Dr. Rafael Bejar reports

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

Data from Aptose Biosciences Inc.'s 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 plus VEN plus AZA triplet) was presented yesterday in an oral presentation at the European Hematology Association Congress (EHA 2026) in Stockholm, Sweden.

• Addition of TUS to standard of care VEN+AZA creates a well-tolerated and mutation agnostic front-line triple drug therapy for newly diagnosed AML;
• 32 AML patients dosed across 40 milligrams, 80 mg, 120 mg and 160 mg TUS with TUS plus VEN plus AZA triplet;
• Composite complete response (CRc) rate in evaluable patients across all dosing groups was 86.2 per cent;
• MRD-negativity in patients who achieved a CR/CRh response was 86.4 per cent;
• AML patients with diverse genetics, including TP53-mutated, complex karyotypes and unmutated FLT3, safely achieved responses and MRD negativity.

The TUS plus VEN plus AZA triplet is being developed as a mutation agnostic front-line therapy to treat large, mutationally unrestricted and diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy. Nikolai Podoltsev, MD, PhD, associate professor medical oncology and hematology, clinical director, malignant hematology, Yale School of Medicine, and an investigator in the Tuscany study, reported updated safety and efficacy data from the 80 mg and 120 mg dose cohorts, as well as new data from the 160 mg dose of TUS in the TUS plus VEN plus AZA triplet.

"While there have been recent successes with targeted therapy in AML treatment, our multitargeted approach with tuspetinib in combination is showing significant efficacy across mutations that have been historically difficult to treat, including TP53 mutations, where we thus far have achieved CRs in all of the four subjects at the highest dose cohort," said Rafael Bejar, MD, PhD, chief medical officer, Aptose. "As a safe and effective inhibitor of multiple growth factor signalling pathways, the TUS plus VEN plus AZA triplet is a first line combination therapy with the potential to improve outcomes in nearly all AML populations."

The oral presentation at EHA included updated safety, complete remission, minimal residual disease (MRD) assessments and longer duration of follow-up:

Presentation 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:  Nikolai Podoltsev, MD, PhD, associate professor (medical oncology and hematology), department of internal medicine; clinical director, malignant hematology, associate program director, hematology/medical oncology fellowship program, Yale School of Medicine

Key findings:

• 32 (29 response evaluable), newly diagnosed AML patients have received the TUS plus VEN plus AZA combination:
  • Four received the 40 mg dose of TUS, 12 received the 80 mg dose of TUS, three received the 120 mg dose of TUS and 13 received the 160 mg dose;
• The overall CRc rate across dose levels in response evaluable (29) patients was 86.2 per cent:
  • The MRD negative rate among all patients dosed was 62.5 per cent; MRD negative rate in CR/CRh patients was 86.2 per cent.
• At the 160 mg TUS dose level (n equals 13):
  • The overall CRc rate was 76.9 per cent (10 of 13 patients), including eight of 11 (72.7 per cent) with unmutated (or wildtype) FLT3 100-per-cent composite complete remission in all four patients with TP53-mutation with complex karyotype (TP53-mut/CK).
• Regardless of mutation status, TUS is active in newly diagnosed AML patients:
  • MRD-negative responses achieved across diverse genetic populations, including adverse TP53 mutations and CK;
  • Responses continue to evolve with 19 subjects remaining on treatment, including six that moved on to stem cell transplantation.
• TUS can be administered safely with standard-of-care dosing of VEN/AZA:
  • TUS PK properties were not significantly altered by VEN, AZA, anti-fungals or food;
  • No treatment-related deaths;
  • No treatment-related adverse events of QTc prolongation, CPK elevations or differentiation syndrome.

Abstracts are available on the EHA2026 website. The presentation is available on the Aptose website.

Tuscany: TUS plus VEN plus AZA Triplet phase 1/2 study

The tuspetinib-based TUS plus VEN plus AZA triplet therapy is being advanced in the Tuscany phase 1/2 clinical study 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. Earlier Aptivate trials of TUS as a single agent and in combination as TUS plus VEN demonstrated favourable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favourable NPM 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.

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.