Bone marrow depression

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Shorla Oncology (‘Shorla’), a U.S.-Ireland specialty pharmaceutical company, announced today that the U.S. Food and Drug Administration has granted approval for 100 mg/10mL multi-dose vial of TEPYLUTE, a ready-to-dilute formulation of thiotepa to treat breast and ovarian cancer, that eliminates the need for reconstitution and may reduce preparation time and errors offering more scheduling flexibility for their patients. Shorla Oncology Announces FDA Approval of TEPYLUTE® 100mg, First and Only Ready-to-Dilute Multi-Dose Vial of Thiotepa to Treat Breast and Ovarian Cancer and Commercial Launch of TEPYLUTE 15mg and 100mg Vials in the U.S. “We are pleased to offer another viable treatment option for patients with breast and ovarian cancer,” said Sharon Cunningham, Chief Executive Officer and Co-Founder of Shorla Oncology. “Once opened, our 100mg vial of TEPYLUTE is stable for 14 days when properly stored, giving providers the flexibility they need when preparing and administering this very important treatment. TEPYLUTE is a ready to dilute formulation of a well-established, standard of care oncology drug thiotepa that has been manufactured as freeze-dried powder since the 1950s. “This is a huge win for providers because TEPYLUTE avoids the need for complicated and time-consuming reconstitution,” said Orlaith Ryan, Chief Technical Officer and Co-Founder of Shorla Oncology. We are excited to bring TEPYLUTE to the US Market. It provides consistent dosing accuracy and allows for “just in time” preparation, which benefits everyone, especially patients.” said Rayna Herman, Chief Commercial Officer, Shorla Oncology. The American Cancer Society estimates that more than 300,000 women will be diagnosed with breast cancer in the U.S in 2025.2 About 20,890 women will be diagnosed with ovarian cancer in the U.S. in 2025.3 About Shorla Oncology Shorla Oncology is a privately- held, U.S. and Ireland- based commercial stage specialty pharmaceutical company established by Sharon Cunningham and Orlaith Ryan. The company has an advanced pipeline of innovative oncology drugs for orphan and pediatric cancers. Shorla is focused on indications where existing treatments are limited, in shortage or the drug applications are inadequate for the target population. The company’s growing portfolio brings accessible, affordable and life-saving treatments to patients, delivering a major contribution to patient care. Shorla currently markets three products, Nelarabine for the treatment of T-cell leukemia, JYLAMVO™ for the treatment of acute lymphoblastic leukemia and other indications and IMKELDI for the treatment of Chronic Myeloid Leukemia, Gastrointestinal Stromal Tumors (GISTs) and other indications. For further information, please visit www.shorlaoncology.com. TEPYLUTE® (thiotepa) Injection for Intravenous Use INDICATION TEPYLUTE is an alkylating drug indicated for the treatment of adenocarcinoma of the breast or ovary. IMPORTANT SAFETY INFORMATION WARNING: SEVERE MYELOSUPPRESSION and CARCINOGENICITY • TEPYLUTE may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. • TEPYLUTE should be considered potentially carcinogenic in humans. CONTRAINDICATIONS TEPYLUTE is contraindicated in patients with severe hypersensitivity to thiotepa and in concomitant use with live or attenuated vaccines. WARNINGS AND PRECAUTIONS Myelosuppression : For patients receiving TEPYLUTE for treatment of adenocarcinoma of the breast or adenocarcinoma of the ovary, if the bone marrow has been compromised by prior irradiation or chemotherapy, or is recovering from chemotherapy, the risk of severe myelosuppression with TEPYLUTE may be increased. Perform periodic complete blood counts during the course of treatment with TEPYLUTE. Provide supportive care for infections, bleeding, and symptomatic anemia. Inform patients of the possibility of developing low blood cell counts and the need for hematopoietic progenitor cell infusion. Instruct patients to immediately report to their healthcare provider if bleeding or fever occurs. Hypersensitivity: Clinically significant hypersensitivity reactions, including anaphylaxis, have occurred following administration of thiotepa. If anaphylactic or other clinically significant allergic reaction occurs, discontinue treatment with TEPYLUTE, initiate appropriate therapy, and monitor until signs and symptoms resolve. Counsel patients on