A-TAP (Antibody-Targeted Anti-vasculogenic Payload) is a fully biological payload platform . It involves the linking of highly potent anti-angiogenic properties of a protein variant with the proven selectivity and anti-tumor activities of tumor-targeting monoclonal antibodies. The genetic combination of the protein variant to an antibody, or an antibody fragment generates a fusion molecule that provides excellent anti-angiogenic and anti-vasculogenic effector functionalities. A-TAP can be applied to antibodies to increase their potency, diversify their functions or generate innovative multifunctional product candidates.
The A-TAP fusion is essentially a “bi-targeted” and poly-functional molecule. The antibody part of the fusion will not only have the ability to deliver the protein payload to the therapeutic locale to inhibit angiogenesis and vasculogenic mimicry, but will also provide anti-tumor signal through the interaction with its own receptors. In addition, the antibody could provide ADCC or CDC functions thereby synergistically augmenting the anti-tumor effects of antibody-TAP.
Over and beyond, independent of the delivery by the targeting antibody, the payload could generate anti-angiogenesis and anti-vasculogenic mimicry functionalities by interacting via its own cellular pathways such as binding to integrins and/or wnt/catenin pathway(s).
There are several unique properties of A-TAP fusions that make them highly differentiated from bevacizumab. For example, they have significantly enhanced anti-angiogenesis functionality, and profound inhibition of vasculogenic mimicry (i.e. the formation of an alternative tumor vasculature assembled directly from tumor cells) relative to no inhibition of VM by bevacizumab.
Both in vivo and in vitro proof of concept of A-TAP have been already established by Anti-HER2-TAP and Anti-EGFR-TAP. The pharmacokinetic data indicate that the A-TAP fusion has a significantly longer half-life in vivo, amounting to several days as compared to only a couple of hours for the TAP payload without its fusion to the targeting antibody.
Comparison with ADC (Antibody Drug Conjugate)
Unlike ADCs (Antibody Drug Conjugates), which involves covalent conjugation of chemical drugs to antibodies, A-TAP is a fully biological payload that genetically fuses endostatin-P125A to antibodies.
The A-TAP fusion can be produced recombinantly in commercial cell lines and thus is less complex as well as less expensive relative to the in vitro chemical conjugation and follow up purification to generate ADCs.
A-TAP serves as a building block for creating next generation polyfunctional therapeutic antibodies.
A-TAP is the only biological payload, outside of cytokines (which have significant toxicity issues) that could generate both “biobetter” and first-in-line products.
A-TAP also provides several benefits that are not possible by ADCs including its ability to utilize both internalizable as well as non-internalizable targets, as compared to ADC’s utility in internalizable targets only.