PBT-434

– Successful End-of-Phase 2 meeting with FDA agreeing on key elements of the proposed Phase 3 design, including study population, dosing regimen, and treatment duration – – FDA agrees on UMSARS Part I as primary endpoint after ATH434 demonstrated 48% slowing of disease progression versus placebo in Phase 2 study – – FDA agrees with 50mg dose level which achieved clinically and statistically significant efficacy in Phase 2 study – – Pivotal Phase 3 trial activities on track to initiate by year-end 2026 – MELBOURNE, Australia and SAN FRANCISCO, June 09, 2026 (GLOBE NEWSWIRE) -- Alterity Therapeutics (ASX: ATH, trading under the ASX code ATHDA until 12 June; NASDAQ: ATHE) (“Alterity” or “the Company”), a biotechnology company dedicated to developing disease modifying treatments for neurodegenerative diseases, today announced the successful outcome of its End-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA), achieving alignment on the key elements of the Company's registrational Phase 3 program for ATH434 in Multiple System Atrophy (MSA), a rare and rapidly progressive neurodegenerative disease with no approved therapy. The pivotal program is designed to support a potential New Drug Application (NDA) in MSA and represents the final stage of clinical development required to seek regulatory approval in the United States. Importantly, the FDA agreed with the proposed Phase 3 trial design, including the study population, treatment duration and primary endpoint ‒ the 11-item UMSARS Part I 1 rating scale. The FDA also concurred with Alterity’s proposed Phase 3 dose regimen of ATH434 50 mg twice daily, which in Phase 2 achieved clinically and statistically significant efficacy on the 11-item UMSARS I, with 48% slowing of disease progression compared to placebo. The FDA further indicated that Alterity’s planned key secondary endpoints for the Phase 3 study were suitable to support efficacy, including the Swallowing Disturbance Questionnaire, the Orthostatic Hypotension Symptom Assessment, and the Clinical Global Impression of Severity. In addition, the FDA agreed with Alterity’s proposed statistical methods for analyzing the primary and key secondary efficacy endpoints and indicated that the size of the anticipated safety database at the conclusion of Phase 3 was reasonable. ATH434 has previously received Fast Track Designation and Orphan Drug Designation from the FDA for the treatment of MSA, recognizing the significant unmet medical need for patients living with this rare and debilitating neurodegenerative condition. The successful outcome of the EOP2 meeting represents an important de-risking milestone for ATH434 and substantially reduces uncertainty around the design of the pivotal Phase 3 program. “Achieving alignment with FDA at the End-of-Phase 2 meeting is a critical step for our Phase 3 program in MSA, providing the clarity we need to advance to this next stage,” said David Stamler, M.D., CEO of Alterity Therapeutics. “We are encouraged by the FDA’s agreement with us on the key elements of our Phase 3 program, namely the study population, efficacy endpoints, treatment regimen and anticipated safety database, providing a well-defined registrational pathway built on the strength of our Phase 2 data. The successful outcome of the meeting is an important de-risking milestone and gives us confidence as we finalize the protocol and prepare to initiate trial activities by year-end 2026. The favorable outcome of the meeting is a testimony to the depth of experience our team brings to collaborating with the FDA, especially on neurology development programs. I am confident that ATH434 is well positioned to become a disease-modifying therapy for individuals living with MSA.” About ATH434 Alterity’s lead candidate, ATH434, is an oral agent designed to redistribute excess iron and inhibit abnormal protein aggregation associated with neurodegeneration. ATH434 has been shown to reduce α-synuclein pathology and preserve neuronal function by restoring normal iron balance in the brain in preclinical models. 