tuspetinib (HM43239) / Hanmi, Aptose Biosci - LARVOL DELTA

Inhibitors of RAD51 as potential novel therapies in Acute Myeloid Leukemia (ASH 2025) - "Furthermore, these compounds often exhibit strong synergy and at least additivity in combination with both on-label and off-label use of FDA-approved compounds, as well as investigational molecularly-targeted agents, in relevant cell lines; these include FLT3 inhibitors quizartinib, gilteritinib and tuspetinib ((in MV-4-11 and HL60 cell lines) and BCR/ABL inhibitors (imatinib and regorafenib) in the K562 cell line (AACR 2025)...We have confirmed the IBRs inhibit multiple RAD51 functions including hydroxyurea-induced RAD51 focus formation, HRR by DR-GFP assay, and RS protection by RPA focus formation and a DNA fibre assay...JKYN-1 is a partially optimized (more soluble and more potent) version of IBR120 but is not resistant to degradation by liver microsomes or sufficiently capable of entry into target cells...Treatment dose and combinations will be pre-screened using a highly predictive cell line as a surrogate of human cancer stem cells for subsequently AML patient..."

Acute Myelogenous Leukemia • Colorectal Cancer • Hematological Malignancies • Leukemia • Solid Tumor • BRCA1 • BRCA2 • FLT3 • HRD • RAD51

Determining sensitivity to FLT3 inhibitors prior to therapy in FLT3 mutant acute myelogenous leukemia (ASH 2025) - "For ex-vivo sensitivity assays, AML cells were treated with several dilutions of a FLT3i(Sorafenib, Midostaurin, Crenolanib, Quizartinib, Gilteritinib, Tuspetinib and MAX-40279 (a dualFLT3/FGFR inhibitor)) and cell viability was assessed with CellTiter-Glo® (Promega). Using our MS-based proteomics measurements and sensitivity results with our proprietary MLmodel, we processed both AML patient samples (N=57) and patient-derived cell lines (N=59), and wewere able to identify 7 distinct clusters. Previously we demonstrated that RPPA proteomics could discriminate FLT3i sensitive andresistant cases and here we present orthogonal confirmation by MS proteomics and ex-vivo sensitivityassays. Moreover, we show that the expression of only three proteins forms a robust biomarker topredict FLT3i sensitivity of FLT3-MUT AML patients prior to therapy. We also identified AML cell lines thatmimic both FLT3i resistance and sensitivity, and combined with deep proteomics data, these..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CD34 • FLT3 • PXN • SMARCA2

Tuscany Study demonstrates safety and efficacy of tuspetinib plus standard of care venetoclax and azacitidine in patients with newly diagnosed AML ineligible for induction chemotherapy (ASH 2025) - "Thecombination of TUS with standard dosing of VEN/AZA in treatment-naïve AML demonstrates promisingsafety, tolerability, and efficacy, including MRD-negative remissions in a broad range of mutationallydiverse pts. Additional enrollment and follow-up will be presented at the meeting."

Clinical • Acute Myelogenous Leukemia • Constipation • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Myelodysplastic Syndrome • Neutropenia • FLT3 • JAK1 • JAK2 • KIT • SYK • TP53

Aptose’s Tuspetinib Triple Drug Therapy Featured at the 2025 ASH Annual Meeting; High Rate of Frontline Clinical Responses Continues Across AML Populations (GlobeNewswire) - "In newly diagnosed AML patients, TUS+VEN+AZA shows promising safety, tolerability and resilient efficacy, including MRD-negative remissions across a broad mutational spectrum High-quality clinical responses (CR/CRh): 90% across 40, 80 and 120 mg dose levels; 100% at the higher 80 mg and 120 mg dose levels; Observed in FLT3-WT, FLT3-ITD, and NPM1c genetic subgroups; Observed in biallelic TP53/complex karyotype and RAS adverse genetic subgroups; Observed in AML with MDS-related mutations; MRD negativity: 78% by central flow cytometry in responding subjects; TUS targets VEN resistance mechanisms; inhibits kinase-driven abnormal signaling....At the recently enrolled 160 mg dose level, preliminary findings show patients achieving early blast clearance with MRD-negativity and formal responses in the first few weeks of treatment (not included in poster data cut)."