the signs and symptoms of hypersensitivity and to seek immediate emergency assistance if they develop any of these signs and symptoms. Cutaneous Toxicity: TEPYLUTE and/or its active metabolites may be excreted in part via skin in patients receiving high-dose therapy. Treatment with TEPYLUTE may cause skin discoloration, pruritus, blistering, desquamation, and peeling that may be more severe in the groin, axillae, skin folds, in the neck area, and under dressings. Instruct patients to shower or bathe with water at least twice daily through 48 hours after administration of TEPYLUTE. Change the occlusive dressing and clean the covered skin at least twice daily through 48 hours after administration of TEPYLUTE. Change bed sheets daily during treatment. Skin reactions associated with accidental exposure to TEPYLUTE may occur. Wash the skin thoroughly with soap and water in case the TEPYLUTE solution contacts the skin. Flush mucous membranes in case of TEPYLUTE contact with mucous membranes. Concomitant Use of Live and Attenuated Vaccines: Do not administer live or attenuated viral or bacterial vaccines to a patient treated with TEPYLUTE until the immunosuppressive effects have resolved. Hepatic Veno-Occlusive Disease: Monitor by physical examination, serum transaminases, and bilirubin, and provide supportive care to patients who develop hepatic veno-occlusive disease. Central Nervous System Toxicity: Fatal encephalopathy has occurred in patients treated with high doses of thiotepa. Other central nervous system toxicities, such as headache, apathy, psychomotor retardation, disorientation, confusion, amnesia, hallucinations, drowsiness, somnolence, seizures, coma, inappropriate behavior, and forgetfulness have been reported to occur in a dose-dependent manner during or shortly after administration of high-dose thiotepa. Do not exceed the recommended dose of TEPYLUTE. If severe or life-threatening central nervous system toxicity occurs, discontinue administration of TEPYLUTE and provide supportive care. Carcinogenicity: Like many alkylating agents, thiotepa has been reported to be carcinogenic when administered to laboratory animals. Carcinogenicity is shown most clearly in studies using mice, but there is some evidence of carcinogenicity in man. There is an increased risk of secondary malignancy with the use of TEPYLUTE. Inform patients that TEPYLUTE can increase the risk of secondary malignancy. Polyethylene glycol (PEG) 400 toxicity : TEPYLUTE contains a high concentration of PEG 400. Based on findings in animals, administration of high amounts of PEG 400 may cause damage to the kidneys and liver at dosages higher than recommended. When prescribing TEPYLUTE, take into consideration the PEG 400 load from concomitant medications. Embryo-Fetal Toxicity: Based on the mechanism of action and findings in animals, TEPYLUTE can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of TEPYLUTE in pregnant women. Thiotepa given by the intraperitoneal (IP) route was teratogenic in mice at doses ≥1 mg/kg (3.2 mg/m 2 ), approximately 8-fold less than the maximum recommended human therapeutic dose (0.8 mg/kg, 27 mg/m 2 ), based on body-surface area. Thiotepa given by the IP route was teratogenic in rats at doses ≥3 mg/kg (21 mg/m 2 ), approximately equal to the maximum recommended human therapeutic dose, based on body-surface area. Thiotepa was lethal to rabbit fetuses at a dose of 3 mg/kg (41 mg/m 2 ), approximately two times the maximum recommended human therapeutic dose based on body-surface area. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use highly effective contraception during TEPYLUTE treatment and for 6 months after therapy/the last dose. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant. Advise males with female partners of reproductive potential to use effective contraception during TEPYLUTE treatment and for 1 year after therapy/the last dose. ADVERSE REACTIONS The most common adverse reactions (incidence greater than 10%) are neutropenia, anemia, thrombocytopenia, elevated alanine aminotransferase, elevated aspartate aminotransferase (AST), elevated bilirubin, mucositis, cytomegalovirus infection, hemorrhage, diarrhea, hematuria, and rash. The clinically significant adverse reactions include myelosuppression, infection, hypersensitivity, cutaneous toxicity, hepatic veno-occlusive disease, central nervous system toxicity, and carcinogenicity. DRUG INTERACTIONS Effect of Cytochrome