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). Positive results from the randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with MSA demonstrated robust clinical efficacy, target engagement as indicated by key biomarkers, and a favorable safety profile. Positive data from a second Phase 2 open-label biomarker trial in patients with more advanced MSA reinforced these results. ATH434 has been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA), and Orphan Drug Designation by the FDA and the European Commission for the treatment of MSA. About the Phase 3 Clinical Trial The Phase 3 clinical trial will be a randomized, double-blind, placebo-controlled investigation in participants with clinical and biomarker evidence of MSA. Approximately 200 patients will be randomly assigned, in a 1:1 ratio, to 12 months treatment with ATH434 50 mg bid or matching placebo. The primary endpoint will be the 11-item UMSARS I and the key secondary endpoints will include the Swallowing Disturbance Questionnaire, the Orthostatic Hypotension Symptom Assessment, and the Clinical Global Impression of Severity. About ATH434-201 Phase 2 Clinical Trial The ATH434-201 Phase 2 clinical trial was a randomized, double-blind, placebo-controlled investigation of 12 months treatment with ATH434 in patients with MSA. The study evaluated the efficacy, safety and pharmacokinetics of ATH434 and assessed neuroimaging measures of brain volume and iron-related parameters, together with protein biomarkers. Wearable sensors were employed to evaluate motor activities outside of the clinic. The study enrolled 77 adults who were randomly assigned to receive ATH434 50 mg or 75 mg twice daily or matching placebo. The data showed that, compared to placebo, ATH434 produced clinically and statistically significant improvement on the modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I, a functional rating scale that assesses disability on activities of daily living affected in MSA. Additional efficacy assessments demonstrated improvement consistent with the positive UMSARS Part I findings including the Clinical Global Impression of Severity Scale and patient reported outcomes that assessed swallowing impairment (the Swallowing Disturbance Questionnaire) and low blood pressure symptoms with standing (the Orthostatic Hypotension Symptom Assessment). Wearable sensors used to assess outpatient activity levels indicated that patients receiving ATH434 also experienced less decline compared with placebo. Biomarkers were used to evaluate potential drug effect and target engagement relative to placebo. Both dose levels reduced the adverse effect of iron accumulation in MSA affected brain regions and demonstrated trends in preservation of brain volume. ATH434 was well tolerated with similar adverse event rates compared to placebo and no serious adverse events attributed to ATH434. Additional information on the Phase 2 trial can be found at ClinicalTrials.gov Identifier: NCT05109091 . About Multiple System Atrophy Multiple System Atrophy (MSA) is a rare, neurodegenerative disease characterized by failure of the autonomic nervous system and impaired