Model-informed drug development (MIDD) has an important role to play at various stages of drug development. In this case study, the application of MIDD in the early clinical development of a small-molecule inhibitor of sickle hemoglobin (Hb) polymerization is highlighted. Starting from the setting of quantitative criteria, to using a combination of PKPD and semi-mechanistic RBC modeling, and key biomarker analysis, based on data from a healthy participant first-in-human (FIH) study and historical data, we chart the strategic approaches planned and taken to inform decisions for the program, and the role of cross-functional collaboration. Based on the projections from the PKPD and semi-mechanistic RBC models, and key biomarker results from healthy participants, an informed decision was made to not proceed to a Phase 1b study in sickle cell disease (SCD) patients, underscoring the value of MIDD in early drug development decision making.
Lim et al. (2026) studied this question.