Abstract: Aspects of the present application provide for methods and apparatuses for modeling, simulating, and treating hereditary angioedema (HAE). According to some aspects, a quantitative systems pharmacology (QSP) model is provided for simulating the efficacy of drug intervention under context of HAE pathophysiology. The QSP model may comprise a plurality of individual models including one or more PK models and/or one or more PD models for simulating drug exposure, target engagements and acute attack rate in HAE patients. A virtual patient population representing a plurality of virtual patients may be developed and input into the QSP model for executing a virtual clinical trial. In some embodiments, the QSP model may be used evaluate a response of the contact system and/or an effectiveness of a therapeutic intervention for treating HAE.