Pharmacokinetics, Immunogenicity, and Safety of a Modified YTE Antibody in Healthy Adults

Abstract REGN17092, a fully human immunoglobulin (Ig) G1 antibody with M252Y/S254T/T256E (YTE) modification in the Fc portion, was assessed in a first‐in‐human study (ClinicalTrials.gov, NCT05923424). REGN17092 was designed to target the severe acute respiratory coronavirus 2 (SARS‐CoV‐2) S protein. However, due to the emergence of new SARS‐CoV‐2 variants, the program was discontinued. In this single‐center, randomized, placebo‐controlled, single‐ascending‐dose study, participants received a single IV dose of REGN17092 (300, 1200, or 2400 mg) or placebo, or a single SC dose of REGN17092 (300 or 1200) or placebo. Endpoints assessed included pharmacokinetics (PK), safety, and immunogenicity. Allometric scaling was used to predict the terminal half‐life of REGN17092 and to ensure adequate exposure multiples relative to the exposure at the NOAEL. Forty participants were included. Mean concentrations of REGN17092 in serum increased in a dose‐proportional manner and were consistent with linear PK for a single dose administered IV or SC. PK analysis of a single dose of REGN17092 administered IV or SC suggests that REGN17092 has a half‐life of 80–90 days and showed detectable penetration into nasal fluid. No anti‐drug antibody responses were noted. In this Phase 1 study, REGN17092 was tolerable with a long half‐life, highlighting the value of YTE modification.