Venetoclax

TUSCANY study is open to enroll patients to receive TUS+VEN+AZA triplet at select US sitesFavorable safety and broad clinical activity make tuspetinib an ideal agent to combine with venetoclax and azacitidine to potentially address larger AML populationsStudy execution update is expected during ASH 2024 SAN DIEGO and TORONTO, Nov. 20, 2024 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral targeted agents to treat hematologic malignancies, today announced initiation of the TUSCANY study, tuspetinib (TUS) in combination therapy with azacitidine (AZA) and venetoclax (VEN) as a frontline triplet combination therapy for patients newly diagnosed with acute myeloid leukemia, or AML. The trial is being conducted at multiple U.S. clinical sites. Tuspetinib is being developed for frontline AML therapy as part of the TUS+VEN+AZA triplet for newly diagnosed AML patients ineligible to receive intensive chemotherapy. Tuspetinib, a convenient once daily oral agent that potently targets SYK, FLT3, mutated KIT, JAK1/2, and RSK2 kinases, avoids many typical toxicity concerns observed with other agents and has the potential to treat the larger AML populations, not just narrow subpopulations. In the recently conducted Phase 1/2 APTIVATE trial in a very ill and heavily pre-treated relapsed or refractory (R/R) AML population, tuspetinib as a single agent (TUS) and in combination with venetoclax (TUS+VEN) safely achieved broad activity across various difficult-to-treat AML subpopulations. This included patients with prior-VEN, prior-FLT3 inhibitor (FLT3i) and prior-hematopoietic stem cell transplantation (HSCT) therapies, those with highly adverse genetics - including mutations in TP53 and RAS genes, and those with mutated or unmutated (wildtype) FLT3 genes. “Initiation of the trial is a key milestone for Aptose. AML treatment has rapidly shifted to combination therapies, and we are pleased to include tuspetinib as part of TUS+VEN+AZA triplet combination therapy in patients with newly-diagnosed AML – representing a new patient population for TUS,” said William G. Rice, Chairman, President and Chief Executive Officer. “We thank our investigators for their enthusiasm and our clinical team for activating the TUSCANY triplet study. As one of our investigators noted, if TUS brings added efficacy to frontline treatment of a broad array of AML patients without the added toxicities that are plaguing some other agents, we may have a game changer in TUS.” TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 StudyThe triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard of care dosing of azacitidine and venetoclax. TUS will be administered in 28-day cycles, beginning with 40mg, with dose escalations planned after safety review of each dose level. A planned 12 sites in the US will enroll in the TUSCANY trial with anticipated enrollment of 18-24 patients by mid-late 2025. More information on the TUSCANY Phase 1/2 study can be found on www.clinicaltrials.gov (here). About AptoseAptose Biosciences is a clinical-stage biotechnology company committed to developing precision medicines addressing unmet medical needs in oncology, with an initial focus on hematology. The Company's small molecule cancer therapeutics pipeline includes products designed to provide single agent efficacy and to enhance the efficacy of other anti-cancer therapies and regimens without overlapping toxicities. The Company has two clinical-stage oral kinase inhibitors under development for hematologic malignancies: tuspetinib (TUS), an oral, kinase inhibitor that has demonstrated activity as a monotherapy and in combination therapy in patients with relapsed or refractory acute myeloid leukemia (AML) and is being developed as a frontline triplet therapy in newly diagnosed AML; and luxeptinib (CG-806), an oral, dual lymphoid and myeloid kinase inhibitor in Phase 1 a/b stage development for the treatment of patients with relapsed or refractory hematologic malignancies. For more information, please visit www.aptose.com. Forward Looking StatementsThis press release may contain forward-looking statements within the meaning of Canadian and U.S. securities laws, including, but not limited to, statements relating to the therapeutic potential and safety profile of tuspetinib and its clinical development, expected study updates and milestones as well as statements relating to the Company’s plans, objectives, expectations and intentions and other statements including words such as “continue”, “expect”, “intend”, “will”, “should”, “would”, “may”, “potential”, and other similar expressions. Such statements reflect our