Verseau is advancing a pipeline of first-in-class monoclonal antibodies (mAbs) that bind to novel targets and repolarize macrophages. Verseau’s lead candidates VTX-0811 targeting PSGL-1 and VTX-1218 targeting VSIG4 are rapidly progressing toward the clinic. PSGL-1 and VSIG4 are involved in different macrophage pathways, have distinct immune cell expression profiles, and show high macrophage expression across a wide range of tumor indications, with some indications offering clear advantages for one of our targets compared to the other. Together our two lead macrophage programs provide a diverse approach to repolarizing macrophages to enhance the treatment of solid tumors.
*3SBio has exercised option rights to manufacture, perform clinical studies, and commercialize VTX-0811 and VTX-1218 in the Greater China region.
VTX-0811 is a mAb that binds to PSGL-1 (P-selectin glycoprotein ligand-1), an adhesion molecule involved in immune cell trafficking in response to tissue injury or inflammation. Verseau discovered that modulation of a specific epitope on PSGL-1 can lead to M2 to M1 macrophage repolarization, without impacting the normal function of PSGL-1. Upon binding to PSGL-1, VTX-0811 induces tumor microenvironment activation, which leads to T-cell activation and naïve immune cell recruitment amounting to a coordinated immune attack on tumors. In ex vivo studies using patient-derived primary tumors, VTX-0811 demonstrated a greater inflammatory response compared to current immunotherapies in both PD-1 responsive and non-responsive tumors. VTX-0811 has been shown to have favorable anti-tumor response compared to PD-1 treatment in a variety of syngeneic preclinical tumor models, as well as a humanized mouse PDX melanoma model (see figure below).
Anti-Tumor Response in Humanized Mouse PDX Melanoma Model
(VTX-0811 compared with PD-1)
VTX-1218 is a mAb that binds to VSIG4 (V-set and immunoglobulin domain containing 4), a type-I receptor from the B7-like family that is highly expressed on tumor-associated macrophages and dendritic cells across most tumor types. VTX-1218 repolarizes macrophages to a pro-inflammatory state, activates T-cells and attracts other immune cells to generate a coordinated and powerful antitumor response. Compared with VTX-0811, VTX-1218 impacts different molecular pathways regulating macrophage biology and has distinct expression profiles across immune cell populations, as well as higher target expression in a number of tumors. In ex vivo studies using patient-derived primary tumors. VTX-1218 has been found to have greater tumor microenvironment immune activation compared to PD-1, as well as to the clinical stage macrophage repolarizer, ILT4. In addition, VTX-0811 has been found to have favorable anti-tumor activity in syngeneic mouse tumor studies, including in combination with PD-1 (see figure below).