CYP3A Inhibitors and Inducers: In vitro studies suggest that thiotepa is metabolized by CYP3A4 and CYP2B6 to its active metabolite triethylene phosphoramide (TEPA). Avoid coadministration of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (e.g., rifampin, phenytoin) with thiotepa due to the potential effects on efficacy and toxicity. Consider alternative medications with no or minimal potential to inhibit or induce CYP3A4. If concomitant use of strong CYP3A4 modulators cannot be avoided, closely monitor for adverse drug reactions. Effect of TEPYLUTE on Cytochrome CYP2B6 Substrates: In vitro studies suggest that thiotepa inhibits CYP2B6. Thiotepa may increase the exposure of drugs that are substrates of CYP2B6 in patients; however, the clinical relevance of this in vitro interaction is unknown. The administration of thiotepa with cyclophosphamide in patients reduces the conversion of cyclophosphamide to the active metabolite, 4‑hydroxycyclophosphamide; the effect appears sequence-dependent with a greater reduction in the conversion to 4-hydroxycyclophosphamide when thiotepa is administered 1.5 hours before the intravenous administration of cyclophosphamide compared to administration of thiotepa after intravenous cyclophosphamide. The reduction in 4-hydroxycyclophosphamide levels may potentially reduce the efficacy of cyclophosphamide treatment. USE IN SPECIFIC POPULATIONS Pregnancy: TEPYLUTE can cause fetal harm when administered to a pregnant woman based on findings from animals and the drug’s mechanism of action. Limited available data on thiotepa use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, administration of thiotepa to pregnant mice and rats during organogenesis produced teratogenic effects (neural tube defects and malformations of the skeletal system of the fetus) at doses approximately 0.125 and 1 times, respectively, the maximum recommended human daily dose on a mg/m2 basis. Thiotepa was lethal to rabbit fetuses at approximately 2 times the maximum recommended human therapeutic dose based on body-surface area. Consider the benefits and risks of TEPYLUTE for the mother and possible risks to the fetus when prescribing TEPYLUTE to a pregnant woman. Lactation: There is no information regarding the presence of thiotepa in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including the potential for tumorigenicity shown for thiotepa in animal studies, advise patients not to breastfeed during TEPYLUTE treatment and for 1 week after therapy/the last dose. Females and Males of Reproductive Potential: TEPYLUTE can cause fetal harm when administered to a pregnant woman. Pregnancy Testing - Verify the pregnancy status of females of reproductive potential before initiating TEPYLUTE therapy. Contraception for Females - Advise females of reproductive potential to avoid pregnancy during TEPYLUTE treatment and for 6 months after therapy/the last dose. Advise females to immediately report pregnancy. Contraception for Males - TEPYLUTE may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during TEPYLUTE treatment and for 1 year after therapy/the last dose. Infertility - Based on nonclinical findings, male and female fertility may be compromised by treatment with TEPYLUTE. Advise patients that TEPYLUTE can produce infertility. Inform male patients about the possibility of sperm conservation before the start of therapy. Pediatric Use: Safety and effectiveness of TEPYLUTE in neonates have not been established. Safety and effectiveness of TEPYLUTE for the treatment of adenocarcinoma of the breast and adenocarcinoma of the ovary in pediatric patients have not been established. Geriatric Use: Clinical studies of thiotepa for treatment of adenocarcinoma of the breast and adenocarcinoma of the ovary did not include sufficient numbers of subjects aged 65 years and over to determine whether elderly subjects respond differently from younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreasing hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Renal Impairment: In patients with moderate (creatinine clearance [CLcr] of 30 mL/min to 59 mL/min) renal impairment, decreased renal excretion may result in increased plasma levels of thiotepa and TEPA. This may result in increased toxicity. Monitor patients with moderate to severe (CLcr <30 mL/min) renal impairment for signs and symptoms of toxicity following treatment with TEPYLUTE for an extended period of time. Hepatic Impairment: