Impact case study database

Antibodies are the most important and successful class of bio-therapeutics with over 100 approved for clinical use in the US, and hundreds more in the pipeline [A]. In 2018 the global market was estimated at USD135,000,000,000, with further growth to over USD200,000,000,000 anticipated [B].

However, the generation of novel antibody therapeutics is currently still primarily a very time-consuming and expensive experimental endeavour. Pharmaceutical companies have therefore begun using databases and computational tools to accelerate the process of engineering an antibody to bind to a particular target or identifying antibodies that are markers for exposure or measures of vaccine efficacy. The SAbDab-SAbPred suite contains leading-edge tools that have provided this capability rapidly and efficiently. The resulting economic impact is realised by over 100 companies that have exploited this suite of tools.

Pathway to Impact

Deane took an early decision to make the SAbDab-SAbPred suite freely available under an open source licence in order to maximise the usage and impact of the tools. Funding from an EPSRC Impact Acceleration Award was used in 2016 to hire a Research Software Engineer (RSE) to further refine and integrate the software tools, making them easily accessible through a web server, and also to assist pharmaceutical companies who wished to bring the tools in-house and wanted help in adding new custom features. In 2020, to make it even easier for companies to use the tools, a second RSE was hired and the SAbDab-SAbPred suite was packaged as a virtual machine, named SAbBox, that can be downloaded as a single encapsulated licensed product.

9 pharmaceutical companies (GSK, UCB, Roche, AstraZeneca, Lonza, Iontas, Kymab, Tikcro, and Agenus Bio) currently have custom installations of the SAbDab-SAbPred suite. Five companies have already purchased SAbBox licences: GlaxoSmithKline plc (GSK), Kotai Biotech, Gritstone Oncology, Cenmed Enterprise, and Dragonfly Therapeutics. These collaborations have resulted in staff from AstraZeneca, Roche, GSK and UCB being involved as co-authors in much of the underpinning research [1,3,4,5,6].

Impact of SAbDab-SAbPred

The SAbDab-SAbPred suite has been utilised by over 100 pharmaceutical companies across the globe as part of their antibody therapeutic development pipelines [C]. These companies include very large multinationals such as Abbott, Medimmune/AstraZeneca, Bristol-Myers, Genentech, GSK, Novartis, Roche, Sanofi, and UCB as well as many smaller companies including Just Evotec Biologics and Voyager Therapeutics.

Components of SAbDab-SAbPred and/or the underlying research papers have been cited in 71 different patents (including 3 from Roche and 1 from UCB) in the area of therapeutic development [D], with some patents being filed in multiple regions (e.g. Europe, USA, Japan, China). Source [D] also includes the full text of 4 of these patents; two by Roche and UCB cite the use of SAbDab, while the other two by Seattle Genetics and Humabs BioMed cite ANARCI. The impact of using SAbDab-SAbPred by pharmaceutical companies has been to enable faster and more accurate results than commercial tools, thereby significantly reducing development costs and avoiding unnecessary expenses. The benefits that have been realised are illustrated below by company representatives of two large multinationals, GSK and UCB, along with two SMEs, Just Evotec Biologics and Voyager Therapeutics. Each outlines the particular impact that the suite of tools has had on their activities.

GlaxoSmithKline plc (GSK) is a British multinational pharmaceutical company with around 100,000 employees. It has collaborated with OPIG from its inception in 2008. A GSK employee was a co-author on publication [5], and GSK has paid for a custom installation of SAbDab-SAbPred and also a licence for SAbBox.

The use by GSK of these University of Oxford tools has been of great economic benefit.

A GSK Scientific Leader & GSK Fellow in Protein Design and Informatics, Data & Computational Sciences [E] states: “ We use ABodyBuilder as our main antibody homology modelling tool, which in-house benchmarking has shown to be an order of magnitude faster, and of higher accuracy, when compared to the antibody modelling tool in [the software package] MOE. High quality homology models are required for many subsequent activities, such as the investigation of experimentally determined developability risks and identification of residues for mutation. ABodyBuilder is also embedded in our in silico assessment pipeline, as homology models are a pre-requisite for our in-house post-translational modification and isomerisation prediction methods… the prediction and mitigation of developability risks during discovery reduces the cost of development by an estimated £500,000 [GBP500,000] to £2,000,000 [GBP2,000,000] in wet work [experiments] and FTE [staff] per campaign depending upon the number of liabilities.” GSK indicate [F] : “unfortunately the number of molecules [campaigns] we put through to development is not something we would disclose externally.”

