Dr. William Rice reports

APTOSE REPORTS EARLY DATA DEMONSTRATING TUSPETINIB IMPROVES STANDARD OF CARE TREATMENT ACROSS DIVERSE POPULATIONS OF NEWLY DIAGNOSED AML IN phase 1/2 Tuscany TRIAL

Aptose Biosciences Inc. today provided a data update from the phase 1/2 Tuscany trial in newly diagnosed AML. The trial was initiated in December, 2024, and the growing body of positive data includes the recently completed third cohort of 120-milligram TUS in the TUS+VEN+AZA triplet therapy. Data to date from 10 patients across all three cohorts, 40 mg, 80 mg or 120 mg TUS dose in TUS+VEN+AZA, support the use of TUS with standard of care treatment across all AML populations, including those carrying mutations that are the most difficult to treat and those with mutated and unmutated (wildtype) FLT3 genes.

The TUS+VEN+AZA triplet is being developed as a safe and well-tolerated mutation agnostic front-line therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy. At the 120 mg TUS dose level in combination with VEN+AZA, as with the prior reported 40 mg and 80 mg TUS dose cohorts, no significant safety concerns or dose limiting toxicities (DLTs) have been observed in the Tuscany trial, including no prolonged myelosuppression in cycle 1 of subjects in remission, no reports of drug-related QTc prolongation or differentiation syndrome (DS), and no treatment-related deaths. Nine out of 10 dosed patients remain on study across all dose cohorts and enrolment is being advanced to the 160 mg TUS dose level following the cohort safety review committee (CSRC) meeting.

"We already have data from three different TUS dose levels in the Tuscany trial, and the data continue to strengthen at higher doses of TUS and over time. We are building a strong case for TUS+VEN+AZA as a triplet front-line therapy of choice to address a broad AML population, including subgroups with the most adverse of mutations," said William G. Rice, PhD, chairman, president and chief executive officer of Aptose.

Data highlights

"As illustrated in the data highlights, the addition of TUS to VEN+AZA appears to boost response rates and MRD-negativity while maintaining favourable safety and tolerability," said Rafael Bejar, MD, PhD, chief medical officer of Aptose, "And the 100 per cent CR/CRh and 100 per cent MRD-negativity rates among the five biallelic TP53-mutant, FLT3-ITD and RAS-mutant AML cases are exciting to see, as this can correlate with longer overall survival. We have observed a trend towards achieving CRs more quickly at the higher dose levels, so we are keen to see the activity as we advance into the 160 mg TUS dose cohort."

Key messages:

• Addition of TUS to VEN+AZA demonstrates excellent CR/CRh rates:
  • 100 per cent 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 seven of nine (78 per cent) 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;
• Broad-spectrum activity including patients with adverse TP53, RAS and FLT3-ITD mutations;
• No loss of MRD-negativity observed to date, including in one patient with over seven months of follow-up;
• MRD-negativity and remissions continue to mature over time on therapy;
• No relapses reported to date and no treatment related deaths;
• The only non-responder was a patient at the initial TUS dose level (40 mg) that did not achieve TUS exposures previously associated with response.

Additional data are included in the new Aptose corporate presentation on-line.

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 trial with the goal of creating an improved front-line therapy for newly diagnosed AML patients that is active across diverse AML populations, durable and well tolerated.

The Tuscany triplet phase 1/2 study, being conducted at 10 leading United States 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 to 24 patients by late 2025. Data will be released as they become available.

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 lead clinical-stage, oral kinase inhibitor tuspetinib (TUS) has demonstrated activity as a monotherapy and in combination therapy in patients with relapsed or refractory acute myeloid leukemia (AML) and is being developed as a front-line triplet therapy in newly diagnosed AML.

We seek Safe Harbor.