Why Breakthrough Drug Discovery Platforms Need Decades to Mature: Lessons from FBDD, DEL, Aptamers, and PROTACs

Abstract Breakthrough hit-finding platforms rarely become routine after the first novel proof-of-concept and realistically take 20−30 years to develop fully. Across FBDD, DEL, Aptamer, and PROTAC drug discovery technologies, the persistent rate-limiting issue in platform development is not the founding concept alone (e.g., chemistry) rather, it is often more likely due to organizations underestimating the time to develop a robust technique in-house and the significant supporting infrastructure and talent required to transform novel technologies into routine hit-finding drug discovery platforms. A consequence for not being “all in” on its development can be a dilution of effort across programs that may lead to fewer clinical candidates and a decrease in ROI. As a result, it can take decades not years to develop a platform. Using lessons learned from these four platforms, this Perspective identifies key (and often unappreciated) hurdles that each new technology needs to resolve before becoming a mainstream hit-finding drug discovery platform driving FDA approvals.