P1/2 data • Acute Myelogenous Leukemia

PHI-101, a Novel FLT3 TKI, Shows Clinical Efficacy in Relapsed/Refractory FLT3-Mutated AML (ASH 2024) - P1a/1b | "75% of these patients had received prior FLT3 inhibitors (Gilteritinib (7), Midostaurin (3), Sorafenib (1), HM43239 (1)). The recommended phase 2 dose will be 160 mg once-daily which resulted in Cmax and AUC0-24 plasma concentrations in Phase 1b of 259 ng/ml and 3,920 ng/ml at cycle 1 day 1. Conclusion : Once-daily dosing of single-agent PHI-101 had a distinct tolerability profile and showed excellent anti-tumor activity across FLT3i-pretreated and FLT3i-naïve patients with R/R FLT3 mutant AML."

Clinical • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Neutropenia • Thrombocytopenia • FLT3

Aptose Biosciences Announces Arrangement Agreement for Acquisition by Hanmi Pharmaceutical (GlobeNewswire) - "During the past 18 months, Hanmi has singularly supported Aptose and the continued development of tuspetinib (TUS) through debt facilities to Aptose totaling more than US$30 million. Under the terms of the Arrangement Agreement, upon the completion of the transactions contemplated under the Arrangement Agreement, Aptose shareholders, other than the Hanmi Purchasers and their respective affiliates that hold any Common Shares, will receive C$2.41 in cash per Common Share..."

M&A • Acute Myelogenous Leukemia

Phase 1 Safety and Efficacy of Tuspetinib Plus Venetoclax Combination Therapy in Study Participants with Relapsed or Refractory Acute Myeloid Leukemia (AML) Support Exploration of Triplet Combination Therapy of Tuspetinib Plus Venetoclax and Azacitidine for Newly Diagnosed AML (ASH 2024) - "CONCLUSIONS : Tuspetinib as monotherapy and in combination with VEN has been well- tolerated with objective responses among diverse AML patient groups including those with FLT3-WT and mutated TP53 or RAS, and in prior-VEN and prior-FLT3i treated pts. These safety and efficacy results support the upcoming combination of TUS/VEN plus azacitidine as a triplet in newly diagnosed AML pts ineligible for intensive chemotherapy, independent of FLT3 mutation status."

Clinical • Combination therapy • P1 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • FLT3 • JAK1 • KIT • SYK • TP53

Tuspetinib Myeloid Kinase Inhibitor Safety and Efficacy As Monotherapy and Combined with Venetoclax in Phase 1/2 Trial of Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) (ASH 2023) - "In an orthotopic mouse model of FLT3-mutant AML, tuspetinib exhibited greater antitumor activity than gilteritinib, entospletinib, venetoclax (VEN), and azacitidine (AZA) and combined favorably with VEN and AZA individually. Tuspetinib was well-tolerated and delivered single agent clinical responses across four dose levels among diverse AML genotypes; with a RP2D of 80 mg chosen for future single agent studies. Although early, the VEN/TUS combination has been well tolerated with preliminary objective responses noted."

Clinical • Monotherapy • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • FLT3 • JAK1 • KIT • NPM1 • SYK • TP53

PHI-101 As a Potent Next-Generation FLT3 Inhibitor, Overcome Resistances in Previously Treated Patients with FLT3-ITD or TKD Acute Myeloid Leukemia: Results of a Phase Ia/Ib Clinical Trial (ASH 2023) - P1a/1b | "Ten pts were R/R following previous treatment with other FLT3 inhibitors (gilteritinib, quizartinib, midostaurin, or HM43239). In dose-escalating phase Ia clinical trials, PHI-101 was well tolerated at all dose levels with no DLTs. Phase Ib dose-expansion trials with 160 mg daily dosing are currently ongoing. PHI-101 has delivered CRcs at 120 mg and 160 mg."

