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Osteogenesis imperfecta (OI) is a heterogeneous group of inherited bone dysplasias characterized by reduced skeletal mass and bone fragility. Although the primary manifestation of the disease involves the skeleton, OI is a generalized connective tissue disorder that requires a multidisciplinary treatment ap- Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?Efficacious human dose prediction is a complex process as compound's biopharmaceutical, pharmacokinetic (PK), and pharmacodynamic (PD) properties informed from preclinical species must be projected to humans. The current knowledge gap was translating pharmacology for patients with osteogenesis imperfecta (OI) because there is not current TGF-β directed treatment. WHAT QUESTION DID THIS STUDY ADDRESS? Evaluation of efficacious dose for a new anti-TGF-β antibody drug candidate (GC2008), for the treatment of OI. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?In this study, we propose the use of a multi-model approach to inform on projected human doses. The tiered modeling approach shown in this work is based on preclinical and sparse clinical PK/PD data in which targeting TGF-β was investigated for the treatment of OI. HOW MIGHT THIS CHANGE DRUG DISCOVERY, DEVELOPMENT, AND/OR THERAPEUTICS?Use of a tiered multi-model approach incorporating mathematical models that evaluate different aspects of disease, can be sued to build confidence in translation projected pharmacology for the treatment of OI.