Pierre Moretti, Ph.D., Head, Cell Line Development, Glenmark Pharmaceuticals is a keynote presenter at the Eighth Annual Applying Expression Platforms conference at the PEGS Europe Summit in Lisbon, Portugal. Below, he discusses his work with cell line platforms, Glenmark’s bispecific BEAT format, the value of early collaborations and more.
Cell Line Platforms and Expression of Novel Bispecific Antibodies
Can you describe how and why you came to work on cell line platforms, and what brought you to Glenmark?
When I joined Glenmark I was given the opportunity to build up a CLD and USP platform for NBE – especially bispecific antibodies – in an exciting interdisciplinary environment. At this time the BEAT format was being developed. I saw a unique opportunity and a great scientific challenge. Together with the RD team in Switzerland we brought the BEAT from a theoretical concept to new biotherapeutics now entering the clinic. It has been and still is a lot of fun.
What challenges do you still face in the expression of novel bispecific antibodies, and what must be addressed to resolve them?
Our bispecific format, the BEAT, was developed to be as close as possible to natural IgGs. We are basically facing the same challenges as for the development of normal antibodies. Some candidates, while biologically extremely promising, may exhibit some challenging features regarding process development. Starting from the primary amino acid sequence and using our in-house knowledge we try to identify the risks early on and optimize the molecule accordingly.
In addition to being the Head of Cell Line Development at Glenmark, you’re the scientific adviser for Early Upstream Process Development there. What factors do you consider most important for ensuring the efficient, cost-effective development of functional proteins and, ultimately, high-quality biotherapeutics?
The development of a high-quality biotherapeutics requires the interactions of many groups and expertise. You need to define a drug profile as early as possible and avoid compartmentalization of the know-how typically between Research and Development teams. At Glenmark we choose to implement the Cell Line Development and the early USP development unit in the Research department precisely for this purpose. We interact constantly with our antibody engineering, in vitro and in vivo Immunology and analytical teams. The functionality of the proteins produced in stable cell lines is addressed at early stage as well as the industrialization potential. I believe this is a time- and cost-effective approach allowing early risk assessment and a great deal of flexibility regarding timelines.
Why have you chosen to speak at this protein conference on Applying Expression Platforms, and what do you hope your keynote presentation on “Alternative Cell Line Development” will convey to your audience?
The PEGS is obviously a great place to meet experts in their respective fields and getting excited by new approaches. During my presentation I will share some ideas we have been following for expression vectors using alternate splicing and what they could bring for the expression of bispecific antibodies. I hope the talk will inspire the audience to follow this approach and trigger nice discussions at the coffee break!
Pierre graduated from the Leibniz University in Hanover (Germany) and completed his Ph.D. thesis with a focus on stem cell and cytokine research in the group of Prof. Thomas Scheper. He joined Glenmark Switzerland in 2010 and developed ever since cell line platforms for the expression of NBE such as monoclonal antibodies and new bispecific formats. He is currently Head of Cell Line Development and scientific adviser for Early Upstream Process Development.
Keynote Presentation: Wednesday, 4 November in the Applying Expression Platforms conference: