Discovery and characterization of COVA322, a clinical-stage bispecific TNF/IL-17A inhibitor for the treatment of inflammatory diseases

Abstract

Biologic treatment options such as tumor necrosis factor (TNF) inhibitors have revolutionized the treatment of inflammatory diseases, including rheumatoid arthritis. Recent data suggest, however, that full and long-lasting responses to TNF inhibitors are limited because of the activation of the pro-inflammatory T_H17/interleukin (IL)-17 pathway in patients. Therefore, dual TNF/IL-17A inhibition is an attractive avenue to achieve superior efficacy levels in such diseases. Based on the marketed anti-TNF antibody adalimumab, we generated the bispecific TNF/IL-17A-binding FynomAb COVA322. FynomAbs are fusion proteins of an antibody and a Fyn SH3-derived binding protein. COVA322 was characterized in detail and showed a remarkable ability to inhibit TNF and IL-17A in vitro and in vivo. Through its unique mode-of-action of inhibiting simultaneously TNF and the IL-17A homodimer, COVA322 represents a promising drug candidate for the treatment of inflammatory diseases. COVA322 is currently being tested in a Phase 1b/2a study in psoriasis (ClinicalTrials.gov Identifier: NCT02243787).

Keywords:

• bispecific antibody
• FynomAb
• IL-17
• inflammatory diseases
• TNF

Disclosure of Potential Conflicts of Interest

All authors are or have been employees of Covagen AG.

Acknowledgments

We would like to thank Dr Nadja Prang for her valuable help and advise on the manufacturing process for COVA322.

Author Contributions

MS, WL, RW, WZ, NB, SB, RS isolated the anti-IL-17A Fynomer and characterized COVA322 in vitro. IAT, UvdB, SKF performed all mice experiments. WL, IAT, BSch and ML designed and executed preclinical development including non-clinical toxicology testing. MS, JB and DG wrote and edited the manuscript. MS, JB, DG designed and planned the study.

Supplemental Material

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