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

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.