On December 9, 2024 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated targeted agents to treat hematologic malignancies, reported a wealth of clinical data for Aptose’s lead compound tuspetinib (TUS) in a poster presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego (Press release, Aptose Biosciences, DEC 9, 2024, View Source [SID1234648889]).

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Poster title: "Phase 1 Safety and Efficacy of Tuspetinib Plus Venetoclax Combination Therapy in Study Participants with Relapsed or Refractory Acute Myeloid Leukemia (AML) Support Exploration of Triplet Combination Therapy of Tuspetinib Plus Venetoclax and Azacitidine for Newly Diagnosed AML"

Key Findings and Messages:

TUS+VEN+AZA triplet trial is proceeding in newly diagnosed AML patients
TUS+VEN retains activity in the difficult-to-treat prior-VEN AML population
TUS+VEN is active in FLT3 wildtype, representing ~70% of AML patients
TUS+VEN is well tolerated and can be safely co-administered
TUS+VEN is active across broad populations of R/R AML
Combination of TUS with VEN may avoid VEN resistance
TUS+VEN+AZA triplet may establish a more effective, mutation agnostic standard of care for chemotherapy ineligible AML patients
Tuspetinib (TUS), being developed by Aptose and originally created by Hanmi Pharmaceutical Co., is being advanced as the TUS+VEN+AZA triplet (tuspetinib+venetoclax+azacitidine) for frontline therapy of newly diagnosed AML patients ineligible for intensive chemotherapy. TUS is a once daily, oral, multi-kinase inhibitor selectively targeting kinases that drive AML cell proliferation. In the Phase 1/2 APTIVATE trial of relapsed/refractory (R/R) AML patients (NCT03850574), TUS single agent and the TUS+VEN doublet demonstrated excellent safety and broad efficacy across AML genetic subgroups – including those with adverse mutations in TP53 and RAS genes, and those with mutated or unmutated (wildtype) FLT3 genes.

"Our extensive dataset with TUS and TUS+VEN support advancement of the TUS+VEN+AZA triplet frontline therapy and we are pleased to now have the TUSCANY triplet clinical trial up and running," said Rafael Bejar, MD, PhD, Chief Medical Officer at Aptose. "TUS targets known VEN resistance mechanisms, and in combination with VEN, could prevent emergence of resistance to both agents. Moreover, with its breadth of activity and unique safety profile, TUS, as part of a triplet therapy regimen, may target AML’s greatest unmet needs and largest markets."

Highlights of the ASH (Free ASH Whitepaper) poster presentation:

TUS as Single Agent (n= 93 Patients)

60% and 42% CR/CRh with 80 mg TUS in FLT3 mutated and all-comer VEN-naïve AML
33% CRc & 42% ORR (CR, CRp, CRh, CRi or PR) in FLT3 mutated and VEN-naïve patients
Includes 40, 80, 120, and 160 mg TUS dose as a single agent
Includes those who failed prior therapy with venetoclax
Includes those with mutated or unmutated FLT3, those who failed prior-HSCT, priorFLT3i, prior-chemotherapy, prior-HMA
TUS once daily orally as a single agent achieved CR/CRh responses at four different dose levels (40, 80, 120, and 160 mg) with no dose limiting toxicities (no DLTs)
TUS showed a favorable safety profile with no DLTs through 160 mg per day, and no drug related discontinuations, no QTc, no differentiation syndrome, and no deaths
TUS/VEN Combination Therapy (n= 79 Patients)

40% ORR with 80 mg TUS + 400 mg VEN in FLT3 mutated patients. Among these 83% (5/6) had failed prior-VEN treatment and 50% (3/6) had failed both prior-VEN and FLT3i treatment.
TUS+VEN achieved responses among diverse R/R AML with adverse mutations in VEN-naïve, prior-VEN, FLT3WT, FLT3MUT, prior-FLT3
TUS+VEN showed favorable safety and tolerability with no new or unexpected safety signals, no drug related CPK elevations, no differentiation syndrome, and no deaths