Antibody-Drug Conjugates (ADCs)

Antibody-Drug Conjugates (ADCs) or “armed antibodies” are steadily entering the therapeutic mainstream, especially for oncology and haematology applications. There are still just seven FDA-approved ADCs on the market, but 80 ADC candidates are now under evaluation in around 600 pre-clinical and clinical trials (Pharmaceutical Technology Europe, May 2020).

Fleet Bioprocessing Ltd. has demonstrated that our unparalleled experience in the development of clinical diagnostic bioconjugates can be directly translated to the development of such molecules, and we now also have substantial experience in ADC development.

Fleet can assist with examining the critical-to-quality variables affecting conjugate behaviour, e.g:

Site of conjugation reaction (i.e. conjugation chemistry and site-specific vs. random coupling).
Conjugate stoichiometry.
In vivo conjugate behaviour: - cleavable vs. permanent linkages.
Immunogenicity and in vitro stability of the linker group.

Ensuring the reproducibility and robustness of any conjugation method is absolutely critical. You can find some more of our thoughts on this topic in the blog post here.

If your ADC development reaches the clinical trial stage, we have good links to suitable CMOs and can guide method transfer into a clinical GMP facility.

Example Projects

Doxorubicin-peptide conjugation method leads to further applications.

Fleet carried out chemical modification of the chemotherapy drug doxorubicin to target formulation of a peptide-drug conjugate. The conjugate synthesis and the results of the customer's testing were positive; Fleet were then asked to extend the conjugation method to other peptide-drug conjugates for the customer's applications.

Optimisation of synthetic methodology for novel ADCs

Fleet have carried out several programs of work for a European biotech company formulating novel, proprietary antibody-drug conjugates (ADCs). From the optimisation of antibody functionalisations and drug-to-antibody ratios (DARs), to the development of an improved two-step/one-pot reaction process, Fleet have taken this project from R&D to the preparation of antibody-drug conjugates at gram scale.

Conjugation of antibody-MMAE for leading US pharmaceutical company

Following the customers preferred method, Fleet were able to demonstrate the preparation of an antibody-MMAE to meet stringent specifications of DAR, purity and sterility.

Redevelopment of an ADC method hits the target

Fleet worked with the customer to modify their conjugation method to successfully make a previously troublesome antibody-drug therapeutic that exceeded their expectations of performance.