HM43239 for AML


Product Mechanism Ownership Indication Preclinical Clinical Proof-of-Concept Pivotal
HM43239 Myeloid Kinome Aptose WW AML
AML Preclinical Phase complete
in progress
Clinical Proof-of-Concept Phase in progress
not started
Pivotal Phase not started

The Story Behind HM43239

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

The History of HM43239

HM43239 was originally discovered by Hanmi Pharmaceutical. Initial in vitro and in vivo work suggested that HM43239 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 HM43239 to a Phase 1 clinical study enrolling patients initially in South Korea and later also in the United States. In October 2018, HM43239 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 HM43239, 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 HM43239

HM43239 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, HM43239 is a potent inhibitor of FLT3, SYK, cKITMUT, JAK, and other kinases. Regarding FLT3, HM43239 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 HM43239 in AML.

Clinical Development

Phase 1/2 Clinical Study of HM43239

The international Phase 1/2 open-label dose-escalation clinical trial of HM43239 is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamic responses of HM43239 as a single agent in patients with relapsed or refractory AML. HM43239 is being administered once daily, over a 28-day cycle. The study design includes a traditional 3+3 dose escalation, with the option to expand patient enrollment at each dose level. Once a go-forward dose is identified, the HM43239 program may then transition, as appropriate, to single-agent expansion cohorts in AML, as well as combination studies.

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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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