Tuspetinib

关注并星标CPHI制药在线FLT3是急性髓系白血病（AML）中经常出现的突变基因。当AML患者的FLT3基因发生突变时，他们的疾病预后往往较差，且更容易复发。因此，及时识别FLT3基因的突变情况，并选择恰当的治疗策略，对AML患者的治疗效果具有重要意义。       Fms样酪氨酸激酶3（FLT3）在细胞信号传递路径中起着关键作用，作为一种受体酪氨酸激酶。实际上，AML中出现的最常见的基因突变，其中一个就是在FLT3。这一基因的突变在成人AML患者中约占了30%的比例。其突变形式主要有两种，即FLT3的内部串联重复序列（FLT3-ITD）和酪氨酸激酶结构域（FLT3-TKD）突变。在这些突变中，FLT3-ITD是最常见的，其在AML中的检出率达到了25% [1]。       FLT3突变急性髓系白血病（AML）患者的临床特点通常为年纪偏大、白细胞与血小板计数偏高，以及骨髓原始细胞比例偏高。尽管这些患者的缓解率较低，且治疗后容易复发，但常规化疗的复发率也相对较高，且往往伴随着其他基因突变。特别值得关注的是，一些最常见的共存基因突变包括NPM1、DNMT3A、WT1、TET2、RAS、RUNX1以及PTPN11。对于FLT3-TKD突变，其预后仍然存在争议；相比之下，FLT3-ITD突变具有较强的异质性，预后受其等位基因比率（AR）、插入位点、ITD长度、核型以及其他伴随基因突变如NPM1、DNMT3A、WT1、RUNX1的影响而有所不同。值得关注的是，与NPM1突变同时出现的FLT3-ITD AML的预后相对较好，然而，当与IDH1/2、TET2、DNMT3A、WT1突变同时出现，或者同时合并NPM1和DNMT3A突变时，FLT3-ITD AML的预后则较差。随着对FLT3突变AML发病机制的深入了解、新的检测技术的出现以及FLT3抑制剂的广泛应用，其预后已得到显著改善。因此，根据欧洲白血病网（ELN 2022）的最新指南，所有FLT3-ITD AML现已被归类为中危。       FLT3抑制剂属于酪氨酸激酶抑制剂，通过竞争激酶活性区域的ATP结合位点抑制FLT3蛋白发生磷酸化，进而抑制相关下游生长信号通路（PI3K/Akt、Ras/MAPK和STAT5等）发挥治疗作用。根据FLT3抑制剂与FLT3结合的程度，可将FLT3抑制剂分为第一代和第二代抑制剂和新型FLT3抑制剂。       一代FLT3抑制剂       索拉非尼       索拉非尼是一种能够同时抑制RAF、VEGFR、KIT和FLT3等多个靶点的小分子药物。南方医科大学血液病研究院的刘启发教授领导的研究团队进行了一项临床研究[7]，他们评估了将索拉非尼与维奈克拉、阿扎胞苷和高三尖杉酯碱（简称VAH方案）联合使用，在患有FLT3-ITD阳性的复发/难治性急性髓系白血病（AML）患者中的治疗效果和患者的耐受程度。研究数据表明，患者接受这一治疗方案后的总缓解率高达82.4%。中位随访期为17.7个月，研究尚未观察到中位复合完全缓解（CRc）的持续时间。这些患者的总生存期（OS）平均为18.1个月，无事件生存期（EFS）平均为11.4个月。在接受治疗的患者中，出现3-4级不良事件（AE）的情况包括中性粒细胞减少症、血小板减少导致的贫血、发热性 中性粒细胞减少症、肺炎和脓毒症等。其中，有2名患者因治疗相关原因不幸去世。       米哚妥林欧洲药品管理局（EMA）和美国食品药品监督管理局（FDA）共同批准了米哚妥林与标准化疗相结合，作为针对FLT3突变成年急性髓系白血病（AML）患者的首选治疗策略。除此之外，对于经历过异基因造血干细胞移植（allo-HSCT）的患者，米哚妥林在维持治疗方面也表现出显著效果，它不仅能够优化患者的预后，而且其安全性也得到了充分验证[8]。这些进展为患有急性髓系白血病（AML）的患者提供了新的治疗选择和更好的康复机会。       二代FLT3抑制剂       吉瑞替尼（Gilteritinib）       2018年11月28日，美国食品药品监督管理局（FDA）正式批准吉瑞替尼作为治疗FLT3突变型复发或难治性急性髓系白血病（AML）成人患者的药物。随后，在2021年，吉瑞替尼获得中国批准并上市，用以治疗患有复发或难治性FLT3突变型AML的患者[9]。       由中国医学科学院血液病医院王健祥教授率领的团队，联合多个国家包括中国、俄罗斯、新加坡、泰国和马来西亚等，开展了一项名为COMMODORE的III期开放、多中心临床试验，对比了吉瑞替尼与挽救性化疗（SC）在治疗FLT3突变复发难治AML患者上的疗效[10]。研究显示，吉瑞替尼组（包含116名患者）的完全缓解（CR）率达到了16.4%，这一数据超过了挽救性化疗（SC）组（包含118名患者，CR率为10.2%）。此外，吉瑞替尼组患者的1年中位总生存期（mOS）也显著长于挽救性化疗（SC）组，分别为9个月和4.7个月（P=0.001 26）。这一研究成果再次确立了吉瑞替尼在针对FLT3突变复发难治AML治疗上的显著优势。       奎扎替尼（Quizartinib）       2023年7月20日，美国食品药品监督管理局（FDA）正式批准了奎扎替尼联合标准阿糖胞苷、蒽环类药物的诱导治疗与阿糖胞苷巩固治疗，以及在巩固化疗后单独使用奎扎替尼作为维持治疗，这一治疗方案针对的是新诊断的FLT3-ITD阳性急性髓系白血病（AML）成年患者。这项医疗进展意味着对白血病治疗的一个重要突破，可以为这些患者提供更好的治疗效果和生存率。       QuANTUM-First（NCT02668653）试验是一项双盲随机、安慰剂对照的研究，共纳入了539名新诊断的FLT3-ITD阳性急性髓系白血病患者。通过对奎扎替尼组与安慰剂组之间的对比分析，结果显示，奎扎替尼组在总生存期（OS）上具有显著的统计学意义改善[风险比（HR）0.78，95%置信区间（CI）0.62-0.98，两组比较p=0.0324]。这一数据进一步证明了奎扎替尼在治疗FLT3-ITD阳性急性髓系白血病患者中的疗效和安全性，为这一病症的治疗提供了新的选择。       Crenolanib       Richard M. Stone教授的研究团队，隶属于美国丹娜法伯癌症研究所，进行了一项关键性的II期研究[7]，旨在评估在新发现的FLT3突变急性髓系白血病（AML）病患中结合使用Crenolanib的治疗成效。       该研究涉及了44名患者（男性占22名），他们的中位数年龄是57岁（年龄范围：19-75岁）。结果显示，总体复合完全缓解（CRc）率高达73%（32/44）。特别是在经过两个周期的治疗后，总CRc率跃升至86%（38/44）。年轻患者的总体缓解率表现尤为突出，达到了90%，且其MRD阴性率高达89%。相较之下，尽管年长患者的总体缓解率为80%，但他们的MRD阴性率相对较低，为45%。此外，值得注意的是，超过70%的年轻患者在接受治疗后的三年时间里仍然存活。       这项研究的结果为FLT3突变急性髓系白血病的治疗提供了新的方向，尤其是对于那些年轻的患者，Crenolanib联合治疗方案展现出了显著的效果。       新型FLT3抑制剂       Tuspetinib       Tuspetinib，这是一种新兴的可口服FLT3抑制剂，凭借其强大的能力，被公认为一种高效的髓系激酶抑制药物。它的作用机制在于能够抑制导致AML细胞增殖异常的多种激酶，这当中就包括了SYK、FLT3、JAK1/2、RSK1/2、突变型KIT和TAK1-TAB1激酶等。       一项涉及I/II期的研究[13]对Tuspetinib单独使用（TUS）和与维奈克拉联合使用（VEN/TUS）治疗复发性或难治性AML（R/R AML）的安全性和疗效进行了评估，并确定了II期推荐剂量（RP2D）。该研究的结果表明，Tuspetinib单药治疗的安全性较高，总体完全缓解/完全缓解伴部分血液学恢复（CR/CRh）的比率为36%。