Clinical • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Aptose Tuspetinib Clinical Data from Ongoing TUSCANY Trial in Newly Diagnosed AML Selected for Presentation at the 2025 ASH Annual Meeting (Aptose Biosci Press Release) - "

P1/2 data • Acute Myelogenous Leukemia

Data from Phase 1/2 TUSCANY trial presented at the European School of Haematology (ESH) 7th International Conference (GlobeNewswire) - "Addition of TUS to VEN+AZA achieves CR/CRh responses in all (6/6, 100%) patients treated at the higher dose levels of 80 mg and 120 mg TUS, exceeding the 66% rate expected from VEN+AZA alone. CR/CRh responses in 7/8 (88%) FLT3 wildtype AML, representing 70% of AML population. TUS+VEN+AZA achieves CR/CRh and MRD-negativity in TP53-mutated (2/2), RAS-mutated (1/1) and FLT3-ITD (2/2) AML patients to date."

P1/2 data • Acute Myelogenous Leukemia

Aptose Biosciences…announced that it has entered into a US$11.9 million loan Amended Facility Agreement ( “Facility Agreement”) with Hanmi Pharmaceutical Co. Ltd. (“Hanmi”) (GlobeNewswire) - "The Facility Agreement is uncommitted and administered through multiple advances until December 31, 2025, and will be used to fund Aptose’s business and clinical operations expenses reasonably related to the advancement of TUS. Aptose has not yet received funds from this Facility Agreement but expects the first advance soon."

Commercial • Acute Myelogenous Leukemia

Aptose Reports Early Data Demonstrating Tuspetinib Improves Standard of Care Treatment Across Diverse Populations of Newly Diagnosed AML in Phase 1/2 TUSCANY Trial (GlobeNewswire) - "Addition of TUS to VEN+AZA demonstrates excellent CR/CRh rates: 100% CR/CRh among all subjects treated at 80 mg and 120 mg TUS dose levels; Appear to be achieving CR earlier with 120 mg TUS than with 40 mg or 80 mg...Addition of TUS to VEN+AZA demonstrates excellent MRD-negativity rates: MRD-negativity in 7 of 9 (78%) already achieved in patients who responded to therapy; Expect patient survival to be extended with continued long-term treatment; Excellent safety and well tolerated with no dose-limiting toxicities (No DLT) at completed dose levels...No loss of MRD-negativity observed to date, including in one patient with over 7 months of follow up....No relapses reported to date and no treatment related deaths."

P1/2 data • Acute Myelogenous Leukemia

Aptose Enrollment is Open for 160 mg Dosing Cohort of Tuspetinib in Phase 1/2 TUSCANY Trial of Frontline Triple Drug Therapy (GlobeNewswire) - "Aptose Biosciences...announced that the Cohort Safety Review Committee (CSRC) monitoring Aptose’s Phase 1/2 TUSCANY trial of TUS in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet) has approved escalating from 120 mg TUS dose to 160 mg TUS dose based on its favorable review of safety and efficacy data from patients in the first three cohorts (40 mg, 80 mg, and 120 mg TUS dose levels) of the trial. Enrollment is open for dosing subjects at the 160 mg TUS dose level. Aptose also announced that it has received an additional advance of US$1.1M from Hanmi Pharmaceutical...as part of a US$8.5M loan facility agreement with Hanmi (the 'Loan Agreement')....To date, Aptose has received an aggregate of US$5.6M under the Loan Agreement....Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by late 2025. Data will be released as it becomes available."

DSMB • Financing • Trial status • Acute Myelogenous Leukemia

Aptose Receives Second Advance under the Loan Agreement with Hanmi Pharmaceutical to Continue Development of Tuspetinib in Triplet Therapy for AML (GlobeNewswire) - "Aptose Biosciences...announced that it has received an additional advance of US$2.0M from Hanmi Pharmaceutical Co. Ltd. ('Hanmi'), as part of a US$8.5M loan facility agreement with Hanmi (the 'Loan Agreement') announced prior on June 20, 2025 (press release here). To date, Aptose has received an aggregate of US$4.5M under the Loan Agreement....The ongoing TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of azacitidine and venetoclax in newly diagnosed patients with AML who are ineligible to receive induction chemotherapy."

