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.
 
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 licensey by Albumedix as part of a platform technology for the half-life extension of therapeutics. Our antibody drug conjugate platform is also being evaluated by several companies currently (confidential). 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. Currently we are in the final stage of negotiations to make our reagents available through several suppliers, which will lead to their wider use in academia and industry.
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 08/2023
 
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 05/2018 
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 09/2016 
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 09/2016 
End 09/2020
 
Description UCL Technology Fund
Amount £100,000 (GBP)
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 07/2017 
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 In 2011 Dr James Baker co-founded Thiologics (www.thiologics.com), to provide a vehicle to translate the Next Generation Maleimide platform for homogeneous protein conjugation towards clinical product development. ThioLogics is a company formed by UCL Business (UCLB) and is in an early pre-seed phase of development supported solely by UCLB funds. The formation of ThioLogics has created a market presence and facilitated early engagement through our existing networks. 
Year Established 2011 
Impact N/A
Website http://www.thiologics.com/