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Reporting Complete Response Data from the Ongoing APTIVATE International Phase 1/2 Study of Tuspetinib (TUS) in Relapsed/Refractory AML PatientsTUS Single Agent and TUS/VEN Combination Demonstrate Favorable Safety and Tolerability TUS/VEN Combination Active Across Broad Populations of AML and Demonstrates 25% Complete Response Rate Among All-comers, including 20% CRc in Wildtype AML TUS Targets VEN Resistance Mechanisms, Enabling TUS/VEN Combination to Achieve Responses in Difficult-to-treat Prior-VEN Failure AMLTotal Enrollment of Patients Receiving TUS or TUS/VEN is Now Over 160 SAN DIEGO and TORONTO, Dec. 09, 2023 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated targeted agents to treat hematologic malignancies, today announced that a growing body of clinical data for Aptose’s lead compound tuspetinib (TUS), demonstrates significant benefit as a single agent and in combination with venetoclax (VEN) in patients with relapsed or refractory acute myeloid leukemia (R/R AML) in the ongoing APTIVATE Phase 1/2 study. Data were presented in an oral presentation today at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition by lead investigator Naval G. Daver, M.D., Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Tuspetinib is a once-daily, oral, precision targeted kinase inhibitor that suppresses select kinases that drive the proliferation of AML. These key kinase targets include the SYK, FLT3, JAK1/2, mutant forms of KIT, RSK2, and the TAK1-TAB1 kinases operative in AML, while avoiding non-therapeutic kinase targets to promote safety. Dr. Daver reported data from more than 100 relapsed/refractory patients from multiple international clinical sites, who had failed prior therapy and then were treated with tuspetinib (TUS) as a single agent or tuspetinib in combination with venetoclax (TUS/VEN). TUS and TUS/VEN delivered multiple composite complete remissions (CRcs) in this very ill AML population, while maintaining a favorable safety profile across all treated patients. “Tuspetinib is clearly an active and surprisingly well tolerated agent in one of the most challenging and heterogeneous disease settings in oncology – relapsed and refractory AML,” said Dr. Daver. “Tuspetinib has demonstrated broad activity, including activity in patients with FLT3 wild-type AML (accounting for more than 70% of the AML population), FLT3 mutated AML, NPM1 mutated AML, as well as in patients with mutations historically associated with resistance to targeted therapy. Most notably, TUS targets VEN resistance mechanisms, enabling TUS/VEN uniquely to treat the very ill prior-VEN AML population, including both FLT3 mutant and FLT3 wildtype disease. From a broader perspective, the growing body of antileukemic activity, and continued favorable safety profile, support advancement of tuspetinib in a TUS/VEN/HMA triplet for the treatment of frontline newly diagnosed AML patients.” Dr. Daver also pointed out that while patients on the TUS/VEN therapy are early in their treatment cycles, most achieving a response remained on treatment and that responses have begun to mature as dosing continues. Highlights of Dr. Daver’s ASH oral presentation: TUS as Single Agent As a single agent at therapeutic doses of 80-160 mg in 68 evaluable patients, TUS was more active in VEN-naïve patients, with an overall CRc rate of 29% (8/28) This included a 42% CRc rate (5/12) in FLT3-mutated patientsAnd a 19% CRc rate (3/16) in FLT3-unmutated, or wildtype, AML patients Responses and blood counts improved with continuous dosingMany bridged to an allogeneic stem cell transplant (HSCT)Durability was observed when HSCT was not performed80 mg was selected as the recommended phase 2 doseTuspetinib showed a favorable safety profile with only mild adverse events (AEs) and no dose-limiting toxicities (DLTs) up to 160 mg per day, and no drug discontinuations from drug related toxicity TUS/VEN Combination Therapy In the TUS/VEN doublet study, 49 patients were dosed with 80 mg of tuspetinib and 200 mg of venetoclax, with 36 evaluable (and 13 patients too early to assess)Patients were heavily exposed to Prior-VEN and Prior-FLT3 inhibitor treatmentTUS/VEN was active in both VEN-naïve and prior Prior-VEN relapsed/refractory patientsTUS demonstrated composite complete remission (CRc) rates: Among all evaluable patients, TUS/VEN demonstrated a CRc rate of 25% (9/36); 43% (3/7) in VEN-naïve patients, and 21% (6/29) in Prior-VEN patients.Among FLT3 wildtype patients, TUS/VEN demonstrated an overall CRc rate of 20% (5/25); 33% (2/6) in VEN-naïve patients, and 16% (3/19) in Prior-VEN patientsAmong FLT3 mutant patients, TUS/VEN demonstrated an overall CRc rate of 36% (4/11); a complete response in a VEN-naïve patient (1/1); a 30% (3/10) in Prior-VEN patients; and 44% (4/9) in patients treated prior with a FLT3 inhibitor Key findings: TUS/VEN is a well tolerated combination therapyTUS/VEN is active across broad populations of R/R AMLTUS/VEN is active in FLT3 wildtype, representing ~70% of AML patientsTUS/VEN retains activity in the difficult-to-treat Prior-VEN AML population “The wealth of data we have generated – and continue to generate – on tuspetinib points to a highly active, well-differentiated drug for AML populations that are in need of options beyond currently available therapies,” said Rafael Bejar, M.D., Ph.D., Chief Medical Officer at Aptose. “Brisk patient enrollment in our APTIVATE trial has led to a fast-growing database that includes many more patients at various stages of treatment. We look forward to reporting our next set of data in the first quarter of 2024.” The slides from Dr. Daver’s presentation are available on Aptose’s website here. About Aptose Aptose Biosciences is a clinical-stage biotechnology company 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 product, tuspetinib, is a once daily oral therapy 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). 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 of tuspetinib, its clinical development, safety profile and upcoming milestones planned for tuspetinib, 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 PietropaoloCorporate Communications & Investor Relations201-923-2049spietropaolo@aptose.com LifeSci Advisors, LLCDan Ferry, Managing Director617-430-7576Daniel@LifeSciAdvisors.com

Tuspetinib (TUS) Targets Venetoclax (VEN) Resistance MechanismsTUS/VEN Combination Therapy Active in R/R VEN Failure AML Patients – Guides Toward Accelerated Approval Path, Including FLT3 Mutated and Wildtype TUS/VEN Overall Response Rate of 48% in Heavily Pre-Treated Relapsed/Refractory AML Patients Tuspetinib Favorable Safety Profile Continues with TUS/VEN Doublet TherapyConference Call and Webcast at 5:00 pm ET Today SAN DIEGO and TORONTO, Nov. 09, 2023 (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 nine months ended September 30, 2023, and provided a corporate update. “The data we presented last week during the European School of Haematology (ESH) conference on acute myeloid leukemia (AML) demonstrate the exciting potential for tuspetinib (TUS) in the treatment of the very ill relapsed/refractory AML population and as part of a frontline triplet combination regimen in newly diagnosed AML,” said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. “Investigator enthusiasm for our tuspetinib/venetoclax (TUS/VEN) doublet has led to brisk enrollment in the APTIVATE trial. The number of evaluable patients and clinical responses continue to grow, and we look forward to reporting the next data set just a few weeks from now during the American Society of Hematology (ASH) meeting.” Key Corporate Highlights Tuspetinib APTIVATE Expansion Trial Ongoing – Tuspetinib, a once daily oral agent with a unique kinase targeting pattern, is being developed for the treatment of patients with R/R AML. As reported at ESH, more than 140 patients have been treated in the ongoing APTIVATE Phase 1/2 clinical trial: 91 patients have received TUS as a single agent; 51 thus far have been treated in the TUS/VEN cohort, with keen investigator interest accelerating patient enrollment in the doublet arm. In the most recent data cut (October 23, 2023), the favorable safety profile remained consistent for TUS and TUS/VEN treated R/R AML patients. TUS avoids many typical toxicities observed with other kinase, IDH1/2, and menin inhibitors. Tuspetinib Single Agent Active with Favorable Safety – As reported at ESH, tuspetinib as a single agent was well-tolerated and highly active among relapsed or refractory (R/R) AML patients with a diversity of adverse genotypes. TUS single agent delivered 42% and 60% CR/CRh response rates across all patients and across FLT3-mutated