Abstract
Bioconjugate therapeutics comprise a fast-growing class of drugs with applications in various disease areas. In the past years, particularly antibody-drug conjugates (ADCs) have undergone a period of great success with eight products approved by the Food and Drug Administration (FDA) between 2019-2022 alone. The rapid emergence of novel bioconjugation technologies, payloads and linkers as well as their application on different protein modalities has made bioconjugate development and manufacturing increasingly complex. Clinical success of bioconjugates depends on the delicate interplay between the protein, linker and payload, which is often not readily predictable. Therefore, it is important to consider a range of different technologies when designing a bioconjugate drug. Since navigation of a constantly evolving technology landscape is challenging, it may be beneficial for many biotech companies to enter partnerships with a contract development and manufacturing organization (CDMO) that can help realize the drug concept by providing access to a range of tools for the development of bioconjugates. Partnering with a CDMO at an early-stage of drug development can greatly de-risk the program as the right CDMO can give guidance on how to design a conjugation process that not only fulfills the requirements in terms of product attributes but that is also robust enough to streamline further process development and upscale for moving towards an IND filing.

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Authors: Nina Hentzen Ph.D.1, Abbas El Sahili, Ph.D.,2, Prof. Julien Lescar, Ph.D.,2 Prof. Chuan Fa Liu, Ph,D., 2 & Raphael Frey, Ph.D.1

Corresponding Author: Raphael Frey, Ph.D.

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Key terms: ADC, bioconjugation, bioconjugation techniques, early development
Published In: ADC Review| Journal of Antibody-drug Conjugates

DOI: https://doi.org/10.14229/jadc.2023.07.10.002.


How to cite:

Nina Hentzen1, Abbas El Sahili2, Julien Lescar2, Chuan Fa Liu2 & Raphael Frey1
Bioconjugation Technology Selection during Early-Stage Development – A Strategy to Streamline IND and Manufacturing Timelines – J. ADC. May 26, 2023. DOI: 10.14229/jadc.2023.07.10.002.

1 Early Development Bioconjugates Services, Lonza, Switzerland
2 Singzyme Pte. Ltd., Singapore


Last Editorial Review: June 16, 2023

Creative Commons License

Article History:

  • Original Manuscript Received May 11, 2023
  • Review results received June 19, 2022
  • Manuscript accepted for publication  July 3, 2023

Featured image: Antibody. Photo courtesy: © 2019 – 2023 – Fotolia/Adobe. Used with permission.

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Nina Hentzen is a Senior Scientist in Early Development Bioconjugates at Lonza in Visp, Switzerland. She is responsible for leading preclinical bioconjugation projects and establishing and managing collaborations with technology partners to enhance innovation in bioconjugates development and manufacturing. Nina is an organic chemist by training and holds a PhD in peptide chemistry from ETH Zurich. Prior to joining Lonza, she was a Swiss National Science Foundation postdoctoral fellow at UC San Francisco where she was working on computational protein design.
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Abbas El Sahili is the Chief Executive Officer of Singzyme, a biotechnology company that provides enzymatic conjugation using Peptide Asparaginyl Ligases. He has a Ph.D. in Biochemistry and Structural Biology and has published 30 research papers. He is also a Senior Research Fellow at the Nanyang Technological University in Singapore. Abbas El Sahili’s research career has been focused on biochemistry and structural biology. He has worked on projects such as the purification of Dengue and Zika Virus Non-structural Protein 5 for Crystallization and Screening of Antivirals. He pursued his research work on Peptide Asparaginyl Ligases using biochemistry techniques, protein engineering and X-ray crystallography to uncover the detailed molecular mechanism of these enzymes and use them to produce novel biologics.
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Prof. Julien Lescar, Ph.D is a biochemist and structural biologist with extensive experience in using X-ray crystallography and cryo-electron microscopy as a main tool for protein structure-function studies. He has determined the 3D structures of numerous viral proteins involved in RNA virus entry and virus replication for several major human pathogens (flaviviruses such as dengue virus or Zika virus, alphaviruses such as chikungunya virus, human metapneumovirus). In the last eight years, he has collaborated extensively with Professors Chuan Fa Liu and James Tam on identifying, characterizing and cloning several peptidyl asparaginyl ligases, with tremendous applications in biotechnology and biomedicine. His lab has conducted structural studies on recombinant asparaginyl ligases leading to a better understanding of their mechanism of action and accelerating their use for the rapid and precise bioconjugation of biomolecules such as nanobodies or full-length antibodies.
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Liu Chuan Fa is a Professor and Lead Principal Investigator at Nanyang Technological University's School of Biological Sciences. His research focuses on chemical biology, biotechnology, drug discovery, and medicinal chemistry. He has developed efficient methods for studying post-translational modifications (PTMs) in proteins and has a particular interest in protein ubiquitination. Liu Chuan Fa's lab has also made significant contributions to biotechnology by developing a platform for the precise manufacturing of antibody-drug conjugates (ADCs), aiming to improve their efficacy and safety for cancer treatment. In addition, he is involved in the development of new antimalarial drugs through structure-based drug design and optimization of lead compounds. His lab has a strong background in peptide chemistry and is working on synthesizing peptides and peptidomimetics using innovative techniques. Overall, Liu Chuan Fa's research has been published in reputable journals, highlighting his valuable contributions to chemical biology, biotechnology, drug discovery, and medicinal chemistry
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Raphael Frey is leading the team for Early Development Services for Bioconjugates at Lonza in Visp, Switzerland. His team offers solutions for preclinical bioconjugate drug development, combining state-of-the art technologies and Lonza’s extensive expertise in bioconjugate manufacturing. Raphael studied organic chemistry at the Swiss Federal Institute of Technology (ETH Zurich) and earned his Ph.D. in chemical biology, focusing on enzyme engineering and biocatalysis.