Shanghai, China, December 22, 2021 - Genor Biopharma (Stock code: 6998.HK) announced today that the company has submitted a clinical trial application to the Bellberry HREC Ethics Committee in Australia on December 20 for the first-in-human (FIH) clinical trial of GB263T, a novel EGFR/cMET/cMET trispecific therapeutic antibody, in patients with advanced malignant tumors.
GB263T is the world's first EGFR/cMET/cMET trispecific antibody, which has been designed as a trispecific antibody targeting EGFR and two different cMet epitopes. The trispecific antibody has two Fabs to bind EGFR. Its Fc fragment has been mutated to enhance Fc functions. Thus, GB263T with a highly differentiated design exhibits multiple action mechanisms to inhibit primary and secondary EGFR mutations and cMet signaling pathway simultaneously. The significant anti-tumor activities have been demonstrated by in vitro studies and in vivo animal models.
Preclinical studies showed GB263T potently blocked ligand-induced phosphorylation of EGFR and c-Met, and demonstrated better dual inhibition of EGFR and cMet signaling pathways compared to theJNJ analogue. GB263T effectively induced internalization of EGFR and cMet, and downregulated the expression levels of both EGFR and cMet proteins. The in vivo anti-cancer efficacy of GB263T was demonstrated in five different tumor models, including Ba/F3 containing EGFR exon20_D770_N771insSVD mutation model, Ba/F3 with EGFR exon20_D770DEL_ins_GY mutation model, Ba/F3 containing EGFR exon19 del/T790M/C797S mutation model, HCC827/ER1 and LU2503 NSCLC patient-derived xenograft (PDX) model with Met exon14 skipping mutation. In all the models studied, GB263T demonstrated significant tumor inhibition dose-dependently. In addition, GB263T did not show any major toxicities in monkeys, even at a high dose given for four weeks in a GLP tox study.
Genor Biopharma is simultaneously preparing the clinical trial applications for this innovative drug in the United States and China.