对于FLT3突变型AML患者，这一比率高达50%，而对于FLT3野生型AML患者，这一比率则为25%。这些结果为Tuspetinib在AML治疗中的潜在应用提供了重要的临床依据。       EmavusertibEmavusertib作为一种创新型的FLT3抑制剂，其独特之处在于可以口服使用，为治疗提供了便利。它能够精确地针对IRAK4和FLT3进行作用，表现出令人满意且可管理的安全性。目前，TakeAim Leukemia试验正在深入研究Emavusertib在治疗复发/难治性急性髓性白血病（R/R AML）和高危骨髓增生异常综合征（HR-MDS）方面的安全性、临床疗效以及潜在的生物标志物，为未来的治疗策略提供更为坚实的科学依据。       EP0042       EP0042是一款口服型的药物，它能够有效抑制FLT3和Aurora激酶。研究表明，Aurora激酶在急性髓系白血病（AML）的发病过程中扮演着关键角色，并与FLT3抑制剂耐药性的产生密切相关。因此，EP0042通过同时针对FLT3和Aurora激酶，有望克服对选择性FLT3抑制所产生的获得性耐药性。为了探索EP0042的最 佳给药方案，一项I/IIa期研究采用了标准的3+3剂量递增设计，并纳入了复发/难治性AML或骨髓增生异常综合征（MDS）的患者进行临床试验[15]。       总结       FLT3抑制剂的研发成功，为那些罹患FLT3突变急性髓性白血病（AML）的患者提供了全新治疗策略。在临床应用中，目前已有一线和二线的FLT3抑制剂可供选用。不仅如此，新型的FLT3抑制剂，如Tuspetinib、Emavusertib和EP0042，也正在接受临床试验的检验，其初步成果显示出了良好的治疗潜力。随着对FLT3突变机制的深入研究以及药物研发的持续进步，我们有理由期待更多高效、精准的靶向治疗药物的出现。这些药物的问世，将为AML患者带来更加显著的治疗效果，帮助他们更好地战胜疾病。       参考文献：       [1] 邱林，马军. 急性髓系白血病靶向治疗研究进展[J]. 白血病·淋巴瘤， 2022,31(4):197-203. DOI：10.3760/cma.j.cn115356-20220210-00033 .       [2] Yu S, Zhang Y, Yu G, Wang Y, Shao R, Du X, et al. Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/ relapsed acute myeloid leukemia with FLT3ITD: A multicenter phase 2 study. J Intern Med.2023;00:1-13.       [3] 袁伟，张世忠，主鸿鹄. FLT3抑制剂治疗急性髓系白血病患者研究进展[J].浙江大学学报:医学版, 2022, 51(4):507-514.       [4]https://www.fda.gov/drugs/fda-approves-gilteritinib-relapsed-or-refractory-acute-myeloid-leukemia-aml-flt3-mutation       [5] Wang JX ， Jiang B ， Li J ，et al. Gilteritinib versus salvage chemotherapy for relapsed/refractory FLT3-mutated acute myeloid leukemia：a phase 3，randomized，multicenter，open-label trial in Asia[J]. Blood， 2021，138Suppl 1：695. doi: 10.1182/blood-2021-145436 .[6] https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-quizartinib-newly-diagnosed-acute-myeloid-leukemia[7] Eunice S. Wang, et al. 2022ASCO.Abstract#7007.[8] Naval Daver, et al. Tuspetinib Myeloid Kinase Inhibitor Safety and Efficacy As Monotherapy and Combined with Venetoclax in Phase 1/2 Trial of Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML). 2023 ASH. Abstract #162.[9] Eric S Winer, et al. Preliminary Safety and Efficacy of Emavusertib (CA-4948) in Acute Myeloid Leukemia Patients with FLT3 Mutation. 2023 ASH. Abstract #2924.[10] David Taussig, et al. EP0042, a Dual FLT3 and Aurora Kinase Inhibitor: Results from an Ongoing Phase I/IIa Dose-Finding/Dose Optimization Study in Patients with Relapsed/Refractory Acute Myeloid Leukemia. 2023 ASH. Abstract #4285.       [6] Zhao J , Agarwal S , Ahmad H ,et al.A review of FLT3 inhibitors in acute myeloid leukemia[J].Blood reviews, 2021:100905.       [7] 张钰, 邵若洋, 刘启发. FLT3突变急性髓系白血病的全程管理[J].临床血液学杂志,2023,36(5):303-308       [8] DöhnerH, WeiAH, Appelbaum FR, et al. Diagnosis ·and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN [J].Blood,2022,140(12):1345-1377.       [9] WANG Z, CAI J, CHENG J, et al. FLT3 inhibitors in acute myeloid leukemia: challenges and recent developments in overcoming resistance[J]. J Med Chem, 2021, 64(6): 2878-2900.       [10] 袁伟，张世忠，主鸿鹄. FLT3抑制剂治疗急性髓系白血病患者研究进展[J].浙江大学学报:医学版, 2022, 51(4):507-514.       [11] TALLMAN M S, WANG E S, ALTMAN J K, et al. Acute myeloid leukemia, version 3.2019, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2019, 17(6): 721-749.       [12] LEVIS M. Midostaurin approved for FLT3-mutated AML[J]. Blood, 2017, 129(26): 3403-3406.       [13] SERVE H, KRUG U, WAGNER R, et al. