CD180 is at the backbone of the Abacus technology. CD180 is a pattern recognition receptor (PRR) expressed on the surface of all antigen-presenting cells (APCs). CD180 normally functions to recognize pathogens and, together with other PRRs, to program APCs to induce effective and potent protective immune responses. Abacus has harnessed the CD180 program by creating novel immunotherapeutic proteins that both bind to CD180 and deliver virus or cancer antigens (Ags) into the immune system. Our recombinant Ag-CD180 proteins induce strong protective and therapeutic immune responses against both viruses and cancers. Abacus has developed an immunotherapeutic for the treatment of patients infected with hepatitis B virus (HBV), a major cause of liver cancer. Our HBV-CD180 drug, SB-301, induces potent immune responses in nonhuman primates (NHPs) and is ready for clinical development.
Abacus was founded in 2015 from technology originally developed by Edward A Clark at the University of Washington (UW). Dr. Clark’s lab has helped to discover and characterize important drug targets on immune cells including CD20, CD40 and CD80. During the last 10 years, the Clark lab screened a variety of monoclonal antibodies (mAbs) to cell surface receptors for their ability to deliver antigens (Ags) attached to the mAbs into the immune system and program effective immune responses, a method called ‘antigen-targeting’. They found that the CD180 (RP105) receptor met all their criteria for an ideal antigen targeting receptor. First, a single inoculation of an Ag attached to a mAb to CD180 (Ag-CD180) could program strong Ag-specific antibody and cytotoxic T cell responses, without the need for the addition of a nonspecific immunostimulant (adjuvant) that might induce toxic side effects. Second, Ag-CD180 not only activated dendritic cells (DCs), the antigen-presenting cells most immunotherapeutic approaches have focused on, but also programmed a second class of APCs, B cells. This is an important finding since B cell APCs are especially effective at overcoming immunosuppressive effects of viruses and cancers. Indeed, the presence of B cells in tumors such as ovarian and breast cancers correlates with a better long-term prognosis. Third, a single inoculation of a West Nile virus (WNV) Ag attached to anti-CD180 (WNV-CD180) protected mice from an otherwise lethal viral infection, and a single inoculation of a tumor Ag surrogate (OVA) attached to anti-CD180 (OVA-CD180) protected mice from an otherwise lethal cancer expressing OVA. These proof of concept data demonstrated that the CD180 platform technology could be used for both viral and cancer immunotherapies. The Clark lab filed patents based on proof-of-concept studies demonstrating the efficacy of the Ag-CD180 platform technology, and Abacus Bioscience has licensed these patents from the UW.
Abacus Bioscience in conjunction with the Clark lab has developed single chain antibody (scAb) and single chain fragment (scFv) recombinant protein immunotherapeutics containing components of a mAb developed by Clark and his colleagues that binds both human and non-human primate (NHP) CD180. For proof-of-concept studies in NHPs, we selected Ags expressed by HBV since HBV is both a chronic viral infection and a leading cause of liver cancer and because there is no cure for the over 300 million chronic hepatitis B (CHB) patients. Compositions of recombinant proteins were designed, which contain anti-CD180 attached to either HBV Ags known to activate cytotoxic T cells to kill HBV-infected cells- the HBV core Ag (HBcAg)- or HBV Ags known to induce neutralizing Abs that block HBV from infecting hepatocytes- (HBpreSAg). Two recombinant candidate immunotherapeutics were expressed, purified and shown to bind to and activate human B cells. They were then tested in macaques and found to induce strong and HBV-specific CD4 and CD8 T cell responses and antibody responses, including neutralizing Abs to HBV. Patents based on these findings have been filed and licensed to Abacus.
TAbacus Bioscience is focused on developing novel and game changing immunotherapies for treating chronic infectious diseases and cancers. Abacus is developing a broad-based platform that can plug-and-play with multiple cancer or viral antigens.