Cloverleaf Bio has closed a $33 million seed financing round led by 4BIO Capital, with participation from AbbVie Ventures, Eli Lilly and Company, Boehringer Ingelheim Venture Fund, Draper Associates, Mission BioCapital and American Cancer Society BrightEdge. The New Haven, Connecticut-based Yale University spinout is developing engineered transfer RNA (tRNA, molecules that help cells produce proteins) payloads for cancer. Proceeds will support an inhibitory tRNA program targeting hepatocellular carcinoma through early clinical testing and an antibody-tRNA conjugate program for colorectal cancer through preclinical development. Cloverleaf says its platform selectively and durably inhibits multiple RNA-modifying enzymes on which proliferating cancer cells become abnormally dependent. Its lead compound, CLB-001, showed greater potency and selectivity for cancer cells than healthy cells in preclinical studies, retained activity against cancer cell lines resistant to frontline chemotherapy and current-generation antibody-drug conjugate payloads, and outperformed frontline standard of care in hepatocellular carcinoma and lung adenocarcinoma models at substantially lower doses. Animal tolerability studies found no increases in liver-damage markers or signs of systemic toxicity across the tested dose range. The company said strategic participation by three major pharmaceutical venture arms at the preclinical stage reflects industry interest in the platform and founding team. Cloverleaf also credited early support from the National Cancer Institute's Small Business Innovation Research and Small Business Technology Transfer program and said federally funded research was foundational to the platform's development.