Receptor.AI Inc. and Sethera Therapeutics announced a strategic research collaboration to establish a closed-loop discovery and optimization workflow for difficult therapeutic targets. Under the collaboration, Sethera will generate and experimentally screen architecture-diverse polymacrocyclic peptide libraries, while Receptor.AI will apply physics-based modeling, artificial intelligence, and multiparameter optimization to interpret data, develop binding hypotheses, prioritize candidate series, and guide optimization cycles. The companies will design, synthesize, and test new candidates, using resulting data to inform each subsequent cycle. Sethera's platform installs one to six stable cross-links to generate polymacrocyclic structures across large, encoded libraries, exploring multiple experimentally accessible topologies. The initial program will focus on a mutually selected hard-to-drug target, with the companies prospectively assessing whether the integrated workflow improves hit confirmation, target selectivity, and lead optimization. Following validation, they intend to pursue additional internal programs and jointly structured discovery collaborations with pharmaceutical and biotechnology partners. Additional terms were not disclosed. Dr. Alan Nafiiev, Founder and CEO of Receptor.AI, and Dr. Karsten Eastman, CEO of Sethera, both commented on the collaboration's potential to create distinctive value through a closed feedback loop and exploration of physical libraries.