CBX

 Innovent has initiated a phase 1 study (NCT06349408 ) of IBI3001, a bispecific ADC that targets B7-H3 and EGFR, in patients with solid tumors. Additionally, Innovent is conducting a phase 1 trial ( NCT05774873 ) of IBI344, a bispecific antibody that also targets B7-H3 and EGFR. Schematic overview of crosstalk between the EGFR signaling and the B7/CD28 family Recent research has suggested that the overexpression of novel B7/CD28 family proteins, including B7-H3 may be linked to EGFR signaling and could potentially lead to resistance to EGFR-targeted treatments by promoting an immune-depressed environment within the tumor microenvironment. IBI3001 According to the statement by Innovent, IBI3001 is a  site-specifically glycan-conjugated ADC that consists of a topoisomerase I inhibitor  with  multiple anti-tumor mechanisms of action : (1) enhanced EGFR signaling blockade; (2) EGFR- and B7-H3-aided payload internalization and cytotoxicity; and (3) potent bystander killing effects of ADC.

 Beigene has registered a Phase 1 clinical trial ( NCT06233942 ) of BG-C9074, an anti-B7H4 antibody-drug conjugate (ADC), as monotherapy or in combination with tislelizumab: enrolling approximately 150 patients with pretreated solid tumors. The study (still no IND application submission in China yet) is estimated to start in May 2024, which is in line with the target for 2024 H1. BG-C9074 According to the Beigene slide deck, BG-C9074, a novel B7-H4-targeted ADC with a drug-to-antibody ratio (DAR) of 6 , is designed to balance efficacy and toxicity, utilizing DualityBio ADC technology.  BG-C9074 The efficacy of BG-C9074 was evaluated in a B7-H4 low/heterogeneous PDX model, as measured by tumor volume reduction. The 10 mpk dose resulted in a greater degree of tumor shrinkage compared to the 3 mpk dose. B7-H4 low/heterogeneous PDX model In addition to BG-C9074, Beigene plans to initiate another ADC targeting B7-H3 with stable DAR8 and a strong bystander effect. -------------------------