Aptose Biosciences is focused on small molecule oncology therapeutics, with first-in-class or best-in-class agents in or nearing clinical development. The company’s goal is to identify niche oncology indications from which genetic or gene expression signatures and validated diagnostic biomarkers may be used to identify the optimal patient population.
The Company’s lead compound, APTO-253, is a small molecule that leads to induction of expression of the master transcription factor, Kruppel-like Factor 4 (KLF4) gene. Epigenetic KLF4 suppression, prevalent in select hematological and solid tumor indications, is considered to be a material driver of the onset of certain subsets of solid and hematologic cancers. KLF4 suppression due to the aberrant expression of another gene, CDX2, could provide a highly specific signature that may be used to identify patients most sensitive to an inducer of KLF4. APTO-253 has demonstrated strong in vitro and in vivo efficacy in relevant AML and hematologic malignant models. Furthermore, the c-Myc oncogene is known to epigenetically acquire super enhancers that dramatically upregulate c-Myc gene expression and contribute to oncogenesis. APTO-253 simultaneously can induce expression of the KLF4 master transcription factor and downregulate expression of the cMyc oncogene in AML cells, leading to apoptotic cell death in AML and other hematologic malignancy cells. Aptose is performing a Phase 1b dose-escalation study at this time in patients with relapsed or refractory blood cancers, including AML, high-risk MDS, lymphomas and multiple myeloma.