–   New Evidence Indicates ATH434 can Function as an Iron Chaperone to Redistribute Iron   –

–新证据表明ATH434可以作为铁伴侣重新分配铁–

MELBOURNE, Australia and SAN FRANCISCO, April 29, 2024 (GLOBE NEWSWIRE) -- Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) (“Alterity” or “the Company”), a biotechnology company dedicated to developing disease modifying treatments for neurodegenerative diseases, today announced that important new data on its lead drug candidate ATH434 was presented at the World Orphan Drug Congress USA 2024 in Boston, MA..

澳大利亚墨尔本和旧金山，2024年4月29日（环球通讯社）--Alterity Therapeutics（ASX:ATH，NASDAQ:ATH）（“Alterity”或“the Company”）是一家致力于开发神经退行性疾病的疾病缓解治疗方法的生物技术公司，今天宣布其主要候选药物ATH434的重要新数据已在2024年美国波士顿世界孤儿药大会上提交。。

The poster, entitled, “Biophysical Characteristics of ATH434, a Unique Iron-Targeting Drug for Treating Friedreich’s Ataxia”, was presented by Ashley Pall, Department of Pharmaceutical Sciences at Wayne State University. The study evaluated the ability of ATH434 to target the toxic form of iron that drives the pathology of Friedreich’s Ataxia, a rare neurodegenerative disease that affects young children to young adults.

这张海报的标题是“ATH434的生物物理特征，ATH434是一种治疗弗里德里希共济失调的独特铁靶向药物”，由韦恩州立大学药物科学系的阿什利·帕尔（AshleyPall）发布。该研究评估了ATH434靶向导致弗里德里希共济失调病理的有毒铁形式的能力，这是一种罕见的神经退行性疾病，会影响幼儿至年轻人。

The study also evaluated traditional iron chelators that are designed to bind iron and remove iron from the body. Conversely, an iron chaperone is designed to bind and redistribute iron within the body..

该研究还评估了旨在结合铁并从体内去除铁的传统铁螯合剂。相反，铁伴侣被设计用于结合和重新分配体内的铁。。

“This investigation provides important insights into the mechanism of action of ATH434, namely that it selectively targets the labile iron implicated in the pathology of important neurodegenerative diseases. In this way, ATH434 behaves like a chaperone to redistribute iron within the body. There has historically been great interest in targeting iron in general to treat these diseases, and we now have clear evidence that ATH434 is very different from traditional iron chelators,” said, David Stamler, M.D., Chief Executive Officer of Alterity..

“这项研究为ATH434的作用机制提供了重要的见解，即它选择性地靶向与重要神经退行性疾病病理学有关的不稳定铁。这样，ATH434的行为就像一个伴侣，可以在体内重新分配铁。历史上，人们一直对靶向铁来治疗这些疾病非常感兴趣，我们现在有明确的证据表明ATH434与传统的铁螯合剂有很大不同，”Alterity首席执行官David Stamler医学博士说道。。

Specifically, the study investigated how strongly ATH434 or traditional iron chelators bind the two forms of cellular iron: ferric iron, the stored form, or ferrous iron, the form required for vital cellular functions such as energy production. In excess, the ferrous or “labile” iron can also promote oxidative stress in diseases like Friedreich’s Ataxia as it does in Parkinson’s disease and Multiple System Atrophy..

具体而言，该研究调查了ATH434或传统铁螯合剂结合两种形式的细胞铁的强度：三价铁（储存形式）或亚铁（能量产生等重要细胞功能所需的形式）。过量的亚铁或“不稳定”铁还可以促进弗里德里希共济失调等疾病的氧化应激，就像帕金森氏病和多系统萎缩一样。。

Dr. Stamler continued, “The genetic defect in Friedreich’s Ataxia leads to reduced function of frataxin, a protein necessary for utilizing labile iron, thus leading to iron accumulation in disease. By acting as an iron chaperone, ATH434 has potential to reduce labile iron levels and thus slow disease progression.

斯坦勒博士继续说：“弗里德里希共济失调的遗传缺陷导致frataxin功能降低，frataxin是利用不稳定铁所必需的蛋白质，因此导致疾病中铁的积累。通过充当铁伴侣，ATH434有可能降低不稳定铁水平，从而减缓疾病进展。

Given these new data, we are excited to evaluate FA as a potential new indication for ATH434.”.

鉴于这些新数据，我们很高兴将FA评估为ATH434的潜在新指标。”。

The novel iron binding properties of ATH434 presented in the poster support the characterization of ATH434 as an iron chaperone based on properties it shares with endogenous iron chaperones such as frataxin and poly-C binding proteins. These include its low micromolar binding affinity for ferrous iron and a bound structure that may allow for transfer of ferrous iron proteins involved in cellular function.

