Artificial intelligence-driven drug developer Insilico Medicine introduced LEGION, an AI workflow designed to exhaustively generate and cover chemical space around the NLRP3 inflammatory target, addressing two key industry challenges: efficiently identifying novel drug candidates amidst a vast universe of over 10⁶⁰ molecules; and preempting competitive patenting of similar compounds. Insilico applied LEGION to their oral NLRP3 inhibitor candidate ISM8969, completing IND-enabling studies aiming for clinical development in Parkinson’s disease and other indications. LEGION’s scalable enumeration and optimization framework seeks to both accelerate discovery and build competitive intellectual property barriers, heralding a new standard in AI-driven drug innovation. This approach was detailed in a preprint uploaded to ChemRxiv.