Tamibarotene for MDS and AML

Tamibarotene (formerly SY-1425) is an oral selective retinoic acid receptor alpha (RARα) agonist we are developing for genomically defined subsets of patients whose disease is characterized by the overexpression of the RARA gene. Approximately 50% of MDS patients and 30% of AML patients have RARA overexpression. When RARα is expressed in excess of its tightly controlled natural ligand, cells in the bone marrow may not differentiate into healthy myeloid cells, which can lead to hematological malignancies. However, when oral tamibarotene is administered, tamibarotene binds to RARα, allowing for the restoration of gene expression and myeloid differentiation.

We are currently investigating tamibarotene in our Phase 3 SELECT-MDS-1 trial in newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) patients with RARA overexpression as well as in our randomized Phase 2 SELECT-AML-1 trial in newly diagnosed unfit acute myeloid leukemia (AML) patients with RARA overexpression. High response rates, rapid onset of responses and clinically meaningful durability were shown in a Phase 2 study of tamibarotene in combination with azacitidine in newly diagnosed AML patients with RARA overexpression who are not suitable candidates for standard chemotherapy. Data also showed that tamibarotene in combination with azacitidine was generally well tolerated, with no increase in toxicities beyond what has been previously seen with either agent alone. Additionally, data from a translational analysis of these trial patients also suggest that patients with RARA overexpression may be less likely to respond to the current standard of care.