海报中介绍的ATH434的新型铁结合特性支持将ATH434表征为铁伴侣，因为它与内源性铁伴侣（例如frataxin和poly-C结合蛋白）具有相同的特性。这些包括其对亚铁的低微摩尔结合亲和力和可能允许转移参与细胞功能的亚铁蛋白的结合结构。

The new data also confirmed that ATH434 has a dramatically lower affinity for ferric iron than traditional iron chelators that are approved for treating systemic iron overload. Together, these properties suggest that ATH434 has the capacity to selectively target pathogenic ferrous iron without impairing normal cellular iron trafficking or functions..

新数据还证实，与被批准用于治疗全身性铁超负荷的传统铁螯合剂相比，ATH434对三价铁的亲和力显着降低。总之，这些特性表明，ATH434具有选择性靶向致病性亚铁的能力，而不会损害正常的细胞铁运输或功能。。

The poster presentation can be found on Alterity’s website here.

海报展示可以在Alterity的网站上找到。

About ATH434

关于ATH434

Alterity’s lead candidate, ATH434, is an oral agent designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration. ATH434 has been shown preclinically to reduce α-synuclein pathology and preserve neuronal function by restoring normal iron balance in the brain. As an iron chaperone, it has excellent potential to treat Parkinson’s disease as well as various Parkinsonian disorders such as Multiple System Atrophy (MSA).

Alterity的主要候选药物ATH434是一种口服药物，旨在抑制与神经变性有关的病理蛋白的聚集。临床前已证明，ATH434可通过恢复大脑中正常的铁平衡来减少α-突触核蛋白病理并保留神经元功能。作为一种铁伴侣，它具有治疗帕金森病以及多种帕金森病（如多系统萎缩（MSA））的巨大潜力。

ATH434 successfully completed Phase 1 studies demonstrating the agent is well tolerated and achieved brain levels comparable to efficacious levels in animal models of MSA. ATH434 is currently being studied in two clinical trials: Study ATH434-201 is a randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with early-stage MSA and Study ATH434-202 is an open-label Phase 2 Biomarker trial in patients with more advanced MSA.

ATH434成功完成了第一阶段研究，证明该药物具有良好的耐受性，并达到了与MSA动物模型中有效水平相当的大脑水平。ATH434目前正在两项临床试验中进行研究：研究ATH434-201是一项针对早期MSA患者的随机，双盲，安慰剂对照的2期临床试验，研究ATH434-202是一项开放标签的2期生物标志物试验，用于晚期MSA患者。

ATH434 has been granted Orphan drug designation for the treatment of MSA by the U.S. FDA and the European Commission..

ATH434已被美国FDA和欧盟委员会授予用于治疗MSA的孤儿药名称。。

About Friedreich’s Ataxia

关于Friedreich的共济失调

Friedreich ataxia (FA) is a rare, inherited disorder that causes progressive damage to the nervous system. In the brain, the cerebellum, part of the brain that coordinates balance and movement, is most affected. FA also may cause heart disease, specifically cardiomyopathy, and diabetes. Symptoms typically begin between the ages of five and 15, although they sometimes appear after age 25.

弗里德里希共济失调（FA）是一种罕见的遗传性疾病，会对神经系统造成进行性损害。在大脑中，协调平衡和运动的大脑部分小脑受到的影响最大。FA也可能引起心脏病，特别是心肌病和糖尿病。症状通常在5至15岁之间开始，尽管有时会在25岁以后出现。

While progression of FA varies from person to person, generally individuals with FA may need to use a wheelchair within 10 to 20 years after the appearance of symptoms. In later stages of the disorder, people may become completely incapacitated. There is no cure for the disorder, and heart disease is the most common cause of death in people with FA.1.

虽然FA的进展因人而异，但通常FA患者可能需要在症状出现后10至20年内使用轮椅。在疾病的后期，人们可能会完全丧失能力。这种疾病无法治愈，心脏病是FA患者最常见的死亡原因。

1Source: National Institutes of Health – National Institute of Neurological Disorders and Stroke

1资料来源：国立卫生研究院-国立神经疾病和中风研究所

About Alterity Therapeutics Limited

关于Alterity Therapeutics Limited

Alterity Therapeutics is a clinical stage biotechnology company dedicated to creating an alternate future for people living with neurodegenerative diseases. The Company’s lead asset, ATH434, has the potential to treat various Parkinsonian disorders and is currently being evaluated in two Phase 2 clinical trials in Multiple System Atrophy.

Alterity Therapeutics是一家临床阶段生物技术公司，致力于为患有神经退行性疾病的人创造另一个未来。该公司的主要资产ATH434具有治疗各种帕金森病的潜力，目前正在多系统萎缩的两个2期临床试验中进行评估。

Alterity also has a broad drug discovery platform generating patentable chemical compounds to treat the underlying pathology of neurological diseases. The Company is based in Melbourne, Australia, and San Francisco, California, USA. For further information please visit the Company’s web site at www.alteritytherapeutics.com..

