Therapeutic peptides are a rapidly expanding class of medicines, driven by the success of long-acting incretin therapies. However, natural peptides face limitations due to rapid degradation, kidney clearance, and short plasma half-lives. Traditional strategies involve chemical modification (e.g., lipid conjugation, cyclization, unnatural amino acids) or genetic engineering (e.g., Fc, albumin fusion proteins). While fusion proteins improve exposure, they are constrained by ribosomal translation, hindering the incorporation of unnatural amino acids, rigid cyclic peptide scaffolds, or non-peptidic linkers.
Antibody-peptide conjugates (APCs) covalently link monoclonal antibodies to chemically engineered peptides. This extends half-life, enables targeted delivery, and provides dual pharmacological activity. Unlike fusion proteins, APCs allow independent optimization of the antibody and peptide. Solid-phase peptide synthesis (SPPS) facilitates the flexible introduction of constrained cyclic structures, non-canonical amino acids, and custom linkers. This design is being applied across various therapeutic areas, including metabolic diseases, oncology, immunology, and rare diseases.
APCs integrate antibodies and bioactive peptides into a single molecule, diverging from traditional ADCs. While ADCs primarily rely on intracellular toxin release, APCs’ peptide modules offer diverse functions, including effector roles, homing signals, lysosomal sorting, immune epitopes, or cell penetration. The antibody component not only targets antigens but can also act as a pharmacokinetic scaffold, modulate immune functions, or directly exert antagonistic activity. This flexible design allows for multiple therapeutic interventions. After antibody-target recognition, the conjugated peptide can exert pharmacological effects through mechanisms such as modulating membrane receptor signaling, mediating lysosomal degradation, penetrating cell membranes, or remodeling the local disease microenvironment.
Medicilon Antibody Platform
Medicilon’s antibody drug R&D platform has accumulated numerous clients from well-known pharmaceutical companies and research institutions worldwide since its establishment. As of June 2026, Medicilon has successfully supported 49 antibody drugs (including mAbs, BsAbs, and TsAbs) in obtaining clinical trial approvals.
Medicilon’s antibody discovery platform integrates hybridoma, single B cell, and other technologies. Utilizing extensive experience in customized antibody development, Medicilon offers diverse immunization methods (proteins, peptides, small molecule compounds, and whole cells) to meet various project antigen requirements. Their single B cell antibody preparation technology provides rapid, high-throughput screening of specific antibodies with naturally paired heavy and light chains. Medicilon also offers services including expression cell line construction, ADC conjugation, antibody drug CMC studies, and GLP-compliant preclinical efficacy, pharmacokinetic, and safety evaluations, providing end-to-end support from discovery to IND filing.
Medicilon Peptide Platform
Medicilon peptide R&D platform leverages mRNA display technology to create diverse peptide/cyclic peptide libraries (over 10¹³), facilitating the discovery of high-affinity macrocyclic peptides. mRNA display offers advantages over phage display, including larger library capacity, greater diversity, shorter screening times, and the ability to incorporate unnatural amino acids via a cell-free PURE in vitro translation system.
The platform supports both solid-phase and liquid-phase peptide synthesis, allowing for the incorporation of natural and unnatural amino acids. It employs various cyclization chemistries, such as disulfide bridges, thioether bonds, Click chemistry, and DBX cyclization. Notably, DBX cyclization uses meta/para-dibromoxylene-mediated cysteine thioether stapling to create rigid bicyclic peptides, enhancing plasma stability and target affinity. To address enzymatic stability issues, Medicilon utilizes strategies like cleavage site modification and serum albumin binding optimization.
With capabilities in peptide synthesis, screening, and analysis, Medicilon integrates AI-assisted design and screening to streamline the R&D process from sequence design to candidate selection. Medicilon also offers comprehensive preclinical research services for peptide drugs, as demonstrated by its full suite of services for semaglutide injection, encompassing efficacy, pharmacokinetics, and safety evaluation.
Core Capabilities of the APC
Medicilon’s APC service platform offers comprehensive, one-stop R&D solutions for conjugated drugs, from target identification to IND filing. This platform integrates peptide, ADC, and small nucleic acid technologies, leveraging expertise in several key areas:
- Molecular design and feasibility assessment: Medicilon helps clients evaluate antibody-peptide compatibility, target combination strategies, linker design, conjugation site selection, and DAR control, providing recommendations based on developability analysis. The ADC platform contributes over 200 linkers and 30 payloads for APC project design and optimization.
