title: 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 TH17/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).
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Michela
authors.initials: M
authors.lastname: Silacci
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Wibke
authors.initials: W
authors.lastname: Lembke
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Woods
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Isabella
authors.initials: I
authors.lastname: Attinger-Toller
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Nadja
authors.initials: N
authors.lastname: Baenziger-Tobler
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Batey
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Santimaria
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Ulrike
authors.initials: U
authors.lastname: von der Bey
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Susann
authors.initials: S
authors.lastname: Koenig-Friedrich
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zha
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schlereth
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Locher
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Julian
authors.initials: J
authors.lastname: Bertschinger
authors.affiliation: a Covagen AG; one of the Janssen Pharmaceutical Companies of Johnson & Johnson ; Wagistrasse 25, 8952 Schlieren , Switzerland.
authors.forename: Dragan
authors.initials: D
authors.lastname: Grabulovski
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D018033:Antibodies, Bispecific; C508717:IL17A protein, human; D020381:Interleukin-17; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: FynomAb; IL-17; TNF; bispecific antibody; inflammatory diseases