Robert M. Garbaccio

Robert Garbaccio

Associate Vice President
Discovery Chemistry, CCAT
Merck & Co., Inc.
Kenilworth, NJ


Investigation of a Site-Specific Antibody-Peptide Conjugate as a Long-Acting GLPR1r/ GCGr Agonist

A long-acting dual agonist of the GLP1/glucagon receptors was developed through site-specific conjugation of an active peptide to a silent antibody through PEG linkers of different length. It was observed that the stability and potency of the resulting conjugates could be optimized by the nature of the linker as well as the position of conjugation on the antibody. A set of conjugates were evaluated in rodent pharmacokinetic and disease model studies and demonstrated to have potent and long acting activity reflecting their in vitro profile. Thorough metabolic characterization of the conjugates in vivo revealed peptide metabolism to potentially be limiting to this strategy.



Robert M. Garbaccio1, Paul Carrington2, Maribel Beaumont3, Gulesi Ayanoglu3, Wolfgang Seghezzi3, Shraddha Sadekar3, Isabel Figueroa3, Mohammad Tabrizifard3, Grigori Ermakov3, Xiaoyan Du3, Yaoli Song3, Michael Judo3, Sheena Mumick4, Dennis Gately5, Anthony Manibusan5, Nick Knudsen5, Elisabetta Bianchi6, Federica Orvieto6


1 Merck Global Chemistry, Kenilworth, NJ, USA; 2 Merck Biology, Diabetes, San Francisco, CA, USA; 3 Merck Biologics, Palo Alto, CA, USA; 4 Merck In Vitro Pharmacology, Kenilworth, NJ, USA; 5 Ambrx, San Diego, CA, USA; 6 IRBM, Pomezia, Italy

Lecture Images

Robert Garbaccio presenting at APS2019 Robert Garbaccio presenting at APS2019 Robert Garbaccio presenting at APS2019