parkinson’s disease and/or dementia with Lewy bodies, 80% demonstrated supportive imaging features of MSA. Two of the 5 participants without evidence of α-synuclein aggregation had imaging consistent with MSA. Therefore, the presentation concludes that a multimodal approach combining α-synuclein aggregation profiles with clinical and imaging data may enhance diagnostic accuracy in MSA."

Biomarker • P2 data • Multiple System Atrophy

ATH434 Slowed Disease Progression in a Phase 2 Study in Multiple System Atrophy (GlobeNewswire) - "There were three arms in the trial comparing two dose levels of ATH434 50 mg (n=25) and 75 mg (n=24) to placebo (n=22), all of which were administered twice daily. Treatment with ATH434 resulted in a clinically significant reduction in disease severity relative to placebo on the modified UMSARS I activities of daily living scale at both dose levels, with a 48% relative treatment effect at the 50 mg dose (p=0.02)2 and a 30% relative treatment effect at the 75 mg dose at 52 weeks. UMSARS I is the key outcome measure of interest to regulatory authorities such as the FDA....Notably, ATH434 demonstrated a beneficial effect on OH symptoms as assessed with the OH Symptom Assessment, a patient reported outcome. On this scale, placebo patients worsened on average by approximately 6 points over 52 weeks whereas the 50 mg and 75 mg groups were stable over the same period of time."

P2 data • Multiple System Atrophy

Alterity Therapeutics…announced that data from the ATH434-201 randomized, double-blind Phase 2 clinical trial in Multiple System Atrophy (MSA) will be featured at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (The Manila Times)

P2 data • Multiple System Atrophy

Alterity Therapeutics Presents ATH434-201 Phase 2 Data at the American Neurological Association Annual Meeting (Alterity Therapeutics Press Release) - "In the study, ATH434 demonstrated clinically meaningful efficacy in modifying disease progression at both 50 and 75 mg doses as well as target engagement by reducing iron accumulation in MSA affected brain regions. Analysis of the data has also shown that the baseline differences in disease severity between the arms largely explain different response in 50 mg and 75 mg treatment groups. ATH434 was well tolerated with similar adverse event rates as placebo, and no serious adverse events were attributed to study drug."

P2 data • Multiple System Atrophy

Alterity Therapeutics Confirms Effectiveness of ATH434 Drug Against Advanced MSA (Small Caps) - P2 | N=10 | ATH434-202 (NCT05864365) | Sponsor: Alterity Therapeutics | "Alterity Therapeutics...has released positive topline data from an open label Phase 2 clinical trial of lead candidate ATH434 on 10 patients with advanced multiple system atrophy (MSA). Data from the ATH434-202 trial showed the oral drug conferred a clinical benefit on areas of impairment in MSA and was able to stabilise key neurological biomarkers that underpin the pathology of the disease...Over the ATH434-202 trial’s 12-month treatment period, disease progression in patients was reduced by approximately 50% (as assessed by the Modified Unified MSA Rating Scale Part I, or UMSARS I) when compared to historical controls.In addition, 30% of patients reported a stabilising of neurological symptoms, an unexpected result in advanced MSA patients."

P2 data • Multiple System Atrophy

Potent antioxidant and mitochondrial-protective effects of ATH434, a moderate affinity iron chaperone. (PubMed, J Biol Chem) - "These behaviors were consistent with the fact that cyclic voltammetry demonstrated ATH434 exhibits a chemically-reversible electrode potential of 328.5 mV, unique to all antioxidants and iron chelators examined in this report. Our results indicate that ATH434 has the capacity to manage excess tissue iron and the oxidant stress induced by that iron."

Journal • CNS Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease

Alterity Therapeutics to Provide Corporate Update in Fireside Chat (GlobeNewswire) - "Alterity Therapeutics...announced that David Stamler, M.D., Chief Executive Officer of Alterity, will participate in a Fireside Chat hosted by MST Access on Wednesday, 25 June 2025 in Australia / Tuesday, 24 June 2025 in the United States. Dr. Stamler will provide a corporate update with a focus on the progress made on the ATH434 development program in Multiple System Atrophy since the Company released positive Phase 2 data in January."

