About Alterity Therapeutics

Alterity Therapeutics Limited engages in the research and development of therapeutic drugs designed to treat the underlying cause of degeneration of the brain focusing on Alzheimer’s disease, Huntington disease, Parkinson’s disease and other neurological disorders. Candidate Product Discovery and Translational Biology Programs The company regards its intellectual property as a ‘platform technology’ as it addresses the causes of a spectrum of neurodegenerative and age-related diseases based on the interrelationship of metals and proteins. As of June 30, 2021, the company had performed in vivo evaluations of its product candidates in a range of mouse animal models, including models of Alzheimer’s disease, Huntington disease, Parkinsonian diseases, brain cancer and traumatic brain injury. Clinical Trials for Product Candidates ATH434 In July 2019, the company announced the completion of clinical trial evaluating the safety and pharmacokinetics of ATH434 in healthy volunteers. The Phase 1 study, conducted in Australia, recruited various adult volunteers and elderly volunteers with the key goals of assessing the safety, tolerability and drug disposition within the body (pharmacokinetics) of ATH434 after single and multiple oral dose administration. The company focuses on the treatment of Parkinsonian disorders, a group of neurodegenerative disorders, which have Parkinsonism as a feature. Its lead indication for ATH434 is Multiple System Atrophy (MSA), a debilitating disease with no approved treatments. The company applied to the Food and Drug Administration (FDA) for Orphan Drug designation for the proposed use of ATH434 for the treatment of MSA, and the designation was granted in January 2019. Orphan designation entitles the company to seven years of market exclusivity for the use of ATH434 in the treatment of MSA and qualifies the sponsor of the drug for various development incentives of the Orphan Drug Act, including tax credits for qualified clinical testing. In January 2020, the company announced that the European Commission granted Orphan Drug designation to ATH434, which entitles it to ten years of market exclusivity in the European Union for the use of ATH434 in the treatment of MSA and other benefits, including assistance in developing clinical protocols, reduced fees and access to EU-funded research grants. In June 2020, the company announced that it had received guidance from the U.S. Food and Drug Administration (FDA) in relation to the development pathway for ATH434 following the completion of its Phase 1 clinical trial. The pre-Investigational New Drug meeting was to obtain input on the clinical development plan for ATH434, including feedback on the Phase 2 study design. The company reached agreement with the FDA on the non-clinical investigations required to support the Phase 2 study. In addition, the FDA agreed to key aspects of the Phase 2 study design, including the proposed patient population, safety monitoring plan and strategy for evaluating drug exposure during the study. In parallel with the U.S. strategy, the company is also pursuing a regulatory pathway in Europe and Australia. Planning is underway to meet with European authorities. In June 2021, the company received guidance from the European Medicines Agency (EMA) regarding key aspects of its Phase 2 clinical trial for investigational drug ATH434 in the treatment of MSA planned to commence in the second half of 2021. In October 2020, the company commenced enrolling patients with MSA in its natural history study referred to as bioMUSE. The study is being conducted in collaboration with Vanderbilt University Medical Center in the U.S. under the direction of the Associate Professor of Neurology and Principal Investigator. The study is providing major information on early stage MSA patients to optimize the design of its Phase 2 study. The study would also inform the selection of biomarkers suitable to evaluate target engagement and preliminary efficacy. The company has continued to build on its body of scientific evidence for ATH434 drug, with the presentation of pre-clinical evidence of ATH434 treatment for MSA at the International Congress of Parkinson’s Disease and Movement Disorders at Hong Kong in October 2018. The pre-clinical data demonstrated that ATH434 prevented a-synuclein aggregation, preserved neurons, decreased the number of glial cell inclusions and reduced motor impairment in an animal model of MSA. These findings are consistent with previous Parkinsonian disease animal models that have undergone ATH434 treatment. In August 2020, the company announced that new clinical and experimental pharmacology data has been selected for presentation at the 2020 International Congress of Parkinson’s Disease and Movement Disorders (MDS 2020) and the American Neurological Association’s 2020 Annual Meeting (ANA 2020). It independently confirmed and extended previous findings demonstrating that ATH434 reduces a-synuclein pathology, preserves neurons, and improves motor performance. In February 2021 further data from the Phase 1 clinical study was presented at the 7th International Congress of Multiple System Atrophy. The company presented data on blood pressure with change in body position, which demonstrated that ATH434 does not lower blood pressure when subjects move to the standing position. This is a major safety finding considering impaired blood pressure is a