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial[J]. J Clin Oncol, 2013, 31(25): 3110-3118.       [14] YILMAZ M, KANTARJIAN H M, MUFTUOGLU M, et al. Quizartinib with decitabine +/- venetoclax is highly active in patients (pts) with FLT3-ITD mutated (mut) acute myeloid leukemia (AML): clinical report and signaling cytof profiling from a phase Ⅰb/Ⅱ trial[J]. Blood, 2020, 136(Supplement 1): 19-20.       [15] PERL A E, MARTINELLI G, CORTES J E, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML[J]. N Engl J Med, 2019, 381(18): 1728-1740.       [16] WANG R, LI Y, GONG P, et al. Arsenic/trioxide and sorafenib induce synthetic lethality of FLT3-ITD acute myeloid leukemia cells[J]. Mol Cancer Ther, 2018,17(9): 1871-1880.       [17] YILMAZ M, KANTARJIAN H, SHORT N J, et al. Hypomethylating agent and venetoclax with FLT3 inhibitor "triplet" therapy in older/unfit patients with FLT3 mutated AML[J]. Blood Cancer J, 2022, 12(5): 77.【智药研习社近期课程预告】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~

Tuspetinib to Advance to TUS+VEN+HMA Triplet Therapy Pilot Study in 1L AML Tuspetinib Continues Broad Activity Across Mutations with Excellent Safety Pro > Luxeptinib G3 Formulation Achieves Desired Levels and Positions for Future Trials ConferenceCallandWebcastat5:00pmETToday SAN DIEGO and TORONTO, March 26, 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 financial results for the three months and year ended December 31, 2023, and provided a corporate update. “The data we have generated from tuspetinib thus far – as a single agent and in combination therapy with venetoclax in relapsed and refractory AML – have demonstrated a distinctly favorable safety pro broad activity for tuspetinib across mutational subtypes. This pro extends to FLT3 wildtype AML, which represents the majority of AML patients, and in which few agents have shown such broad activity,” said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. “These data have propelled us to initiate a clinical study of tuspetinib in a triplet combination with venetoclax and azacitidine in frontline therapy for newly diagnosed AML, including both FLT3 wild type and FLT3 mutated subtypes.” KeyCorporateHighlights Aptose Completes Public Offering – On January 30, 2024, Aptose closed a public offering of 5,649,122 common shares of the Company and warrants at a combined offering price of US $1.71 per share. This included 736,842 Common Shares and warrants pursuant to a full exercise by the underwriter of its over-allotment option. Total gross proceeds from the public offering were approximately $9.7 million before deducting underwriting costs, placement agent commissions and other offering-related expenses. Private Placement– On January 31, 2024, Aptose closed a US $4 million private placement of common shares with strategic partner Hanmi Pharmaceutical. Under the terms of the strategic investment, Hanmi purchased each common share at a price of US $1.90, representing an 11% premium over the price of the common shares issued as part of the public offering. The Company also issued Hanmi warrants to purchase common shares at an exercise price of US $1.71 per warrant share. Total gross proceeds from the private placement were approximately $4 million, excluding underwriting discounts, placement agent commissions and other offering-related expenses. Tuspetinib Advancing to Triplet Therapy Pilot Study – Tuspetinib (TUS), a once daily oral agent with a unique kinase targeting pattern, is being developed for the treatment of patients with acute myeloid leukemia (AML). More than 170 patients to date received TUS alone or in combination with the BCL-2 inhibitor venetoclax (VEN) during the Phase 1/2 clinical program in the very ill relapsed or refractory (R/R) AML patient population. At the single agent 80 mg recommended Phase 2 dose, TUS achieved a favorable safety pro a CR/CRh rate of 36% among patients who were naive to VEN. The safety pro TUS remained favorable when TUS was combined with VEN in R/R AML patients, and responses were achieved in both patients naive to VEN and those who failed prior therapy with VEN. TUS avoids many typical toxicities observed with other agents and achieves broad activity across AML patients with a diversity of adverse genetics. Tuspetinib is now being advanced to a triplet combination therapy of tuspetinib, venetoclax and a hypomethylating agent (TUS/VEN/HMA) for the frontline treatment of newly diagnosed AML patients ineligible for induction chemotherapy. Luxeptinib G3 Evaluation Completed – During 2023 and early 2024, clinical evaluation of the new generation 3 (G3) formulation of luxeptinib (LUX) was completed. The G3 formulation was tested in a single dose bioavailability study in 20 patients, including both B-cell cancer and AML patients, and across 5 dose levels (10mg to 200mg). The G3 formulation then was evaluated in R/R AML patients with continuous dosing using two different dose levels (50mg BID and 200mg BID) in a total of 11 patients. Data show the G3 formulation dosed at 200mg twice daily can achieve 2-3uM steady state plasma levels, with approximately 10-fold better absorption, and interestingly even better tolerability, than the original G1 formulation. Thus, the G3 formulation achieved the desired plasma exposure benchmark and can serve as the formulation of choice for future studies with LUX. Aptose is exploring alternative development paths and collaborations to advance LUX as a single agent or in combination with VEN to treat defined R/R patient populations of high unmet need. Multiple Planned Value-creating Milestones Ahead TUS/VEN doublet synopsis in R/R AML: EHA 2024 TUS/VEN/HMA planned initiation of pilot triplet study in 1L AML: Summer 2024 Triplet pilot dose escalation planned with early CR/MRD/safety data in 1L AML: ASH 2024 Triplet pilot completed with CR/MRD data and dose selection: EHA 2025 Triplet initiation of Ph2/Ph3 pivotal program: 2H 2025 FINANCIAL RESULTS OF OPERATIONS Balance Sheet Data (unaudited) ($ in thousands) December 31, December 31, 2023 2022 Cash, cash equivalents and short-term investments $ 9,252 $ 46,959 Working capital (3,375 ) 37,235 Total assets 12,989 51,027 Non-current liabilities 621 1,002 Deficit (515,537 ) (464,330 ) Total shareholders’ equity (2,901 ) 37,741 Cash and cash equivalents, January 31, 2024 (unaudited) was $18.6 million, after gross proceeds from January 2024 financings (unaudited) of $13.7 million. Total cash and cash equivalents and investments as of December 31, 2023, were $9.3 million, a decrease of $37.7 million as compared to $47.0 million at December 31, 2022. Based on current operations, the Company expects that cash on hand and available capital provide the Company with sufficient resources to fund planned Company