DC Discussion Group

Conjugation Design and its Impact on CMC: Clinical Evaluation and Lifecycle Management of Antibody-Drug Conjugates (ADCs) | Rockville, MD | October 30, 2024 15:00 - 17:00 EST

Join us in person at the IBBR campus where you can network with DC-area CASSS members. The October Discussion Group will be fully in-person. Registration is extended to October 28, 2024.

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Location:
Institute for Bioscience and Biotechnology Research
9600 Gudelsky Dr.
Rockville, MD, USA 20850

Conjugation Design and its Impact on CMC: Clinical Evaluation and Lifecycle Management of Antibody-Drug Conjugates (ADCs)

The impressive versatility of targets, payloads, and conjugation chemistry opens many possibilities to explore new types of ADCs. An ADC molecule is composed of three components: antibody, drug, conjugation (including site of conjugation, chemical reactions, and linker). It is the conjugation that make the whole ADC greater than the sum of antibody and drug.

With more successful stories of approved ADCs and gained regulatory experience of health authorities, it’s crucial to explore what contributes to success and where challenges arise in the development of ADCs, and to exchange ideas and lessons among R&D, CMC, and lifecycle management groups. The discussion will start with an overview of the current landscape of ADCs, and discuss the following questions, which are generated from the impact of conjugation and linker design on CMC, clinical evaluation, and lifecycle management:

• What lessons have been learned about product attributes that are relevant to apply to the design and development of ADCs? At the design phase, how much weight, if any, do assessments of manufacturability, development, and CMC factors carry?
• ADCs require precise analytical tools to ensure product quality and manufacturing consistency. These analytical tools for diverse ADCs encompass applications for process-related impurities, product-related impurities, product quality attributes, and product/process understanding via in-depth characterization. What is the key consideration when developing analytical methods for DAR, which is the unique CQA of ADCs? What are the analytical challenges for other CQAs caused by conjugation (e.g. much more complex charge variants)?
• How can the recently published FDA guidance on clinical pharmacology evaluation of ADCs foster ADC development?
• To what degree might Post-Approval Change Management Protocols (PACMP) and other regulatory tools facilitate lifecycle improvements of ADCs?

Roman Drews, Arcellx, Inc.

Dr. Drews has experience that spans over 30 years in development, quality, and regulation of complex biologics. In his current capacity, he oversees RA CMC function and develops CMC regulatory strategy at Arcellx, a late-stage clinical gene and cell therapy company innovating CAR-T treatments for blood cancers and solid tumors. Prior to that, Drews was part of the Daiichi-Sankyo regulatory team, where he played a key role in the development of several antibody-drug conjugates (ADCs), including the HER-2 targeting ADC product, Enhertu®️, which has been approved in global markets. In his role in LFB—USA regulatory team, he contributed to the approval process for Sevenfact®️, a novel recombinant coagulation factor. 

Drews had served more than 13 years in the FDA. He led a team of CMC reviewers in CBER, Office of Blood Research and Review, Laboratory of Hemostasis, chairing the BLA committees, and contributed to policy and compliance-related issues.

Drews has volunteered in different capacities for CASSS activities for more than 20 years. 

Ling He, Daiichi Sankyo, Inc.

Dr. Ling He received his PhD degree in analytical chemistry at the University of Michigan under the direction of Prof. David Lubman. He is currently the Senior Director, Clinical Bioanalysis, Quantitative Clinical Pharmacology, heading the Clinical Bioanalysis function at DSI (Daiichi Sankyo, Inc.), which supports a diverse portfolio of global clinical development programs. He has worked at various stages (discovery, preclinical and clinical) of pharmaceutical R&D, in both Pharma and CRO companies. His areas of research interests include regulated bioanalysis, lab automation, drug metabolism, and clinical pharmacology, with close to 60 authored or co-authored publications (papers and meeting presentations) in all technical areas mentioned above. Besides being an expert for small and large molecule bioanalysis, he also led clinical DDI studies and sNDA submission, which applied clinical pharmacology and pharmacometrics disciplines to inform study design and improve data interpretation. He also represented DSI in collaborative diagnostic assay development and registrational projects. He has been serving, as DSI representative, on the Board of Directors and the Translational and ADME Sciences Leadership Group (TALG) of IQ organization. He is also a member of AAPS and ASCPT.

Pete Lau, Eli Lilly and Company

Pete Lau joined Eli Lilly and Company in 2023 as a director of global regulatory affairs – CMC. He is part of the Lilly bioconjugate team responsible for expanding clinical capabilities towards commercialization in the bioconjugate space. Prior to Lilly, Lau was at Daiichi Sankyo, Inc. contributing towards increasing post approval ADC supply to alleviate the market demand. Lau joined the pharmaceutical industry after spending 7 years at the Food and Drug Administration as a product quality reviewer and team lead. His experience includes reviewing both small molecule and biologic drug product, and was part of the task force in OPQ that applied a risk-based approach in reviewing backlog supplements. Lau is passionate about using technology in improving efficiency in the regulatory affairs CMC space, with the hope that safe and efficacious medicines can be brought to patients faster. 

Chunlei Wang, AstraZeneca 

Chunlei Wang serves as the director of analytical sciences in biopharmaceutical development at AstraZeneca, overseeing the analytical development of clinical-stage ADC projects. Previously, he held the role of senior research investigator in pharmaceutical candidate optimization at BMS, where he provided support for pre-clinical projects. Wang holds a PhD in separation sciences and maintains a strong passion for developing analytical methods tailored to new drug modalities, including macrocyclic peptides, antibody-drug conjugates, bispecific antibodies, and adeno-associated viruses.