The development of bifunctional/multifunctional therapeutics have gained tremendous traction in recent years. Preclinical efficacy evaluation of bi-functional antibody drugs faces two main problems: first is the often limited cross-reaction between the anti-human antibody and murine target in animals; second is the reduced efficacy as a result of neutralization of antibodies by anti-drug antibodies (ADA) in animals due to the high immunogenicity of some bi-specific antibodies.