Public Funding for The Protein Forge Ltd

Artificial Intelligence (AI) is already used extensively by a range of industries, including healthcare. However, a lack of understanding of how the hidden internals of these systems operate (in/out of definition), raises concerns about the level of trust we can or should place in each specific tool. Trustworthiness is key, regardless of whether the system is performing a service for an end user (e.g. cancer diagnostics) or as a tool in product creation (e.g. drug development). One of AI's headline successes came in late 2018 when AlphaFold, a tool created by UK's DeepMind, largely solved a problem that has taxed the best biochemists for decades - that of protein folding. In subsequent years, AI has demonstrated that it can not just predict the three-dimensional structure of the thousands of proteins that allow life to function (i.e. "fold" them) but also create new and unique proteins ("inverse fold" them). This should allow new functions beneficial in healthcare and beyond. The Protein Forge is an Oxford-based start-up specialising in protein engineering, and designing novel protein-based vaccines and therapeutics. The opportunities afforded to SMEs, academics and pharmaceutical companies working in this sector by the new AI tools that have been made freely available are enormous. Designing novel proteins to tackle a disease was typically a lengthy and expensive process. Therapeutic development uses one of a small number of naturally occurring proteins, usually an antibody, to bind to some part of a cell or virus. Vaccines use dead organisms or one of the organism's own proteins. AI now offers the opportunity to use entirely new proteins as platforms for treatments against pathogens, tumours and other conditions. Unfortunately, AI currently assists very much towards the start of the drug development pipeline. It is neither tractable nor affordable to test the many hundreds of possible drugs that can now be designed in seconds or minutes using these new methods. It is, therefore, key that we develop trusted tools to assess which of the many suggested by the AI are likely to fail, like most drugs, to pass the rigorous testing before they are cleared for clinical use by the public. This proposal is for a feasibility study bringing together key stakeholders from throughout the drug development process with leading AI experts. It will create methodologies to establish trustworthiness, and form a consortium in which data, skills and the need to develop these tools can be evaluated.

The ideal vaccine is safe, effective and adapted to low-income countries (i.e., cheap and easy to manufacture, store and administer). These features are difficult to combine and strongly affected by delivery platforms (the way the vaccine is made and presented to the immune system). Trusted delivery platforms that can easily be adapted to fit a new disease are crucial to preparedness for 'disease X', the as yet unknown pathogen that will bring the next pandemic. This project is the first step towards one such platform. Newly developed vaccines are based on platforms such as RNA/DNA, viruses, and subunit scaffolds (engineered nanoparticles or virus-like-particles). Each of these approaches has distinct advantages and disadvantages: there is unlikely to be a "one-size-fits-all" vaccine platform that addresses pathogens as diverse as the Covid-19 virus, the TB bacterium, and the malaria parasite. Increasing the diversity of delivery platforms strengthens our hand against real global threats: antibiotic resistance, the evolution of new variants, and the transfer of diseases from another species to our own. Against this danger, this project will exploit our existing nanotechnology which has many characteristics of a potent platform. It provides a scaffold for the active ingredient of a vaccine and presents it to the immune system in a highly effective way. Recent reviews herald engineered nanoparticles as opening a new era in the rational design of effective vaccines. There is good reason to think that ours is amongst the most promising. We anticipate that our platform will be both flexible and effective and this research is the first stage of demonstrating its potential. In it, we aim to produce early-stage candidate vaccines against a variety of globally significant pathogens. Success will trigger collaborative work with vaccine specialists to test the safety and effectiveness of these candidates, first in the laboratory and then in humans. The history of research into vaccines is one of many failures and a few outstanding successes. Choosing the wrong platform leads researchers to blind alleys and delays vaccine development. Our work packages will demonstrate our platform's potential, engage our partners and meet the urgent need for platform choice. The rewards of success remain very great. A platform that allows the creation or enhancement of even just one key vaccine has the potential to save thousands or even millions of lives.