ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1491

Discovery and Characterization of COVA322, a Clinical Stage Bispecific TNF/IL-17A Inhibitor for the Treatment of Inflammatory Diseases

Dragan Grabulovski, Michela Silacci, Wibke Lembke, Wenjuan Zha, Richard Woods, Roger Santimaria, Julian Bertschinger and Mathias Locher, Covagen AG, Schlieren, Switzerland

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Novel therapies, Biosimilars, Strategies and Mechanisms in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Biologics such as TNF inhibitors have revolutionized the treatment of inflammatory diseases including rheumatoid arthritis (RA), psoriasis and psoriatic arthritis. However, recent data suggest that full and long-lasting responses to TNF inhibitors are limited because of the activation of the pro-inflammatory TH17/IL-17 pathway in patients. Therefore, an attractive avenue to achieve superior efficacy levels in inflammatory diseases represents the combined inhibition of TNF and IL-17A. We present here COVA322, a bispecific TNF/IL-17A inhibitor that is currently being tested in a Phase Ib/IIa study in psoriasis patients.

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 characterized for its stability, dual binding characteristics, and IL-17A and TNF inhibition properties, including the inhibition of human T cell derived cytokines.

Results: The fusion of the anti-IL-17A Fynomer to the fully human anti-TNF antibody did not alter the favorable biophysical properties of the antibody: COVA322 was monomeric and its stability was comparable to the stability of the unmodified antibody. Furthermore, COVA322 could be produced and purified with very high yields (3.3 g/L obtained from our 1000 L GMP run). Importantly, COVA322 inhibited TNF and IL-17A with picomolar inhibition potencies as shown in a variety of different cell assays. Moreover, we could show that COVA322 was able to inhibit human derived cytokines from different donors.

Conclusion: COVA322 is a unique bispecific TNF/IL-17A inhibitor with excellent biophysical properties. It is currently being tested in a first in man, single dose escalation, tolerability, safety, PK and efficacy Phase Ib/IIa study in psoriasis.

Disclosure:

D. Grabulovski,

Covagen AG,

1,

Covagen AG,

3,

Covagen AG,

4;

M. Silacci,

Covagen AG,

1,

Covagen AG,

3;

W. Lembke,

Covagen AG,

3,

Covagen AG,

1;

W. Zha,

Covagen AG,

1,

Covagen AG,

3;

R. Woods,

Covagen AG,

1,

Covagen AG,

3;

R. Santimaria,

Covagen AG,

3;

J. Bertschinger,

Covagen AG,

4,

Covagen AG,

1,

Covagen AG,

3;

M. Locher,

Covagen AG,

1,

Covagen AG,

3.

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/discovery-and-characterization-of-cova322-a-clinical-stage-bispecific-tnfil-17a-inhibitor-for-the-treatment-of-inflammatory-diseases/