Day One

• Compare the resolution and denaturing conditions of HIC versus reversed-phase LC-MS for DAR species separation to select the optimal stability method
• Implement native mass spectrometry for intact DAR analysis to provide a direct measurement without disrupting the native protein structure, gaining a true representation of drug distribution and identifying critical low-abundance species
• Develop orthogonal methods to overcome HIC’s poor resolution and HPLC RP’s denaturation, to understand DAR distribution, providing a robust package for regulatory filings, andensure consistent product quality

• Navigate the increasing complexity of novel ADC modalities and chemotypes to accelerate development timelines and reduce costs across a growing portfolio of assets
• Establish a suite of robust, chemotype-agnostic platform methods for critical quality attributes, to minimize the number of methods requiring development, validation, and transfer, achieving greater efficiency, speed, and consistency across ADC development
• Implement a holistic, platform-based analytical strategy to de-risk project timelines, simplify tech transfer to QC, and create a more scalable, cost-effective framework for the future of ADC development

• Utilize first-dimension cation-exchange chromatography separation coupled online to a 2DLC/MS system to isolate and mass spectrometrically characterize individual charge variants peaks, providing identification of molecular modifications
• Implement a comprehensive, automated 2D-LC/MS platform with minimal manual fraction handling to increase analytical throughput and reproducibility, enabling high-resolution characterization of charge variants

This informal session provides the perfect opportunity to connect with industry frontrunners and key opinion leaders focusing on physicochemical, bioanalytical, and impurity control in ADC analytical development. This is your chance to establish meaningful connections to build upon for the rest of the conference and gain exclusive, first-hand insights into the latest research and developments.

• Analyze serum aggregation propensity of higher DAR ADCs to measure drug load and identity of novel ADCs, and understand drug loading, structural stability, and early pharmacokinetic clearance
• Optimize intact high-res mass spec of novel ADCs in biological matrices to monitor average DAR, drug load distribution, and biotransformation
• Assess a true one-pot assay for ADC quantitation from in vivo studies to streamline bioanalysis and reduce methodological variability

• Employ high-resolution peptide mapping with LC-MS/MS to identify and quantify conjugation sites beyond the engineered interchain cysteines, to create residue-specific map of all drug linker attachments, revealing unexpected modifications on hinge region cysteines
• Utilize advanced data analysis software to perform comparative quantitation of on-target vs. off-target conjugation levels across different process conditions and ADC batches to facilitate data-driven process optimization and establishing meaningful in-process controls (IPCs) to ensure batch-to-batch consistency in drug distribution

Looking beyond current techniques to debate the next frontier in characterization, from continuous manufacturing control to analyzing single molecules. This panel discussion will challenge the status quo on what is “good enough” and explore the technologies that will redefine our understanding of ADC structure by:

• Speculate on the potential of single-molecule sequencing and mass spectrometry to fully resolve ADC populations, and whether this ultimate level of characterization is a necessary future standard or an analytical fantasy
• Debate the hurdles and rewards of implementing real-time PAT and in-line analytics for continuous ADC manufacturing, moving from batch release to a state of perpetual verification
• Explore the role of computational models and AI in predicting ADC biophysical behavior and long-term stability from early structural data, potentially rendering months of stability studies obsolete

• Implement a platform analytical strategy using orthogonal methods to structurally characterize a recurring payload-linker, enabling proactive risk assessment and establishing a platformwide control strategy
• Conduct forced degradation studies and spiking experiments to model the variant’s behavior to quantify the kinetic formation rate of the variant and provide critical data to justify setting appropriate specification limits

• Implement a novel enzymatic digestion step coupled with LC-MS/MS analysis, to achieve highly selective and complete cleavage of the maleimide linker from the antibody framework providing an accurate and reliable measure DAR
• Utilize a stable isotope-labeled internal standard for the payload-linker fragment, to precisely normalize for variability in sample preparation and instrument response, ensuring superior precision and reproducibility of the hydrolysis data
• Automate the sample preparation workflow in a 96-well plate format, to significantly reduce error, enabling acceleration of high-throughput analysis

• Apply high-resolution mass spectrometry and MS/MS fragmentation to payload degradation products, to propose potential structures for novel species, enabling proactive identification and risk assessment of new impurities
• Leverage NMR spectroscopy for definitive structural elucidation, to unambiguously identify the chemical structure of major degradation products, providing the highest level of confidence for regulatory filings and understanding structure-activity relationships
• Utilize software tools designed for small molecule structure elucidation, to automate data analysis and hypothesis generation, accelerating the identification process and bridging the analytical gap

Connect with peers in a relaxed atmosphere and continue to forge new and existing relationships while exploring the latest in ADC analytical development approaches and research advancements.

To submit a poster, please contact [email protected]

• Establish and deploy a robust platform of core analytical method to standardize procedures and reduce the need for method re-development, accelerating the transfer of analytics to new internal and external manufacturing sites
• Co-develop unambiguous method instructions with QC and CMO partners to eliminate variability introduced by differences in interpretation or execution, ensuring robust assay performance
• Design the analytical control strategy around a pre-qualified platform from the outset to build flexibility and resilience into the supply chain, enabling faster and more robust tech transfers for global product roll-outs

• Provide comprehensive, hands-on training for QC analysts in aseptic technique and cell culture to ensure consistent andsterile handling of living cell lines, minimize contamination events, and ensure the reliability of the potency data generated at the QC site
• Co-develop detailed and unambiguous method instructions with the receiving lab to eliminate variability introduced by differences in interpretation or execution, ensuring the assay performs identically at both the development and QC sites
• Establishing a joint trending program for key assay performance indicators during transfer to identify and troubleshoot any drift or performance issues, maintaining the long-term robustness and GMP compliance of the potency method

Moving beyond solving individual transfer issues to envision a future state of fully integrated development, powered by AI and automation. This panel will debate the cultural, technical, and regulatory roadblocks to achieving the transformative impact it would have on speed, cost, and quality.

Join a strategic discussion on building the agile ADC development organization of the future by:

• Envisioning how AI platforms analyze development data to automatically recommend optimal process parameters, analytical methods, and specifications, changing the role of scientists
• Exploring digital replica of the ADC process to virtually simulate the impact of changes, predict outcomes, and eliminate failed tech transfers
• Debating the organizational and cultural changes required to break down walls between process, analytical, and regulatory functions, enabling a truly agile and data-driven development lifecycle