Financing • Acute Myelogenous Leukemia

Aptose and Hanmi Enter New Loan Agreement to Advance Development of Tuspetinib in Triplet Therapy for AML (GlobeNewswire) - "Aptose Biosciences Inc...announced that it has entered into a new loan agreement (the 'Loan Agreement') with Hanmi Pharmaceutical Co. Ltd. ('Hanmi'). The Loan Agreement is an uncommitted facility for up to US$8.5million, administered through multiple advances for the purpose of continued clinical development of TUS."

Financing • Acute Myelogenous Leukemia

TUSCANY STUDY OF SAFETY AND EFFICACY OF TUSPETINIB PLUS STANDARD OF CARE VENETOCLAX AND AZACITIDINE IN STUDY PARTICIPANTS WITH NEWLY DIAGNOSED AML INELIGIBLE FOR INDUCTION CHEMOTHERAPY (EHA 2025) - "Tuspetinib, both as monotherapy and in combination with VEN has been well-tolerated with objective responses in a diverse group of R/R AML pts, including those with FLT3-WT and mutated TP53 or RAS. Early results with the VEN/AZA+TUS triplet in treatment-naïve AML indicate promising safety, tolerability, and efficacy, including an MRD-negative remission in Cycle1. Additional pts are being enrolled, and updated results will be presented at the meeting."

Clinical • Acute Myelogenous Leukemia • FLT3 • JAK1 • JAK2 • KIT • SYK • TP53

Aptose Presents Safety, Response, and MRD Clinical Data from TUSCANY Phase 1/2 Clinical Trial of Tuspetinib Triplet Therapy in Newly Diagnosed AML at the 2025 EHA Congress (GlobeNewswire) - P1/2 | N=240 | TUSCANY (NCT03850574) | Sponsor: Aptose Biosciences Inc. | "Key findings: (i) To date, ten newly diagnosed AML patients have received the TUS+VEN+AZA combination: Four received the 40 mg dose of TUS, three received the 80 mg dose of TUS, and three received the 120 mg dose of TUS; (ii) At the initial dose of 40 mg TUS (n=4), with patients on longest duration of drug: Three subjects achieved CRs and were MRD-negative, including: Patient with FLT3-ITD; Patient with FLT3-WT; Patient with TP53/CK; (iii) At the 80 mg TUS dose level (n=3): All three patients (100%) already achieved composite complete remissions (CR and CRi); A TP53-mutated/CK AML patient achieved an early CRi; Too early in treatment for final MRD assessment; (iv) At the 120 mg TUS dose level (n=3): All three patients at the 120 mg TUS dose level remain on therapy; Too early in treatment for formal response and MRD assessments."

P1/2 data • Acute Myelogenous Leukemia

Aptose Announces Dosing of First Patient with 120 mg of Tuspetinib in Phase 1/2 Tuscany Trial of Frontline Triple Drug Therapy after Dose Escalation Decision by Safety Review Committee (The Manila Times) - "Aptose Biosciences Inc...announced that the Cohort Safety Review Committee (CSRC) monitoring Aptose's Phase 1/2 TUSCANY trial of tuspetinib in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet) has approved escalating from 80 mg dose TUS to 120 mg dose TUS based on its favorable review of safety and efficacy data from patients in the first two cohorts of the trial. Dosing of the first subject at the 120 mg TUS dose level has commenced....No significant safety concerns or dose limiting toxicities (DLTs) have been reported in the TUSCANY trial, including no prolonged myelosuppression of subjects in remission. Patients treated in the 40 mg and 80 mg dose cohorts remain on study while enrollment is open for the 120 mg dose cohort....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."

Trial status • Acute Myelogenous Leukemia

Aptose Provides Clinical Update for the Tuspetinib-based Triple Drug Frontline Therapy in Newly Diagnosed AML Patients from the Phase 1/2 TUSCANY Trial (GlobeNewswire) - P1/2 | N=240 | TUSCANY (NCT03850574) | Sponsor: Aptose Biosciences Inc. | "To date, four newly diagnosed AML patients received the initial dose of TUS (40 mg) as part of the (TUS+VEN+AZA) combination....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 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....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."

