Tuspetinib

Highlights Progress in TUSCANY Clinical Trial of Tuspetinib in AML Triple Frontline TherapySAN DIEGO and TORONTO, May 08, 2025 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (TSX: APS and OTC: APTOF), a clinical-stage precision oncology company developing a tuspetinib (TUS)-based triple drug frontline therapy to treat patients with newly diagnosed acute myeloid leukemia (AML), today announced financial results for the first quarter ended March 31, 2025, and provided a corporate update. “Our TUSCANY clinical trial of tuspetinib in combination with venetoclax (VEN) and azacitidine (AZA) for frontline treatment of newly diagnosed acute myeloid leukemia (AML) continues to deliver robust safety and response data, with support and enthusiasm from our clinical investigators,” said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. “We recently escalated the TUS dose to 80 mg from the initial dose of 40 mg in the TUS+VEN+AZA triplet therapy. Three patients receiving the initial dose of 40 mg and three patients receiving the 80 mg dose all have achieved complete remissions (CRs*) and continue on treatment. We are especially encouraged that two patients having highly adverse TP53 mutations have achieved objective responses and remain on treatment.” Key Corporate Highlights Tuspetinib Data Reported from First Two Cohorts of TUSCANY Phase 1/2 Trial - Tuspetinib based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 trial with the goal of creating a one-of-a-kind frontline therapy for newly diagnosed AML patients that is safe and active across diverse AML populations (mutation agnostic triplet frontline therapy), including patients without FLT3 mutations (wildtype FLT3). Data from the first two cohorts, with a 40 mg or 80 mg dose of tuspetinib in the TUS+VEN+AZA combination, reveal promising clinical safety and antileukemic activity (press release here). In the first cohort, our newly diagnosed AML patients received the initial 40 mg dose of TUS as part of the TUS+VEN+AZA combination. No safety concerns or dose limiting toxicities (DLTs) were observed. Three patients experienced rapid bone marrow blast reductions to achieve CRs; one having biallelic mutated TP53, complex karyotype (CK) chromosomal abnormalities, and wildtype FLT3; one having an IDH2 mutation wildtype FLT3; and one having FLT3-ITD and mutated NPM1. Clinical sites or central labs reported all these patients also achieved MRD-negative status. The fourth patient at the 40 mg dose of TUS, did not achieve a complete remission and discontinued the study. The first three patients continue on treatment. In the second cohort, three newly diagnosed AML patients having diverse mutation profiles have received the 80 mg dose of TUS, as part of the TUS+VEN+AZA combination. To date, no safety concerns or DLTs have been reported. All patients at the 80 mg dose of TUS rapidly achieved CRs; one patient with biallelic TP53 mutations and a complex karyotype and wildtype FLT3 status, a second patient having mutated DDX41 and wildtype FLT3 status, and a third patient having FLT3-ITD and NPM1 mutations. All three patients at the 80 mg dose of TUS are early in their course of treatment, are expected to achieve normal blood count recovery as their leukemia is resolved, and MRD status will be monitored as the patients move through their courses of therapy. OTC Exchange - Aptose common shares (“the Common Shares”) are now listed for trading on the OTC Markets (OTC) under the ticker “APTOF,” in addition to the Company’s continued listing on the Toronto Stock Exchange (TSX) under the symbol “APS”. This significantly expands Aptose accessibility for U.S.-based investors and enhances overall share liquidity by enabling trading through U.S. broker-dealers. Listing on the OTC Markets is part of Aptose’s strategy to align with TSX capital markets while increasing visibility and participation from the U.S. investment community. Aptose’s Common Shares were delisted from The Nasdaq Stock Market effective April 2, 2025 because of non-compliance with the Exchange’s equity requirements. Completed and Planned Value-Creating Milestones 2025: 1H Reported safety and efficacy with 40mg TUS+VEN+AZAReported safety and efficacy with 80mg TUS+VEN+AZA 2025: European Hematology Association (EHA) Report maturing data from TUS+VEN+AZA triplet study 2025: American Society of Hematology (ASH) Report response rate and durability of TUS+VEN+AZA tripletSelect TUS dose for TUS+VEN+HMA triplet Ph 2/3 PIVOTAL trialsPrepare for initiation of Ph 2/3 PIVOTAL program FINANCIAL RESULTS OF OPERATIONSAptose Biosciences Inc.Statements of Operations Data(unaudited)($ in thousands, except for share and per share data) Quarter endedMarch 31, 2025 2024 Expenses: Research and development$2,364 $6,445 General and administrative 3,097 3,315 Operating expenses 5,461 