On December 3, 2024 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral targeted agents to treat hematologic malignancies, reported that the National Cancer Institute (NCI), part of the National Institutes of Health, and Aptose Biosciences Inc. have entered into a Cooperative Research and Development Agreement ("CRADA") (Press release, Aptose Biosciences, DEC 3, 2024, View Source [SID1234648744]). Under the CRADA, the NCI and Aptose will collaborate on the clinical development of Aptose’s proprietary lead clinical-stage compound tuspetinib (TUS), an inhibitor of key signaling kinases involved in myeloid malignancies, in the NCI Cancer Therapy Evaluation Program (CTEP) sponsored myeloMATCH trials employing combinations of targeted therapy for the treatment of molecularly defined acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) populations. These trials will be conducted by NCI’s National Clinical Trials Network (NCTN), with the participation of the NCI Community Oncology Research Program (NCORP) in the U.S. and Canada.

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The myeloMATCH precision medicine trials (NCT05564390), funded by the NCI, were officially launched on May 16, 2024. myeloMATCH aims to expedite the development of tailored drug combination treatments for patients with newly diagnosed AML and MDS and to treat patients with these aggressive cancers of the blood and bone marrow from diagnosis throughout their treatment journey.

"We’re grateful to be a part of NCI’s myeloMATCH precision medicine trials," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. "The executed CRADA will facilitate our collaboration with NCI on clinical studies of novel-novel combinations with early phase II signal finding endpoints in AML and MDS. Tuspetinib will provide the NCI and AML/MDS patients with an investigational agent that can be used to treat a broad spectrum of AML/MDS populations, including those among the most genetically challenging."

"We are indeed privileged to have tuspetinib selected to be part of this one-of-a-kind initiative, which recognizes that significant breakthroughs and higher response rates for AML and MDS may be possible with triplet combination therapies," said Rafael Bejar, M.D., Ph.D., Aptose’s Chief Medical Officer. "We expect that tuseptinib’s safety profile and breadth of activity will make it an ideal combination agent and we are pleased to have NCI’s support in its clinical development."

In addition, Aptose is separately developing tuspetinib as a key component of a triple drug combination (tuspetinib, venetoclax, and azacitidine; TUS+VEN+AZA) in newly diagnosed AML patients unfit for chemotherapy, with plans to begin dosing at the 40 mg dose of tuspetinib that was previously shown active as a single agent in relapsed or refractory AML patients. The dose of tuspetinib then can be further escalated after safety review. The protocol for the Phase 1/2 TUSCANY study of TUS+VEN+AZA in newly diagnosed AML has been submitted to sites and reviewed by the U.S, Food and Drug Administration (FDA). The study is on track to commence during the fourth quarter.

About Tuspetinib

Tuspetinib (TUS) is being developed as a TUS + venetoclax (VEN) + hypomethylating agent (HMA) triple drug combination (or TUS+VEN+HMA triplet) as frontline therapy for newly diagnosed AML patients. Aptose’s APTIVATE Phase 1/2 trial illustrated the safety and breadth of activity of TUS monotherapy and the TUS+VEN doublet combination in relapsed or refractory (R/R) AML patients and supports the launch of the TUS+VEN+HMA (using azacitidine, AZA, as the HMA) triplet frontline therapy in newly diagnosed AML patients. Tuspetinib, a convenient once daily oral agent that potently targets SYK, mutated and wild type forms of FLT3, mutated KIT, JAK1/2, and RSK2 kinases, while avoiding many typical toxicity concerns observed with other agents. In the APTIVATE trial, TUS achieved broad activity across AML patients with a diversity of adverse genetics as a single agent and in combination with venetoclax in a very ill and heavily pre-treated AML population. Blast reductions and objective responses were observed in patients with prior-VEN, prior-FLT3 inhibitor (FLT3i) and prior-HSCT therapies, those with highly adverse genetics – including mutations in TP53 and RAS genes, and those with mutated or unmutated (wildtype) FLT3 genes.