Evicenter
P&T meetings

Tovecimig (CTX-009)

Second-line advanced biliary tract cancer

Also known as ABL001
Last updated
89 sources

Product information and disease descriptionProduct descriptionProduct informationPharmacology

Mechanism of action

4 evidence topics · 4 sources

Dual target: DLL4 and VEGF-A

“Our lead product candidate, tovecimig (formerly known as CTX-009), is a bispecific antibody targeting Delta-like ligand 4 (“DLL4”), a ligand of Notch-1, and vascular endothelial growth factor A (“VEGF-A”). Simultaneous blockade of the VEGF-A and the Notch pathways is known to turn productive angiogenesis into non-productive angiogenesis, which leads to tumor shrinkage and apoptosis.” (opens the source at this quote in a new tab)

“Tovecimig (formerly known as CTX-009) is an investigational bispecific antibody that is designed to simultaneously block the DLL4 and VEGF-A signaling pathways, which are critical to angiogenesis and tumor vascularization.” (opens the source at this quote in a new tab)

Molecular format: anti-VEGF IgG backbone with C-terminal anti-DLL4 single-chain variable fragments

“ABL001 is a bispecific antibody that simultaneously targets both DLL4 and VEGF, by linking each C-terminal of an anti-VEGF antibody (bevacizumab-similar) with a DLL4-binding single-chain Fv (scFv)” (opens the source at this quote in a new tab)

“The ABL001 bispecific antibody consists of an anti-VEGF antibody (bevacizumab-like) backbone C-terminally linked with a DLL4-targeting single-chain variable fragment which shows potent binding affinity to VEGF” (opens the source at this quote in a new tab)

“CTX-009 is a recombinant bispecific antibody that contains two single chain variable fragments (scFv) binding to human DLL4 linked to the C-terminus of heavy chains that bind to human VEGF-A” (opens the source at this quote in a new tab)

Rationale for adding DLL4 blockade to VEGF blockade

“VEGF/VEGFR blockade can inhibit VEGF-driven tumor angiogenesis, and the regression of tumor vessels is dependent on the VEGF signaling pathway. However, VEGF inhibitors alone are not capable of destroying all tumor blood vessels.” (opens the source at this quote in a new tab)

“Several preclinical xenograft studies have demonstrated that DLL4/Notch blockade inhibited tumor progression by promoting hyperproliferation of endothelial cells, which resulted in an increase in vascular density and a decrease in functional tumor vasculature” (opens the source at this quote in a new tab)

“Hence, given that the VEGF/VEGFR signal transduction pathway and the DLL4/Notch signal transduction pathway affect angiogenesis via different mechanisms of action, CTX-009 was designed to block both pathways in a novel therapeutic format” (opens the source at this quote in a new tab)

Target biology in biliary tract cancer

“VEGF-A overexpression has been reported in BTC, correlating with stage, the presence of metastases and prognosis of the disease” (opens the source at this quote in a new tab)

“DLL4 is highly expressed in BTC and up-regulation of DLL4 expression is associated with poor survival in patients with BTC” (opens the source at this quote in a new tab)

“Importantly, DLL4-Notch 1 signaling can be a part of the development of resistance to anti-VEGF therapeutics” (opens the source at this quote in a new tab)