Paxalisib plus Radiotherapy Data Shows Promise for Treating Patients with PI3K Pathway Mutation Brain Metastases

Paxalisib加放疗数据显示有望治疗PI3K通路突变脑转移患者

SYDNEY, Feb. 21, 2024 /PRNewswire/ -- Kazia Therapeutics Limited (NASDAQ: KZIA), a biotechnology company specializing in oncology, today announced the early conclusion based on positive safety and promising clinical response findings observed to date of an important two-part Phase I trial. This investigator-initiated trial evaluated the use of paxalisib (an oral PI3K/mTOR dual inhibitor) with radiation therapy for the treatment of patients with PI3K pathway mutation brain metastases from solid tumors..

悉尼，2024年2月21日/PRNewswire/-Kazia Therapeutics Limited（纳斯达克：KZIA），一家专门从事肿瘤学的生物技术公司，今天宣布了基于积极安全性和迄今为止观察到的有希望的临床反应结果的早期结论。一项重要的两部分I期试验。这项由研究者发起的试验评估了paxalisib（一种口服PI3K/mTOR双重抑制剂）与放射治疗联合用于治疗实体瘤PI3K途径突变脑转移患者。。

Part I of the study established the maximal tolerated dose (MTD) of paxalisib in combination with radiation therapy, while also demonstrating promising signs of clinical activity in all nine evaluable patients. Part II was a follow-on expansion cohort to further evaluate safety and efficacy of the MTD (45mg daily) combined with radiation therapy in up to 12 additional patients..

该研究的第一部分确定了paxalisib联合放射治疗的最大耐受剂量（MTD），同时在所有9名可评估患者中也显示出有希望的临床活性迹象。第二部分是一个后续扩展队列，以进一步评估MTD（每日45mg）联合放射治疗在另外12名患者中的安全性和有效性。。

After reviewing the Part II patient data generated to date, the three lead investigators have determined that the primary endpoint of the study has been reached. In addition, the investigators continued to observe encouraging signs of clinical response in patients in the expansion cohort. Detailed findings from Part II of this study are slated for submission and presentation at a forthcoming global scientific meeting, where they will contribute to the ongoing conversation about treatment options for patients with these complex brain metastases..

在回顾了迄今为止产生的第二部分患者数据后，三位主要研究人员确定研究的主要终点已经达到。此外，研究人员继续观察到扩展队列患者临床反应的令人鼓舞的迹象。这项研究第二部分的详细研究结果将提交给即将举行的全球科学会议，并在会上发表，他们将为正在进行的关于这些复杂脑转移患者治疗选择的对话做出贡献。。

Kazia's CEO, Dr. John Friend, shared his enthusiasm: 'We are extremely excited about these findings, which include not only encouraging safety data but also some promising efficacy signals for paxalisib in combination with radiation therapy. We are now preparing to engage with the Food and Drug Administration to discuss the data and seek guidance on the conduct of a pivotal registration study, with the goal of rapidly progressing paxalisib's development to potentially provide a more effective treatment option for patients with brain metastases.'.

卡齐亚的首席执行官约翰·弗里德博士分享了他的热情：“我们对这些发现感到非常兴奋，这些发现不仅包括令人鼓舞的安全性数据，还包括帕沙利西联合放射治疗的一些有希望的疗效信号。我们现在正准备与美国食品和药物管理局（Food and Drug Administration）合作，讨论数据并寻求关键注册研究的指导，目标是迅速推进帕唑西布的发展，为脑转移患者提供更有效的治疗选择。”。

Previous research by Dr. Jonathan Yang, Director of Metastatic Disease and Developmental Therapeutics, Department of Radiation Oncology, University of Washington School of Medicine, and others, has shown that activation of the PI3K pathway is common in brain metastases. Moreover, PI3K pathway activation appears to result in tumor resistance to radiotherapy, which supports the rationale for evaluating paxalisib with radiotherapy in order to potentially sensitize the tumor cells to radiotherapy and achieve better disease control.