P2 data • Multiple System Atrophy

Alterity Therapeutics Prominently Featured at the International MSA Congress (Alterity Therapeutics Press Release) - P2 | N=77 | NCT05109091 | Sponsor: Alterity Therapeutics | "The clinical analysis included 71 patients who had at least one post-baseline assessment of the key clinical endpoint, the modified UMSARS1 I activities of daily living scale. On this endpoint, ATH434 demonstrated a clinically significant reduction in disease severity versus placebo, with a 48% relative treatment effect at the 50 mg dose (p=0.02)^ and a 30% relative treatment effect at the 75 mg dose (p=0.16) at 52 weeks. Additional efficacy assessments showed improvement consistent with the UMSARS I findings: the Clinical Global Impression of Severity Scale demonstrated improvement compared to placebo at both dose levels, with difference at 50 mg achieving nominal statistical significance (p=0.0088)."

P2 data • Multiple System Atrophy

Alterity Therapeutics Announces Multiple Oral and Poster Presentations to be Featured at the International MSA Congress (GlobeNewswire) - "Alterity Therapeutics...today announced that multiple oral and poster presentations related to Alterity’s clinical programs in Multiple System Atrophy (MSA) will be featured at the 2025 International MSA Congress taking place May 9 - 11, 2025 in Boston, MA, USA."

Clinical data • Multiple System Atrophy

Alterity Therapeutics Granted U.S. FDA Fast Track Designation for ATH434 to Treat Multiple System Atrophy (Alterity Therapeutics Press Release) - "Alterity Therapeutics...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for ATH434 for the treatment of Multiple System Atrophy (MSA)....Alterity’s Fast Track application included top-line data from the ATH434-201 randomized, double-blind Phase 2 clinical trial which demonstrated efficacy on the modified UMSARS I in addition to preclinical data confirming that ATH434 is a low to moderate affinity iron chaperone."

Fast track • Multiple System Atrophy

Alterity Therapeutics Presents ATH434-201 Phase 2 Clinical Trial Results at European MSA Symposium (GlobeNewswire) - P2 | N=77 | NCT05109091 | Sponsor: Alterity Therapeutics | "On this endpoint, ATH434 demonstrated a clinically significant reduction in disease severity versus placebo, with a 48% relative treatment effect at the 50 mg dose (p=0.02)^ and a 30% relative treatment effect at the 75 mg dose (p=0.16) at 52 weeks. Additional efficacy assessments showed improvement consistent with the UMSARS I findings: the Clinical Global Impression of Severity Scale2 demonstrated improvement compared to placebo at both dose levels, with difference at 50 mg achieving nominal statistical significance (p=0.0088). On the Orthostatic Hypotension Symptom Assessment (a patient reported outcome), on average placebo patients worsened by approximately 6 points over 52 weeks whereas both ATH434 treatment groups improved over the same period (p=0.08 at 50 mg, p=0.14 at 75 mg)....Overall, the study results support continued advancement of ATH434 for the treatment of MSA."

P2 data • Multiple System Atrophy

Alterity Therapeutics Presents Encouraging New Data from its ATH434 Phase 2 Trial in Multiple System Atrophy at the American Academy of Neurology Annual Meeting (GlobeNewswire) - P2 | N=77 | NCT05109091 | Sponsor: Alterity Therapeutics | "The data showed that on the modified UMSARS I rating scale, ATH434 demonstrated a clinically significant treatment effect versus placebo with a 48% decrease in clinical progression at the 50 mg dose (p=0.02)^ and a 30% decrease in clinical progression at the 75 mg dose at 52 weeks. Additional assessments showed improvement: the Clinical Global Impression of Severity Scale2 (7-point scale, higher score worse), including a nominally significant difference at the 50 mg dose (p=0.0088) at 52 weeks. The Orthostatic Hypotension Symptom Assessment (patient reported outcome) showed trends favoring benefit in both groups (p=0.08 at 50 mg dose, p=0.14 at 75 mg dose). Increased activity in the outpatient setting was seen on wearable sensors at both dose levels as compared to placebo, with observed improvements in step count, bouts of walking, total walking time, and total standing time."

P2 data • Multiple System Atrophy

Alterity Therapeutics to Deliver an Oral Presentation of the Positive ATH434 Phase 2 Trial Results at the American Academy of Neurology Annual Meeting (GlobeNewswire) - "Alterity Therapeutics...today announced that an oral presentation and a poster presentation related to Alterity’s clinical programs in Multiple System Atrophy (MSA) will be delivered at the American Academy of Neurology (AAN) 2025 Annual Meeting taking place April 5 - 9, 2025 in San Diego, CA."

P2 data • Multiple System Atrophy