Modern molecules are artworks: masterpieces of design. Everything about them is carefully thought out. Their size, binding sites, active and inactive elements, choice of antigens, residues, toxins, and linkers. Even size and proportions come into play when we are directing cells to interact. Whether we are aiming for blocking, simple binding, or activation is dictated by the epitope targeted. If we link a toxin to an epitope, we want targeted toxicity. We need to think about how to aim for clinical differentiation that illustrates the effect we are targeting. If we are binding more than one molecule, we have to know whether that binding involves two sites on a single cell or two different cells. How large is the construct? How close are we bringing cells together? Does it work as we imagined? Is translation robust? Can we buttress our claims with references to solid publications?

How can we visualize what we are doing? How will we differentiate ourselves against other medicines? What questions will regulators have? What do clinicians want to know? What concerns will payers raise, and what will other players in the market say?

Taking the time to comprehend the biology in depth, allowing ourselves to ask the simple questions and understanding the underlying medicine are critical at every stage of therapeutic or diagnostic development. They allow us to be far more exact in our clinical plans, anticipate regulatory questions and build a secure scientific basis for differentiation. The biology has to come first.