Drug discovery and development is a complex and tedious process that requires a significant amount of resources and capital investment (~USD 2.6 billion). In fact, on an average, the journey from the establishment of initial proof-of-concept to commercial launch, is estimated to take around 10-12 years. However, only a small fraction of early stage therapeutic candidates are able to make it past preclinical testing, into clinical evaluation. Further, even fewer clinical stage candidates are eventually approved for commercialization. Given the growing complexity in drug discovery research, the overall expenditure on pharmaceutical / biotechnology R&D has steadily increased over time. Specifically, in 2019, R&D spending was estimated to be around USD 182 billion, with more than 16,000 drug molecules evaluated during the course of the whole year. The industry is presently under tremendous pressure to not only identify ways to mitigate the risks of failure of drug discovery programs, but also to meet the expectations / medical needs of a growing patient population.
Despite its many advantages, high-throughput screening (HTS) is an expensive process and pharmacological leads generated via this process have been associated with high attrition rates during preclinical development. In addition, this approach is also limited in terms of the number of compounds that can be developed and stored in compound libraries. Fragment-based drug discovery (FBDD), is a relatively new hit screening approach. which has been shown to offer a number of benefits, including a cost advantage and the potential to enable the generation of hits with improved physiochemical properties, over HTS. In this context, it is worth highlighting that three marketed drugs, namely Vemurafenib (ZELBORAF®), Venetoclax (VENCLEXTA®), and Erdafitinib (BALVERSA™), originated from fragment-based library screens. Nearly 40 candidates discovered via the FBDD approach are in clinical trials.