Over the past 10 years, biopharmaceuticals (BP) - i.e. therapeutic peptides, proteins, and nucleic acids (NA) have witnessed a dramatic acceleration in development and currently represent a growing fraction of all compounds in drug development pipelines. In fact, 24% of biopharmaceutical companies now have BP registered in their R&D remits and an even larger proportion is currently broadening their compound portfolio with BP. The increasing popularity of BP is strongly related to their exquisite specificity at the receptor level, their highly selective mode of action and predictable activity profiles. Such characteristics make it possible to more effectively intervene in disease pathways and to avoid non-specific side effects. This improves both the drug efficacy and safety profile.
Furthermore, BP allow for targeting novel targets that cannot be achieved with small-molecule drugs, enabling the development of entirely new treatments for diseases with serious unmet medical needs. The inclusion of innovative BP in pharmaceutical pipelines is also a strategic option for industry to balance overall R&D risk, to flatten the patent cliff and to build or uphold competitive power. BP thus represent a powerful new class of drugs and their potential is reflected by the recent blockbuster sales of Enbrel, Remicade and Humira (all biologics for arthritis and related diseases). However, large-scale development of BP is restricted by very specific issues including poor stability in vivo, lack of cellular uptake and insufficient capability to reach intracellular targets – and in this relation, the market. Despite significant R&D spending, the real BP potential can only be unlocked once the formulation and delivery issues are resolved. These issues exist at chemical, pharmacological, molecular, (sub-)cellular, tissue and systemic level and hinder successful translation of BP into highly selective medicines.