LM-364TME

LM-364TME is a next-generation, conditionally active antibody-drug conjugate (ADC) targeting Nectin-4, developed by LaNova Medicines. It is designed to address the on-target, off-tumor toxicities (such as skin rash and neuropathy) associated with first-generation Nectin-4 ADCs like enfortumab vedotin. The drug utilizes a humanized antibody engineered for adenine nucleotide (ANP)-dependent binding, ensuring high affinity in the tumor microenvironment (where ANP levels are high) while maintaining negligible binding in healthy tissues. LM-364TME features a topoisomerase I inhibitor payload conjugated via a cleavable linker with a drug-to-antibody ratio (DAR) of 8. Preclinical studies have demonstrated potent anti-tumor activity across various models, including urothelial, esophageal, and cervical cancers, with a favorable safety profile in rodents and non-human primates.