Public Funding for 17Cicada Ltd

Paclitaxel (branded as Taxol) is one of the most important anticancer drugs and has been used for therapy of different types of cancer. It first gained FDA approval in 1992\. The compound, considered a blockbuster anticancer drug, was originally isolated from _Taxus brevifolia_ (Pacific yew), but is now known to be present in the approximately eleven _Taxus_ species. Global demand for paclitaxel is increasing, given it is the primary chemotherapeutic agent utilised against many forms of cancer including ovarian, lung and breast cancers. Cancer remains one of the greatest challenges faced by medicine today and is a leading cause of deaths worldwide, accounting for nearly 10 million deaths in 2020, or nearly one in six deaths (WHO, 2022). The global paclitaxel injection market was valued at US$ 4.5 billion in 2021 and is predicted to rise to US$ 11.2 billion by 2030, with a CAGR of 12.5% (VerifiedMarketReports, 2022). Commercial paclitaxel is currently sourced either from the bark or needles of the Pacific yew (_Taxus brevifolia_), which is both destructive and low yielding, or via chemical semi synthesis which involves the chemical modification of late precursors extracted from plant cell culture. These processes are limited by high costs. Therefore, the development of a more sustainable source is critical to meet growing global demands. **Our vision** is a sustainable, high-added value, bio-based production of paclitaxel which will spur medical innovation, reduce costs, and expand paclitaxel's use into fields such as skin disorders, renal and hepatic fibrosis, inflammation, axon regeneration, limb salvage, and coronary artery restenosis. We envisage a revolution where small, digitally controlled bioreactors are operated by highly qualified personnel -- producing little/no waste, while consuming carbon and utilising less resource-intensive feedstocks (e.g., waste, instead of resource-intensive sugars used in fermentation). **Our key objectives** involve research on three engineered strains: carbon consuming cyanobacteria and algae, paving the way towards carbon-negative paclitaxel; and Actinobacteria which feed on biological waste (instead of sugars). **We will focus** on producing 0.1g/L of paclitaxel in both a batch and continuous process, coupled with robust techno-economic analyses to select the best strain for scale-up. **Our innovation** is a first-of-a-kind attempt to produce commercial paclitaxel via bacterial strains which consume carbon dioxide and/or waste -- paving the way for lower-cost, more circular, sustainable medical products.

17Cicada anticipates the development of a revolutionary process that will allow individual farms to independently produce their own animal feed in a way that is sustainable, cost effective and with minimal environmental impact. 17Cicada aims to generate a robust and innovative way of utilising wastewater to support the growth of nutritional microalgae that can be converted into high quality animal feed. The global population is predicted to reach 9.8 billion by 2050 and 11.2 billion in 2100 (UN), significantly increasing the pressure on food production. Global events, such as the war in Ukraine, have had a significant impact on the cost of animal wheat feed, which has increased by 26.5 % over the last year. This has impacted on food inflation, which has risen to 13 % in the UK, compounding the current cost-of-living crisis. To provide food for the world's growing population, a significant increase in crop production is necessary to support livestock production. Unfortunately, the availability of arable land and fresh water is limited. Climate change is also predicted to affect the production of both maize and wheat by 2030, reducing maize crops by 24 % and wheat crops declining by 17 %. Microalgae are an exciting solution to this problem. Microalgae have a high protein content (\>75 %) and are highly efficient in their utilisation of nitrogen and phosphate. This contrasts with conventional agricultural protein production, which results in nitrogen and phosphate run off, leading to pollution of lakes and rivers as well as ocean acidification. With microalgae protein production almost all the nitrogen and phosphates are converted to protein with minimal environmental impact. **Our vision is the sustainable production of microalgae-based animal feed** which will significantly help the farming industry to increase production and reduce costs. We envisage a revolution where our simple but innovative photobioreactors are operated by the farm, producing little or no waste, remediating agricultural wastewater and consuming carbon dioxide to produce microalgae for animal feed. **Our key objectives** involve the isolation of fast-growing microalgae strains with excellent nutritional profiles capable of growth using wastewater. We will also focus on optimising our photobioreactor technology to integrate seamlessly with existing farm infrastructure, coupled with robust techno-economic analyses. **Our innovation** is a first-of-a-kind attempt to produce industrial microalgae strains pre-optimised for growth using agricultural wastewater to produce high-quality animal feed in a way that is sustainable and cost effective.

17Cicada anticipates market entry for its bacterial Hyaluronic Acid (HA) by 2025\. Our projected cumulative 5-year profits are of the order of £5.2 million (by 2029), i.e. 1033% return on investment (ROI) on project costs of £506,366 GBP. HA is widely distributed throughout connective, epithelial and neural tissues in human and animal bodies. It plays a significant range of biological roles, and is used in cosmetics (e.g. skin-moisturising and wrinkle-reducing products), cosmetic procedures (HA-based dermal fillers), medical treatment (e.g. eye surgery) and effective relief from osteoarthritis (by injecting HA into the joints). The global market for finished HA products was $20 billion in 2019 (Grand View Research), including $9b for medical products, $8b for cosmetics and $3 billion for nutraceutical products. Despite its chemical simplicity, HA-biochemistry is complex because it interacts differently with cell receptors depending on its molecular weight -- a property which paves the way for more technologically advanced medical products. The market anticipates a growth rate of 7.19% (CAGR) between Y2021-2028, driven mainly by an aging population and increasing aesthetic consciousness. Commercial HA is sourced from animals (rooster-comb) and competing, fermentation-based, non-animal products. The latter is based on bacterial cultures (especially _Streptococcus equi_) which are human pathogens. Although there is a powerful shift towards non-animal products, the use of human pathogens is problematic due to the immunogenic effect of protein/toxin residuals. This significant drawback can be greater in streptococcal-HA than in animal-sourced HA despite its low overall protein content. **It is therefore anticipated that microbial HA-production will shift towards non-pathogenic bacterial strains**. **Our vision** is a sustainable, bio-based HA which will spur medical innovation, reduce costs, abolish animal-sourced HA, and expand use of HA into stem cell therapy and tissue engineering. We envisage a revolution where small, digitally controlled HA bioreactors are operated by highly qualified personnel -- producing little or no waste, while consuming carbon and utilising less resource-intensive feedstocks. **Our key objectives** involve research on two engineered bacterial strains which are non-pathogenic, and which can consume either carbon dioxide or waste feedstocks. **We will focus** on producing HA in continuous production, coupled with robust techno-economic analyses to select the best strain for scale-up. **Our innovation** is a first-of-a-kind attempt to produce commercial HA via bacterial strains which are non-pathogenic _and_ which consume carbon dioxide and/or less resource-intensive feedstocks -- paving the way for novel nutraceuticals and lower-cost, more circular/sustainable HA-based cosmetic and medical products.