Early-stage drug discovery is often hindered by two major challenges. The first is identifying initial hits against difficult-to-drug targets. The second is advancing HTS-derived hits into high-quality lead candidates. Many hits fail due to off-target activity, poor ADME-Tox profiles, limited SAR opportunities, or insufficient tractability for medicinal chemistry optimization. These limitations can slow project progression and reduce the likelihood of discovering differentiated candidates, highlighting the growing interest in innovative approaches to improve both hit identification and hit expansion.