Driving Expression of Differentiation Genes
SY-1425 is an oral first-in-class selective retinoic acid receptor alpha (RARα) agonist that is currently in a Phase 2 clinical trial to assess its efficacy and safety in combination with azacitidine, a standard-of-care therapy, in genomically defined subsets of acute myeloid leukemia (AML) patients.
Using our gene control platform to analyze cells from patients' tumors, we discovered subsets of AML and MDS patients with highly specialized regulatory regions of DNA, known as super-enhancers, associated with the RARA and IRF8 genes. These super-enhancers lock cells in an immature, undifferentiated and proliferative state. We developed biomarkers to identify these subsets of patients.
Initial data from the ongoing Phase 2 study in biomarker-positive AML patients showed that SY-1425 in combination with azacitidine had high response rates and rapid onset of responses in biomarker-positive newly diagnosed AML patients who are not suitable candidates for standard chemotherapy. The initial data also showed that SY-1425 in combination with azacitidine was generally well-tolerated with no increase in toxicities beyond what has been previously seen with either agent alone.
The clinical data to date, coupled with preclinical data on SY-1425 in combination with other standard-of-care and targeted agents, lead us to believe that SY-1425 may have broad potential as a combination agent for patients with AML and a related blood disorder known as higher-risk myelodysplastic syndrome (MDS) who are positive for our RARA and IRF8 biomarkers.