patients, respectively, among evaluable VEN-naïve patients at the 80mg daily recommended phase 2 dose (RP2D). Tuspetinib demonstrated a 29% CR/CRh rate in VEN-naïve FLT3 unmutated (wildtype) AML at 80 mg daily RP2D, unlocking the potential for TUS to treat the additional 70-75% of the AML population without FLT3-mutation not currently addressed by any approved tyrosine kinase inhibitors. Tuspetinib single agent response rates compared favorably to the marketed FLT3 inhibitor gilteritinib, which has not demonstrated meaningful activity in FLT3 unmutated AML. TUS/VEN Doublet Delivers Responses in Tough to Treat Populations – As reported in the ESH update from a data cut taken on October 23, 2023, the TUS/VEN doublet showed a 48% overall response rate (ORR) in 31 evaluable patients (15 of 31). 81% of those patients had previously failed VEN treatment, representing an increasing AML population in need of improved salvage therapies, and TUS/VEN had a 44% ORR in those VEN failure patients. TUS/VEN showed a 60% ORR (6 of 10) in FLT3-mutant AML, and a 43% (9 of 21) ORR in FLT3-wildtype AML. Analyses from the October 23rd data cut included preliminary data from patients very early in their treatment who may see their responses to treatment mature over time. TUS Targets VEN Resistance Mechanisms; ESH Poster Presentation – Aptose presented a poster at ESH, Tuspetinib Oral Myeloid Kinase Inhibitor Creates Synthetic Lethal Vulnerability to Venetoclax, demonstrating the ability of TUS to suppress a set of key oncogenic signaling pathways that mediate resistance to AML drugs by potently inhibiting SYK, mutated and unmutated forms of FLT3, JAK1/2, RSK2, mutant forms of KIT, and TAK1-TAB1 kinases. Aptose researchers investigated the effects of TUS on key elements of the phospho-kinome and apoptotic proteome in both parental and TUS-resistant AML cells. In parental cells, TUS acutely inhibits key oncogenic signaling pathways and shifts the balance of pro- and anti-apoptotic proteins in favor of apoptosis, suggesting that it may generate vulnerability to VEN. Indeed, acquired TUS resistance generated a synthetic lethal vulnerability to VEN of unusually high magnitude, making cells more than 2,000 times more sensitive to VEN. Concurrent administration of TUS and VEN may eliminate cells that carry this form of TUS resistance at the start of therapy and discourage the emergence of TUS resistance during treatment. Tuspetinib Clinical Data Selected for Oral Presentation at 2023 ASH Annual Meeting – Aptose announced last week that clinical data for tuspetinib was selected for oral presentation at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 9-12, 2023 in San Diego, CA. Lead investigator Dr. Naval Daver, Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, will present data from Aptose’s ongoing APTIVATE trial of tuspetinib (TUS) single agent and the TUS/VEN doublet in relapsed/refractory patients with acute AML. Multiple Planned Value-creating Milestones Ahead APTIVATE oral presentation at ASH 2023 by Dr. Naval DaverTUS/VEN incremental data readout in R/R AML planned: ASH 2023TUS/VEN further data on duration of response in R/R AML planned: 1Q & 2Q2024TUS/VEN/HMA planned initiation of pilot triplet study in 1L AML: 1H2024Extension into HR-MDS and CMML planned: 4Q2023 FINANCIAL RESULTS OF OPERATIONS Aptose Biosciences, Inc.Statements of Operations Data(unaudited)($ in thousands, except per share data) Three months endedNine months ended September 30, September 30, 2023 2022 2023 2022 Expenses: Research and development$8,256 $6,578 $27,649 $21,312 General and administrative 3,425 3,448 12,580 10,887 Operating expenses 11,681 10,026 40,229 32,199 Other income, net 234 249 977 376 Net loss$(11,447) $(9,777) $(39,252) $(31,823)Net Loss per share, Basic and diluted$(1.76) $(1.59) $(6.14) $(5.17)Weighted average number of common shares outstanding used in computing net loss per share, basic and diluted (in thousands) 6,495 6,153 6,391 6,150 Net loss for the three-month period ended September 30, 2023 increased by $1.7 million to $11.4 million, as compared to $9.8 million for the comparable period in 2022. Net loss for the nine-month period ended September 30, 2023 increased by $7.4 million to $39.3 million, as compared to $31.8 million for the comparable period in 2022. Aptose Biosciences, Inc.Balance Sheet Data(unaudited)($ in thousands) September 