Introduction
The therapeutic antibody field continues to evolve with modalities such as ADCs, ISACs, AOCs, and RLTs. To meet their precision needs, Xcellon Biologics has developed a modular Fc glycan conjugation platform that delivers highly uniform and stable antibody conjugates at scale.
Traditional cysteine- and lysine-based conjugation approaches, while widely used, often introduce heterogeneity, stability challenges, and compromised effector function. To overcome these limitations, Xcellon Biologics has developed a one-pot site-specific Fc glycan conjugation platform that delivers highly uniform, stable antibody conjugates at scale.
Why Traditional Conjugation Methods Fall Short
The majority of commercial ADCs rely on random conjugation to lysine or engineered cysteine residues. Although effective, these strategies create broad drug-to-antibody ratio (DAR) distributions, impacting:
- Stability – heterogeneous conjugates often aggregate or degrade faster.
- Safety – unpredictable DAR increases risk of off-target effects.
- Efficacy – loss of Fc effector functions can compromise therapeutic performance.
For next-generation antibody therapeutics, precision and reproducibility are no longer optional, they are required.
Xcellon’s Modular Fc Glycan Conjugation Platform
Our platform leverages proprietary chemoenzymatic glycan remodeling to achieve site-specific conjugation at the native Fc glycan (Asn-297).
Key Features:
- Site-specific DAR control – precisely tuned to DAR with exceptional uniformity.
- Broad IgG compatibility – applicable to IgGs and bispecific formats without genetic engineering.
- One-pot workflow – chemoenzymatic transglycosylation with azido disaccharide oxazolines, followed by bioorthogonal “click” chemistry for payload installation.
- Validated payloads – platform demonstrated with diverse small molecules including MMAE, DM1, MMAF, and exatecan.
This modularity allows seamless integration of cytotoxic, immunostimulatory, oligonucleotide, or radionuclide payloads, accelerating timelines for next-gen therapeutics.
Demonstrated Performance
Our Fc glycan conjugation approach has been validated across multiple IgG subclasses and formats, consistently yielding:
- >90% site occupancy with minimal aggregation.
- Homogeneous, stable conjugates with highly reproducible DAR.
- Retained Fc functionality.
- Potent tumor cell killing demonstrated in both in vitro and in vivo models.
- Favorable safety profiles, reducing concerns linked to heterogeneous ADC mixtures.
Why It Matters for the Future of Biologics
The ability to precisely engineer conjugates at the Fc glycan enables more than just better ADCs. This platform opens the door to a broad range of non-canonical modalities:
- ISACs – immune-stimulating antibody conjugates targeting innate immunity.
- AOCs – antibody-oligonucleotide conjugates for targeted gene modulation.
- RLTs – radio-labeled therapeutics for targeted radiation delivery.
- Custom payloads – beyond toxins, including degraders, immune agonists, and nucleic acids.
By combining uniformity, stability, and broad applicability, glycan-based conjugation is poised to become a cornerstone technology for the next wave of antibody therapeutics.
Conclusion
At Xcellon Biologics, we believe antibody conjugation must evolve to meet the demands of emerging modalities. Our modular Fc glycan conjugation platform provides the precision, scalability, and flexibility needed to accelerate development of safer, more effective biologics.
