AB1

AB1 is an orally bioavailable, non-cytotoxic small molecule DNA methyltransferase 1 (DNMT1) protein depleter developed by AkiraBio. It is designed to treat sickle cell disease (SCD) by inducing the expression of fetal hemoglobin (HbF). Unlike nucleoside analogs like decitabine, AB1 does not incorporate into DNA, which avoids the cytotoxicity and myelosuppression typically associated with that class of drugs. By depleting DNMT1 protein, AB1 promotes the hypomethylation of the γ-globin gene promoter, leading to increased γ-globin transcription and HbF production. Preclinical studies in mouse models and early clinical data from Phase 1/2 trials (NCT05261711) have shown significant increases in F-cells and HbF levels with a favorable safety profile.