华盛顿大学医学院放射肿瘤学系转移性疾病和发育治疗学主任乔纳森·杨博士和其他人之前的研究表明，PI3K通路的激活在脑转移瘤中很常见。此外，PI3K途径激活似乎导致肿瘤对放疗的抵抗，这支持了用放疗评估帕沙利西的基本原理，以便潜在地使肿瘤细胞对放疗敏感并实现更好的疾病控制。

Dr. Yang presented the Part I data at the 2022 Annual Conference on CNS Clinical Trials and Brain Metastases, jointly organized by the Society for Neuro-Oncology and the American Society for Clinical Oncology, held in Toronto, Canada..

杨博士在2022年中枢神经系统临床试验和脑转移年度会议上介绍了第一部分的数据，该会议由神经肿瘤学会和美国临床肿瘤学会在加拿大多伦多联合举办。。

Last year, paxalisib was awarded Fast Track Designation (FTD) on the basis of the Part I clinical data by the United States Food and Drug Administration (FDA) for the treatment of solid tumor brain metastases harboring PI3K pathway mutations in combination with radiation therapy.

去年，paxalisib根据美国食品和药物管理局（FDA）的第一部分临床数据被授予快速通道指定（FTD），用于治疗携带PI3K途径突变的实体瘤脑转移瘤并结合放射治疗。

Approximately 200,000 cancer patients develop brain metastases in the United States each year. Radiotherapy is the mainstay of treatment for brain metastases, and generally consists of either stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) or some combination thereof. The efficacy in patients who receive WBRT differs according to the type of tumor and the number and volume of brain metastases, but several recent publications cite overall response rates of 20-45%.

美国每年约有200000名癌症患者发生脑转移。放射治疗是脑转移瘤的主要治疗方法，通常包括立体定向放射外科（SRS）或全脑放射治疗（WBRT）或其组合。接受WBRT的患者的疗效因肿瘤类型以及脑转移的数量和体积而异，但最近的一些出版物引用的总有效率为20-45%。

The increasing incidence of brain metastasis and the low response rates to existing treatments underscores the need for new treatment options..

脑转移发病率的增加和对现有治疗的低反应率强调了对新治疗选择的需求。。

About Kazia Therapeutics Limited

关于Kazia Therapeutics Limited

Kazia Therapeutics Limited (NASDAQ: KZIA) is an oncology-focused drug development company, based in Sydney, Australia.

Kazia Therapeutics Limited（纳斯达克股票代码：KZIA）是一家专注于肿瘤的药物开发公司，总部位于澳大利亚悉尼。

Our lead program is paxalisib, an investigational brain-penetrant inhibitor of the PI3K / Akt / mTOR pathway, which is being developed to treat multiple forms of brain cancer. Licensed from Genentech in late 2016, paxalisib is or has been the subject of ten clinical trials in this disease. A completed Phase 2 study in glioblastoma reported early signals of clinical activity in 2021, and a pivotal study in glioblastoma, GBM AGILE, is ongoing, with final data expected in 1H2024.

我们的主要项目是paxalisib，一种PI3K/Akt/mTOR通路的研究性脑渗透抑制剂，正在开发用于治疗多种形式的脑癌。paxalisib于2016年末从Genentech获得许可，目前或已经成为该疾病十项临床试验的主题。一项已完成的胶质母细胞瘤2期研究报告了2021年临床活动的早期信号，胶质母细胞瘤的关键研究GBM AGILE正在进行中，最终数据预计将在2024年1月发布。

Other clinical trials are ongoing in brain metastases, diffuse midline gliomas, and primary CNS lymphoma, with several of these having reported encouraging interim data..

脑转移瘤，弥漫性中线神经胶质瘤和原发性中枢神经系统淋巴瘤的其他临床试验正在进行中，其中一些报告了令人鼓舞的中期数据。。

Paxalisib was granted Orphan Drug Designation for glioblastoma by the FDA in February 2018, and FTD for glioblastoma by the FDA in August 2020. Paxalisib was also granted FTD in July 2023 for the treatment of solid tumour brain metastases harboring PI3K pathway mutations in combination with radiation therapy.

