AMG966 / Amgen - LARVOL DELTA

DEVELOPMENT AND CHARACTERIZATION OF SL-846: A HALF-LIFE EXTENDED, DUAL-RECEPTOR (DR3 X IL23RA) TARGETING BISPECIFIC ANTIBODY (UEGW 2026) - "However, TL1A blocking monoclonal antibodies cause high rates of anti-drug antibody formation, and this propensity was compounded in a bispecific format, leading to >95% ADA, nearly all neutralizing, in the case of AMG966 (TL1A x TNFα) and RG6730 (TL1A x IL-23p40)...In healthy donor and IBD patient PBMC assays, SL-846 blocked combined TL1A- and IL-23–induced IFNγ, IL-17A/F and IL-22 production with efficacy equivalent to individual monotherapy agents or combined SL-325 (anti-DR3 mAb) plus Risankizumab or icotrokinra treatment controls... Together, these data demonstrate that SL-846 is a potent, dual-specific antagonist of TL1A and IL-23 signaling. Its dual-receptor targeting and durable antagonism support its potential as a first-in-class bispecific therapeutic with superior efficacy prospects for the treatment of IL-23 and TL1A-driven inflammatory diseases."

Bispecific • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • CD123 • IFNG • IL17A • IL22 • IL23A • TNFA

Immune Complex Formation Is Associated With Loss of Tolerance and an Antibody Response to Both Drug and Target. (PubMed, Front Immunol) - "In addition to ADA against AMG 966, antibodies to endogenous TNFα were also detected in the sera of subjects dosed with AMG 966. This suggests that the formation of immune complexes between a therapeutic and target can cause loss of tolerance and elicit an antibody response against the target."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • TNFA