current views with respect to future events and are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by us are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors could cause our actual results, performance or achievements to be materially different from any future results, performance or achievements described in this press release. Such factors could include, among others: our ability to obtain the capital required for research and operations and to continue as a going concern; the inherent risks in early stage drug development including demonstrating efficacy; development time/cost and the regulatory approval process; the progress of our clinical trials; our ability to find and enter into agreements with potential partners; our ability to attract and retain key personnel; changing market conditions; inability of new manufacturers to produce acceptable batches of GMP in sufficient quantities; unexpected manufacturing defects; and other risks detailed from time-to-time in our ongoing quarterly filings, annual information forms, annual reports and annual filings with Canadian securities regulators and the United States Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should the assumptions set out in the section entitled "Risk Factors" in our filings with Canadian securities regulators and the United States Securities and Exchange Commission underlying those forward-looking statements prove incorrect, actual results may vary materially from those described herein. These forward-looking statements are made as of the date of this press release and we do not intend, and do not assume any obligation, to update these forward-looking statements, except as required by law. We cannot assure you that such statements will prove to be accurate as actual results and future events could differ materially from those anticipated in such statements. Investors are cautioned that forward-looking statements are not guarantees of future performance and accordingly investors are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty therein. For further information, please contact: Aptose Biosciences Inc.Susan PietropaoloCorporate Communications & Investor Relations201-923-2049spietropaolo@aptose.com

关注并星标CPHI制药在线 前言 2024年11月16日，亚盛医药自主研发的新型选择性BCL-2抑制剂APG-2575的新药上市申请（NDA）已获得国家药品监督管理局（NMPA）药品审评中心（CDE）的受理，并拟纳入优先审评，用于治疗难治性/复发（r/r）慢性淋巴细胞白血病（CLL）/小淋巴细胞淋巴瘤（SLL）患者。这一消息标志着国产原研BCL-2抑制剂首次在国内提交上市申请，并有望成为全球第二个上市的BCL-2抑制剂。 BCL-2抑制剂安全性评估 APG-2575的临床数据为其上市申请提供了有力的支持。据悉，APG-2575的NDA是基于一项在中国开展的关键注册II期临床研究（APG2575CC201）结果。该研究旨在评估APG-2575单药治疗r/r CLL/SLL患者的有效性和安全性，主要终点指标为总缓解率（ORR）。研究结果显示，APG-2575在r/r CLL/SLL患者中表现出良好的疗效和安全性。具体而言，APG-2575的ORR达到了较高的水平，且不良反应可控，为患者提供了有效的治疗选择。 此外，APG-2575还在不断开展多项注册III期临床试验，包括联合BTKi治疗经治CLL/SLL患者的全球注册III期临床试验、联合阿可替尼一线治疗初治CLL/SLL患者的全球注册III期临床试验等。这些临床试验将进一步验证APG-2575在不同适应症中的疗效和安全性，为全球血液肿瘤患者带去更多的治疗希望。值得一提的是，除了APG-2575外，其他在研的BCL-2抑制剂也在积极开展临床试验。例如，正大天晴的TQB3909在复发或难治性非霍奇金淋巴瘤（NHL）和急性髓系白血病（AML）的I期研究中表现出显著的疗效和安全性。这些临床数据为BCL-2抑制剂领域的发展提供了有力的支持，也为患者提供了更多的治疗选择。 BCL-2抑制剂优势 BCL-2是一种细胞凋亡抑制因子，它在许多恶性血液肿瘤特别是CLL/SLL中过度表达，是癌细胞逃避凋亡的重要机制之一。因此，靶向并抑制BCL-2蛋白一度成为癌症治疗的热门研究策略，BCL-2也成为了理想的药物作用靶点。然而，BCL-2靶点的药物开发难度极高，这主要是因为其作用机制涉及蛋白-蛋白相互作用（PPI），靶点结合界面较大，难以设计小分子去抑制并发挥阻断作用。此外，BCL-2靶点位于线粒体膜上，线粒体是双膜结构，属于细胞中结构最复杂、最难的部分之一，药物需要先通过细胞膜进入细胞后才能进一步作用于线粒体膜上，这无疑进一步加大了成药的难度。 自1985年BCL-2靶点被首次发现以来，经过数十年的不懈努力，终于在2016年迎来了全球首款BCL-2抑制剂——艾伯维的维奈克拉。维奈克拉的上市标志着BCL-2抑制剂在癌症治疗领域的突破，也为后续药物的研发提供了宝贵的经验和借鉴。然而，自维奈克拉上市以来，长达八年的时间里，全球范围内再无第二款BCL-2抑制剂问世，这进一步凸显了该领域药物研发的难度和挑战。 APG-2575是一种新型口服BCL-2选择性抑制剂，通过选择性抑制BCL-2蛋白，恢复肿瘤细胞的正常凋亡过程，从而达到治疗肿瘤的目的。与维奈克拉相比，APG-2575在选择性、药效和安全性等方面可能具有更突出的表现。首先，APG-2575对BCL-2的选择性更高，能够更精确地靶向并抑制BCL-2蛋白，减少对正常细胞的损伤。其次，APG-2575在临床试验中表现出良好的药效和安全性，为患者提供了更多的治疗选择。此外，APG-2575还在不断开展多项注册III期临床试验，探索其在不同适应症中的疗效和安全性，为全球血液肿瘤患者带去新的治疗希望。 BCL-2抑制剂市场预估 随着全球癌症发病率的不断上升，患者对新型、有效、安全的抗癌药物的需求日益迫切。BCL-2作为重要的细胞凋亡抑制因子，在癌症治疗中具有重要的地位和作用。因此，BCL-2抑制剂的研发和上市将为患者提供更多的治疗选择，同时也将带来巨大的市场价值。 以维奈克拉为例，自2016年上市以来，其全球销售额持续攀升。2023年，维奈克拉的全球销售额达到了22.88亿美元，同比增长13.9%。据市场分析，维奈克拉的峰值销售有望在2026年达到60亿美元。这一数据充分说明了BCL-2抑制剂在市场上的巨大潜力和价值。 APG-2575作为国产首个提交上市申请的BCL-2抑制剂，其市场前景同样值得期待。首先，APG-2575在疗效和安全性方面表现出色，为患者提供了有效的治疗选择。其次，APG-2575在不断开展多项注册III期临床试验，探索其在不同适应症中的疗效和安全性，这将为其未来的市场拓展提供有力的支持。此外，随着国内医药市场的不断发展和政策的支持，国产原研药物的市场竞争力日益增强，APG-2575有望成为国内BCL-2抑制剂市场的领军者。 除了APG-2575外，其他在研的BCL-2抑制剂也具有巨大的市场潜力。随着临床试验的不断推进和数据的积累，这些药物有望在未来几年内陆续上市，为患者提供更多的治疗选择，同时也将推动BCL-2抑制剂市场的快速发展。 结语与展望 国产首个BCL-2抑制剂APG-2575的上市申请受理标志着中国在BCL-2抑制剂领域的重大突破。未来，随着APG-2575等国产BCL-2抑制剂的不断上市和临床应用的拓展，中国将在全球BCL-2抑制剂市场中占据更加重要的地位。同时，我们也期待更多的国产原研药物能够不断涌现，为全球患者带来更多的健康和希望。 参考文献： 1.NMPA官网 2.亚盛医药官网 END 【智药研习社线上研习会报名】 来源：CPHI制药在线 声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。 投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~