- Peptide payload synthesis and optimization: Utilizing mRNA display and solid/liquid-phase synthesis, Medicilon screens and optimizes peptide sequences from diverse libraries through modifications like unnatural amino acid incorporation, cyclization, and fatty acid or PEG conjugation.
- Antibody preparation and engineering: Services include antibody discovery, recombinant expression and purification, and quality attribute control, with experience in high-expression cell line construction.
- Site-specific conjugation process: Medicilon employs various conjugation chemistries, including Click chemistry (DBCO-azide), maleimide-thiol, enzymatic conjugation (e.g., mTGase), and site-specific conjugation via antibody site mutation. Flexible process selection and precise DAR control are achieved through methods like TCEP reduction and quantitative addition, coupled with AEX for efficient purification.
- Analytical characterization: The platform is equipped with AEX, SEC, UPLC-MS, and TOF-MS for conjugate purification, DAR distribution analysis, molecular weight confirmation, and impurity characterization, with routine tests including HPLC/UPLC, LC-MS, CE-SDS, SEC, IEC, and peptide mapping.
- In vitro/in vivo pharmacology and PK/PD evaluation: Medicilon’s pharmacology department has established over 1,100 efficacy models, including more than 800 oncology models (xenograft, orthotopic, syngeneic, transgenic, humanized, PDXO/PDX organoid, and standard-of-care resistant) and approximately 300 non-oncology models covering inflammation, autoimmune, neurological, metabolic, cardiovascular, and digestive system diseases. Large animal models (non-human primates, dogs, rabbits, minipigs) are also available for standard and customized disease development. For PK/PD, the platform offers systematic analytical and evaluation methods for biotherapeutics like peptides, monoclonal antibodies, and conjugated drugs, encompassing in vitro/in vivo PK, DMPK, and large animal biopsy platforms.
- Preclinical safety and IND filing: With NMPA GLP accreditation, Medicilon provides pharmacokinetic and safety evaluations compliant with NMPA, FDA, and other international GLP standards, supporting IND dossier preparation and regulatory strategy consulting.
Medicilon’s Deep Engagement in Early-Stage APC R&D
Medicilon is deeply engaged in early-stage R&D for APCs and other diversified conjugated drugs, pushing the boundaries of innovative therapeutics. Through innovative technologies and integrated services, Medicilon supports the conjugated drug industry. As of June 2026, the company has facilitated clinical trial approvals for 36 ADCs. Meanwhile, innovative conjugation formats continue to emerge, reflecting the industry’s advancement toward more complex and multifunctional antibody therapeutics. Medicilon has established technology platforms and R&D service systems covering multiple categories, including degrader-antibody conjugates (DACs), antibody-oligonucleotide conjugates (AOCs), and APCs, showcasing its expertise in bioconjugates.
Summary
Antibody conjugation can extend the half-life of peptide drugs, reducing dosing frequency. For antibodies with limited pharmacological activity, peptides can broaden therapeutic mechanisms. Chemical conjugation offers a flexible approach for fusion proteins that are difficult to modify. Medicilon’s platform supports programs in metabolic diseases (dual-target synergy, long-acting dosing), oncology, immunology, and rare diseases.
Medicilon’s APC service platform provides integrated support from early discovery to IND filing, with flexible collaboration options for molecular design, peptide synthesis, antibody discovery, conjugation process development, analytical characterization, and pharmacological evaluation. Contact Medicilon’s business team for details on their APC platform and project support.
Reference:
- [1] Fei Xie, et al. Antibody peptide conjugates as multifunctional therapeutics: Mechanisms, challenges, and prospects. Acta Pharmaceutica Sinica B. 3 August 2026
- [2] Junming Yie, et al. Design and therapeutic rationale of antibody-peptide conjugates: insights from maridebart cafraglutide (AMG133) and emerging applications. Antib Ther. 2026 Jun 1;9(3):367-380. doi: 10.1093/abt/tbag029. eCollection 2026 Jul.
