Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Biologic therapeutics such as TNF inhibitors have revolutionized the treatment of inflammatory diseases, including rheumatoid arthritis (RA), psoriasis and psoriatic arthritis. However, there is still a significant unmet medical need in these indications. In RA for example, only about half of all patients achieve an ACR50 score and many become refractory to anti-TNF treatment after a few years. Several studies in preclinical mouse models of arthritis have demonstrated that simultaneous treatment with antibodies to TNF and IL-17 is significantly more efficacious than treatment with either antibody alone. We present here the non-clinical safety package of COVA322, a bispecific TNF/IL-17A inhibitor that is currently being tested in a Phase Ib/IIa study in psoriasis patients.
Methods: COVA322 was analyzed for its cross-reactivity in a GLP study with human and Cynomolgus tissues. In addition, a cytokine release study using human whole blood cells was performed. In Cynomolgus monkeys, COVA322 was tested in a single dose PK/dose range finding study and a GLP 4-week repeat-dose toxicity study at 5, 25 and 100mg/kg doses.
Results: COVA322 showed no unexpected tissue cross-reactivity and no indication for the potential to cause a cytokine release syndrome. COVA322 was well tolerated in single- and repeat-dose toxicity studies in Cynomolgus monkeys. In particular, no adverse effects on the cardiovascular-, respiratory- and central nervous system were observed. The toxicology package (no observed adverse effect level (NOAEL) = 100mg/kg) support the clinical starting dose as well as the anticipated clinical dose range.
Conclusion: COVA322 is a unique bispecific TNF/IL-17A inhibitor, which was well tolerated in non-clinical safety studies. The non-clinical data package supports the planned dose range for the currently ongoing first in man, single dose escalation, tolerability, safety, PK and efficacy Phase Ib/IIa study in psoriasis.
Disclosure:
W. Lembke,
Covagen AG,
3,
Covagen AG,
1;
B. Schlereth,
Covagen AG,
3,
Covagen AG,
1;
J. Bertschinger,
Covagen AG,
4,
Covagen AG,
1,
Covagen AG,
3;
D. Grabulovski,
Covagen AG,
1,
Covagen AG,
3,
Covagen AG,
4;
M. Locher,
Covagen AG,
1,
Covagen AG,
3.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cova322-a-clinical-stage-bispecific-tnfil-17a-inhibitor-for-the-treatment-of-inflammatory-diseases/