A Chemical Technology to Generate Homogeneous Antibody-Drug-Conjugates (ADCs) and Bispecifics
Lead Research Organisation:
University College London
Department Name: Chemistry
Abstract
Using antibodies as therapeutics and diagnostics is one of the most promising areas of research into new healthcare products. Antibodies represent the fastest growing class of therapeutics, with over 20 approved for clinical use to date and over 150 in clinical development. It is estimated that the global market for antibody therapeutics is currently around $50 billion. Two particularly promising classes of antibody based therapeutics are antibody-drug-conjugates (ADCs) and bispecifics, commonly referred to as 'magic-bullet' therapies due to their ability to seek and destroy just diseased cells within the body (e.g. cancer cells). However, a major hindrance to the area is the lack of suitable chemical methods for the construction of homogeneous, well defined, antibody conjugates. Here we propose to exemplify a powerful new chemical technology that we have developed to overcome these limitations, to enable the design of superior next generation ADCs and bispecifics.
Publications
Smith ME
(2015)
A platform for efficient, thiol-stable conjugation to albumin's native single accessible cysteine.
in Organic & biomolecular chemistry
Nunes JP
(2015)
Functional native disulfide bridging enables delivery of a potent, stable and targeted antibody-drug conjugate (ADC).
in Chemical communications (Cambridge, England)
Morais M
(2017)
Optimisation of the dibromomaleimide (DBM) platform for native antibody conjugation by accelerated post-conjugation hydrolysis.
in Organic & biomolecular chemistry
Forte N
(2018)
Tuning the Hydrolytic Stability of Next Generation Maleimide Cross-Linkers Enables Access to Albumin-Antibody Fragment Conjugates and tri-scFvs.
in Bioconjugate chemistry
Description | In this project we optimized a new approach to the synthesis of antibody-drug conjugates (ADCs), which represent the archetypal 'magic-bullet' therapies for cancer therapy. We showed that using our proprietary 'Next Generation Maleimide' reagents we could produce ADCs of extremely high homogeneity, stability and efficacy. Our approach is now being increasingly cited in the literature as a leading method for the construction of next generation ADCs. |
Exploitation Route | Ultimately a new chemical platform for the construction of ADCs and bispecifics will allow the efficient generation of improved classes of therapeutics and diagnostics. |
Sectors | Chemicals Healthcare Pharmaceuticals and Medical Biotechnology |
Description | Our reagents for protein modification were licensed by Albumedix as part of a platform technology for the half-life extension of therapeutics. Our antibody drug conjugate platform has been evaluated by several companies and we have received venture capital support in the form of a UCL Technology Fund proof-of-concept grant (£100k) for a spin-out company (Thiologics) which may lead on to a full investment. ADCs based on this conjugation platform are also being taken into the clinic. For example, by the company Mabwell: https://www.prnewswire.com/news-releases/mabwell-announces-the-cde-approval-of-novel-nectin-4-targeting-adc-for-phase-iii-clinical-trial-302011037.html |
Sector | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | C-Terminal Selective Ligation to Access Homogeneous Antibody Conjugates |
Amount | £444,295 (GBP) |
Funding ID | EP/T016043/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2020 |
End | 08/2024 |
Description | EPSRC |
Amount | £514,721 (GBP) |
Funding ID | EP/R034621/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2018 |
End | 04/2021 |
Description | EPSRC CASE Award with Albumedix |
Amount | £100,567 (GBP) |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2016 |
End | 09/2020 |
Description | EPSRC CASE Award with MRCT |
Amount | £95,000 (GBP) |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2016 |
End | 09/2020 |
Description | UCL Technology Fund |
Amount | £100,000 (GBP) |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2017 |
End | 01/2018 |
Description | Collaboration with Novozymes |
Organisation | Novozymes Biopharma UK ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | Option and evaluation agreement signed between Novozymes and UCL Business to exploit our protein conjugation technology for the development of albumin conjugates for therapy. Our role is to provide the expertise on the use of next generation maleimides for protein conjugation. |
Collaborator Contribution | Novozymes are providing funds (contractually confidential) and are also carrying out proof of concept experiments as part of the collaboration. |
Impact | N/A |
Start Year | 2013 |
Title | REVERSIBLE COVALENT LINKAGE OF FUNCTIONAL MOLECULES |
Description | The present invention relates to the use of a compound containing a moiety of formula (I) as a reagent for linking a compound of formula R1-H which comprises a first functional moiety of formula F1 to a second functional moiety of formula F2 wherein X, X', Y, R1, F1 and F2 are as defined herein. The present invention also provides related processes and products. The present invention is useful for creating functional conjugate compounds, and specifically conjugates in which at least one of the constituent molecules carries a thiol group. |
IP Reference | WO2011018611 |
Protection | Patent granted |
Year Protection Granted | 2011 |
Licensed | Yes |
Impact | Ongoing evaluations with other companies in biopharmaceutical area. |
Company Name | ThioLogics |
Description | ThioLogics develops immunotherapies. |
Year Established | 2011 |
Impact | N/A |
Website | http://www.thiologics.com |