Aptose Enrollment is Open for 160 mg Dosing Cohort of Tuspetinib in Phase 1/2 TUSCANY Trial of Frontline Triple Drug Therapy

Executive Summary

• Aptose Biosciences announced that the Cohort Safety Review Committee (CSRC) has approved escalating the tuspetinib (TUS) dose from 120 mg to 160 mg in the Phase 1/2 TUSCANY trial for newly diagnosed AML, based on favorable safety and efficacy data from the first three cohorts (40 mg, 80 mg, and 120 mg).
• The company reported no dose-limiting toxicities (DLTs) and no need for dose reductions to the standard-of-care venetoclax/azacitidine backbone across the completed cohorts, with some patients achieving complete remission (CR) and minimal residual disease (MRD) negativity.
• Aptose received a third advance of US$1.1 million from Hanmi Pharmaceutical under an existing US$8.5 million loan facility, bringing the total amount received to US$5.6 million to date.

Key Details

• Dose Escalation: The CSRC approved escalation to 160 mg TUS dosing; enrollment is now open for this dose level.
• Safety Profile: No dose-limiting toxicities (DLTs) were reported in the 40 mg, 80 mg, and 120 mg cohorts. No prolonged myelosuppression was observed in Cycle 1 for subjects in remission. No dose reductions were required for the standard-of-care VEN/AZA combination.
• Efficacy Signals: Patients treated in the 120 mg cohort remain on study. Previous data presented at EHA 2025 showed CRs and MRD negativity across diverse mutations.
• Specific Patient Populations: Patients with adverse biallelic TP53 or FLT3-ITD mutations, and those without FLT3 mutations, safely achieved complete remissions with MRD negativity.
• Financing Update: Aptose received an additional US$1.1M advance from Hanmi Pharmaceutical.
• Loan Facility Status: The total aggregate amount received under the US$8.5M Loan Agreement (announced June 20, 2025) is now US$5.6M.
• Trial Design: The TUSCANY Phase 1/2 trial tests various doses/schedules of TUS with standard AZA and VEN for newly diagnosed AML patients ineligible for induction chemotherapy.
• Enrollment Metrics: The trial is conducted at 10 leading U.S. clinical sites with an anticipated enrollment of 18-24 patients by late 2025.

Notable Quotes

• “Data from three cohorts, with a 40, 80 or 120 mg dose of TUS in the TUS+VEN+AZA triplet, continue to build a strong case for TUS as a therapeutic option for some of the most difficult to treat AML populations,” said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. “In particular, patients with adverse biallelic TP53 or FLT3-ITD mutations, and those without FLT3 mutations, were able to safely achieve complete remissions with MRD negativity. After review of the most recent safety and efficacy data, our CSRC recommended that we continue to escalate dosing.”