UCB is a multinational bio-pharmaceutical company headquartered in Brussels, with around 7,500 employees. Like GSK, it has been involved in OPIG from its inception with a paid custom-installation of SAbDab-SAbPred. UCB has co-authors on publications [1,3,4,5,6].

At UCB, SAbDab and SAbPred have become an integral part of their antibody therapeutic discovery pipelines and have provided them with significant savings. The Senior Director, Head of Global Computer-Aided Drug Design at UCB [G], says of SAbDab : “ This comprehensive antibody structure database provides the data foundation for UCB’s computational antibody design. The antibody design team within my department would not function without this data source. Should my team lose access to SAbDab, we will have to recruit a full-time contractor for data curation and database maintenance. The expected cost would be £150,000 [GBP150,000] per year.” Concerning SAbPred, they say [G]: “The toolbox is used routinely by the antibody design team in my department to support every antibody therapeutic project at UCB. This toolbox is indispensable to our antibody optimization workflow and, in our hands, produces more informative results than commercial toolkits offered by two well-recognized software companies specialized in computational drug discovery. Each of the commercial toolkits would cost over £250,000 [GBP250,000] annually for the size of UCB.”

With their database, tools and an understanding of company needs, OPIG were ideally placed to respond when UCB commissioned a study to rapidly evaluate software developed by Massachusetts Institute of Technology. The Senior Director states [G]: “ In July 2020, UCB wanted to evaluate the feasibility of adopting an open-source AI software developed by Massachusetts Institute of Technology and published in Science. Within a month UCB received from your team not only an annotated, enhanced version of the open-source software, but also a report detailing components/functions that are missing from the software. This analysis led to UCB’s conclusion that it will take £450,000 [GBP450,000] and 1 year to adopt this AI software. Therefore, UCB invested in an alternative solution which costs £130,000 [GBP130,000] and 2 months to implement. The savings of £320,000 [GBP320,000] and 10 months, thanks to the Impact Software Engineer Service which costed UCB only £40,000 [GBP40,000] …”.

Just Evotec Biologics is a Seattle-based biotech company focussed on bio-therapeutics, with approximately 200 employees. Just Evotec Biologics rely on tools from the SAbDab-SAbPred suite, using them to assess developability of antibodies on important development campaigns including an anti-HIV antibody. Use of these tools has led to the company realising huge savings. A Principal Scientist at Just Evotec Biologics [H] states: “…we rely on tools such as those provided by the Oxford Protein Informatics Group (OPIG)… Optimization with respect to developability has been shown to have a profound beneficial impact on conformational stability… Additionally, well behaved, developable antibodies can be used… saving tens of thousands of dollars [USD10,000] and months of process development time during the development process alone and ultimately leading to lower drug costs for patients. Most recently, this work benefited the optimization and process development of an anti-HIV bnAb with a potential global impact”.

Voyager Therapeutics is a Boston-based biotech company with around 200 employees. They have replaced commercial tools with ABodyBuilder, TAP and ANARCI to realise significant financial savings. A Senior Scientist in Vector Engineering, Antibody Discovery / Design at Voyager Therapeutics [I] states they have used ABodyBuilder, TAP and ANARCI: “…to predict antibody homology models which saves substantial cost (>$100K/Ab [more than USD100,000 per antibody] ) towards experimental structure determination…[and have]… replaced huge licenses costs incurred from Schrodinger, Chemical Computing Group and others ($50K/yr [USD50,000 per year] ).”

In summary, research from OPIG has enabled and accelerated antibody therapeutic discovery in pharmaceutical companies, both large and small, saving both time and money, reducing the costly experimental effort required, and bringing treatments to patients faster.