Antibody-Drug Conjugates (ADC) have rapidly emerged as one of the most transformative classes of targeted therapeutics, especially in oncology.
ADCs combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs, delivering targeted therapy directly to tumor cells and minimizing off-target effects.
Since the first ADC gained FDA approval in 2000, the field has rapidly expanded, resulting in 15 ADCs currently on the market, representing $13.6 billion in sales in 2024. Not far behind in the race for targeted therapies, there are currently over 200 ADC candidates in clinical development, reflecting the growing momentum and investment in this innovative sector.
In this article, we explore the role of ADCs in modern medicine and how Kymos Group can support developers through characterization, quality control and stability studies.
Introduction to ADCs: Structure, mechanism of action and indications
ADCs consist of three main components:
- The antibody: A monoclonal antibody that recognizes and binds to specific antigens expressed on target cells.
- The cytotoxic payload: Highly potent small molecule drug designed to induce cell death or destruction upon internalization. Common payloads include microtubule inhibitors and DNA-damaging agents. Interestingly, despite the rapid expansion of the ADCs, the number of clinically validated payloads remains limited, and the development relies on a narrow set of well-established cytotoxic payloads. However, an emerging advancement is the incorporation of two different cytotoxic agents with complementary mechanisms of action within a single conjugate, resulting in dual-payload ADCs capable of enhancing activity and overcoming resistance.
- The linker: A critical component that binds the antibody to the payload. The linker must be stable enough for the drug to remain attached to the antibody in circulation, preventing premature release, while enabling efficient and controlled release once inside the target cell. The choice of the linker has a significant impact on pharmacokinetics, efficacy, and safety as premature release can lead to off-target toxicity, while an overly stable linker may reduce therapeutic efficacy. Linkers are categorized as cleavable or non-cleavable. Cleavable linkers are designed to exploit intracellular conditions such as enzymatic activities, as well as reductive and acid environment, whereas non-cleavable linkers are designed to remain intact until the ADC is fully internalized and the antibody is degraded within the cell, releasing the active drug.
As suggested by their structure, the mechanism of action of ADCs consists in the specific binding of the antibody with the antigen expressed on the surface of target cells, ADC-antigen complex internalization through endocytosis, drug release by cleavage or antibody degradation, and once released, the drug interferes in critical cellular processes leading to cell death.
ADCs are currently approved for a variety of indications, primarily in oncology, including hematologic malignancies and solid tumors such as breast cancer and urothelial carcinoma. Beyond cancer, ADCs are also being explored in other therapeutic areas such as autoimmune diseases.
ADCs contribute to expanding treatment options for patients with hard-to-treat cancers and enable more precise, better-tolerated therapeutic strategies, ultimately contributing to improved outcomes and a more advanced approach to oncology care.
Kymos Group Supporting ADC analytical challenges
Antibody-Drug Conjugates are structurally complex molecules, combining antibodies, highly potent payloads, and chemical linkers. This complexity creates several key analytical challenges. At Kymos group, we combine state-of-the-art analytical technologies with deep expertise in biopharmaceutical analytics to support ADC developers.
Heterogeneity
ADCs often exist as mixtures with varying drug-to-antibody ratios (DAR), different conjugation sites, and variable payload distribution. Measuring and controlling this heterogeneity is critical for efficacy, safety, and regulatory compliance. At Kymos, we can address these challenges through a comprehensive analytical toolbox and the expertise of our team. Some of our activities include:
- Determination ADC entire mass by LC-MS
- Determination of antibody drug conjugate ratio (DAR) by HPLC
- Analysis of the number and the position of payloads by LC-MS
- Evaluation of glycosylation integrity before and after conjugation by LC-MS
- Prediction of conjugation sites in the monoclonal antibody by peptide mapping (LC-MS/MS)
- Determination of free drug and free drug-related impurities (FDRI) by LC-MS
Stability and Degradation
Linkers can be sensitive to pH, temperature, or enzymatic activity, potentially leading to premature payload release, structural changes, or aggregation. For this reason, stability must be carefully monitored to ensure that all critical quality attributes are maintained throughout the product lifecycle. At Kymos Group, we address these challenges through ICH-compliant stability studies, including long-term, accelerated, in-use, and thermal cycling programs. These studies are supported by a comprehensive analytical panel to evaluate key aspects of ADC such as integrity and biological activity, under a wide range of storage and handling conditions.
Potency and Biological Activity
ADCs must retain both antibody binding and cytotoxic activity, which can be affected by conjugation or degradation. Measuring antibody binding activity and biological function using ELISA and cell-based assays plays a pivotal role in potency determination. At Kymos, we have years of experience working with a wide range of biologics, including ADCs, using both techniques.
Regulatory Compliance
To meet regulatory expectations, ADC developers must provide robust analytical evidence that all critical quality attributes are carefully assessed in both early-stage and commercial ADCs, ensuring readiness for clinical and market release.
Leveraging over 20 years of experience in biologics and fully GMP-certified laboratories, Kymos provides end-to-end support for ADCs with a wide range of both molecule-specific and general analytical techniques.
Conclusions
The growing number of clinical trials evaluating ADCs, together with the increasing number of approved molecules entering the market, has transformed the landscape of targeted therapies. Kymos Group can support ADCs developers across a wide range of analytical needs throughout the product lifecycle, from product characterization and analytical method development and validation to stability studies and quality control testing for routine batch release.
Backed by extensive experience in biologics and GMP-compliant analytical services, Kymos provides the expertise and reliability required to support the successful development and commercialization of ADCs.
If you require assistance with your ADC or other type of biologics, please do contact us or send us an email to commercial@kymos.com
