New Therapeutic Modalities: Transforming Drug Discovery and Development

Drug discovery and development has undergone an impressive transformation over recent years driven by the emergence of new chemical modalities. Scientists have seen the expansion of the drug modality toolbox in the strong pursuit of undruggable targets to treat urgent medical needs. As more sophisticated approaches were developed, including new technology innovations to drug delivery, the society has seen the consolidation of novel drug modalities with regulatory approvals of new medicines. In the past 5 years (2018–2022), there has been a rise in the number of Food and Drug Administration (FDA) approvals, including novel modalities beyond the traditional small molecules and biologics. As a result, the field has experienced a boost in different modalities like protein degraders, PROteolysis TArgeting Chimeras (PROTACs), molecular glues, antisense oligonucleotides, small interfering RNA, antibody-drug conjugates, and beyond rule of five molecules. Even within the small-molecule world, exciting new chemical modalities continue to emerge conquering challenging targets, like drugging Kirsten rat sarcoma viral oncogene (KRAS) for the first time. In this chapter, we are describing an overview of the recent breakthroughs leading to marketed drugs within the new therapeutic modalities field.