Tuspetinib is Aptose Biosciences’ lead clinical-stage program and a once-daily oral multi-kinase inhibitor being developed as part of a frontline triplet regimen with venetoclax (VEN) and azacitidine (AZA) for newly diagnosed AML. Designed to selectively target key kinases involved in AML pathogenesis while avoiding off-target toxicities associated with other kinase inhibitors, tuspetinib has demonstrated broad activity across AML molecular subtypes, including patients with adverse genetic features. The US FDA granted orphan drug designation to tuspetinib for AML in 2018. Aptose is currently evaluating the TUS+VEN+AZA combination in the Phase I/II TUSCANY study, aiming to improve upon the current frontline standard of care of VEN plus a hypomethylating agent. Supported by encouraging safety and efficacy data from prior tuspetinib monotherapy and combination studies in relapsed/refractory AML, the program has also received strategic support through a Cooperative Research and Development Agreement with the US National Cancer Institute and ongoing development funding from long-term partner Hanmi Pharmaceutical. At EHA 2026, Aptose presented updated clinical data from the TUSCANY study evaluating the TUS+VEN+AZA triplet in newly diagnosed AML patients. As of May 2026 data cutoff:

Key Efficacy Highlights: 

• Overall response rate (ORR; MLFS + CRi + CRh + CR): 81.3%

• Composite complete remission (CRc; CRi + CRh + CR): 78.1%

• CRc rate in response-evaluable patients (n=29): 86.2%

• CR/CRh rate: 68.8%

• Complete remission (CR) rate: 50.0%

• Response Rates by Dose Level: 

 

 

• CRc by Molecular Subgroup

• FLT3-unmutated (n=25): 72.0% 

• FLT3-mutated (n=7): 100% 

• NPM1-mutated (n=5): 80.0% 

• TP53-mutated/complex karyotype (n=10): 70.0% 

• Minimal Residual Disease (MRD) Negativity

• MRD negativity among CRc responders: 76.0%

• MRD negativity rate in all treated patients: 62.5% 

• MRD negativity rate among CR/CRh responders: 86.4% 

• MRD Negativity by Dose Level (Among CRc Responders)

• 40 mg (n=3): 100% 

• 80 mg (n=9): 77.8% 

• 120 mg (n=3): 66.7%

• 160 mg (n=10): 70.0%

 Key Safety Highlights:

• No dose-limiting toxicities (DLTs) reported

• No related non-hematologic serious adverse events (SAEs)

• No QTc prolongation, differentiation syndrome, treatment-related deaths, or treatment discontinuations

KOL insights

“Safe and effective inhibitors capable of targeting multiple growth factor signaling pathways while remaining compatible with the current azacitidine–venetoclax standard of care have the potential to improve outcomes in newly diagnosed AML across diverse molecular subtypes. A mutation-agnostic approach such as tuspetinib may help broaden clinical benefit beyond genetically defined patient populations while preserving tolerability in the frontline setting.” – Expert Opinion

“The combination of tuspetinib, venetoclax, and azacitidine has the potential to benefit a broad population of newly diagnosed AML patients, including those harboring traditionally high-risk or difficult-to-treat genetic abnormalities. By delivering deep responses early in the treatment course, this triplet strategy may improve long-term outcomes and reshape frontline management of AML.”– Expert Opinion

Conclusion 

AML remains a highly aggressive hematologic malignancy, with almost 3,100 people diagnosed annually in the UK, and outcomes remain particularly poor among older newly diagnosed patients who are ineligible for intensive chemotherapy. While venetoclax-based doublets have improved frontline treatment, durable remissions remain challenging, and outcomes are often influenced by underlying molecular risk factors. In this setting, tuspetinib has emerged as a promising addition to the venetoclax-azacitidine backbone, demonstrating high remission rates, encouraging minimal residual disease negativity, and activity across key molecular subgroups, including FLT3-mutated and TP53-mutated/complex karyotype disease. Coupled with a favorable safety profile, absence of unexpected toxicities, and mutation-agnostic activity, the TUS+VEN+AZA triplet has the potential to evolve into a differentiated frontline treatment option and may contribute to redefining the standard of care for newly diagnosed AML.