operations including research and development through August of 2024. Working capital is a non-GAAP measure and represents cash, cash equivalents, investments, prepaid expenses and other current assets less current liabilities. Common shares issued and outstanding as at March 26, 2024 were 15,717,701. Statements of Operations Data (unaudited) Year ended December 31, (in thousands except per Common Share data) 2023 2022 Revenues $ - $ - R&D, related party 3,492 3,556 Research and development expenses 33,273 24,532 General and administrative expenses 15,591 14,514 Net finance income 1,149 779 Net loss $ (51,207 ) $ (41,823 ) Basic and diluted loss per Common Share $ (7.58 ) $ (6.80 ) Weighted average number of common shares outstanding used in the calculation of basic loss per share 6,755 6,151 Net loss for the year ended December 31, 2023 increased by $9.4 million to $51.2 million, as compared to $41.8 million for the comparable period in 2022. Research and Development Expenses The research and development expenses for years ended December 31, 2023, and 2022 are as follows: Twelve months ended December 31, (in thousands) 2023 2022 Program costs – Tuspetinib $ 24,925 $ 10,083 Program costs – Luxeptinib 3,510 8,426 Program costs – APTO-253 40 141 Personnel related expenses 6,878 7,181 Stock-based compensation 1,373 2,218 Depreciation of equipment 39 39 Total $ 36,765 $ 28,088 R&D expenses increased by $8.7 million to $36.8 million for the year ended December 31, 2023, as compared with $28.1 million for the comparative period in 2022. Changes to the components of our R&D expenses presented in the table above are primarily related to the following activities: Program costs for tuspetinib increased by $14.8 million. The higher program costs for tuspetinib in 2023 represent the enrollment of patients in our APTIVATE clinical trial, our healthy volunteer trial, manufacturing activities to support clinical development, purchase of clinical trial materials, and related expenses. Program costs for luxeptinib decreased by approximately $4.9 million, primarily due to lower clinical trial costs and lower manufacturing costs as a result of the current formulation requiring less API than the prior formulation. Program costs for APTO-253 decreased by approximately $101 thousand due to the Company's decision on December 20, 2021, to discontinue further development of APTO-253. Personnel-related expenses decreased by $0.3 million due to lower headcount in 2023. Stock-based compensation decreased by approximately $845 thousand in the year ended December 31, 2023, compared with the year ended December 31, 2022, primarily due to stock options granted with lower grant date fair values in the current period. General and Administrative Expenses General and administrative expenses consist primarily of salaries, benefits, and travel, including stock-based compensation for our executive, finance, business development, human resources, and support functions. Other general and administrative expenses and professional fees include auditing, and legal services, investor relations and other consultants, insurance. and facility related expenses. We expect that our general and administrative expenses will increase for the foreseeable future as we incur additional costs associated with being a publicly traded company and to support our pipeline of activities. We