Alterity Therapeutics Limited 2020 Annual Report CONTENTS Alterity Therapeutics Limited ACN 080 699 065 Annual report - 30 June 2020 Page Corporate directory 3 Chairman's letter 4 Review of operations and activities 5 In

Therapeutics Limited

report - 30 June 2020

pleased to present the FY20 Annual Report for Alterity Therapeutics. While the world responds and adjusts to the COVID-19 pandemic,

we've remained highly focussed on preparing our lead compound ATH434 (formerly PBT434) for further clinical development.

Neurodegenerative diseases like our lead disease indication Multiple System Atrophy (MSA) continue to devastate the patients inflicted

and we remain committed to this patient population in advancing our treatment as quickly as possible whilst balancing the importance

of building a strong foundation of data and evidence.

diseases don't halt in response to other medical and social crisis like we're currently seeing, and neither have we.

Since announcing our Phase 1 clinical trial in May 2019, we've continued to analyse and build on the data and we are in

a strong position to move into the next phase of clinical development.

presented the fully analysed data results in July 2019 adding data from elderly participants to the healthy volunteers already

presented. Encouragingly this data supported the strong safety profile and continued to be well tolerated. Systemic exposure to

ATH434 was comparable between elderly and healthy volunteers. This information, along with previous results in the Phase 1 study,

indicated that clinically tested doses achieve concentrations in the brain that are comparable with those associated with efficacy

in animal models of disease. It's also been encouraging to see the growing interest in ATH434 by the clinical and scientific

communities with Alterity presenting data at conferences throughout the year.

strong safety data and the dire outlook for patients with MSA supported both the US Food and Drug Administration (FDA) and European

Commission granting Orphan Drug designation to ATH434. Orphan status is given to biologics that are intended for the safe and

effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or

that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug.

Orphan Drug designation entitles Alterity to periods of market exclusivity and qualifies us for various development incentives.

were also pleased to receive guidance from the FDA on the development pathway for ATH434 including the Phase 2 design study. We

reached agreement with the FDA on the non-clinical investigations required to support the Phase 2 study and key elements of the

study design including the proposed patient population, safety monitoring plan, and strategy for evaluating drug exposure during

with any commercialisation strategy, but more now than ever with the impact of COVID-19 limiting the availability of clean clinical

trial sites, it's important to have optionality in our strategy. As such we're pursuing a dual strategy in Europe

and the US to ensure we can continue to advance the development program as rapidly as possible in the current environment. There

is no doubt that COVID-19 has slowed down clinical programs around the world, and we have not been immune to this impact but remain

confident of the path forward.

also continue to mine our entire library of compounds for future opportunities including the potential for PBT2 to be a compelling

antimicrobial agent as one non-neurological option.

I'd like to thank the Alterity team in San Francisco, USA, and Melbourne, Australia, for their tireless effort and to you

our shareholders for remaining on this journey with us.

OF OPERATIONS AND ACTIVITIES

report provides details of activities and progress for Alterity Therapeutics Limited for the year ended 30 June 2020.

is developing first-in-class therapies to treat neurodegenerative diseases. The Company's lead drug candidate, ATH434 (formerly

PBT434), is the first of a new generation of small molecules designed to block the accumulation and aggregation of -synuclein.

Alpha-synuclein, when aggregated in the brain, is a pathological hallmark of Parkinsonian conditions and is considered an important

biologic target for treating these neurodegenerative diseases.

is an oral small molecule drug candidate with potential for treating synucleinopathies such as Parkinson's disease and Multiple

System Atrophy (MSA), a type of parkinsonian disorder which has been selected as the first disease target. MSA is a rare and rapidly

progressive neurological disorder affecting adults.

has demonstrated pre-clinical evidence as a potential treatment of MSA and produced encouraging results in its Phase 1 clinical

program. The company is in the preparatory phase of planning for its Phase 2 clinical trial.

with US FDA provides development pathway for ATH434

June 2020, Alterity received guidance from the US Food and Drug Administration (FDA) in relation to the development pathway for

ATH434 following the successful completion of its Phase 1 clinical trial. The pre-IND (Investigational New Drug) meeting was to

obtain input on the clinical development plan for ATH434, including feedback on the Phase 2 study design.

