A Prosperity Partnership for the Design of Next-Generation Antibody Drug Bioconjugates (Next-Gen ADC)
Lead Research Organisation:
University of Strathclyde
Department Name: Pure and Applied Chemistry
Abstract
GlaxoSmithKline (GSK) is a leading global healthcare company that discovers, develops and manufactures medicines for respiratory disorders, cancer, heart disease, and skin conditions like psoriasis. GSK manufactures over 4 billion packs of medicines each year, with the goal of addressing society's healthcare grand challenges.
GSK continually seeks to improve the efficiency, efficacy and sustainability of new medicines. One area of interest to GSK is the expansion of their antibody drug conjugate (ADC) portfolio. Antibody-drug conjugates are hybrid medicines based on attaching antibodies to small molecule drugs, which improves the targeting of the medicine. ADCs combine the ability to deliver medicines to diseased cells and tissues a drug payload of interest. The advantage of ADCs over conventional medicines is they have the potential to reduce side effects associated with a drug by only delivering the it to the diseased parts of the body.
This Prosperity Partnership aims to build on an existing vibrant collaboration between GSK and the University of Strathclyde (UoS). The strengths of each partner will be leveraged to deliver a range of new methods and approaches to address some of the major challenges in the discovery, development, and application of ADCs and a broader array of bioconjugates. Our vision is to increase the efficiency of discovering and turning ADCs into future medicines in terms of the time and energy it takes to make new medicines. Our approaches and research will mean that transformative new ADCs will be made at lower costs, with a greater speed of production, and turn into new medicines at a much faster pace.
The two key challenge areas covered in our partnership include:
1. The curation and standardisation of data acquisition across the entire landscape of experimental analysis of an ADC. The use of data in designing ADCs is usually protected by individual companies and are not accessible to researchers. We will develop a standardised data analytical platform that forms the basis for an artificial intelligence informed decision-making process towards the end of the partnership. This will help the broader pharmaceutical industry and academics to successfully design new medicines based on ADCs.
2. Making Next generation ADCs. The discovery and development of new ADCs require efficient and flexible chemical reactions to link drugs to antibodies. We will develop a toolbox of new reagents to facilitate the more expedient and streamlined preparation of ADCs.
Through integrating the individual scientific themes of the projects, and the expertise from both GSK and the University of Strathclyde, we will make a major contribution to the wider pharmaceutical and biotechnology sectors. We will also train and develop the next generation of the drug discovery workforce that will develop future medicines based on ADCs. Finally, a key outcome of this partnership will be to assist GSK in achieving its mission of discovering and developing transformative medicines faster to help people do more, feel better, and live longer.
GSK continually seeks to improve the efficiency, efficacy and sustainability of new medicines. One area of interest to GSK is the expansion of their antibody drug conjugate (ADC) portfolio. Antibody-drug conjugates are hybrid medicines based on attaching antibodies to small molecule drugs, which improves the targeting of the medicine. ADCs combine the ability to deliver medicines to diseased cells and tissues a drug payload of interest. The advantage of ADCs over conventional medicines is they have the potential to reduce side effects associated with a drug by only delivering the it to the diseased parts of the body.
This Prosperity Partnership aims to build on an existing vibrant collaboration between GSK and the University of Strathclyde (UoS). The strengths of each partner will be leveraged to deliver a range of new methods and approaches to address some of the major challenges in the discovery, development, and application of ADCs and a broader array of bioconjugates. Our vision is to increase the efficiency of discovering and turning ADCs into future medicines in terms of the time and energy it takes to make new medicines. Our approaches and research will mean that transformative new ADCs will be made at lower costs, with a greater speed of production, and turn into new medicines at a much faster pace.
The two key challenge areas covered in our partnership include:
1. The curation and standardisation of data acquisition across the entire landscape of experimental analysis of an ADC. The use of data in designing ADCs is usually protected by individual companies and are not accessible to researchers. We will develop a standardised data analytical platform that forms the basis for an artificial intelligence informed decision-making process towards the end of the partnership. This will help the broader pharmaceutical industry and academics to successfully design new medicines based on ADCs.
2. Making Next generation ADCs. The discovery and development of new ADCs require efficient and flexible chemical reactions to link drugs to antibodies. We will develop a toolbox of new reagents to facilitate the more expedient and streamlined preparation of ADCs.
Through integrating the individual scientific themes of the projects, and the expertise from both GSK and the University of Strathclyde, we will make a major contribution to the wider pharmaceutical and biotechnology sectors. We will also train and develop the next generation of the drug discovery workforce that will develop future medicines based on ADCs. Finally, a key outcome of this partnership will be to assist GSK in achieving its mission of discovering and developing transformative medicines faster to help people do more, feel better, and live longer.
Technical Summary
The development of Ab drug conjugates (ADCs) has furnished a step change in the treatment of cancer, and holds significant potential in other areas of unmet clinical need, with over 100 ADC candidates under development. Despite this expanding pipeline of ADCs, their attrition during development remains unsustainably high (~ 90%).
To address this, we advocate that an integrated developability assessment of prototype ADCs is made during early-stage Ab candidate synthesis. We will develop an interconnected technology platform which forges links with high throughput synthesis of ADCs and holistic measurements of key developability parameters. A key aspect of the partnership is that data acquired during this 'risk assessment' phase is incorporated into an AI/ML-led feedback loop to triage bioconjugates with desirable properties.
Development of a high throughput synthesis platform will utilise a direct to biology approach pioneered initially at GSK for the synthesis PROTACs. Parallel exploration of novel and existing conjugation chemistry, linkerology, and payload (inhibitors and degraders) will align with world-leading bioanalytical capability to assess the impact these variables have on key parameters including efficacy, drug-antibody ratio, aggregation potential, solubility, formulation, and metabolic stability. Curation and machine-driven prosecution of these datasets will allow us to develop predictive models to inform the iterative design of higher quality Ab bioconjugate lead compounds in an expedient fashion.
The analytical and molecular tools developed in this Prosperity Partnership have considerable transformative potential. This technology base will provide significant impetus and agency towards expansion and adoption of the ADC approach in therapy areas beyond oncology, endowing the scientific community with a means of fully capitalising on the power of the unique modality Ab bioconjugates can offer across the spectrum of bioscience.
To address this, we advocate that an integrated developability assessment of prototype ADCs is made during early-stage Ab candidate synthesis. We will develop an interconnected technology platform which forges links with high throughput synthesis of ADCs and holistic measurements of key developability parameters. A key aspect of the partnership is that data acquired during this 'risk assessment' phase is incorporated into an AI/ML-led feedback loop to triage bioconjugates with desirable properties.
Development of a high throughput synthesis platform will utilise a direct to biology approach pioneered initially at GSK for the synthesis PROTACs. Parallel exploration of novel and existing conjugation chemistry, linkerology, and payload (inhibitors and degraders) will align with world-leading bioanalytical capability to assess the impact these variables have on key parameters including efficacy, drug-antibody ratio, aggregation potential, solubility, formulation, and metabolic stability. Curation and machine-driven prosecution of these datasets will allow us to develop predictive models to inform the iterative design of higher quality Ab bioconjugate lead compounds in an expedient fashion.
The analytical and molecular tools developed in this Prosperity Partnership have considerable transformative potential. This technology base will provide significant impetus and agency towards expansion and adoption of the ADC approach in therapy areas beyond oncology, endowing the scientific community with a means of fully capitalising on the power of the unique modality Ab bioconjugates can offer across the spectrum of bioscience.
