Tuspetinib for AML


Product Mechanism Ownership Indication Preclinical Clinical Stage Phase 1/2
Tuspetinib* Myeloid Kinase Aptose WW AML
AML Preclinical Phase complete
in progress
Clinical Stage Phase 1/2 Phase in progress

The Story Behind Tuspetinib

Tuspetinib, formerly HM43239, is a potent oral Myeloid Kinome Inhibitor (MKI) being developed for the treatment of patients with AML

The History of Tuspetinib

Tuspetinib (HM43239) was originally discovered by Hanmi Pharmaceutical. Initial in vitro and in vivo work suggested that tuspetinib specifically targets mutations commonly found in AML patients, while overcoming drug resistance observed with currently approved drugs. Based on its unique and promising preclinical profile, Hanmi advanced tuspetinib to a Phase 1 clinical study enrolling patients initially in South Korea and later also in the United States. In October 2018, tuspetinib was granted Orphan Drug Designation (ODD) in AML in the US. On November 4, 2021, Aptose and Hanmi entered into an exclusive worldwide license agreement for the development and commercialization of tuspetinib, and on January 1, 2022, Aptose took over the management of the ongoing study and clinical program. The dose escalation portion of the ongoing study thus far has delivered multiple complete responses in a diverse set of patients with various AML genotypes, and no toxicity trends that prevent further dose escalation to date.

The Profile of Tuspetinib

Tuspetinib is an oral genotype-agnostic small molecule inhibitor of a constellation of kinases operative in myeloid malignancies and known to be involved in tumor proliferation, resistance to therapy, and differentiation. Specifically, tuspetinib is a potent inhibitor of FLT3, SYK, cKITMUT, JAK, and other kinases. Regarding FLT3, tuspetinib is highly active in vivo against FLT3 internal tandem duplication (ITD), as well as resistance-conferring D835 and gatekeeper (F691) tyrosine kinase domain (TKD) mutations. In vivo murine xenograft models suggest superior antitumor activity and favorable tolerability relative to established kinase inhibitor in AML, including gilteritinib (FLT3 inhibitor) and entospletinib (SYK inhibitor). Additionally, in vivo xenograft models suggest synergy with inhibitors of DNMT, BCL-2, and other key therapeutic targets, highlighting the combinatorial optionality of tuspetinib in AML.

Clinical Development

Phase 1/2 Clinical Study of Tuspetinib (HM43239)

The international Phase 1/2 open-label dose-escalation clinical trial of tuspetinib is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamic responses of tuspetinib in patients with relapsed or refractory AML. Aptose has completed Phase 1/2 dose escalation and dose exploration of tuspetinib (formerly HM43239), an oral, myeloid kinase inhibitor in an international Phase 1/2 trial in patients with relapsed or refractory AML and is now recruiting patients for the expansion trial. The company has identified a safe therapeutic range with a broad therapeutic window, spanning the dose levels of 40, 80, 120 and 160 milligrams, and has selected 120 milligrams as the initiating single agent expansion dose and 80mg as the initiating dose selected for combination with venetoclax.

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Posters & Presentations

Posters & Presentations

Our robust library includes numerous publications, including presentations, posters, and other media that provide additional information on our drug candidates, pre-clinical and clinical studies.

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