A pharmacologically relevant species is an animal in which the drug recognizes its target and produces the intended biological effect. For denosumab, a fully human IgG2 antibody against RANKL, that species turned out to be the cynomolgus monkey, because ordinary mice and rats cannot recognize the antibody’s target at all. The review record shows the full evidence chain: binding, selectivity, functional activity, and in vivo response, with knock-in mice and an OPG-Fc surrogate filling the gaps. Why species selection is the first make-or-break decision In nonclinical development of an antibody, the choice of species is not a logistical detail. It decides whether every later pharmacology and toxicology result can be…