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 Company's Phase 2 study design including the proposed patient population, safety monitoring

plan, and strategy for evaluating drug exposure during the study.

there are currently no approved treatments for MSA and therefore no regulatory precedent regarding accepted efficacy endpoints,

the FDA and Alterity will work together to develop an endpoint that is best suited for the MSA patients to be studied. The FDA

has also encouraged Alterity to utilise data from a natural history study that Alterity has planned with clinical and neuroimaging

experts at Vanderbilt University Medical Center in the US.

natural history study, referred to as bioMUSE, or biomarkers of Progression in Multiple System Atrophy, will enrol early stage

MSA patients and track change in clinical parameters and biomarkers for up to one year. Natural history studies are important

for characterising disease progression over time in selected patient populations. Well-conducted, these studies can provide vital

information to optimise clinical trial design and inform the selection of biomarkers to evaluate target engagement of drug candidates.

parallel with the US strategy, Alterity is also pursuing a regulatory pathway in Europe and Australia. Given the uncertainty of

study conduct and recruitment in the COVID-19 era, and with the need to target sites that are minimally impacted, it is prudent

for the Company to be flexible in identifying and recruiting sites around the world and maintaining optionality. Planning is underway

to meet with European authorities.

Commission approves Orphan Designation for ATH434

European Commission (EC) granted Orphan Drug designation to ATH434, which entitles Alterity 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. This followed the US FDA granting ATH434 orphan drug status for

the treatment of MSA in January 2019.

approval was based on the recommendation of a positive opinion from the European Medicines Agency's Committee for Orphan

Medicinal Products, which was announced on the 18th of November 2019.

of Operations and Activities (Continued)

of Phase 1 Clinical Trial

July 2019 Alterity announced that it had successfully completed its Phase 1 study of ATH434. The completed trial included data

from elderly volunteers receiving repeated doses and demonstrated that the drug was safe and well-tolerated, with an adverse event

profile like adult volunteers. As was observed in healthy adult volunteers, no elderly subject experienced a serious adverse event

that led to discontinuation of the study drug.

findings built on the data from healthy volunteers announced in May 2019 at the American Academy of Neurology Annual Meeting.

exposure to the drug was comparable between elderly and healthy volunteers. This information, along with previous results in the

Phase 1 study, indicate that clinically tested doses achieve concentrations in the brain that are comparable with those associated

with efficacy in animal models of disease.

Phase 1 Clinical Trial for ATH434 recruited healthy adult and elderly ( 65) volunteers with the primary goals of assessing

the safety and tolerability of ATH434 after single and multiple oral dose administration. Secondary goals included evaluating

pharmacokinetics in plasma and cerebrospinal fluid that enabled determination of how ATH434 is absorbed and metabolised by the

scientific interest for ATH434

May, data on ATH434 was presented at the American Academy of Neurology virtual meeting. Chief Medical Officer & Senior VP

Clinical Development, Dr David Stamler made the virtual presentation as part of the Parkinson's Disease Interventions and

Clinical Trials session.

presentation was based on an abstract entitled A Phase 1 Study of PBT434, a Novel Small Molecule Inhibitor of a-Synuclein Aggregation,

in Adult and Older Adult Volunteers published in the journal Neurology.

September, Dr Stamler presented a poster titled: A First in Human Study of PBT434, a Novel Small Molecule Inhibitor of -Synuclein

Aggregation at the 2019 International Congress of Parkinson's Disease and Movement Disorders (MDS Congress) in Nice,

France. The poster presented findings from the completed Phase 1 trial of ATH434.

the reporting period, Alterity announced that new clinical and experimental pharmacology data was selected for presentation at

the 2020 International Congress of Parkinson's Disease and Movement Disorders and the American Neurological Association's

2020 Annual Meeting. The new data were generated from an experiment testing ATH434 in an animal model of Multiple System Atrophy

(MSA) in the laboratory of Dr. Nadia Stefanova, Professor of Translational Neurodegeneration Research at the Medical University

of Innsbruck. It independently confirmed and extended previous findings demonstrating that ATH434 reduces -synuclein pathology,

preserves neurons and improves motor performance.