Alterity还拥有一个广泛的药物发现平台，产生可申请专利的化合物，以治疗神经系统疾病的潜在病理。公司总部位于澳大利亚墨尔本和美国加利福尼亚州旧金山。有关更多信息，请访问公司网站www.alteritytherapeutics.com。。

Authorisation & Additional information

授权和附加信息

This announcement was authorized by David Stamler, CEO of Alterity Therapeutics Limited.

本公告由Alterity Therapeutics Limited首席执行官David Stamler授权。

Investor and Media Contacts:

投资者和媒体联系人：

Australia

澳大利亚

Hannah Howlett

汉娜·霍利特

we-aualteritytherapeutics@we-worldwide.com

we-aualteritytherapeutics@we-worldwide.com

+61 450 648 064

+61 450 648 064

U.S.

U、 S。

Remy Bernarda

雷米·贝尔纳达

remy.bernarda@iradvisory.com

remy.bernarda@iradvisory.com

+1 (415) 203-6386

+1 (415) 203-6386

Forward Looking Statements

前瞻性声明

This press release contains 'forward-looking statements' within the meaning of section 27A of the Securities Act of 1933 and section21EoftheSecuritiesExchangeActof1934.TheCompanyhastriedtoidentifysuchforward-lookingstatementsbyuse of such words as 'expects,' 'intends,' 'hopes,' 'anticipates,' 'believes,' 'could,' 'may,' 'evidences' and 'estimates,' and other similar expressions, but these words are not the exclusive means of identifying suchstatements..

本新闻稿包含《1933年证券法》第27A节和《1934年证券交易法》第21E节所指的“前瞻性声明”。公司试图通过“预期”、“意图”、“希望”、“预期”、“相信”、“可能”、“可能”、“证据”和“估计”等词语来识别此类前瞻性声明，但这些词语并不是识别此类声明的唯一手段。。

Importantfactorsthatcouldcauseactualresultstodiffermateriallyfromthoseindicatedbysuchforward-lookingstatements aredescribedinthesectionstitled“RiskFactors”intheCompany’sfilingswiththeSEC,includingitsmostrecentAnnualReport onForm20-FaswellasreportsonForm6-K,including,butnotlimitedtothefollowing:statementsrelatingtotheCompany's drug development program, including, but not limited to the initiation, progress and outcomes of clinical trials of the Company'sdrugdevelopmentprogram,including,butnotlimitedto,ATH434,andanyotherstatementsthatarenothistorical facts.Suchstatementsinvolverisksanduncertainties,including,butnotlimitedto,thoserisksanduncertaintiesrelatingtothe difficultiesordelaysinfinancing,development,testing,regulatoryapproval,productionandmarketingoftheCompany’sdrug components,including,butnotlimitedto,ATH434,theabilityoftheCompanytoprocureadditionalfuturesourcesoffinancing, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug compounds, including, but not limitedto,ATH434,thatcouldslowor prevent productscomingtomarket,the uncertaintyof obtaining patent protectionfortheCompany's intellectualpropertyortradesecrets, the uncertainty of successfully enforcing the Company’s patent rights and the uncertainty of the Company freedom to operate..

可能导致结果与这些前瞻性陈述所示结果产生实质性差异的重要因素在公司与SEC的文件中“风险因素”部分进行了描述，包括其最新的20-FASWELLAS Form6-K年度报告，包括但不限于以下内容：关于公司药物开发计划的声明，包括但不限于公司药物开发计划临床试验的启动、进展和结果，包括但不限于ATH434和任何其他声明历史事实。此类陈述涉及风险和不确定性，包括但不限于与公司药物成分的融资、开发、测试、监管批准、生产和营销困难相关的风险和不确定性，包括但不限于ATH434，公司未来的融资能力，意外的不良副作用或公司药物化合物的治疗效果不足，包括但不限于ATH434，这可能会阻止产品进入市场，公司获得专利保护的不确定性知识产权或商业秘密、成功实施公司专利权的不确定性以及公司运营自由的不确定性。。

Any forward-looking statement made by us in this press release is based only on information currently available to us and speaksonlyasofthedateonwhichitismade.Weundertakenoobligationtopubliclyupdateanyforward-lookingstatement, whetherwrittenororal,thatmaybemadefromtimetotime,whetherasaresultofnewinformation,futuredevelopmentsor otherwise..

我们在本新闻稿中所作的任何前瞻性声明均仅基于我们目前可获得的信息，以及我们所发表的声明。我们不准备公开更新任何前瞻性声明，无论是书面的还是书面的，无论是由于新信息、未来发展还是其他原因。。