9,760 Other (loss) income, net (82) 120 Net loss$(5,543) $(9,640) Net loss per share, basic and diluted$(2.61) $(22.02) Weighted average number ofcommon shares outstanding used incomputing net loss per share, basicand diluted 2,126,287 437,750 Net loss for the quarter ended March 31, 2025 decreased by $4.1 million to $5.5 million, as compared to $9.6 million for the comparable period in 2024. Aptose Biosciences Inc.Balance Sheet Data(unaudited)($ in thousands) March 31,2025 December 31,2024 Cash, cash equivalents and restricted cashequivalents$4,743 $6,707 Working capital 651 5,053 Total assets 7,467 10,127 Long-term liabilities 8,542 10,193 Accumulated deficit (546,510) (540,967) Shareholders’ deficit (7,393) (4,543) Total cash, cash equivalents and restricted cash equivalents as of March 31, 2025 were $4.7 million. Based on current operations, the Company expects that cash on hand and available capital provides the Company with sufficient resources to fund planned Company operations including research and development until the end of May 2025. The Company is proactively implementing financing and cost reduction efforts to extend its cash runway. As of May 1, 2025, we had 2,552,429 Common Shares issued and outstanding. In addition, there were 38,736 Common Shares issuable upon the exercise of outstanding stock options and there were 1,267,585 Common Shares issuable upon the exercise of the outstanding warrants. RESEARCH AND DEVELOPMENT EXPENSES Research and development expenses for the three months ended March 31, 2025 and 2024 were as follows: Quarter ended (in thousands) March 31,2025 March 31,2024 Program costs – Tuspetinib$1,479 $3,923 Program costs – Luxeptinib 98 208 Program costs – APTO-253 - 22 Personnel related expenses 646 1,924 Stock-based compensation 141 328 Depreciation of equipment - 10 Total$2,364 $6,445 Research and development expenses decreased by $4.1 million to $2.3 million for the quarter ended March 31, 2025, as compared to $6.4 million for the comparable period in 2024. Changes to the components of our research and development expenses presented in the table above are primarily as a result of the following events: Program costs for tuspetinib were $1.5 million for the quarter ended March 31, 2025, compared with $3.9 million for the comparable period in 2024. The lower program costs for tuspetinib in the current period are attributable to reduced activity in our APTIVATE clinical trial, reduced manufacturing activity, and related expenses. Program costs for luxeptinib decreased by approximately $0.1 million primarily due to lower clinical trial and manufacturing activities. Program costs for APTO-253 were zero. This was due to the Company’s decision to discontinue further development of APTO-253. Personnel-related expenses decreased by $1.3 million due to lower headcount for research and development personnel in the current quarter. Stock-based compensation decreased by approximately $0.2 million in the quarter ended March 31, 2025, primarily due stock options forfeited and/or vested in prior periods that are no longer being expensed resulting in lower expense in the current period. About Aptose 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’s lead clinical-stage compound tuspetinib (TUS), is 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. For more information, please visit www.aptose.com. Forward Looking Statements 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 profile of tuspetinib, clinical trials, upcoming milestones, financing activities, expectations regarding capital available to the Company to fund planned Company operations, the Company’s cash runway, use of proceeds from financings, 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; unexpected manufacturing defects, the evolving regulatory and political landscape and the funding of government programs and other risks detailed from time-to-time in our ongoing current reports, quarterly filings, annual information forms, annual reports and 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

Aptose is developing TUS+VEN+AZA as a one-of-a-kind safe and mutation agnostic frontline triple drug therapy for newly diagnosed AML patients First two dose cohorts of TUS+VEN+AZA triplet demonstrate safety, complete remissions, and MRD negativity across patients with diverse mutations, including TP53-mutated/CK AML and FLT3-wildtype AML patients SAN DIEGO and TORONTO, May 05, 2025 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (TSX: APS; OTC: APTOF), a clinical-stage precision oncology company, today reported updated and new data from Aptose’s Phase 1/2 TUSCANY trial in newly diagnosed acute myeloid leukemia (AML) patients dosed with a 40 mg or 80 mg dose of tuspetinib (TUS) in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet). The TUS+VEN+AZA triplet is