movement. The symptoms reflect the progressive loss of function and death of different types of nerve cells in the brain and spinal cord. It is a rapidly progressive disease that causes profound disability. MSA is a Parkinsonian disorder characterized by a variable combination of slowed movement and/or rigidity, autonomic dysfunction affecting involuntary functions such as blood pressure maintenance and bladder control, and impaired balance and/or coordination that predispose patients to falls. A pathological hallmark of MSA is the accumulation of abnormal clumping of the protein α-synuclein within oligodendrocytes, the myelin-producing support cells of the central nervous system, along with progressive neuronal loss in multiple brain regions. MSA affects up to 50,000 individuals in the U.S., and while some of the symptoms of MSA can be treated with medications, currently there are no drugs that are able to slow disease progression and there is no cure. 2 About 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 is focused on developing disease-modifying therapies in Multiple System Atrophy (MSA) and related Parkinsonian disorders. Alterity is preparing to initiate a Phase 3 pivotal trial in MSA, a rare and rapidly progressive disease. ATH434, the Company’s lead asset, has demonstrated clinically meaningful efficacy in a randomized, double-blind, placebo-controlled Phase 2 clinical trial in participants with MSA. Alterity has further reported positive data in its open label Phase 2 clinical trial in participants with advanced MSA. In addition, Alterity 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 website at . References: 1 11-item UMSARS Part I (previously described as modified UMSARS I): Unified Multiple System Atrophy Rating Scale, 11-Items include: Orthostatic symptoms, Swallowing, Speech, Handwriting, Cutting food, Dressing, Hygiene, Walking, Falling, Urinary and Bowel function. 2 Multiple System Atrophy | National Institute of Neurological Disorders and Stroke (nih.gov) Authorization & Additional information This announcement was authorized by the Board of Directors of Alterity Therapeutics Limited. Contacts: Investors: Elyse Shapiro ir@alteritytx.com Remy Bernarda Investor Relations Advisory Solutions ir@alteritytx.com +1 (415) 203-6386 Media Casey McDonald Tiberend Strategic Advisors, Inc. cmcdonald@tiberend.com +1 (646) 577-8520 Forward Looking Statements This press release contains “forward-looking statements” within the meaning of section 27A of the Securities Act of 1933 and section 21E of the Securities Exchange Act of 1934. The Company has tried to identify such forward-looking statements by use 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 such statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are described in the sections titled “Risk Factors” in the Company’s filings with the SEC, including its most recent Annual Report on Form 20-F as well as reports on Form 6-K, including, but not limited to the following: statements relating to the Company's drug development program, including, but not limited to the initiation, progress and outcomes of clinical trials of the Company's drug development program, including, but not limited to, ATH434, and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to the difficulties or delays in financing, development, testing, regulatory approval, production and marketing of the Company’s drug components, including, but not limited to, ATH434, the ability of the Company to procure additional future sources of financing, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug compounds, including, but not limited to, ATH434, that could slow or prevent products coming to market, the uncertainty of obtaining patent protection for the Company's intellectual property or trade secrets, the uncertainty of successfully enforcing the Company’s patent rights and the uncertainty of the Company freedom to operate. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

