▎WuXi AppTec Content Team Report

Public information shows that the ATP (adenosine triphosphate) - adenosine pathway is one of the key immune regulatory mechanisms in the tumor microenvironment.CD39 and CD73 proteins are key enzymes affecting this pathway.Among them, CD39 is a transmembrane ecto-ATPase-1 with two transmembrane domains and an extracellular domain. Its active site is located on the extracellular domain, and the interaction between the two transmembrane domains may also affect its enzymatic activity. CD73 is an ecto-5'-nucleotidase that exists as a homodimer on the cell surface and can also be present in a free form in the extracellular space.

CD39 converts ATP into AMP (adenosine monophosphate), CD73 catalyzes the conversion of AMP into adenosine, and adenosine can inhibit immune cell function by binding to receptors on the surface of tumor cells.Studies show that simultaneously blocking the functions of CD39 and CD73 can synergistically enhance anti-tumor effects.

According to the announcement by Huahai Pharmaceutical, HB0046 is a bispecific antibody independently developed by Huaota.Composed of a VHH (variable domain of heavy chain) fragment against CD39 and a monoclonal antibody against CD73.This bispecific antibody has high affinity for CD39 and CD73, and can effectively inhibit the enzymatic activity of both membrane-bound and soluble CD39 and CD73. It demonstrates significant synergistic effects in the inhibition of CD39 and CD73 enzymatic activity as well as ATP-mediated T cell proliferation suppression.

Multiple solid tumor and hematological tumor models have shown that HB0046 exhibits excellent anti-tumor effects; preclinical trials conducted in non-human primates have demonstrated non-linear pharmacokinetic characteristics, good plasma stability, a long half-life, and satisfactory pharmacokinetic properties; toxicology studies have indicated that HB0046 has good safety and tolerability.