P1/2 data • Acute Myelogenous Leukemia

Aptose Selected for Prestigious Oral Presentation of Data from TUSCANY Phase 1/2 Clinical Trial of Tuspetinib Triplet Therapy in Newly Diagnosed AML at the 2025 EHA Congress (GlobeNewswire) - "Aptose Biosciences...announced that data from its Phase 1/2 TUSCANY trial in newly diagnosed patients treated with tuspetinib (TUS) in combination with standard of care dosing venetoclax and azacitidine (TUS+VEN+AZA triplet) has been selected for oral presentation at the European Hematology Association Congress (EHA 2025)....The oral presentation at EHA will include updated safety, complete remission, minimal residual disease (MRD) clinical findings, and longer duration of follow-up."

P1/2 data • Acute Myelogenous Leukemia

The third-generation FLT-3 inhibitor, PLM-102, is a promising therapeutic option for venetoclax-resistant AML (AACR 2025) - "Notably, PLM-102 demonstrated the highest tumor growth inhibitory (TGI) efficacy compared with those of other FLT3 inhibitors including tuspetinib, gilteritinib and PHI-101. In conclusion, PLM-102 completely inhibited FLT3 kinase and its downstream signaling including AKT and STAT3, inducing apoptosis in VR AML cells along with significant inhibition of the tumor growth in the VR xenograft mouse model. These findings suggest that PLM-102, a third-generation FLT-3 inhibitor, is a promising candidate for overcoming venetoclax resistance and could serve as a therapeutic option for venetoclax-resistant AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • CASP3 • FLT3 • MCL1 • STAT3

Aptose Reports Year End 2024 Results and Corporate Highlights (GlobeNewswire) - "2025: 1H - Expect to report CR/MRD/Safety data from TUS+VEN+AZA triplet therapy trial; Expect to execute Hanmi/Aptose Collaboration; EHA2025 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 trials; Prepare for Ph 2 portion of Ph 2 / Ph 3 pivotal program; American Society of Hematology (ASH) Update."

P1/2 data • Trial status • Acute Myelogenous Leukemia

Aptose Announces Positive Clinical Safety Review Committee (CSRC) Approval to Dose Escalate in Phase 1/2 Tuscany Trial of Frontline Triple Drug Therapy with Tuspetinib Amid Complete Responses and Favorable Safety in First Cohort (GlobeNewswire) - "Aptose Biosciences...announced that the Cohort Safety Review Committee (CSRC) monitoring Aptose’s Phase 1/2 TUSCANY trial of tuspetinib in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet) has unanimously approved escalating from 40 mg TUS to 80 mg TUS based on its favorable review of data from the first four patients in the trial. The TUS+VEN+AZA triplet is being developed as a frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy...No significant safety concerns or dose limiting toxicities (DLTs) have been reported, including no prolonged myelosuppression of subjects in remission. All four subjects treated in the 40 mg cohort remain on study while enrollment is open for the 80 mg cohort."

DSMB • Acute Myelogenous Leukemia

Aptose’s Frontline Triple Drug Therapy with Tuspetinib Achieves Notable Responses in Newly Diagnosed AML Patients in the Phase 1/2 TUSCANY Trial (GlobeNewswire) - P1/2 | N=240 | TUSCANY (NCT03850574) | Sponsor: Aptose Biosciences Inc. | "Aptose Biosciences Inc...reported promising early safety and response results from newly diagnosed acute myeloid leukemia (AML) patients dosed in Aptose’s Phase 1/2 TUSCANY trial with a 40 mg dose of tuspetinib in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet)....Three patients with unmutated (wildtype) FLT3 (FLT3-WT) completed Cycle 1 of treatment with no dose-limiting toxicities (DLTs) and no dose adjustments. Two FLT3-WT patients achieved complete remissions (CR and CRh) by the end of Cycle 1. Notably, a patient with biallelic TP53 mutations and a complex karyotype obtained CR. The third FLT3-WT patient experienced significant reductions in bone marrow leukemic blasts during Cycle 1 and remains on therapy in Cycle 2."

P1/2 data • Acute Myelogenous Leukemia