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Anti-TNFα monoclonal antibodies, such as adalimumab, have become the standard of care for treating a number of inflammatory and autoimmune diseases, including rheumatoid arthritis, psoriasis, Crohn’s disease, and ulcerative colitis. Many patients undergoing anti-TNF therapy eventually fail to respond to the treatment, even if treatment was previously effective. Furthermore, even in those patients that do respond, only a small subset gains full control of the disease. As such, there is a significant need for better therapeutic interventions.
Angiopoietin-2 (Ang2) is both a growth and inflammatory cytokine that modulates the function of the endothelial cells that are responsible for maintaining the structure and integrity of blood vessels. In many inflammatory diseases, the levels of Ang2 are elevated, and the endothelial cell barrier is disrupted. A single biotherapeutic that simultaneously targets the cytokines TNFα and Ang2, both of which are critically involved in inflammation, has the potential to locally address different components of the inflammatory pathway(s) and, therefore, more effectively treat inflammatory disease.
Zyngenia Inc. is advancing an adalimumab-based therapeutic that also contains a potent anti-Ang2 modular recognition domain. This allows for the simultaneous targeting of TNFα and Ang2, which results in the enhanced clearance of these two inflammatory cytokines. This dual-action makes the Zybody ideally suited for clinical applications in inflammatory diseases, including ulcerative colitis, without any additional immuno-compromising of the patient. Zyngenia Inc. has demonstrated that this Zybody therapeutic exhibits enhanced efficacy over adalimumab alone in preclinical models of colitis and autoimmune polyarthritis. This program is anticipated to be ready for Phase 1 clinical trials in early 2014.