Public Funding for Labgenius Limited

LabGenius is a UK biotechnology company that combines robotic automation, synthetic biology and advanced machine learning to explore protein fitness landscapes and improve multiple drug properties simultaneously. LabGenius' mission is to accelerate the discovery of next-generation therapeutic antibodies by pioneering the development of a smart robotic platform (**EVA(tm)**) that is capable of designing, conducting and, critically, learning from its own experiments. Cancer is the number one cause of death worldwide with over 40% of men and women being diagnosed with cancer in their lifetime (John Hopkins, 2022). The economic cost of cancer was estimated at £930 billion in 2021 and this cost is expected to rise. In the UK alone there are \>350,000 new cases of cancer a year (ONS,2022). Common cancers include those affecting the lungs (13%), bladder (3%) and ovaries (2%) (Siegel,2022). T-cell engagers (TCE) are seen as a way forward to treat cancers successfully without negatively impacting the rest of the body, however, to date only two TCEs have been marketed as many fail in clinical trials due to severe adverse side effects and low efficacy. In this project, LabGenius will use their machine learning-driven approach to optimise a T-cell engager for the treatment of advanced cancers, enabling candidates with better efficacy and safety to be taken forward for future development. LabGenius' technology platform sets it apart from the competition in speed and quality of drug candidates discovered.

LabGenius uses robotic automation, synthetic biology and advanced machine learning to explore protein fitness landscapes and improve multiple drug properties simultaneously. LabGenius' mission is to accelerate the discovery of next-generation therapeutic antibodies by pioneering the development of a smart robotic platform ('EVA') that is capable of designing, conducting and, critically, learning from its own experiments. The current **state-of-the-art** is sequential optimisation, which takes a long time and is less effective. No-one else is currently using a data-led approach to TCE optimisation and LabGenius' highly multidisciplinary team of data-scientists alongside the robotics set-up are well ahead of others' capabilities. However, they are currently not able to optimise T-cell engaging domains because large amounts of data (gathered in-house, drawing heavily on team and resources) are required for training and developing this capability.

**The Company** LabGenius is a drug discovery company that develops protein therapeutics using its novel drug discovery platform, EVA. This next-generation protein engineering platform integrates several cutting-edge technologies from the fields of synthetic biology, robotics and Machine Learning. EVA can design, conduct and learn from experiments to discover novel therapeutic assets that the lifescience industry is currently unable to achieve and to progress to pre-clinical and clinical trials. The biologics drug discovery market is valued at approximately £9.2 billion, of which the phase of lead optimization was valued at about £4.6 billion (Statistica, 2019). **Project Motivation** LabGenius aims to use the novel EVA platform to deliver a first-in-class oral delivered drug for the treatment of Inflammatory Bowel Disease (IBD), a gastrointestinal condition comprising Crohn's disease (CD) and ulcerative colitis (UC). IBD is a chronic disease that affects 0.5-1% of the population with an estimated 620,000 affected in the UK. The average annual care cost is over £4,600 per patient in the UK. Gold standard treatment is with biologic therapeutics. However, biologic drugs can only be administered systemically as the harsh conditions of the stomach and small bowel result in rapid degradation. This project would result in protein antibodies resistant to the pH, proteases and temperature of the GI tract. If successful, it would allow biologics to be delivered orally and would not only be a paradigm shift for the treatment of IBD but also open an entirely new method of administration of antibodies which are currently only administrable parenterally. The chosen drug target is a valid one as there is already a successful injectable drug on the market that is directed to it. This project is anticipated to deliver transformative effects for LabGenius opening new markets, generating revenues and team growth, and driving R&D investment - benefiting the UK economy.

- BACKGROUND: Peptides are a versatile class of biomolecule that can be deployed as critical components in advanced materials. These materials have tremendous commercial potential across several sectors (e.g. oil and gas, aerospace and medical). - PROBLEM: Peptide components that are developed using traditional approaches frequently lack the biophysical and biochemical properties to perform as required in a real-world setting. These problems are further exacerbated by poor manufacturability and material integration. As a consequence, only a handful of peptide-based materials have made it to market, with their commercialisation taking on the order of 15-20 years. - PROPOSED SOLUTION: In this project, LabGenius and QinetiQ will develop an AI-driven synthetic biology process that yields high performing peptide components. This novel manufacturing process will combine machine learning, high throughput library screening, next generation sequencing and automation. If successful, this project will position the UK as a “first-to-market” contender in the area of peptide-based materials.

Enzymes are biological molecules that facilitate chemical reactions in living cells. Many products in the food, fine chemical, flavour & fragrance, pharmaceutical and biotherapeutic industries use enzymes in their manufacturing processes. Many enzymes on the market are isolated from their original wild-type organism, many more need to be produced in a different host organism that is more suitable for large-scale industrial production and is capable of providing commercially viable yields of the enzyme. To optimise the level of production of the enzyme is time consuming and costly and often results in failure to achieve commercial yield targets due to the inherent biology of the host and the enzyme. Therefore, this project will develop a broad-host range expression system for expressing any new enzyme in a selection of industrially compatible microorganisms and assessing enzyme production in these multiple hosts prior to selecting the one that provides the highest yields for that enzyme.

Synthetic biology is an emerging discipline that seeks to build new biological systems for useful purposes. This task is achieved by inserting new arrangements of genes (sequences of DNA that encode proteins) into living organisms. The genes used in these engineered systems are frequently synthesized from scratch by commercial vendors. Currently, synthetic gene procurement is time consuming and expensive. These problems stem from inefficient pricing and poor market transparency. In this 12-month project, we will address these issues through the development and validation of BaseHunter - an online synthetic gene procurement tool that will ensure researchers are free to spend their time and resources solving scientific problems, not logistical ones.