Driving Expression of Differentiation Genes in AML Patients
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 AML patients, including those with relapsed or refractory (r/r) AML.
Using our gene control platform, we discovered a subset of AML patients with a highly specialized regulatory region of DNA, known as a super-enhancer, associated with the RARA gene. The super-enhancer locks cells in an immature, undifferentiated and proliferative state. We developed a biomarker to identify this subset of patients.
Initial data from the ongoing Phase 2 study 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.