Seminars

Translational risk remains a major challenge in obesity and kidney disease drug development, often leading to uncertainty in preclinical decision-making. In obesity, the success of GLP-1 therapies has set a new benchmark, driving the development of both novel mechanisms beyond GLP-1 and combination strategies to address its limitations, including nausea, muscle loss, and weight regain. However, conventional preclinical evaluation based on body weight alone often fails to distinguish true pharmacological efficacy from adverse effect–driven outcomes.

Translational risk remains a major challenge in oncology and immunology drug discovery. In oncology, the complexity of the tumor microenvironment and the growing diversity of therapeutic modalities—including antibody-drug conjugates (ADCs) and protein degraders—make it difficult to evaluate efficacy and predict clinical outcomes using conventional preclinical models. In immunology, disease heterogeneity and fundamental differences between rodent and human immune systems often limit confidence in target validation and candidate selection.