Background/Purpose: The generation of bispecific antibody molecules with excellent biophysical and pharmacokinetic properties has been a challenging task in the past. We present here COVA322, a bispecific anti-TNF/IL-17A drug candidate moving towards the clinic that shows IgG-like pharmacokinetic properties.

Methods:  Using phage display technology we have isolated Fynomers inhibiting human IL-17A. Fynomers are small binding proteins (7 kDa) derived from the human Fyn SH3 domain which can be engineered to bind to essentially any target of interest with high affinity and specificity. After genetic fusion of the anti-IL-17A Fynomer to a commercially validated anti-TNF antibody, the resulting bispecific molecule COVA322 was injected in mice and cynomolgus monkeys to determine its pharmacokinetic parameters. As controls, the commercially available antibodies adalimumab and golimumab were also injected into animals.

Results: The fusion of the anti-IL-17A Fynomer to the fully human anti-TNF antibody did not alter the favorable pharmacokinetic parameters of the parental anti-TNF antibody. COVA322 demonstrated comparable pharmacokinetic properties in mice and cynomolgus monkeys as adalimumab and golimumab. In addition, we could demonstrate that COVA322 stays fully functional and intact for at least ten days in cynomolgus monkeys, indicating that the Fynomer is not cleaved from the antibody.

Conclusion: These encouraging preclinical results indicate that COVA322 has highly promising pharmacokinetic properties. Through its unique mode-of-action of inhibiting simultaneously TNF and the IL-17A/A homodimer, COVA322 has game changing potential in the treatment of inflammatory diseases.

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« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/cova322-a-novel-bispecific-tumor-necrosis-factor-alpha-interleukin-17a-tnfil-17a-inhibitor-with-excellent-pharmacokinetic-properties-in-mice-and-cynomolgus-monkeys/