30, December 31, 2023 2022 Cash, cash equivalents and short-term investments$17,717 $46,959 Working capital 7,291 37,235 Total assets 20,876 51,027 Long-term liabilities 720 1,002 Accumulated deficit (503,582) (464,330)Stockholders’ equity 7,776 37,741 Total cash and cash equivalents and investments as of September 30, 2023, were $17.7 million, a decrease of $5.6 million as compared to $23.3 million at June 30, 2023, and a decrease of $29.2 million as compared to $46.9 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 March of 2024. Common shares outstanding on November 9, 2023, were 7,816,923. RESEARCH AND DEVELOPMENT EXPENSES The research and development expenses for the three-month and nine-month periods ended September 30, 2023, and 2022 were as follows: Three months ended Nine months ended September 30, September 30,(in thousands) 2023 2022 2023 2022 Program costs – Tuspetinib$5,814 $3,049 $18,659 $6,570Program costs – Luxeptinib 648 1,390 2,643 6,624Program costs – APTO-253 2 66 28 345Personnel related expenses 1,523 1,627 5,107 5,821Stock-based compensation 259 440 1,183 1,923Depreciation of equipment 10 6 29 29Total$8,256 $6,578 $27,649 $21,312 Research and development expenses increased by $1.7 million to $8.3 million for the three-month period ended September 30, 2023, as compared to $6.6 million for the comparative period in 2022. 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 $5.8 million for the three-month period ended September 30, 2023. The higher program costs for tuspetinib in the current period represent the enrollment of patients in our APTIVATE clinical trial, our healthy volunteer trial, manufacturing activities to support clinical development, and related expenses.Program costs for luxeptinib decreased by approximately $742 thousand, 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 $64 thousand, due to the Company’s decision on December 20, 2021 to discontinue further clinical development of APTO-253.Personnel-related expenses decreased by $104 thousand, related to fewer employees in the current three-month period, partially offset by salary increases.Stock-based compensation decreased by approximately $181 thousand in the three months ended September 30, 2023, compared to the three months ended September 30, 2022, primarily due to stock options granted with lower grant date fair values, in the current period. Research and development expenses increased by $6.3 million to $27.6 million for the nine-month period ended September 30, 2023, as compared to $21.3 million for the comparative period in 2022. 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 $18.7 million for the nine-month period ended September 30, 2023, an increase of $12.1 million compared with $6.6 million in the corresponding period in 2022. The higher program costs for tuspetinib in the current period represent the enrollment of patients in our APTIVATE clinical trial, our healthy volunteer trial, manufacturing activities to support clinical development, and related expenses.Program costs for luxeptinib decreased by approximately $4 million from $6.6 million in the nine months ended September 30, 2022 to $2.6 million in the current period, 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 $317 thousand, due to the Company’s decision on December 20, 2021 to discontinue further clinical development of APTO-253.Personnel-related expenses decreased by $714 thousand, related to fewer employees in the current nine-month period and partially offset by salary increases.Stock-based compensation decreased by approximately $740 thousand in the nine months ended September 30, 2023, compared to the three months ended September 30, 2022, primarily due to stock options granted with lower grant date fair values, in the current period. Conference Call & Webcast: Date: Thursday, November 9, 2023 Time: 5:00 PM ETAudio Webcast Only:link Q&A Participant Registration Link*:link(https://register.vevent.com/register/BIb770b610b0744016870ec2150989ea78) *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 quarter ended September 30, 2023 will be available on SEDAR+ at www.sedarplus.ca and EDGAR at www.sec.gov/edgar.shtml. 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 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 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 expected cash runway of the Company, the Company’s clinical development plans, the clinical potential, anti-cancer activity, therapeutic potential and applications and safety profile of tuspetinib and luxeptinib, clinical trials, patient enrollment, upcoming updates regarding the clinical trials, 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: Aptose Biosciences Inc. LifeSci Advisors, LLCSusan Pietropaolo Dan Ferry, Managing DirectorCorporate Communications & Investor Relations 617-430-7576201-923-2049 Daniel@LifeSciAdvisors.com spietropaolo@aptose.com

