VivoGenie Anti-Human EGFR (Necitumumab) - Fc Reduced Biosimilar (IVMB0516)

Epidermal growth factor receptor (EGFR, also known as ErbB1 or HER-1) belongs to the receptor tyrosine kinase superfamily and is a transmembrane glycoprotein that activates various signaling pathways fundamental to cellular proliferation, differentiation, and survival^{1, 2}. EGFR plays important roles during embryogenesis, organogenesis, and in the growth, differentiation, maintenance, and repair of adult tissues², including autophagy³. EGFR is also a host factor that facilitates viral entry for hepatitis B⁴, hepatitis C⁵, and gastroenteritis⁶ and plays a role in SARS-CoV-2 infection^{7, 8, 9}. Dysregulation, somatic mutation, and/or altered signaling of EGFR are associated with disease (Parkinson’s², Alzheimer’s^1,2, and amyotrophic lateral sclerosis²) and various cancers (lung, glioblastoma, brain, breast, colorectal, ovarian)³. Additionally, in cancer, aberrant activation of EGFR is associated with increased cell proliferation, invasion, metastasis, angiogenesis, and decreased apoptosis¹⁰. As such, EGFR is the target of multiple cancer therapies, including monoclonal humanized antibodies, such as necitumumab, as well as selective small molecule inhibitors.

Necitumumab inhibits EGFR-dependent tumor cell proliferation and metastasis¹¹ by acting as an EGFR antagonist that binds specifically and with high affinity to human EGFR, thereby blocking ligand binding and neutralizing ligand-induced EGFR phosphorylation and downstream signaling pathways^{10, 11, 12}. Anti-tumor activity has been demonstrated in vitro and in vivo ¹⁰, and necitumumab is FDA approved for treatment of adult patients with locally advanced or metastatic EGFR-expressing squamous non-small cell lung cancer¹¹. In vitro studies have shown that necitumumab induces internationalization and degradation of EGFR, leading to antibody-dependent cellular cytotoxicity in EGFR-expressing cells^{10, 11}. Necitumumab was generated from the Dyax Corp proprietary phage display library by ImClone Systems, a wholly owned subsidiary of Eli Lilly¹⁰.