ATH434 / Alterity Therap - LARVOL DELTA

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

ATH434-202: A Biomarker Study of ATH434 in Participants With MSA (clinicaltrials.gov) - P2 | N=10 | Completed | Sponsor: Alterity Therapeutics | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Multiple System Atrophy

Alterity Therapeutics Completes Last Patient Visit in ATH434-202 Open-Label Phase 2 Trial in Multiple System Atrophy (GlobeNewswire) - "Alterity Therapeutics...today announced that the last patient in the ATH434-202 Phase 2 trial has completed the study. The ATH434-202 is an open label study designed to evaluate the safety, efficacy and target engagement of ATH434 in participants with advanced multiple system atrophy (MSA)....We look forward to reporting topline data from this study in mid-year 2025."

P2 data • Multiple System Atrophy

Topline Data from a Randomized, Double Blind, Placebo Controlled Phase 2 Study of ATH434 in Multiple System Atrophy (AAN 2025) - "Early MSA patients have elevated plasma NfL and increased iron in multiple brain regions, most commonly in the SN. Reduced subcortical volume was most frequent in the PT. ATH434 is a potential disease modifying treatment based on its ability to redistribute excess labile iron and reduce α‑synuclein aggregation in the CNS."

Clinical • P2 data • Ataxia • CNS Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease • NEFL • Plasma NfL

Alterity Therapeutics Raises A$40.0 million in Placement (GlobeNewswire) - "Alterity Therapeutics...today announced it has received binding commitments for a capital raising of A$40.0 million via a two tranche placement (the 'Placement') of fully paid ordinary shares ('New Shares') to Australian and international institutions and other unrelated sophisticated, professional or exempt investors...'We will use funds from this capital raise to accelerate ATH434 regulatory and development activities and to continue research and discovery of novel compounds for major indications such as Parkinson’s disease.'"

Financing • Parkinson's Disease

Alterity Therapeutics Announces Funding to Accelerate ATH434 Clinical and Business Development Activities (Alterity Therapeutics Press Release) - "Alterity Therapeutics...announced that it raised capital in the U.S. to accelerate clinical development and business development activities for the Company’s lead asset, ATH434...Based on the positive topline results reported on 30 January 2025 from the ATH434-201 Phase 2 trial in multiple system atrophy (MSA), the Company was afforded the opportunity to raise capital in the U.S. via its at-the-market (ATM) facility. In addition to raising approximately A$2.13M on the ATM, the Company expects to receive in Q1 CY2025 approximately A$5.69M in rebates from the from the Australian Taxation Office under the Australian Government’s Research and Development Tax Incentive (R&DTI) Scheme....Combined, these proceeds will enable the Company to advance its clinical and regulatory activities, and to accelerate business development activities for ATH434."

Financing • Multiple System Atrophy

Alterity Therapeutics Announces Positive ATH434 Phase 2 Trial Results in Multiple System Atrophy Led By Robust Clinical Efficacy (GlobeNewswire) - P2 | N=77 | NCT05109091 | Sponsor: Alterity Therapeutics | "There were approximately 20 patients per arm in the mITT. Both clinical doses demonstrated improvement relative to placebo over 52 weeks, with the 50 mg dose showing a greater treatment effect. Additional analyses are ongoing to understand the differences between the two groups...Demonstrated target engagement of ATH434; The 50 mg dose reduced iron accumulation in the substantia nigra, putamen, and globus pallidus; The reduced accumulation of iron was significant at 26 weeks (putamen, P=0.025) and approached statistical significance at 52 weeks...The 75 mg dose reduced iron accumulation in the globus pallidus...The 50 mg dose declined by a mean of 4.3 points over 52 weeks, equivalent to a 48% slowing of clinical progression (p=0.03); The 75 mg dose declined by a mean of 5.8 points over 52 weeks, equivalent to a 29% slowing of clinical progression (p=0.2); The 75 mg dose declined by a mean of 1.8 points over..."

P2 data • Multiple System Atrophy

Appendix 4C – Q2 FY25 Quarterly Cash Flow Report (GlobeNewswire) - "Topline data for ATH434-201 randomized, double-blind Phase 2 clinical trial on track for expected release by early February 2025...'The topline 12-month results from the 202 trial are expected in the first half of calendar year 2025'..."

