ASP-8731: An Investigational BACH1 Inhibitor for Sickle Cell Disease – Development and Discontinuation

I. Introduction to ASP-8731: An Investigational BACH1 Inhibitor

A. Overview of ASP-8731 and Therapeutic Rationale

ASP-8731, also identified by the code ML-0207, is an investigational small molecule drug that was developed as a novel inhibitor of BTB and CNC homolog 1 (BACH1).[1] The primary therapeutic indication for which ASP-8731 was being investigated was sickle cell disease (SCD), a severe and debilitating inherited hemoglobinopathy characterized by chronic hemolysis, vaso-occlusive crises, and progressive organ damage.[3] The fundamental rationale for its development in SCD stemmed from its potential to induce the expression of fetal hemoglobin (HbF). Increased levels of HbF are known to ameliorate the clinical manifestations of SCD by interfering with the polymerization of sickle hemoglobin (HbS).[5] Beyond HbF induction, the inhibition of BACH1 by ASP-8731 was also anticipated to modulate pathways related to oxidative stress and inflammation, which are key contributors to the pathophysiology of SCD.[3]

B. Origin and Development History