cardinal problem in MSA, thus extending the cardiac and overall safety profile previously presented. In April 2021, the company gave an oral presentation of expanded animal data to support the commercialization of ATH434 at the American Academy of Neurology virtual annual meeting. The presentation titled ATH434 Preserves Dopaminergic Neurons, Reduces a-synuclein Oligomerization, and Improves Motor Function in a Transgenic Murine Multiple System Atrophy Model further strengthened the evidence that ATH434 is neuroprotective in brain regions implicated in Parkinsonian disorders. PBT2 In 2005, the company completed the first Phase I trial for PBT2, a double blind, placebo-controlled single dose escalation study, conducted on various healthy male volunteers between the ages of 18 and 50, which was designed to evaluate the safety, tolerability and pharmacokinetics of PBT2. Data from the study showed that PBT2 was tolerated with little difference in the incidence of adverse events between those receiving PBT2 and those receiving the placebo. As of June 30, 2021, notwithstanding the clinical safety demonstrated with PBT2 in the company’s Phase II programs in Alzheimer’s disease and Huntington disease, in February 2015 it reported that the FDA had placed PBT2 on Partial Clinical Hold (PCH) based on particular nonclinical neurotoxicology findings in a dog study. These dog findings limit the dose of PBT2 that the company could use in future trials. With the assistance of third party specialist pharmacometricians, clinical safety physicians and clinical pharmacologists, it has undertaken safety analyses to characterize the behavior of PBT2 drug exposure in the dog and human and how this translates to the comparative safety profile in the dog relative to humans. Based on the emerging strong safety profile for PBT2, the company has prepared a safety monitoring plan for future trials in Huntington disease. These plans, the pharmacological evidence and a Phase 3 protocol were submitted to the FDA in 2016 as part of its response to the PCH and to the Swedish Medical Products Agency and the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) for non-binding scientific advice. The collective response from the FDA and advice from the European regulators was that characterization of the nature of the dog neurotoxicity findings and its reversibility would be required to support the future development of PBT2 in Huntington disease. Patent Portfolio As of June 30, 2020, the company had continued to advance its patent portfolio. The company’s previously reported March 2019 provisional patent application, which exemplifies approximately 150 novel compounds all of which modulate biological iron for the treatment of Parkinson’s, Alzheimer’s and other neurological diseases and titled ‘Compounds for and Methods of Treating Diseases’, matured on 13 March 2020 to a PCT application, No. PCT/AU2020/050235. Contemporaneously with filing the PCT application in March 2020, the company also filed the United States complete application, application No. 17/239,375, deriving from the same provisional application, under track 1, which is the United States procedure for expedited review of patent applications. The company announced allowance of the United States application in November 2020 and announced its grant in July 2021. In June 2020, the company filed another provisional application to register a patent that claims another 80 novel compounds, also that modulate biological iron and also titled ‘Compounds for and Methods of Treating Diseases’. This application matured to a an PCT application No. PCT/AU2021/050633 in June 2021. Similarly to the first mentioned patent application, contemporaneously with filing the PCT application in April 2021, the company also filed United States complete application, application No. 16/818,641, deriving from the same provisional application, under track 1. It announced allowance of the United States application in August 2021 and in securing the allowance, no prior art was cited against the application. Subsequent to the end of the period, in August 2021, the company filed a PCT application No. PCT/AU2021,050,986 to register a patent that claims an additional 150 novel compounds all of which modulate biological Zinc for the treatment of neurological, cancer, viral and other infectious diseases and titled ‘Compounds for and Methods of Treating Diseases’. In the past 12 months, the company has advanced those of its patent families that are pending registration and that align with its development programs. Research and Development The company’s research and development expenses were A$12,283,848 for the year ended June 30, 2021. Regulation Prior to marketing, any therapeutic product developed must undergo rigorous pre-clinical testing and clinical trials, as well as a regulatory approval process mandated by the Therapeutics Goods Administration and, to the extent that any of the company’s pharmaceutical products under development are marketed worldwide, by foreign regulatory agencies, including the FDA, EMA and MHRA. The company and its contract manufacturers must comply with good manufacturing practices regulations and guidelines. History The company was founded in 1997. It was incorporated under the laws of the Commonwealth of Australia in 1997. The company was formerly known as Prana Biotechnology Limited and changed its name to Alterity Therapeutics Limited in 2019.