AMT-116 + AMT-253

AMT-116 + AMT-253 is a **combination of two antibody-drug conjugates (ADCs) targeting distinct tumor-associated antigens in solid tumors**. - **AMT-116** targets **CD44v9**, a variant isoform of CD44 found on various solid tumors (including head and neck, lung, esophageal, pancreatic, colorectal, breast, bladder, hepatic, cervical, and gastric cancers). The ADC uses a humanized anti-CD44v9 IgG1 antibody conjugated to the novel topoisomerase I inhibitor belotecan derivative KL610023 via a hydrolysable linker[3][7]. - **AMT-253** targets **MUC18 (MCAM/CD146)**, overexpressed in melanoma and multiple solid malignancies. AMT-253 consists of an MUC18-specific antibody conjugated to the topoisomerase I inhibitor exatecan using a self-immolative linker. It exhibits potent bystander killing, DNA damage (histone H2A.X phosphorylation), and apoptosis (cleaved caspase-3), with superior stability and therapeutic index compared to comparator ADCs. AMT-253 demonstrates activity in melanoma and in a range of MUC18-expressing tumors, and combination therapy with an antiangiogenic agent enhances efficacy[1][5][8]. Both ADCs are being investigated as monotherapies and are in early-phase clinical development, primarily for advanced solid tumors.