also expect our intellectual property related legal expenses to increase as our intellectual property portfolio expands. The general and administrative expenses for the years ended December 31, 2023 and 2022 are as follows: Year ended December 31, (in thousands) 2023 2022 General and administrative, excluding items below: $ 13,262 $ 11,444 Stock-based compensation 2,280 2,989 Depreciation of equipment 49 81 Total $ 15,591 $ 14,514 General and administrative expenses increased by approximately $1.1 million $15.6 million for the year ended December 31, 2023, as compared with $14.5 million for the comparative period in 2022. The increase was primarily as a result of higher salaries expenses, higher professional fees, and higher travel expenses, partly offset by a decrease in stock-based compensation costs. Stock-based compensation decreased by $709 thousand mostly as a result of options having a lower grant date fair value as compared with the options granted in the comparative period. Conference Call & Webcast: Date: Tuesday, March 26, 2024 Time: 5:00 PM ET Audio Webcast Only: link Q&A Participant Registration Link*: link ( ) *Analysts interested in participating in the question-and-answer session will pre-register for the event from the participant registration link above to receive the dial-in numbers and a unique PIN, which are required to access the conference call. They also will have the option to take advantage of a Call Me button and the system will automatically dial out to connect to the Q&A session. The audio webcast also can be accessed through a link on the Investor Relations section of Aptose’s website here. A replay of the webcast will be available on the company’s website for 30 days. The press release, the financial statements and the management’s discussion and analysis for the year ended December 31, 2023 will be available on SEDAR at and EDGAR at . AboutAptose Aptose 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 (HM43239), an oral, myeloid kinase inhibitor being studied as monotherapy and in combination therapy in the APTIVATE international Phase 1/2 expansion trial in patients with relapsed or refractory acute myeloid leukemia (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 . ForwardLookingStatements This press release contains forward-looking statements within the meaning of Canadian and U.S. securities laws, including, but not limited to, statements regarding the Company’s clinical development plans, the clinical potential, anti-cancer activity, therapeutic potential and applications and safety pro tuspetinib and luxeptinib, clinical trials, alternative development paths and collaborations to advance luxeptinib, upcoming milestones, expected increase of expenses and statements relating to the Company’s plans, objectives, expectations and intentions and other statements including words such as “continue”, “expect”, “intend”, “will”, “hope” “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; 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 and economic 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 current reports, 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: AptoseBiosciencesInc. LifeSciAdvisors,LLC Susan Pietropaolo Dan Ferry, Managing Director Corporate Communications & Investor Relations 617-430-7576 201-923-2049 Daniel@LifeSciAdvisors.com spietropaolo@aptose.com