Dr. Rafael Bejar reports

APTOSE'S TUSPETINIB TRIPLE DRUG THERAPY FEATURED AT THE 2025 ASH ANNUAL MEETING; HIGH RATE OF FRONTLINE CLINICAL RESPONSES CONTINUES ACROSS AML POPULATIONS

Aptose Biosciences Inc. has featured clinical data for its lead compound tuspetinib combined with standard dosing of venetoclax and azacitidine in a poster presentation at the 67th American Society of Hematology annual meeting in Orlando, Fla. Updated data from patients in the Tuscany trial across all three cohorts, 40 milligrams, 80 milligrams or 120 milligrams Tuscany, reveal promising clinical safety and antileukemic activity and support the use of Tuscany in combination with standard of care treatment across a broad range of acute myeloid leukemia populations, including those with adverse mutations regardless of FLT3 mutation status.

Poster title 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

Key findings and messages:

• In newly diagnosed AML patients, tuspetinib, venetoclax and azacitidine shows promising safety, tolerability and resilient efficacy, including MRD-negative remissions across a broad mutational spectrum;
• High-quality clinical responses (CR/CRh):
  • 90 per cent across 40-, 80- and 120-milligram dose levels;
  • 100 per cent at the higher 80-milligram and 120-milligram 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 per cent by central flow cytometry in responding subjects;
• TUS targets VEN resistance mechanisms; inhibits kinase-driven abnormal signalling;
• Two subjects transitioned to stem cell transplantation and both returned for TUS maintenance;
• Tuspetinib, venetoclax and azacitidine triplet therapy was well tolerated with no dose-limiting toxicities across all evaluable TUS dose levels:
  • No DLTs including no prolonged myelosuppression for subjects in remission in Cycle 1;
  • No drug-related deaths, differentiation syndrome, QTc prolongation or CPK elevation reported;
  • Eight out of 10 evaluable subjects experienced red cell and platelet transfusion independence for greater than eight weeks after their best response;
  • Febrile neutropenia was reported in two subjects (16.7 per cent), with one subject related to TUS;
• At the recently enrolled 160-milligram 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).

"Tuspetinib, as part of a triple drug therapy, continues to perform well, achieving 100-per-cent clinical response in the two higher doses we have evaluated to date," said Dr. Rafael Bejar, MD, PhD, chief medical officer at Aptose. "We recently commenced treating patients at the highest dose level of 160 mg TUS and have already achieved early responses. With no dose-limiting toxicities and activity across diverse mutations, TUS+VEN+AZA targets AML's greatest unmet needs and largest populations."

About tuspetinib

Aptose's lead compound tuspetinib, is a convenient once-daily oral agent that potently targets SYK, mutated and wild type forms of FLT3, mutated KIT, JAK1/2, and RSK2 kinases, while avoiding many typical toxicity concerns observed with other agents. The continuing tuscany triplet phase 1/2 study is designed to test various doses and schedules of tuscany in combination with standard dosing of azacitidine and venetoclax in newly diagnosed patients with AML who are ineligible to receive induction chemotherapy. Data from the first three dose cohorts demonstrate safety, CRs and minimal residual disease negativity across patients with diverse mutations. The early data showed that nine out of 10 patients responded to the TUS triplet therapy, with 100-per-cent complete remission (CR/CRh) achieved in the 80-milligram and 120-milligram cohorts. Notably, patients with difficult-to-treat mutations in TP53, RAS and FLT3 genes also achieved a 100-per-cent CR/CRh rate.

About Aptose Biosciences Inc.

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 without overlapping toxicities. The company's lead clinical-stage compound tuspetinib is an oral kinase inhibitor that has demonstrated activity as monotherapy and in combination therapy in patients with relapsed or refractory acute myeloid leukemia and is being developed as a front line triplet therapy in newly diagnosed AML.

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