AMT-562

AMT-562 is an antibody-drug conjugate (ADC) developed by Multitude Therapeutics for the treatment of solid tumors, including colorectal, gastric, and non-small cell lung cancers. It consists of a humanized monoclonal antibody targeting HER3 (ErbB3), conjugated site-specifically to the cytotoxic payload exatecan via a valine-alanine cleavable linker with a drug-to-antibody ratio (DAR) of 8.0. The anti-HER3 antibody component (Ab562) was selected for moderate affinity to minimize toxicity and improve tumor penetration. Upon binding to HER3-expressing tumor cells, the ADC is internalized and releases exatecan intracellularly, leading to DNA damage and cancer cell death. Preclinical studies have shown that AMT-562 demonstrates potent antitumor activity in models with low HER3 expression and in tumors resistant to other HER3-targeted ADCs such as Patritumab-GGFG-DXd (U3-1402). The drug has favorable pharmacokinetic and safety profiles in animal models and is currently being evaluated in phase I clinical trials for solid tumors[1][2][4][5][6]. AMT‑562 uses exatecan as its cytotoxic payload, which has higher potency than DXd used in some other ADCs; it shows particular promise against tumors with low or heterogeneous HER3 expression or resistance to prior anti-HER3 therapies[1][2][5]. Clinical development is ongoing.