tuspetinib (HM43239) / Hanmi - LARVOL DELTA

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

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

A Potent Small Molecule Inhibitor of FLT3, PHI-101 Overcomes Resistance in Acute Myeloid Leukemia: Efficacy and PK/PD Profile in Phase 1 First in Human Study (ASH 2022) - P1a/1b | "Seventy percent of enrolled patients had more than 3 prior anti-leukemic treatment attempts, and four patients had relapsed or refractory disease after treatment with other FLT3 inhibitors including gilteritinib, quizartinib, or HM43239. A dose-escalating phase 1a clinical data of PHI-101, which reflects up to cohort 4 of the study, indicates that PHI-101 generated potent FLT3 inhibition leading to encouraging anti-leukemic responses in R/R AML patients, including in those with prior FLT3 TKI therapeutic failure. PHI-101 showed good tolerance and favorable safety profile and reduced leukemic blasts significantly with 28-day dosing. PHI-101 sustained its activity to clear FLT3-ITD and/or FLT3-TKD mutations including D835Y or N676K identified in AML patients."

Clinical • P1 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3

Novel imidazothiadiazole-based TAK1 inhibitors with anticancer and anti-inflammatory activity (ACS-Fall 2026) - "Our compounds demonstrate potent TAK1 inhibitory activity, surpassing known inhibitors such as Takinib and Tuspetinib, and effectively reduce pro-inflammatory cytokines including IL-6 and TNF-α. Furthermore, these inhibitors exhibit significant antitumor activity in ovarian cancer models, suppressing A2780 tumor growth both in vitro and in vivo. Future studies will focus on optimizing pharmacokinetic properties and further evaluating the clinical potential of these inhibitors."

Immunology • Oncology • Ovarian Cancer • Solid Tumor • IL6 • TNFA

Design and development of small molecule kinase inhibitors targeting TAK1 for inflammatory diseases | Poster Board #1190 (ACS-Fall 2026) - "The optimized compounds demonstrated strong TAK1 inhibition, outperforming the known inhibitor Takinib and Tuspetinib. In macrophage-based assays, the lead candidates effectively suppressed pro-inflammatory cytokines, including TNF-α and IL-6, with submicromolar IC50 values, showing markedly improved activity compared to the reference inhibitor HS-276. Following evaluation of pharmacokinetic properties and safety profiles, including cardiotoxicity assessment, these compounds are being advanced for in vivo validation in an arthritis mouse model. Overall, these findings highlight imidazothiadiazole-based TAK1 inhibitors as promising candidates for the development of new anti-inflammatory therapeutics"

Cardiovascular • Immunology • Inflammation • IL6 • TNFA

Design and development of small molecule kinase inhibitors targeting TAK1 for inflammatory diseases | Poster Board #1755 (ACS-Fall 2026) - "The optimized compounds demonstrated strong TAK1 inhibition, outperforming the known inhibitor Takinib and Tuspetinib. In macrophage-based assays, the lead candidates effectively suppressed pro-inflammatory cytokines, including TNF-α and IL-6, with submicromolar IC50 values, showing markedly improved activity compared to the reference inhibitor HS-276. Following evaluation of pharmacokinetic properties and safety profiles, including cardiotoxicity assessment, these compounds are being advanced for in vivo validation in an arthritis mouse model. Overall, these findings highlight imidazothiadiazole-based TAK1 inhibitors as promising candidates for the development of new anti-inflammatory therapeutics"

Cardiovascular • Immunology • Inflammation • IL6 • TNFA

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 2026) - "Early results from the VEN/AZA/TUS triplet in treatment-naïve AML indicate promising safety, tolerability, and high rates response with MRD-negative remissions. Updated results including additional pts will be presented at the meeting."

Clinical • Acute Myelogenous Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • 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 2026 EHA Congress in Oral Presentation (GlobeNewswire) - "Addition of TUS to standard of care VEN+AZA creates a well-tolerated and mutation agnostic frontline triple drug therapy for newly diagnosed AML. 32 AML patients dosed across 40 mg, 80 mg, 120 mg and 160 mg TUS with TUS+VEN+AZA triplet. Composite complete response (CRc) rate in evaluable patients across all dosing groups was 86.2%. MRD-negativity in patients who achieved a CR/CRh response was 86.4%. AML patients with diverse genetics, including TP53-mutated, complex karyotypes, and unmutated FLT3, safely achieved responses and MRD negativity."

P1/2 data • Acute Myelogenous Leukemia

Data from Aptose’s 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 2026) (GlobeNewswire) - "As reported prior, the first two dose cohorts at 40 mg of TUS or 80 mg of TUS in the TUS+VEN+AZA triplet, demonstrated safety, complete remissions, and MRD negativity across patients with diverse mutations, including TP53-mutated/CK AML and FLT3-wildtype AML patients. The oral presentation at EHA will include updated data at the 80 mg and 120mg dose levels, as well as new data from the 160 mg dose of TUS, updated safety, complete remissions, minimal residual disease (MRD) and other clinical findings with a 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

Tuspetinib enhances the activity of polymyxin B by inhibiting the GlcNAc6P deacetylase. (PubMed, J Antibiot (Tokyo)) - "Finally, we demonstrated the efficacy of TUS plus PMB therapy in a mouse model of pulmonary infection with a clinical PMB-resistant K. pneumoniae isolate. In all, this work discovers a promising drug combination strategy based on PMB and TUS and underlies the special mode of action that involves inhibiting the activity of NagA."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • FLT3

Research and development expenses (GlobeNewswire) - "Program costs for tuspetinib decreased by $1.7 million to $7.9 million for the year ended December 31, 2025 compared to $9.6 million for the comparable period in 2024. The increased costs associated with the TUSCANY study were offset by a decrease in tuspetinib development expenses during the current year. This reduction is due to the conclusion of activities in our APTIVATE clinical trial during the current year as compared to higher APTIVATE activities during the prior year, as well as lower manufacturing and related development costs...Program costs for luxeptinib decreased by approximately $0.1 million compared to the prior year."

Commercial • Acute Myelogenous Leukemia

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

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