Thiotepa is extensively metabolized in the liver. Patients with moderate (bilirubin levels greater than 1.5 times to 3 times the upper limit of normal and any AST) hepatic impairment may have increased plasma levels of thiotepa. This may result in toxicity. Monitor patients with moderate to severe (bilirubin levels greater than 3 times the upper limit of normal and any AST) hepatic impairment for signs and symptoms of toxicity following treatment with TEPYLUTE for an extended period of time. To report suspected adverse reactions, contact Shorla Oncology at 1-844-668-3940 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For Print: Please see the accompanying full Prescribing Information, including Boxed Warning. For Digital: Please click here for full Prescribing Information, including Boxed Warning. All trademarks are the property of Shorla Oncology. ©SHORLA ONCOLOGY® 2025. PRO-TEP-1377-v1 04/2025

Tuspetinib Triple Drug Frontline Therapy Advancing in TUSCANY Clinical Trial Results to Date Highlight TUS Potential as an Ideal Third Drug to Include in AML Triplet Therapy Aptose Signs Debt Conversion Agreement with Hanmi SAN DIEGO and TORONTO, March 28, 2025 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), 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 year ended December 31, 2024, and provided a corporate update. "During 2024 and into 2025, we continue to advance our lead investigational drug tuspetinib in combination with venetoclax (VEN) and azacitidine (AZA) for frontline treatment of newly diagnosed acute myeloid leukemia (AML),” said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. “Tuspetinib brings favorable safety and broad activity across AML genetic subtypes to the TUS+VEN+AZA triplet therapy, which already has achieved complete remissions (CRs) in difficult-to-treat and underserved TP53-mutated/CK AML and FLT3-wildtype AML patients in our ongoing TUSCANY trial. We look forward to sharing more data as the trial evolves.” Key Corporate Highlights Tuspetinib Phase 1/2 TUSCANY Trial Well Under Way with Responses Noted - 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 (mutation agnostic triplet frontline therapy), including FLT3-wildtype AML. This activity differentiates TUS from other drugs in development. In January 2025, Aptose announced initiation of dosing in the first TUSCANY trial cohort with the starting dose of 40 mg TUS in combination with standard-of-care doses of VEN+AZA. At 40 mg TUS, the triplet therapy achieved complete remissions (CRs) in difficult-to-treat TP53-muated AML and FLT3-wildtype AML patients, including a measurable residual disease (MRD) negative remission (press release here). In February 2025, amid the promising early results and favorable safety from patients treated at the 40 mg dose level, the Cohort Safety Review Committee (CSRC) monitoring the TUSCANY trial approved escalating to 80 mg TUS in the triplet therapy (press release here). Subjects have now begun treatment at the 80 mg TUS dose level of the triplet therapy and further recruitment is under way. No significant safety concerns have been reported to date, including no prolonged myelosuppression of subjects in remission. This TUS+VEN+AZA triplet therapy study in newly diagnosed AML was supported with robust safety and efficacy data from the TUS single agent dose escalation study and the TUS+VEN doublet APTIVATE study in relapsed or refractory (R/R) AML, both of which were completed during 2024 after treating more than 170 patients.Financing Activity – During 2024, Aptose completed several financings for a total of approximately $37 million to support the TUS-based TUS+VEN+HMA triplet therapy development for AML. This included a $10 million loan Facility Agreement with Hanmi Pharmaceutical Co. Ltd. (“Hanmi”). Subsequently in March 2025, Hanmi and Aptose executed a Debt Conversion Agreement to convert a portion of the debt into equity, subject to Hanmi owning no more than 19.99% of the issued and outstanding common shares of Aptose. Therefore, an amount of $1.5 million has been converted into 409,063 common shares as of this date. Beyond the $10 million, Aptose and Hanmi are negotiating a new tuspetinib co-development collaboration agreement intended to provide additional funding to accelerate clinical development of tuspetinib. Aptose licensed tuspetinib from Hanmi Pharmaceutical in November 2021.Aptose Signs CRADA with NCI – In December, Aptose announced that it