HER2 and TROP2 are co-expressed in a wide range of tumor types. Of note, TROP2 was also expressed in many HER2-low solid tumors, such as HER2-low breast cancers, suggesting broad therapeutic indications of YH012. YH012 demonstrated superior internalization compared to its parental monospecific Abs. YH012 was shown to increase tumor cell specificity and minimize side effects in normal cells. YH012 showed increased anti-tumor activity in both HER2-high and HER2-low CDX and PDX models, as well as durable efficacy than benchmarks, indicating that YH012 has strong therapeutic potential, especially in HER2-low expressing cancers. By targeting dual TAAs, YH012 has the potential to increase tumor specificity and potency, reduce toxicity, and overcome tumor heterogeneity. The backbone of YH012 molecule is constructed using RenLite plus knobs-into-holes technology, offering excellent BsAb assembly efficiency, good physicochemical properties and CMC developability.