P2 data • Multiple System Atrophy

Alterity Therapeutics Issues Shareholder Letter Highlighting Pipeline Advances and Key Upcoming Milestones (GlobeNewswire) - "'Most prominently, we completed our 12-month, double-blind Phase 2 clinical trial of ATH434 in early-stage Multiple System Atrophy (MSA). This milestone leads us to a topline data readout expected in late January or early February'...This year promises to be pivotal for Alterity with topline data expected from both of our Phase 2 clinical trials in MSA."

P2 data • Multiple System Atrophy

ATH434-201: Study of ATH434 in Participants with Multiple System Atrophy (clinicaltrials.gov) - P2 | N=77 | Completed | Sponsor: Alterity Therapeutics | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Multiple System Atrophy

Alterity Therapeutics Completes Last Patient Visit in ATH434-201 Phase 2 Clinical Trial in Early-Stage Multiple System Atrophy (GlobeNewswire) - "Alterity Therapeutics...announced that the last patient in the ATH434-201 Phase 2 trial, a randomized, double-blind, placebo-controlled investigation in early-stage multiple system atrophy (MSA), has completed the study. With the achievement of this milestone, topline results are expected to be reported in late January or early February 2025."

Enrollment closed • P2 data • Multiple System Atrophy

Alterity Therapeutics Announces New Publication Describing Novel Mechanism of Action for ATH434 (GlobeNewswire) - "The novel iron binding properties of ATH434 presented in the publication support the characterization of ATH434 as an iron chaperone. The publication describes how ATH434 targets the toxic form of iron that drives the pathology of a rare neurodegenerative disease known as Friedreich’s Ataxia....The study also evaluated iron chelators that are designed to irreversibly bind the stored form of iron and remove it from the body. Specifically, the study investigated how strongly ATH434 or iron chelators bind the two forms of cellular iron: ferric iron, the stored form, or ferrous iron, the active form required for vital cellular functions such as energy production but which is associated with toxicity when in excess. The new data confirmed that ATH434 has a dramatically lower affinity for ferric iron than iron chelators which are approved for treating systemic iron overload."

Clinical • Friedreich ataxia

Appendix 4C – Q1 FY25 Quarterly Cash Flow Report (GlobeNewswire) - "ATH434–202: Open-label, Biomarker Phase 2 Clinical Trial in Advanced MSA...The trial remains ongoing with Topline 12-month results expected in the first half of calendar year 2025. ATH434–201: Randomized, Double-Blind Phase 2 Clinical Trial in Early-State MSA...The trial remains on track to complete in November 2024. The data from the trial will then be analyzed and the Company expects to report topline results in January 2025."

P2 data • CNS Disorders • Multiple System Atrophy

Potent antioxidant and mitochondrial-protective effects of ATH434, a novel therapeutic with moderate iron-binding affinity, in HT22 and iPSC-derived neuron models of neurodegenerative diseases (Neuroscience 2024) - "Deferiprone (DFP) is a drug with high ferric iron affinity (Kd 10-21) approved for treating systemic iron-overload disorders. ATH434 has been evaluated for protective effects on mitochondrial function, glycolytic and oxidative metabolism, iron status, oxidative stress including lipid peroxidation, and expression of disease-related proteins. Together, our results suggest that antioxidant activity is an important contributor to the efficacy of ATH434 in neurodegenerative disorders characterized by excess labile subcortical iron and oxidative stress, thus enhancing the efficacy of its moderate iron binding."

Ataxia • CNS Disorders • Multiple System Atrophy • Parkinson's Disease

Preliminary Efficacy and Safety of ATH434 in Multiple System Atrophy (GlobeNewswire) - P=NA | N=NA | "The interim data suggest that ATH434 may have a disease-modifying effect in MSA, with 30% of participants showing stable or improved clinical outcomes (clinical responders). The average change in Unified MSA Rating Scale Part I (UMSARS I) scores over 6 months is smaller than typically observed in untreated MSA patients. At 6 months all participants exhibited brain volume declines consistent with MSA progression; however, the clinical responders maintained stable brain volumes at 12 months. Importantly, ATH434 was well tolerated with no drug-related serious adverse events, and most adverse events were mild to moderate, showing a favorable safety profile."