entered into a Cooperative Research and Development Agreement (“CRADA”) with the National Cancer Institute (NCI), part of the National Institutes of Health (press release here). Under the CRADA, the NCI and Aptose will collaborate on the clinical development of TUS, an inhibitor of key signaling kinases involved in myeloid malignancies, in the NCI Cancer Therapy Evaluation Program (CTEP) sponsored myeloMATCH trials employing combinations of targeted therapy for the treatment of molecularly defined AML and myelodysplastic syndromes (MDS) populations. These trials will be conducted by NCI's National Clinical Trials Network (NCTN), with the participation of the NCI Community Oncology Research Program (NCORP) in the U.S. and Canada.Aptose Meets Nasdaq Minimum Bid Compliance – Earlier this month, Aptose announced that it received a written notification from the Listing Qualifications Department of The Nasdaq Stock Market, LLC notifying the Company that it is in compliance with Nasdaq’s minimum bid price requirement (press release here). On March 14, 2025, Nasdaq confirmed that, for ten consecutive business days, the closing bid price of the Company’s common shares has been $1.00 per share or greater. Accordingly, the Company has regained compliance with Listing Rule 5550(a)(2). Separately, Aptose is not in compliance with the $2.5 million shareholders equity requirement and is operating under an exception granted by the Nasdaq Hearing Panel, which provides Aptose additional time to regain compliance, although there is no assurance that the Company will successfully achieve full compliance with the Nasdaq shareholders equity requirement. Completed and Planned Value-Creating Milestones 2024 Accomplishments Completed $10 million loan from Hanmi as Advance on CollaborationCompleted $8 million S-1 financingExecuted CRADA with NCI MyeloMATCH for tuspetinib in AML/MDSInitiated dosing of TUS+VEN+AZA triplet therapy in newly diagnosed AML patients in TUSCANY trialASH: Reported CR/Safety from APTIVATE TUS and TUS+VEN trialASH: Reported dosing accrual from TUS+VEN+AZA triplet therapy trial 2025: 1H Demonstrated safety and efficacy with 40mg TUS+VEN+AZA in triplet therapy trialDosing 80mg TUS in TUS+VEN+AZA dose cohort in triplet therapy trialExecuted Debt Conversion agreement with HanmiExpect to report CR/MRD/Safety data from TUS+VEN+AZA triplet therapy trialExpect to execute Hanmi/Aptose CollaborationEHA2025 Congress - Report maturing data readout from TUS+VEN+AZA triplet therapy trial 2025: 2H Select optimal TUS doses for TUS+VEN+HMA triplet therapy Ph 2/3 pivotal trialsPrepare for Ph 2 portion of Ph 2 / Ph 3 pivotal programAmerican Society of Hematology (ASH) Update FINANCIAL RESULTS OF OPERATIONSAptose Biosciences Inc.Statements of Operations Data(unaudited)($ in thousands, except for share and per share data) Year ended December 31, 20242023Expenses: Research and development$15,103 $36,765 General and administrative 11,154 15,591 Operating expenses 26,257 52,356 Other income, net 827 1,149 Net loss$(25,430)$(51,207) Net loss per share, basic and diluted$(36.38)$(227.43)Weighted average number of common shares outstanding used in computing net loss per share, basic and diluted 698,980 225,154 Net loss for the year ended December 31, 2024 decreased by $25.8 million to $25.4 million, as compared to $51.2 million for the comparable period in 2023. Aptose Biosciences Inc.Balance Sheet Data(unaudited)($ in thousands) December 31, December 31, 2024 2023Cash, cash equivalents and restricted cash equivalents$6,707 $9,252 Working capital 5,071 (3,375)Total assets 10,127 12,989 Long-term liabilities 10,211 621 Accumulated deficit (540,967) (515,537) Shareholders’ deficit (4,543) (2,901) Total cash, cash equivalents and restricted cash equivalents as of December 31, 2024, were $6.7 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 April 2025.As of March 21, 2025, we had 2,552,429 Common Shares issued and outstanding. In addition, there were 39,219 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 The research and development expenses for the years ended December 31, 2024 and 2023 were as follows: Year ended December 31,(in thousands)20242023Program costs – Tuspetinib$9,606 $24,925Program costs – Luxeptinib 422 3,510Program costs – APTO-253 (19) 40Personnel related expenses 4,735 6,878Stock-based compensation 346 1,373Depreciation of equipment 13 39Total$15,103 $36,765 Research and development expenses decreased by $21.7 million to $15.1 million for year ended December 31, 2024, as compared to $36.8 million for the comparable period in 2023. 