Abstract 586: Combining advanced peptide screening methods to identify candidates for PDC/RDC/POC development

Abstract Peptide-based therapeutics, including peptide-drug conjugates (PDCs), peptide-radionuclide conjugates (RDCs), and peptide oligonucleotides (POCs), are gaining recognition as highly promising targeted treatment options due to their exceptional specificity, low toxicity, and flexible pharmacokinetic profiles. To expedite the identification of effective peptide candidates, we have developed an advanced peptide discovery platform that combines Peptide Information Compression Technology (PICT), Disulfide-Rich Peptides (DRPs) phage display, animal toxin libraries, nano macrocyclic peptides, and virtual peptide libraries. This cutting-edge platform efficiently discovers multicyclic peptide hits with antibody-like binding affinity (sub-nM to pM), enhanced serum stability (lasting from hours to days), and bi-functional properties optimized to engage multiple receptor targets within a six-month timeframe. Our integrated screening approach employs high-throughput techniques to swiftly identify peptide leads that meet the stringent criteria required for PDC, RDC, and POC development. We have successfully discovered peptide leads with high binding affinity and endocytosis on over 40 targets, including tumor biomarkers such as FAP, Nectin-4, Trop2, GRPR, FGFR2, GPC3 and DLL3. The platform’s combination of diverse peptide libraries and sophisticated computational modeling enhances the selection of candidates with superior binding affinities, structural stability, and functional adaptability. By leveraging these advanced screening technologies, we address the limitations of traditional peptide discovery methods, shortening development timelines and reducing the reliance on extensive medicinal chemistry optimization. Our findings illustrate that this platform significantly streamlines the discovery process for peptide-based therapeutics, establishing a powerful pipeline for the development of next-generation bi-functional peptides with broad applications in oncology, inflammation, and other therapeutic areas. Citation Format: Weiliang Xu, Jin Zhang. Combining advanced peptide screening methods to identify candidates for PDC/RDC/POC development. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 586.