Clinical data • Late-breaking abstract • Multiple System Atrophy

A Phase 2 Study of ATH434, a Novel Inhibitor of α-Synuclein Aggregation, for the Treatment of Multiple System Atrophy (GlobeNewswire) - P2 | N=77 | NCT05109091 | Sponsor: Alterity Therapeutics | "The oral presentation and poster describe the baseline characteristics for the 77 participants from Alterity’s ATH434-201 randomized, double-blind Phase 2 clinical trial, with a focus on baseline fluid biomarkers, neuroimaging and clinical data....The accuracy of diagnosing clinically probable MSA may be increased using a multimodal approach that includes neuroimaging biomarkers (increased iron content, reduced subcortical volumes) and fluid biomarkers such as NfL....Importantly, increased iron levels were evident in multiple subcortical brain regions, with increased levels being observed in the substantia nigra in nearly all subjects."

Biomarker • P2 data • Multiple System Atrophy

Alterity Therapeutics Raises Profile with Multiple Data Presentations at the International Congress of Parkinson’s Disease and Movement Disorders (GlobeNewswire) - "The presentation demonstrated that ATH434 treatment led to lower iron levels in the affected area of the brain, the substantia nigra, and improved motor performance and general function in monkeys with experimentally induced Parkinson’s disease. At week 12, all 5 ATH434-treated macaques had stable or improving scores from Baseline while two of three vehicle-treated macaques did not demonstrate improvement. The improved general behavior was well-correlated with reduced motor impairment."

Preclinical • Parkinson's Disease

Preliminary Efficacy and Safety of ATH434 in Multiple System Atrophy (MDS Congress 2024) - "At the conference, we plan to report clinical, biomarker, and imaging data for 10 participants at baseline and 6-months, and 5 participants at 12 months of treatment. Interim analysis in 7 participants indicates that clinical response (stable or improved) was apparent in 2 participants based on UMSARS I and PGIC/CGIC scores. For N=7, the mean (SD) change in UMSARS I at 6 months was +1.7 (5.1)."

Clinical • Late-breaking abstract • Ataxia • CNS Disorders • Multiple System Atrophy • Parkinson's Disease • CSF NfL • NEFL • Plasma NfL

Effects of ATH434, a Clinical-Phase Small Molecule with Moderate Affinity for Iron, in a Parkinson's Disease Model in Macaques (MDS Congress 2024) - "ATH434 improved motor performance in MPTP-injured primates in this small study. Efficacy may reflect reduction or sequestration of labile iron in areas of pathology, facilitating neurite recovery in the nigrostriatal pathway by reducing iron-mediated oxidative damage[5]."

Clinical • CNS Disorders • Multiple System Atrophy • Parkinson's Disease • SYP

A Phase 2 Study of ATH434 a Novel Inhibitor of α-Synuclein Aggregation for the Treatment of Multiple System Atrophy (MDS Congress 2024) - "Clinically probable MSA patients have elevated plasma NfL and significantly increased iron in multiple brain regions, with predominant accumulation in the SN, PT and GP. ATH434 is being evaluated as a disease modifying treatment based on its ability to redistribute excess iron and reduce α-synuclein aggregation in the CNS. These data were presented at the AAN Annual Meeting on 4/14/24"

P2 data • Ataxia • CNS Disorders • Multiple System Atrophy • Parkinson's Disease • NEFL • Plasma NfL

ATH434, a promising iron-targeting compound for treating iron regulation disorders. (PubMed, Metallomics) - "To understand previous treatment failures and identify beneficial factors for Fe2+-targeted therapeutics, we compared traditional Fe3+ chelators deferiprone (DFP) and deferasirox (DFX) with additional iron-binding compounds including ATH434, DMOG, and IOX3. ATH434 significantly stabilized bound Fe2+ from ligand-induced autooxidation, reducing reactive oxygen species (ROS) production, whereas DFP and DFX promoted production. The comparable affinity of ATH434 for Fe2+ and Fe3+ position it to sequester excess Fe2+ and facilitate drug-to-protein iron metal exchange, mimicking natural endogenous iron binding proteins, at a reduced risk of autooxidation-induced ROS generation or perturbation of cellular iron stores."

Journal • Ataxia • CNS Disorders • Friedreich ataxia • Hematological Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease