Why Life Cycle Integration Is Critical To ADC And XDC Success

By Dr. Campbell Bunce, Chief Scientific Officer, Abzena;, Abzena; and Unmesh Lal, Vice President, Healthcare & Life Sciences, Frost & Sullivan

Antibody drug conjugates (ADCs) have evolved from a niche oncology tool to a mainstream therapeutic modality. According to Frost & Sullivan market research, the global ADC market is projected to reach $22 billion in 2026 with a compound annual growth rate of 23.3% through 2030; this growth is driven by increased clinical validation, regulatory momentum, and a highly productive oncology pipeline. To remain competitive amid ongoing market expansion, developers must account for the core obstacles of ADC development: bioconjugation complexity, vendor limitations, tumor heterogeneity, and linker-payload optimization.

The most costly mistakes in an ADC program are made during upstream development and CMC, and poorly designed bioconjugation chemistry and analytical characterization cannot be corrected in Phase 3. Instead, these missteps become program-ending events or lead to significant approval delays. To ensure a strategic competitive advantage, sponsors — both emerging biotechs and large pharma — must frontload risk identification and mitigation to protect their late-stage programs.

The Growth Of The ADC Field

ADCs have expanded beyond hematological malignancies into solid tumor territory, including HER2-positive breast cancer and Trop2 expressing gastric, breast, and bladder cancers. The chemistry behind ADCs continues to mature, leading to novel linker-payload combinations, site-specific conjugation, and improved control of drug-to-antibody ratio (DAR), thereby broadening the therapeutic window.

The industry is also seeing growth in ADC acquisitions, with large pharma deploying billions into platform deals, including Gilead Sciences’ acquisition of Tubulis and Eli Lilly’s acquisition of CrossBridge Bio. Both instances underscore the strategic prioritization of differentiated ADC technology, particularly linker-payload innovation and next-generation conjugation platforms.

From a manufacturing perspective, ADC CDMOs are evolving to provide greater support in derisking the path to clinic. ADC manufacturing involves several interconnected steps across biological, chemical, and conjugation domains, with each handoff creating a high-risk event. To accommodate emerging modalities, CDMOs must be prepared to fulfill distinct chemistry and conjugation needs.

The Challenges Of Increasingly Complex Offerings

Across the industry, experts are noticing a shift from ADCs to X-drug conjugates (XDCs), evolving beyond antibody targeting technology to include peptides, small molecules, and/or viral components. XDCs include bispecific XDCs, dual payload ADCs, and antibody oligonucleotide conjugates (AOCs). These innovations present a new manufacturing paradigm.

Consider bispecific ADCs, which feature two antibody arms that may require distinct conjugation chemistries to target distinct tumor antigens with a shared payload and must maintain a therapeutic index across both targeting domains. The result is a significant analytical burden to characterize heterogeneity, confirm DAR integrity, and validate complex immunogenicity assays. AOCs, another XDC modality, require the conjugation of a biologic antibody to a nucleic acid payload, which entails robust chemistry, containment, and stability considerations that are distinct from small molecules and cytotoxic payloads.

Ultimately though, these manufacturing bottlenecks represent opportunities for pharma companies and CDMOs to build their skillsets and expertise. CDMOs that invested in conjugation, linker-payload chemistry, and analytical technology for ADCs, AOCs, and XDCs ahead of the commercial wave are now well-positioned to support this demand.

The Key Features Of An Effective Bioconjugate CDMO

Like any drug, location is critical when selecting a CDMO for bioconjugate manufacturing. Sponsors should prioritize partnerships that mitigate geopolitical risks and trade tensions via supply chain resilience, regional diversification, dual sourcing, EU- or US-based facilities, and established FDA and EMA track records.

Integration is another essential quality. Working with separate antibody CDMOs, payload chemistry partners, and conjugation specialists introduces risk at every transfer point, increasing the likelihood of process deviations, timeline delays, and data loss. Choosing to work with one partner is not just commercially beneficial; it is a powerful step toward risk mitigation. A single partner from antibody to vial secures life cycle accountability, institutional process knowledge, consistent analytical methods and regulatory documentation, and early-stage manufacturing design.

If a CDMO’s CMC team is first introduced to a molecule during IND-enabling studies, key process-limiting decisions may already be in place. For example, linker chemistry designed in a lab could be incompatible with GMP-scale synthesis or antibody constructs with excellent in vitro data could have catastrophic aggregation profiles under GMP conditions. However, a CDMO that serves as a discovery partner can contribute to antibody engineering decisions and linker-payload selection to help formulate the CMC strategy from day one.

And while capacity is necessary, it does not reliably indicate a CDMO’s capability for ADC development, predictability, technology transfer quality, and analytical depth. An experienced ADC CDMO will be able to characterize DAR distribution at every step, validate host cell protein clearance, and detect aggregation trends before they manifest as failed batches. Mid-size CDMOs are gaining ADC relevance due to their proactive work on bioconjugate assets. While many large CDMOs prioritize optimization for throughput and standardization, a strong approach for mAbs, this approach can be a liability with novel bioconjugates that require bespoke process development. A mid-size partner offers scientific depth, dedicated bandwidth, and ongoing partnerships with sponsor teams. In many cases, a precise, flexible, science-driven approach will outperform pure scale.

The Abzena Advantage

At Abzena, our global team offers two decades of bioconjugation experience, a dual operating footprint in the US and UK, proprietary conjugation technology, and service architecture that spans concept to commercial manufacture. We are committed to tracking trends across the ADC approval space, including consistently reported toxicities and the common use of microtubulin inhibitors alongside increased use of topoisomerase inhibitors. Our research shows that approved drugs are showing limited conjugation across lysine and cysteine, which contrasts with the significant amount of ongoing development activity in new bioconjugation platforms.

Abzena is leveraging these insights to explore potential areas of improvement across ADC manufacturing technologies and platforms to further open the therapeutic window. In the discovery and selection phase, our team is considering linker and payload design in combination with different antibodies and recombinant proteins. We leverage a deep toolbox to design the most effective ADCs, including antibodies, Fabs, common proteins, conjugation units, stabilizing molecules, linker architecture, and payloads. Experts thoroughly evaluate which combination of these technologies is most likely to lead to a successful manufacturing campaign. Our team condenses sponsor timelines by parallel tracking key deliverables and activities while generating data in real time to mitigate risk, minimize challenges, and identify the optimal molecules.

Our proprietary bioconjugation technology, ThioBridge®, is a highly stable and scalable platform that allows for high-yield production processes and different DAR designs. Two Abzena customers using ThioBridge® are currently in the clinic, and ThioBridge®-derived drugs have been found to consistently outperform competitor ADCs in preclinical in vivo studies.

The Next Step

For sponsors targeting commercialization of their bioconjugate drugs as soon as possible, it is critical to prioritize selecting a manufacturing partner that can support discovery through commercial manufacturing. With an experienced CDMO invested across the full product life cycle, ADC and XDC sponsors can mitigate conjugation failures, secure robust analytical panels, and streamline their product’s pathway to approval.

About The Authors

Dr. Campbell Bunce, Chief Scientific Officer, Abzena, has over 25 years of experience across biotech and diagnostics, holding senior R&D and leadership roles in immunology and drug development. His work spans vaccines, biologics, and small molecules across oncology, inflammation, infectious disease, and addiction. He holds a PhD in Immunology, an executive MBA, and has published extensively in immunotherapy and vaccine research.

Unmesh Lal, Vice President, Healthcare & Life Sciences, Frost & Sullivan, brings over 20 years of experience advising global life sciences companies on strategy, innovation, and growth within the precision health ecosystem. He has authored thought leadership, spoken at major industry conferences worldwide, and guides organizations across personalized therapeutics, diagnostics, and discovery solutions. He holds a master’s degree in biomedical engineering from the University of Michigan.