imgatuzumab (RO5083945)

Using an anti-receptor tyrosine kinase-like orphan receptor 1 (ROR1) mAb as a proof-of-concept anchoring arm and an array of affinity-modulated variants of the anti-epidermal growth factor receptor (EGFR) GA201 mAb as active arms, we show in vitro conditional engagement and elimination of double-positive human NCI-H358 non-small cell lung cancer cells over single-positive, non-target NCI-H358.ROR1.KO cells by affinity-modulated TriMab TCEs...Lastly, we demonstrate that the TriMab modality exhibits a favorable developability profile and mAb-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, this work presents a generalizable approach to utilizing the TriMab modality by leveraging avidity effects and molecular geometry to achieve conditional AND-gated dual TAA-targeting with a significantly improved TI.