Aptose (APS) announces data from TUSCANY trial evaluating tuspetinib

Aptose Biosciences Inc. (“Aptose” or the “Company”) (TSX: APS; OTC: APTOF), a clinical-stage precision oncology company, today announced data from its Phase 1/2 TUSCANY trial in newly diagnosed AML patients treated with tuspetinib (TUS) in combination with standard of care dosing venetoclax and azacitidine (TUS+VEN+AZA triplet) in an oral presentation at the European Hematology Association Congress (EHA 2025), being held June 12-15, 2025, in Milan, Italy.

The TUS+VEN+AZA triplet is being developed as a mutation agnostic frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy. Dr. Gabriel Mannis, Associate Professor of Medicine, Stanford University School of Medicine, and an investigator in the TUSCANY study, reported safety and efficacy data from the first two dose cohorts at 40 mg of TUS or 80 mg of TUS in the TUS+VEN+AZA triplet. Dr. Mannis also noted three patients were rapidly enrolled on the third dose cohort of 120 mg TUS in the TUS+VEN+AZA triplet, and that no DLTs have been observed to date.

The oral presentation at EHA included updated safety, complete remission, minimal residual disease (MRD) assessments, and longer duration of follow-up:
Title: 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
Presenter: Dr. Gabriel Mannis, Associate Professor of Medicine, Stanford University School of Medicine
Abstract #: S139

Key findings:

• 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
• 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
• 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
• 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
• Regardless of mutation status, TUS is active in newly diagnosed AML patients
  • MRD-negative responses achieved across diverse genetic populations, including adverseTP53 mutations and CK
  • Responses continue to evolve, and the triplet continues to be well tolerated with no DLTs
• TUS can be administered safely with standard-of-care dosing of VEN/AZA
  • TUS PK properties not altered by VEN, AZA, antifungals or food
  • No prolonged myelosuppression in Cycle 1 in the absence of AML
  • No treatment-related deaths; all 10 subjects treated to date remain alive
  • No treatment related QTc prolongation, CPK elevations, differentiation syndrome or non-hematologic SAEs

“The TUSCANY triplet trial is well under way, and we are observing exciting activity with the addition of TUS to the VEN+AZA standard treatment,” said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. “The data presented today reveal complete responses across patients with diverse mutations, including TP53-mutated/CK AML and FLT3-wildtype AML patients. TUS appears to have tremendous opportunity in the largest markets and the most challenging of AML cases.”

Abstracts are available on the EHA2025 website here. The presentation is available on the Aptose website here.

TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study

The tuspetinib-based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 clinical study with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Indeed, responses were also in R/R AML patients with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes.

The TUSCANY Phase 1/2 study, being conducted at 10 leading U.S. clinical sites by elite clinical investigators, is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS, is being administered in 28-day cycles. 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.

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