Oligonucleotide ADC Design and Development – An Emerging Field Building on the Success of ADCs in Cancer

Antibody-drug conjugates (ADCs) are an established class of biopharmaceuticals with therapeutic applications in oncology and beyond.

Antibody-oligonucleotide conjugates (AOCs) are a growing sub-class of ADCs that utilize the oligonucleotide functionality in combination with the antibody’s exquisite targeting ability and improved biodistribution profile. This approach significantly broadens the therapeutic potential of oligonucleotide-based drugs.

Oligonucleotide Conjugates

Oligonucleotides, as drug molecules, suffer from several drawbacks such as instability, impaired pharmacokinetics (PK), poor cellular uptake and sub-optimal tissue targeting. Chemical modification of oligonucleotides is therefore frequently required to transform a base sequence into a viable medicine. Backbone modifications impart enhanced stability and PEGylation has been employed to improve PK properties. Tissue-specific delivery of oligonucleotides can be facilitated via conjugation to a targeting moiety (e.g. a monoclonal antibody). A wide array of heterobifunctional linkers exist which can be utilized for oligonucleotide bioconjugation. Oligonucleotides functionalized with 3’ or 5’-terminal amine, thiol or click chemistry groups facilitate conjugation to PEG or a targeting protein (Figure 1).

Figure 1: A general approach to oligonucleotide conjugation

As AOC therapeutic drug development grows, there is a need to for robust, reproducible, and well-defined scale–up and manufacture processes to generate well characterised material for clinical trials. While the process development challenges of ADCs are focused on maximizing the loading of drug molecules to the antibody and minimizing the release of free payload, AOC development and manufacture has its own set of unique challenges.

In this webinar, panelists will review oligonucleotide bioconjugates focusing upon their design, development, analysis and manufacture. Case studies which illustrate the chemical processes used in oligonucleotide conjugation and the analytics required to support development and manufacture will be presented.

Register for this webinar to learn more about the drug development applications of oligonucleotide conjugation and hear about case studies which illustrate the chemistry used to overcome challenges in their construction.

Speakers

(Moderator) Campbell Bunce PhD, Chief Scientific Officer, Abzena

Campbell is the Chief Scientific Officer at Abzena, a global Partner Research organisation supporting development of drugs and vaccines from discovery to GMP manufacture.  His focus is in delivering high quality and tailored services to ensure a quick and de-risked route from drug concept and design to clinical testing.  Campbell has been with Abzena for 5 years and beforehand spent 20 years working in the biotech sector for companies such as Cantab Pharmaceuticals, Piramed Pharma and Immune Targeting Systems.   He has led the development of many novel vaccine and therapeutic technologies targeting infectious disease, cancer, inflammatory and autoimmune disease, taking them through discovery and design stages to clinical evaluation.  Campbell has a PhD in Immunology from the University of Manchester and has published numerous papers on immune mechanisms and novel drug development.

Message Presenter

Dr. Matthew Bird, PhD, Scientific Fellow, Abzena

Dr. Matthew Bird is Scientific Fellow in the Chemistry division at Abzena and is responsible for the development and application of Abzena’s bioconjugation technology offering. Matthew’s core expertise is in the bioconjugation field where he has wide ranging experience including protein and peptide PEGylation, antibody and antibody fragment drug conjugation (ADCs) and nucleic acid modifications, and is a named author on several patents and publications. Matthew has group resourcing and project management responsibilities, and leads technical proposal planning for protein PEGylation and oligonucleotide conjugation projects.

Message Presenter

Dr. Juan Carlos Cordova, Principal Scientist, Abzena

Dr Juan Carlos Cordova is a Principal Scientist in the Bioconjugation team at Abzena. He is responsible for process development, optimization, and scale up for antibody drug conjugates and conjugate vaccine projects. Juan Carlos’ expertise is in downstream process development for antibody drug conjugates, conjugate vaccines, and viral vector gene therapies. He has wide ranging experience in optimization, scaling and quantitative determination of scalable process parameters and bioconjugation reactions. In addition Juan Carlos has extensive experience of the processing of biotherapeutics from bench scale to manufacturing scale.

Message Presenter