Tuspetinib (TUS) Combination with Venetoclax (VEN) Clinical Findings Highlighted TUS Targets VEN Resistance Mechanisms toRe-sensitize VEN Failure Patients to VEN 44% ORR with TUS/VEN in Difficult-to-Treat VEN Failure R/R AML Patients 48% ORR with TUS/VEN in Heavily Pre-treated R/R AML Patients Consistent Favorable Safety with TUS Single Agent and TUS/VEN Doublet SAN DIEGO and TORONTO, Oct. 30, 2023 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral kinase inhibitors to treat hematologic malignancies, released highlights from a clinical update event held today, October 30, 2023, in conjunction with the European School of Haematology (ESH) 6th International Conference: Acute Myeloid Leukemia “Molecular and Translational”: Advances in Biology and Treatment, being held in Estoril, Portugal (the “ESH 2023 Conference”). The webcast event featured a comprehensive review of up-to-date clinical data for Aptose’s lead compound tuspetinib (TUS) by Rafael Bejar, MD, PhD, Aptose’s Chief Medical Officer, and featured Naval G. Daver, MD, Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Dr. Daver is the lead investigator on Aptose’s APTIVATE trial of tuspetinib and is recognized for significant achievements in the development of novel acute myeloid leukemia (AML) treatments, including several combination therapies. Tuspetinib (TUS) is a once-daily, oral, precision targeted kinase inhibitor that suppresses select kinases that drive the proliferation of AML. These key kinase targets include the SYK, FLT3, JAK1/2, mutant forms of KIT, RSK2, and the TAK1-TAB1 kinases operative in AML, while other kinases are avoided to promote safety. AML care has shifted toward venetoclax (VEN) containing combination regimens and a new population of difficult-to-treat VEN relapsed patients (“VEN failures”) is emerging. Tuspetinib’s safety, activity, mechanism of action, and convenient dosing make it ideal for combination therapy. Importantly, TUS directly targets VEN resistance mechanisms (suppresses mutated FLT3, mutated KIT, SYK and mutated JAK1/2 of the JAK/STAT pathway, RSK2 of the RAS/MAPK pathway, key oncogenic growth and proliferation signals, and MCL-1 expression). This means that TUS targets pathways and may lead to re-sensitizing VEN-resistant cells to VEN when given in combination. TUS/VEN may safely and successfully treat these VEN failures, as we already have observed clinically, and an accelerated approval path may be available for VEN failure relapsed or refractory (R/R) AML patients treated with TUS/VEN. “We are really pleased by our growing safety and efficacy data on tuspetinib in very difficult-to-treat AML patient populations,” said Dr. Bejar. “This includes activity in FLT3-unmutated patients, a population that accounts for more than 70% of AML and has few effective treatment options. Additionally, tuspetinib’s significant activity in patients who have failed venetoclax treatment – a rapidly-emerging population of particularly high unmet medical need – provides a clear development pathway for tuspetinib with the potential for accelerated approval.” “The safety and efficacy data we’ve seen with the tuspetinib/venetoclax combination is very encouraging, suggesting that tuspetinib may effectively treat the large number of VEN failures we are seeing frequently in our clinics,” said Dr. Daver. “Data from the TUS/VEN doublet gives us confidence to move tuspetinib forward into a TUS/VEN/HMA triplet for the treatment of frontline newly-diagnosed AML patients. Tuspetinib is an exciting agent, and I am happy to be part of the clinical development team.” Clinical Findings Aptose provided updated clinical findings from the ongoing APTIVATE study of tuspetinib: Patient Enrollment More than 140 patients have been treated with tuspetinib to date 91 patients have received TUS as a single agent Aptose anticipated dosing up to 30 patients with TUS/VEN by the ESH 2023 Conference; however, investigator enthusiasm resulted in dosing of 49 patients (as of October 23, 2023), and patients continue being enrolled Safety Pro > In the most recent data cut (October 23, 2023), the favorable safety pro consistent for TUS and TUS/VEN treated R/R AML patients: No TUS related adverse events (AEs) of QTc prolongation No observed differentiation syndrome No TUS related non-hematologic serious AEs No TUS related deaths No rhabdomyolysis or AEs of elevated creatine phosphokinase (CPK) No TUS related dose-limiting toxicities (DLT) from 20 mg level through 160 mg level One DLT of muscle weakness at 200 mg Occurred in patient with high exposure Not rhabdomyolysis │ No muscle destruction Avoids many typical toxicities observed with other FLT3, IDH1/2, and menin inhibitors In TUS/VEN doublet, no unexpected or new safety signals were observed Tuspetinib Single Agent Tuspetinib as a single agent was well-tolerated and highly active among relapsed or refractory (R/R) AML patients with a diversity of adverse genotypes. TUS single agent delivered 42% and 60% CR/CRh response rates across all patients and across FLT3-mutated patients, respectively, among evaluable VEN-naïve patients at the 80mg daily recommended phase 2 dose (RP2D) Tuspetinib demonstrated a 29% CR/CRh rate in VEN-naïve FLT3 unmutated (wildtype) AML at 80 mg daily RP2D, unlocking the potential for TUS to treat the additional 70-75% of the AML population without FLT3-mutation not currently addressed by any approved tyrosine kinase inhibitors Responses were achieved across four dose levels Responses were shown to mature over time with sustained blood count recovery during continuous dosing Several responders were bridged to potentially lifesaving transplant (HSCT) Durability was observed when HSCT was unavailable Tuspetinib single agent response rates compare favorably to gilteritinib FLT3 inhibitor TUS/VEN Doublet (TUS 80mg/VEN 400mg) Patients who have failed venetoclax treatment represent an increasing AML population in need of improved salvage therapies Over 90% of recent U.S. patients enrolled in the APTIVATE trial were VEN failures VEN resistance involves mutations in multiple pathways to evade BCL-2 blockade Tuspetinib directly targets pathways involved in VEN resistance By shutting down these pathways, tuspetinib appears to re-sensitize prior-VEN failures to venetoclax (see poster presented at the ESH 2023 Conference here) Overall Response Rates (ORR) with TUS/VEN Doublet (see Table below, includes recent preliminary responses) 31 evaluable patients showed an ORR 48% (15 of 31) 81% (25 of 31) of patients were VEN failures 44% ORR (11 of 25) in VEN failures 60% ORR (6 of 10) in FLT3-mutant 43% ORR (9 of 21) in FLT3-wildtype Most patients are very early in treatment, having initiated dosing in the past 2-6 weeks, and responses are expected to mature over time Overall Response Rates Patient Population Aug 1, 2023 10 patients evaluable of 15 dosed Sep 1, 2023 15 patients evaluable of 26 dosed Oct 23, 2023 31 patients evaluable of 49 dosed Prior-VEN Failures 44% (4 of 9) 38% (5 of 13) 44% (11 of 25) FLT3-Mutant 67% (2 of 3) 67% (4 of 6) 60% (6 of 10) FLT3-Wildtype 43% (3 of 7) 33% (3 of 9) 43% (9 of 21) Overall 50% (5 of 10) 47% (7 of 15) 48% (15 of 31) Response Types 1CR│3CRi│1CRp 1CR│6CRi 2CR│7CRi│6PR Multiple Planned Value-creating Milestones Ahead TUS/VEN incremental data readout in R/R AML planned: ASH 2023 TUS/VEN further data on duration of response in R/R AML planned: 1Q & 2Q2024 TUS/VEN/HMA planned initiation of pilot triplet study in 1L AML: 1H2024 Extension into HR-MDS and CMML planned: 4Q2023 The associated slides from the presentation are available on Aptose’s website here. The webcast of the presentation will be archived here. AboutAptose Aptose Biosciences is a clinical-stage biotechnology company 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 . 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 of tuspetinib, its clinical development and safety pro potential for accelerated approval, the value creating milestones planned for tuspetinib, 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. LifeSci Advisors, LLC Susan Pietropaolo Dan Ferry, Managing Director Investor Relations 617-430-7576 201-923-2049 Daniel@LifeSciAdvisors.com spietropaolo@aptose.com