Streamlining MS-based Analytics for the Investigation of In Vivo Biotransformation of Biotherapeutics

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Webinar Date/Time: Thu, Jun 20, 2024 10:00 AM EDT

Learn about the development of flexible and automated data acquisition and data processing approaches for a more reliable workflow for MS-based intact and middle-down analysis to accelerate biotransformation characterization.

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Event Overview:

Although monoclonal antibodies (mAbs) still represent the backbone of current immunotherapies, next-generation biotherapeutics are becoming increasingly important players in the field. These alternative therapeutic protein modalities cover a wide range of biological constructs with increased molecular diversity and complexity. Biotransformation is the structural modification of a drug — either chemically or enzymatically — after its administration. For biotherapeutics, typical biotransformations can include proteolysis, post translational modifications (PTMs), or other chemical changes such as payload deconjugation. Unlike for small molecules, evaluation of biotransformation was not a major concern for mAbs because the associated risks were considered relatively low. But the increasing diversity and complexity of new constructs could make them more prone to in vivo biotransformation, which could impact both efficacy and safety. Biotransformation should, therefore, be investigated as early as possible to maximize success rate of biotherapeutic drug candidates.

Thanks to its sensitivity and versatility, mass spectrometry (MS) has become the analytical technique of choice to support the characterization of biotherapeutics at various stages of development. Among these stages, pharmacokinetics (PK) allows the evaluation of the fate of drugs administrated to a living organism. The traditional peptide-based approach (bottom-up) provides a rapid and highly sensitive in vivo stability assessment of biotherapeutics, but it offers only a limited understanding of the molecular structures of eventual biotransformation products. Extending PK investigations to include the alternative and complementary intact and middle-down MS approaches could provide a more comprehensive overview of biotransformation at the protein level. However, the analysis, review, and reporting of intact and subunit data can present a significant bottleneck, especially when biotransformation is occurring.

This webinar highlights the development of flexible and automated data acquisition and data processing approaches that could overcome these challenges and provide a reliable workflow for intact and middle-down analysis to accelerate biotransformation characterization.

Key Learning Objectives:

  • Automate MS-based intact mass and middle-down approaches for high-throughput therapeutic protein analysis from plasma samples.
  • Enable qualitative and semi-quantitative monitoring of the different molecular forms of a biotherapeutic (i.e., proteoforms) that are present in plasma samples.
  • Increase understanding of key in vivo biotransformation.

Who Should Attend:

  • Biopharma analytical scientists, lab heads, and directors who are looking to develop mass spectrometry-based workflows for intact and middle-down characterization of biotherapeutics.


Jonathan Dhenin, PhD
Senior Scientist
Metabolism, DMPK Research Platform Sanofi R&D, Chilly Mazarin, France

Dr. Jonathan Dhenin has an engineer degree in Analytical Chemistry from the ECPM Strasbourg (2018) and a PhD in Biological Mass Spectrometry from the Université Paris Cité (2023). Between 2018 and 2023, Dr Dhenin gained expertise at the Institut Pasteur in various proteomics approaches to study protein–protein interactions as well as to characterize antibody-based biotherapeutics. In his thesis work, he developed innovative LC-MS strategies to characterize the in vivo metabolism of multi-specific hybrid biotherapeutics. Dr Dhenin permanently joined Sanofi in 2023 as a Senior Scientist, supporting the Metabolism team of the DMPK department. In his current role, he pursues the implementation of innovative MS-based approaches to support in vivo metabolism studies of complex next-generation biotherapeutic modalities. 

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