ZB-004 (XmAb10717): A Bioengineered CTLA-4-Ig Fusion Protein for Autoimmune Diseases

1. Introduction to ZB-004 (XmAb10717)

1.1. Overview and Therapeutic Class

ZB-004, also identified by the research designation XmAb10717, is an investigational biopharmaceutical agent currently under clinical development.[1] It is a bioengineered fusion protein, specifically classified as a cytotoxic T-lymphocyte-associated antigen 4‑immunoglobulin (CTLA-4-Ig).[3] Functionally, ZB-004 acts as an immunomodulator by selectively inhibiting the costimulatory signals essential for T-lymphocyte activation, a pivotal process in the adaptive immune response.[2] The primary therapeutic focus for ZB-004 is the treatment of autoimmune diseases, conditions wherein aberrant T-cell activity contributes significantly to pathogenesis.[1]

ZB-004 represents a second-generation therapeutic within the CTLA-4-Ig class. This classification is underscored by its design, which incorporates specific bioengineering modifications aimed at optimizing its pharmacological profile relative to earlier CTLA-4-Ig molecules, such as abatacept. The explicit design goals for ZB-004 include "increased binding affinity" to its target ligands (CD80 and CD86) and an "extended half-life".[3] These enhancements are intended to build upon the clinically validated mechanism of action of CTLA-4-Ig [7] by potentially offering superior pharmacological properties. Such improvements could manifest as enhanced efficacy, possibly due to more potent target engagement, and improved patient convenience through a less frequent dosing schedule.

1.2. Originator and Current Developer