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Biological Principles, Applications and AMG133 Case Study of Antibody-Peptide Conjugates (APCs)

Abstract:

Therapeutic peptides have emerged as an important class of medicines, fueled by the success of long-acting incretin therapies. However, their broader application remains limited by rapid proteolytic degradation, fast renal clearance, and short plasma half-lives. Antibody-peptide conjugates (APCs) have recently emerged as a promising modality that combines the prolonged systemic exposure and targeting capability of monoclonal antibodies with the pharmacological versatility of chemically optimized peptides. Unlike fusion proteins, APCs enable independent optimization of the antibody and peptide, allowing incorporation of unnatural amino acids, cyclic structures, and other chemical modifications that are difficult to achieve through recombinant expression. This presentation will discuss the biological rationale and molecular design principles underlying APCs, using the GIPR antagonistic mAb/GLP-1R peptide agonist conjugate maridebart cafraglutide (AMG133) as a representative example. We will illustrate how APCs can integrate complementary mechanisms of action while achieving pharmacokinetic profiles that are challenging to obtain with conventional fusion proteins. Emerging APC strategies across metabolic disease, oncology, and other therapeutic areas will also be highlighted to demonstrate how different disease requirements drive APC design. Finally, we will discuss key opportunities and remaining challenges for this rapidly evolving platform, and why APCs may represent an important next generation of biologics for therapeutic mechanisms that cannot be fully addressed by peptides or antibodies alone.

Sppeaker Bio:

Dr. Junming Yie currently serves as the Chief Scientific Officer of the Biopharmaceutical R&D Center at Shenzhen Salubris Pharmaceuticals. He received his bachelor’s degree from the University of Science and Technology of China (USTC), earned his Ph.D. with distinction in Biochemistry and Molecular Biophysics from Columbia University College of Physicians and Surgeons, and completed his postdoctoral training at Harvard Medical School/Dana-Farber Cancer Institute. He also holds an MBA from the University of California, Los Angeles (UCLA).

Dr. Yie brings more than 21 years of research and drug development experience from leading biopharmaceutical companies, including Pfizer, Amgen, and Merck. His expertise spans the full spectrum of biologics and small-molecule drug development, from discovery research to CMC, with a focus on metabolic diseases, oncology, and autoimmune diseases. Dr. Yie has successfully initiated and led numerous programs from concept through clinical development. Representative programs include AMG133 (MariTide), efruxifermin (AMG876), and late-stage development of sotatercept.

Dr. Yie returned to China in 2022 and served as Chief Scientific Officer at Ark Biopharmaceuticals before joining Salubris in 2024. Throughout his career, he has remained deeply engaged in innovative drug discovery and has published numerous influential scientific papers in leading international journals, including Nature, Cell, Proceedings of the National Academy of Sciences (PNAS), and Science Translational Medicine.