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 $9.6 million for the year ended December 31, 2024, compared with $24.9 million for the comparable period in 2023. The lower program costs for tuspetinib in the current year were due to reduced activity in our APTIVATE clinical trial, reduced manufacturing costs, and related expenses. In the comparable period in 2023, Tuspetinib program costs included the healthy volunteer study, which was completed in the same year.Program costs for luxeptinib decreased by approximately $3.1 million primarily due to lower clinical trial and manufacturing activities.Program costs for APTO-253 decreased by approximately $59 thousand. This reduction was due to the Company’s decision to discontinue further development of APTO-253.Personnel-related expenses decreased by $2.1M due to lower headcount 2024.Stock-based compensation decreased by approximately $1.0 million in the year ended December 31, 2024, primarily due to stock options granted with lower grant date fair values when compared to the options granted in the prior period, coupled with option forfeitures recorded in the current year. 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, the enrollment in clinical trials and the data therefrom, the submission of a compliance plan to Nasdaq and available options to regain compliance, upcoming milestones and presentation of additional data, financing activities, expectations regarding capital available to the Company to fund planned Company operations, maintenance of the Nasdaq and TSX listings, use of proceeds from financings, the conversion of debt into equity contemplated by the Debt Conversion Agreement entered into with Hanmi, the negotiation of a co-development collaboration agreement with Hanmi, the collaboration with the NCI for the clinical development of tuspetinib 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 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

On March 28, 2025, the Food and Drug Administration expanded the indication for lutetium Lu 177 vipivotide tetraxetan (Pluvicto, Novartis Pharmaceuticals Corporation) to include adults with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy.Patients with previously treated mCRPC should be selected for Pluvicto using Locametz (active ingredient gallium Ga 68 gozetotide) or another approved PSMA positron emission tomography (PET) product based on PSMA expression in tumors.Full prescribing information for Pluvicto will be posted on Drugs@FDA. Efficacy and SafetyEfficacy was evaluated in PSMAfore (NCT04689828), a randomized, multicenter, open-label trial enrolling 468 patients with PSMA-positive mCRPC and progression on one ARPI, who the investigator considered appropriate for delay of taxane-based chemotherapy. Patients were randomized (1:1) to receive lutetium Lu 177 vipivotide tetraxetan (7.4 GBq [200 mCi] every 6 weeks for 6 doses) or a change in ARPI. Patients who progressed on the ARPI arm were allowed to crossover to the experimental therapy.The major efficacy outcome was radiographic progression-free survival (rPFS) by blinded independent central review. Overall survival (OS) was an additional efficacy outcome. Median rPFS was 9.3 months (95% confidence interval [CI]: 7, not estimable) in the lutetium Lu 177 vipivotide tetraxetan arm and 5.6 months (95% CI: 4, 6) in the ARPI arm (hazard ratio [HR] 0.41 [95% CI: 0.29, 0.56]; p-value <0.0001). Median OS was 24.5 months (95% CI: 19.5, 28.9) and 23.1 months (95% CI: 19.6, 25.5) in the respective arms (HR 0.91 [95% CI: 0.72, 1.14]; p-value was not statistically significant). Sixty percent (n=141) of patients who were randomized to receive a change in ARPI crossed over to receive lutetium Lu 177 vipivotide tetraxetan after progression.Adverse reactions were consistent with prior experience with lutetium Lu 177 vipivotide tetraxetan. Treatment with lutetium Lu 177 vipivotide tetraxetan may result in risk from radiation exposure, myelosuppression, and renal toxicity.The recommended lutetium Lu 177 vipivotide tetraxetan dose is 7.4 GBq (200 mCi) intravenously every 6 weeks for 6 doses, or until disease progression or unacceptable toxicity.  Expedited ProgramsThis review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.Follow the Oncology Center of Excellence on X: @FDAOncology.