being developed as a safe and mutation agnostic frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy. Earlier this year, Aptose announced the initiation of the TUSCANY trial and dosing in newly diagnosed AML patients at an initial dose of 40 mg TUS in the first cohort of four patients. The second cohort of patients is now receiving 80 mg TUS. Data from the first two cohorts, with a 40 mg or 80 mg dose of tuspetinib in the TUS+VEN+AZA combination, reveal promising clinical safety and antileukemic activity. To date, four newly diagnosed AML patients received the initial dose of TUS (40 mg) as part of the (TUS+VEN+AZA) combination. Notably, a patient with biallelic TP53 mutations and a complex karyotype (TP53-mutated/CK) and FLT3-wildtype achieved a complete remission (CR) and the clinical site reported no measurable residual disease (MRD-negative status) in this patient.One FLT3-wildtype patient having an IDH-2 mutation achieved a CR and MRD-negative status.Another FLT3-wildtype patient achieved a CRi during Cycle 1 and MRD-negative status.The first three patients continue on treatment, while a fourth patient did not respond at this 40 mg dose level of TUS and was discontinued.The 40 mg dose of the TUS+VEN+AZA triplet remains safe, and no dose-limiting toxicities (DLTs) have been reported. To date, three newly diagnosed AML patients having diverse mutation profiles have received the 80 mg of TUS, as part of the TUS+VEN+AZA combination. The 80 mg TUS dose has been considered the optimal dose that has demonstrated safety and consistent blood exposure levels that exert potent antileukemic activity. All patients achieved blast reductions in Cycle 1 that met the criteria for complete remissions (CR or CRi) and continue on treatment. Notably, another TP53-mutated/CK and FLT3-wildtype patient achieved blast reductions that met CRi criteria in Cycle 1 and is now receiving additional therapy in Cycle 2.The second patient, having FLT3-wildtype status, achieved a CR.The third patient, having FLT3-ITD and NPM1 mutations and entering the trial with a 75% bone marrow blast count, achieved a CRi. All three patients are early in their course of treatment and are expected to show further improvements in their disease status as they are all continuing with treatment, and MRD status will be monitored as the patients move through their courses of therapy.The 80 mg dose of TUS, as part of the TUS+VEN+AZA triplet, continues to show favorable safety with no dose-limiting toxicities (DLTs) having been reported. “The treatment paradigm for AML is shifting to triplet combination therapy,” said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. “We have always maintained that tuspetinib, with its notable safety profile and ability to treat the larger, difficult-to-treat AML populations with high-risk mutations, could be an ideal drug for a triplet combination therapy in the frontline setting. With the majority of patients already achieving complete responses -- including early responses in patients with adverse mutations -- the clinical findings to date are bearing that out.” William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose, will review the data at a presentation today, Monday, May 5th, 2025, 3:00 p.m. EDT, at the 2025 Bloom Burton & Co. Healthcare Investor Conference. The presentation and webcast can be accessed here and will be available on the Aptose website. TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study Tuspetinib based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 trial with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Responses to TUS were also observed in those with prior-VEN and prior-FLT3 inhibitor (FLT3i) therapies, those with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes. The TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS will be administered in 28-day cycles, beginning at 40mg once daily, with dose escalations planned after a safety review of each dose level. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by mid-late 2025. Data will be released as it becomes available. More information on the TUSCANY Phase 1/2 study can be found on www.clinicaltrials.gov (here). About Aptose 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 lead clinical-stage, oral kinase inhibitor tuspetinib (TUS) 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. For more information, please visit www.aptose.com. Forward Looking Statements This 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 (including the triplet therapy) and its clinical development, the anticipated enrollment rate in the TUSCANY trial and the timing thereof, 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”, 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 Pietropaolo Corporate Communications & Investor Relations 201-923-2049 spietropaolo@aptose.com