点击蓝字关注“Aevita” 点亮星标不错过每一篇精彩内容~ 走路像踩棉花、抬手困难、爬楼梯要歇好几次…… 这些是多发性硬化症（MS）、肌萎缩侧索硬化（ALS）、脊髓性肌萎缩症（SMA）等神经疾病患者每天都要面对的噩梦。长期以来，这些疾病的治疗主要集中在延缓神经损伤，但对于已经出现的肌无力、易疲劳等症状，一直没有特别有效的解决办法。不过，丹麦 NMD Pharma 公司最近公布的一项重磅专利（WO 2024/261020）带来了革命性突破：一种原本用于治疗肌强直的 ClC-1 抑制剂，竟然能快速改善多种神经疾病患者的肌肉功能！ ClC-1 是骨骼肌细胞膜上的一种氯离子通道，被称为肌肉兴奋性的 "总开关"。在正常情况下，它负责维持肌肉细胞膜 80% 的导电能力，让肌肉在收缩后能快速放松。但当神经和肌肉之间的信号传递出现问题时 —— 比如 MS 患者的神经髓鞘受损、ALS 患者的运动神经元死亡 —— 到达肌肉的神经信号会变得非常微弱。这时候，ClC-1 这个 "开关" 就会变得过于灵敏，稍微一点信号就会让肌肉放松，导致肌肉很难被激活，从而出现严重的无力和疲劳。 研究人员在大鼠模型中验证了这个想法。从下图可以看到，当神经肌肉传递被药物抑制后，大鼠的肌肉力量下降到了正常水平的 30% 左右。但在使用 ClC-1 抑制剂 NMD712 后，仅仅几分钟，肌肉力量就几乎完全恢复了！同时，神经信号传递的不稳定（jitter）和中断（block）也得到了显著改善。 ClC-1 抑制剂 NMD712 显著恢复受损的肌肉功能。A：肌肉复合动作电位比值；B：肌肉力量；C：信号抖动（jitter）；D：信号中断（block） 更令人惊喜的是，研究人员还在腓骨肌萎缩症（CMT）患者中进行了临床观察。他们发现，和健康人相比，CMT 患者的神经肌肉接头传递存在明显异常 —— 信号抖动增加了 90% 以上，信号中断的比例也大幅上升。这说明，神经肌肉接头功能障碍并不是某一种疾病的特例，而是至少 20 多种神经肌肉疾病的共同特征NMD Pharma。 CMT 患者与健康人的神经肌肉接头功能对比。可以看到，CMT 患者的信号抖动（jitter）和中断（block）都显著高于健康人 这项专利的最大价值在于，它开辟了神经疾病治疗的全新范式。传统的治疗方法都是 "上游治疗"，试图保护或修复受损的神经，但对于已经出现不可逆神经损伤的患者来说，这些方法往往效果有限。而 ClC-1 抑制剂是一种 "下游治疗"，它直接作用于肌肉本身，提高肌肉的兴奋性，让微弱的神经信号也能触发有效的肌肉收缩。 目前，NMD Pharma 公司的领先化合物 NMD670 已经完成了 I 期临床试验，安全性良好。现在正在进行三个 II 期临床试验，分别针对脊髓性肌萎缩症 3 型、全身型重症肌无力和腓骨肌萎缩症。如果试验成功，这将是神经疾病治疗领域的一个里程碑。 对于数百万受神经肌肉疾病困扰的患者来说，ClC-1 抑制剂带来的不仅仅是症状的改善，更是生活质量的根本提升。它让患者能够重新走路、自己吃饭、照顾自己，重新找回生活的尊严。让我们一起期待这款新药早日上市，给更多患者带来希望！ 关于ClC-1 抑制剂的后续研发进展，Aevita会持续跟踪官方披露的第一手信息，为大家带来客观、严谨的深度解读。你是否关注 ALS领域的新药研发？对于神经退行性罕见病的治疗进展，你最想了解哪些方向的内容？欢迎在留言区分享你的想法与疑问，我们会尽力在后续的科普内容中为大家逐一解答。 大脑 “毒蛋白” 有了克星！新型 CAR-Treg 疗法直击渐冻症、阿尔茨海默 这种鼻喷疗法竟能延长渐冻症小鼠近 20% 生存期，人类有戏了？ 含笑内酯横空出世，渐冻症等肌肉病治疗迎新契机！ 大脑 "救命开关" 被激活！新一代神经保护药专利公布，帕金森、渐冻症迎来曙光 西班牙科学家逆天发明，几秒钟筛选新药，剑指渐冻症等神经疾病！ 渐冻症新曙光！阻断这个 “厌食开关”，不仅止体重暴跌，还能护运动神经元 渐冻症终于有了 “看得见” 的诊断利器，能提前锁定致病元凶 肌肉萎缩新希望！哥伦比亚大学破解肌肉干细胞早衰密码，SMA/DMD 迎来全新疗法 新生儿心脏细胞竟能 “解冻” 渐冻症，有望打破无药困局！ 7 个氨基酸的 "肌肉守护肽" 火了！不用猛练也能防流失、促再生？ 抗艾滋老药跨界神逆袭，或为渐冻症等老年病按下 “逆转键” 星形胶质细胞异常成阿尔茨海默与渐冻症 “罪魁”，新疗法来了！ 亮氨酸逆袭！从餐桌常客到老年健忘、走路不稳的 “救星”，还能治绝症？ Nura Bio 神药 NB-4746，阻断神经元 “自杀”，渐冻症治疗迎新转机 “鸡尾酒配方” 助力干细胞移植，中风、ALS 等神经疾病治疗迎新希望！ 渐冻症有救了？Kv3 通道药物，从肌肉神经双管齐下破难题 渐冻症新药曙光！印度 Zydus 公布 ALS 全新专利，口服 NLRP3 抑制剂进入 Ⅱ 期临床 绝境逢生！30 年老药特拉唑嗪，能否成为渐冻症患者的 “救命稻草”？ 能治还能早诊断，这款抗 TDP - 43 抗体为渐冻症带来新曙光 Science 重磅：短 RNA 竟能逆转 TDP - 43 病理，为神经退行性疾病 “破冰” 多系统萎缩患者曙光初现！安普洛西汀，开启站立与生活新篇章！ 超罕见 ALS 迎来曙光！NIH1500 万美元资助 ASO 疗法，9 名患者已获益 能 “跑” 进大脑的渐冻症口服药，动物实验成绩斐然 从 KCNN1 回溯源头：耶鲁 10 年 ALS 攻坚前传 ——Hsp110 分子伴侣如何率先让渐冻小鼠寿命翻倍 从靶点发现到寿命翻倍！KCNN1：跨越 5 年的渐冻症奇迹之路 寿命翻倍！耶鲁大学重磅突破：渐冻症基因疗法让小鼠多活一倍时间 谁能想到？调脂药、降糖药居然能治渐冻症！住友制药专利曝光惊人发现 渐冻症患者的新希望！这项脑刺激技术，能重启受损的运动功能 藏不住的突破！冷门化工试剂逆袭，成为渐冻症治疗全新靶点 改写渐冻症药物开发剧本！AI 发现全新靶点，97% 患者有望受益 48 名患者参与！渐冻症首个双途径免疫疗法启动 52 周临床试验 被忽视的渐冻症核心症状：流涎，终于有了成熟的治疗新选择 藏红花里炸出医学奇迹！一个分子同时对抗帕金森和渐冻症两大绝症 32% 生存期延长！渐冻症治疗迎来里程碑式进展 线粒体修复重大突破！渐冻症在研新药数据惊艳 用了 70 年的肺结核药，被 AI 发现能治渐冻症！ 体细胞嵌合突变，是 90% 散发性ALS病例的隐形病因 渐冻症迎来颠覆性突破！CREB3 蛋白成 “神经元保护神”，降低发病风险、延长生存期 无创电刺激让 ALS 生存期延长 84%！多部位神经调控改写治疗格局 97% 渐冻症患者的希望：降脂药靶向 STMN2 修复神经 大脑 “垃圾蛋白” 克星来了！新型 TDP-43 抗体攻克渐冻症 / 痴呆关键靶点 京都大学最新专利：6 款老药新用，覆盖所有类型 ALS 瞄准线粒体 "大门"！X-tosis 全新靶点为 ALS 带来疾病修饰新希望 延髓型 ALS 迎来首个血清诊断金标准，治疗监测也有了新标尺 跳出传统套路！这项新专利，让ALS患者的脊髓重新“发电” ALS 新药 PLL001临床数据亮眼，亚太布局按下快进键 黑暗中的一束光！ALS 治疗迎来全新靶点药物 渐冻症患者的曙光！全球首个血液预测指标诞生 MSA 新药研发再传新进展！ATH434 的 FDA 反馈，到底意味着什么？ 这个天然植物成分，居然能逆转肌肉流失？ 神经损伤的 “晴雨表”：顶刊综述带你读懂 NfL，这些脑病都能用上 ALS 免疫治疗里程碑：NP001 核心专利数据公布，FDA 上市路径已敲定 美国退伍军人事务部联合 NIH！ALS 肌肉萎缩或迎来里程碑突破 突破血脑屏障！AB126 外泌体疗法，为 ALS 治疗带来全新可能