Early Therapeutic Antibody Development: Addressing the Challenges to Expedite a CMC Program

The FDA recently approved the 100^th monoclonal antibody (mAb) product for commercial use. In the 35 years since the first approval, monoclonal antibody therapies have become main-stream and their production is considered as a routine, platform process. However, a high proportion of candidate therapeutic antibody drugs fail to come through early development and Chemistry, Manufacturing and Control (CMC) without challenges. Despite the obvious similarities between mAbs and the application of novel discovery and engineering techniques, each product is essentially unique with considerable variability of primary amino acid sequences and post translational modifications (PTMs) contributing to significant differences in physiochemical and biological properties.

Consequently, therapeutic antibodies may show less-than-ideal properties, leading to the possibility of challenges at different stages of the development pathway, from early development through to downstream manufacturing and even to pre-clinical and clinical studies. These can manifest in several ways from low production yields and inconsistent product quality attributes through to immunogenicity, safety and efficacy concerns. This webinar will focus on how to address these challenges, highlighting examples of where they have been overcome to de-risk early-stage CMC and delivery of clinical trials material.

Register for this webinar to hear a discussion about how the use of stage-appropriate tools (combining both in-silico analyses together with empirical data from laboratory studies) can be employed to unearth potential issues in biological products. Early awareness of such issues allows scope for removal through re-engineering or, if they are critical to function and cannot be avoided, helps inform process design and control strategies, using quality-by-design (QbD) principles, leading to the same end goal of a de-risked molecule that will ultimately reduce development timelines.

The discussion will also highlight the value of utilizing fast and stable CHO cell transfection pools in the development process as a means of generating representative material for in vitro and in vivo assessment to inform the impact of liabilities and mitigation actions to improve successful manufacturing and IND outcomes.

Speakers

Simon Keen, Scientific Leader, Abzena

Simon has over 25 years of experience in molecular biology and cell line development in the biotechnology industry. His career began with him working on antibody humanisation technologies at the Medical Research Council (MRC) antibody engineering group, before moving to work for multiple small and mid-size biotech companies in the Cambridge UK ecosystem. Simon has developed a deep expertise in different production systems for vaccine, antibody and fusion protein therapies. Having spent the last 15 years at Abzena, Simon has helped to develop mammalian cell line development technologies suitable for the manufacture of biological drugs and is now VP of Cell Line Development. He sits on Abzena’s Scientific Leadership Group, working with clients to shape projects to meet the demands of pre-clinical and clinical development for their drug candidates, to guide them through to regulatory submission.

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Arron Hearn, PhD. Group Leader Protein Engineering, Abzena

Arron Hearn joined Abzena in 2013 as a Research Manager and has been a Group Leader in the Protein Engineering Department since 2018. His primary role is to oversee and deliver affinity maturation, humanization, and other protein optimization projects for Abzena’s clients. Arron was previously at Medimmune following his postdoctoral fellowship at the Department of Pathology at the University of Massachusetts and PhD in Biochemistry at The University of Bristol.

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