Public Funding for Cytochroma Limited

Unexpected cardiac adverse effects and lack of testing in distinct genetic backgrounds are the leading causes of clinical trial discontinuation, the withdrawal of drugs from the market and post-approval withdrawal of medicines. VISION This project aims to deliver physiologically relevant multicellular cardiac models from a diverse genetic background to more accurately predict the safety and effect of new drugs in a global population. Cytochroma is a pioneering biotechnology company that supplies the pharmaceutical industry with ethnically diverse models for drug discovery and development. FOCUS To provide robust, reliable and scalable models that are cost effective, viable alternatives to the current gold standard to provide more accurate testing and capture a large market share. PLAN Cytochroma will utilise its expertise in developing 3D iPSC derived models and work with the Medicines Discovery Catapult, to exploit their access to industry contacts, expertise and state-of-the-art equipment. Together we will develop these models from proof of concept through to scale up for commercial manufacture. 1. Cytochroma will produce genetically diverse models containing multiple cardiac lineage cells. 2. The MDC and Cytochroma will characterise these models and conduct independent testing to validate the models. 3. To qualify the multicellular models for use by industry, a range of cardiotoxins will be evaluated and cell manufacture translated to automated systems for large scale manufacture. 4. Post-project these models will be supplied to MDC partners such as Astrazeneca and Merck for commercial validation and feedback. OBJECTIVES 1. Identification of a method to generate functional cardiac models 2. Externally validate models in response to known cardio-toxins. 3. Scale production and identify optimal methods of transport. INNOVATION Lineage specific cardiotoxic models and responses have been reported in simple 2D configurations, (Burnett 2019, Grimm 2018) however, access to multicellular 3D cardiac models from different backgrounds is a global first. OUTCOMES * Accelerated drug development * Preventing late stage clinical drug failure * Providing stratified healthcare We seek a revolution in preclinical testing and substantial improvements in the efficiency of new drug development and are sourcing public and private funding to develop translational science and technologies that provide substantial social, economic and environmental impact. With a regulatory drive to eliminate animal testing by 2035, pharmaceutical industry is investing in iPSC models and technology. Cytochroma is well placed to take advantage of this emerging and profitable market.

Access to medicines and anti-viral vaccines would have significant societal, environmental, and economic impacts, both in the short and long term. The current COVID-19 pandemic has highlighted the inefficiency in how novel therapeutics are made and tested. New drug and vaccine development takes on average \>10 years, with costs in excess of 2 and 0.5 billion USD respectively. Latter stage therapeutic failures amount to over 90% in clinical trials, because predicting reactions in humans cannot be determined with current models and tests. Cytochroma manufacturers liver models to accurately test the safety and effect of new drugs early in the drug development process. These stem cell-derived liver models are made from induced pluripotent stem cells (iPSC) - an unlimited, sustainable, and ethical source of cells for testing. Years of research combined with cutting-edge-technology has resulted in Cytochroma's novel, highly reproducible, and scalable method of differentiating iPSC into liver models. These are ideal for drug development/toxicity testing but must be shipped live, which enables rapid testing as cells are ready for immediate use. However, global disruption to numerous academic and commercial institutions as a result of COVID-19 has highlighted the need for a more flexible cell source and supply. Cytochroma proposes to utilise this funding to develop a cryopreserved (frozen), shippable format for its liver models. This flexible, ethical, and diverse source of cells has the potential to help identify novel treatments for COVID-19 and offset the negative impact on Cytochroma's loss of sales. Frozen liver models can be shipped worldwide, significantly increasing our customer base and enabling access to a growing global market worth over 14 billion USD by 2025\. Cytochroma has recruited a talented, diverse, and capable team and are based in a building that has been selected as "essential" to allow vital research, such as ours, to continue during lockdown. Furthermore, our automation means we have the capacity to generate cells at a significant scale. We seek a revolution in preclinical testing and substantial improvements in the efficiency of new drug and vaccine development. However, the COVID-19 pandemic and the widely forecast economic recession has adversely impacted Cytochroma's efforts to raise seed capital. As such, the Company needs access to a relatively small amount of grant funding in order to get this project underway. Global access to more accurate models of human tissue will reduce the need for animal testing, saving time and money. Furthermore, models that can recapitulate the world's diversity will enable the identification of much needed universal treatments for pandemics such as COVID-19\.

Access to medicines and anti-viral vaccines would have significant societal, environmental and economic impacts, both in the short and long term. The current Covid-19 pandemic has highlighted the inefficiency in how novel therapeutics are made and tested. New drug and vaccine development takes on average \>10 years, with costs in excess of 2 and 0.5 billion USD respectively. Latter stage therapeutics failures amount to over 90% in clinical trials, because predicting reactions in humans cannot be determined with current models and tests. Global pandemics are predicted to become more common, and subsequently, there is an increased and immediate need for 1) more accurate preclinical models, and 2) better, predictive tests to identify safety of drugs and vaccines. Cytochroma addresses the first need; by providing physiologically relevant, stem-cell-derived, human models for preclinical testing. We specialise in liver cell manufacture, a tissue that is often damaged and in which testing is required. We propose to address the second need and develop a more efficient method of testing the safety of new drugs and vaccines. This Robust Automated Phenotypic Identification of cell Damage or 'RAPID' test would use observational-based screening. By tagging cells with fluorescent dyes and viewing via a powerful microscope we can visualise how tissues react to drugs and vaccines at a single-cell level. This provides vastly more information than traditional tests and can be combined with machine learning to understand, modify and feedback to directly improve the development of new therapeutics. Cytochroma manufacturers liver models from a unique stem cell bank. These stem cells reflect a diverse genetic background that allows testing of a global population in vitro -- enabling identification of a _universal_ treatment for diseases. Our state-of-the-art technology and robotic based cell production can be easily adapted to tag cells and screen for toxicity on a high- content microscope. This automated approach enhances our capacity and enables us to provide cells at a scale and quality required for testing. These cells and the RAPID test will enable more accurate identification of toxicity, reduce late-stage attrition and accelerate development to make essential drugs and vaccines available faster. Cytochroma is based in Scotland, where over half of all Europe's biosafety is undertaken. The Company is well connected at all levels within the sector and it has strong relationships with several leading Contract Research Organisations and pharmaceutical giants, both of which offer an attractive route to market.