4th Analytical & Bioanalytical Day
Wednesday October, 9

8.30 Chair’s Opening Remarks

Leo Kirkovsky, Director, Clinical Assay Group, Pfizer

8.40 Keynote: 1 Year on – Were the Goals Achieved?

• Introduction to the Analytical and Bioanalytical day
• Lessons learned from previous years
• How the analytical and bioanalytical field has progressed over the last year?

Leo Kirkovsky, Director, Clinical Assay Group, Pfizer

9.10 The Evolution & Current Status of Antibody-Drug Conjugate Bioanalysis

• Overcome technical challenges in ADC bioanalysis with advancing technologies and strategies
• Learn how to select and correlate various analytes, technologies and platforms
• Stage specific and continuity of bioanalytical approaches, platforms and strategies at different phrases of ADC development
• Regulatory perspectives along with challenges and strategies of bioanalysis for new conjugate modalities

Jian Wang, Senior Principal Scientist/LC-MS Technical Integration Lead, Bristol Myers Squibb

9.40 Analytical Strategies for Accelerated Approval of ADCs

  • CQA elucidation from candidate selection to marketing application
  • Holistic approach to mAb, DS, and DP comparability
  • Lessons learned from an accelerated timeline

Hillary Schuessler, Scientific Leader, GSK

10.10 From Deep Characterization to Sub-Ppb Payload Metabolite ID: HighResolution MS Applications in ADC Analysis

• High-resolution MS-based techniques are widely employed to address a number of complex analytical problems related to the structural
characterization of ADCs, their components, formulation excipients and biotransformation products
• Here we present our current approach, in which the information obtained from the MS fragmentation behavior of the molecule under study is used to design highly specific and sensitive characterization methods
• Explore real life examples in different application fields

Antonio Triolo, Head of Advanced Analytics for Development, Menarini Ricerche

10.40 Speed Networking

11.10 Morning Break

Adaptations to Characterization Techniques as the Field Evolves

12.00 Streamlining Analytics to Support Research & Early Development of Novel ADC Modalities

  • We describe implementation of 2 distinct MS approaches for bottom-up and top-down characterization of ADC quality attributes in a H/T environment. In the bottom up approach, peptide map has been implemented for H/T screening of mAb and ADC PTMs and sequence variants. For top-down ADC characterization, native size exclusion chromatography mass spectrometry (SEC-MS) has been utilized for accurate, quantitative assessments of drug-to-antibody ratio (DAR) and drug-distribution on a diverse portfolio of ADC chemotypes
  • These cases highlight a broader strategy at Seattle Genetics whereby we seek to future-proof analytical development activities and timelines by developing chemotype-agnostic, platform H/T approaches. Our vision is to have a suite of MS-based methodologies that sensitively detect and quantitate molecular product quality attributes so that critical process development activities are not delayed unnecessarily by molecule specific analytical method development.

John Valliere-Douglass, Associate Director, Seattle Genetics

12.30 Single Molecule 3D Image: An Approach to Reveal Antibody Structural Dynamics & Conformational Changes

• Determination of 3D structure of a single protein by individual particle electron tomography (IPET)
• 3D structural dynamics and fluctuation of IgG1 antibody
• Conformational changes and aggregation of antibody by peptide conjugation

Gary Ren, Scientist, Lawrence Berkeley National Laboratory

1.00 Lunch & Networking

2.00 Explore Advances in Preclinical Analytical Strategies

• PK of ADCs are more complex than that of antibody and cytotoxic drug alone
• Novel assays are required to truly understand the behavior of ADCs and drug intermediates in vivo
• Lessons learned from working with PBD-ADCs

Kathryn Pugh, Analytical Chemist, Spirogen

Bioanalytical Support Strategies

2.30 ADME Considerations & Bioanalytical Strategies for Pharmacokinetic Assessments of Antibody-Drug Conjugates

• Overview of structural complexity of ADCs
• Current bioanalytical approaches commonly employed to assess pharmacokinetics of ADCs
• Emerging bioanalytical tools for the assessment of ADC biotransformations

Anton Rosenbaum, Translational Sciences Group Leader, AstraZeneca

3.00 Afternoon Break & Networking

Bioanalytical Support Strategies

4.00 A View from the Top: Integrated LC-MS Strategy for Intact ADC/Antibody Analysis

• Novel development of chromatographic column for native ADC separation and online LC-MS analysis
• Top down analysis of antibody/ADC variants
• Establish characterization of conjugation site heterogeneity by LC-MS

Cexiong Fu, Principle Scientist, Shire

4.30 Challenges Associated with PK & Immunogenicity Support for Antibody Drug Conjugates

  • Quantitative modeling and simulations aid in preclinical to clinical translation of ADC and rely on high-quality bioanalytical (BA) measurements to integrate PK, PD and immunogenicity data
  • Changes in BA critical reagents, assay format and/or assay platform across different stages of drug-development may impact observed PK profile/parameters
  • Immunogenicity risk assessment drives ADC immunogenicity testing strategies and mitigation plans
  • Highly potent cytotoxic payloads pose challenge in their DMPK assessments
  • An integrated bioanalytical and translational strategy should be defined early on for ADC development, keeping in mind that one strategy may not fit all

Seema Kumar, Associate Director, EMD Sereno

5.00 Chair’s Closing Remarks
Leo Kirkovsky, Director, Clinical Assay Group, Pfizer