帕沙利西于2018年2月被FDA授予胶质母细胞瘤孤儿药称号，2020年8月被FDA授予胶质母细胞瘤FTD。帕沙利西还于2023年7月获得FTD，用于治疗携带PI3K途径突变的实体瘤脑转移瘤并结合放射治疗。

In addition, paxalisib was granted Rare Pediatric Disease Designation and Orphan Drug Designation by the FDA for diffuse intrinsic pontine glioma in August 2020, and for atypical teratoid / rhabdoid tumours in June 2022 and July 2022, respectively..

此外，paxalisib于2020年8月被FDA授予弥漫性内在桥脑胶质瘤罕见儿科疾病和孤儿药物称号，并分别于2022年6月和2022年7月被授予非典型畸胎样/横纹肌样肿瘤。。

Kazia is also developing EVT801, a small-molecule inhibitor of VEGFR3, which was licensed from Evotec SE in April 2021. Preclinical data has shown EVT801 to be active against a broad range of tumour types and has provided evidence of synergy with immuno-oncology agents. A Phase I study is ongoing and preliminary data is anticipated in CY2024..

Kazia还在开发EVT801，一种VEGFR3的小分子抑制剂，于2021年4月从Evotec SE获得许可。临床前数据显示EVT801对多种肿瘤类型具有活性，并提供了与免疫肿瘤学药物协同作用的证据。一期研究正在进行中，初步数据预计将于2024年发布。。

For more information, please visit www.kaziatherapeutics.com or follow us on Twitter @KaziaTx.

有关更多信息，请访问www.kaziatherapeutics.com或在推特上关注我们@KaziaTx。

Forward-Looking Statements

前瞻性声明

This announcement may contain forward-looking statements, which can generally be identified as such by the use of words such as 'may,' 'will,' 'estimate,' 'future,' 'forward,' 'anticipate,' or other similar words. Any statement describing Kazia's future plans, strategies, intentions, expectations, objectives, goals or prospects, and other statements that are not historical facts, are also forward-looking statements, including, but not limited to, statements regarding: the timing for results and data related to Kazia's clinical and preclinical trials and investigator-initiated trials of Kazia's product candidates, and Kazia's strategy and plans with respect to its programs, including paxalisib and EVT801.

本公告可能包含前瞻性陈述，通常可以通过使用“可能”、“将”、“估计”、“未来”、“展望”、“预期”或其他类似词语来识别。任何描述卡齐亚未来计划、战略、意图、期望、目标、目标或前景的声明，以及其他非历史事实的声明，都是前瞻性声明，包括但不限于，声明涉及：与卡齐亚的临床和临床前试验以及卡齐亚候选产品的研究者启动试验相关的结果和数据的时间安排，以及卡齐亚关于其计划的策略和计划，包括帕沙利西和EVT801。

Such statements are based on Kazia's current expectations and projections about future events and future trends affecting its business and are subject to certain risks and uncertainties that could cause actual results to differ materially from those anticipated in the forward-looking statements, including risks and uncertainties: associated with clinical and preclinical trials and product development, related to regulatory approvals, and related to the impact of global economic conditions.

此类报表基于卡齐亚对影响其业务的未来事件和未来趋势的当前预期和预测，并受到某些风险和不确定性的影响，这些风险和不确定性可能导致实际结果与前瞻性报表中的预期结果产生重大差异，包括风险和不确定性：与临床和临床前试验和产品开发有关，与监管批准有关，与全球经济状况的影响有关。

These and other risks and uncertainties are described more fully in Kazia's Annual Report, filed on form 20-F with the United States Securities and Exchange Commission (SEC), and in subsequent filings with the SEC. Kazia undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required under applicable law.

这些以及其他风险和不确定性在卡齐亚以表格20-F提交给美国证券交易委员会（SEC）的年度报告以及随后提交给SEC的文件中有更全面的描述。卡齐亚没有义务公开更新任何前瞻性声明，无论是由于新信息、未来事件或其他原因，除非适用法律要求。

You should not place undue reliance on these forward-looking statements, which apply only as of the date of this announcement..

您不应过度依赖这些前瞻性声明，这些声明仅在本公告之日适用。。

This announcement was authorized for release by Dr John Friend, CEO.

该公告由首席执行官约翰·弗里德博士授权发布。

SOURCE Kazia Therapeutics Limited

SOURCE Kazia Therapeutics Limited公司