This A4I project will support Innovate-UK funding for development of a novel "**S**upra**M**olecular" **R**NA **T**herapeutic (**SMRT**) delivery system and flexible, scalable RNA-manufacturing process for the sustainable manufacture of biologic drugs. Combined, the material and process will reduce considerably the material-use and energy-costs compared to the current state-of-the-art. Specifically, the **SMRT-FIT** project will address opportunities and complexities which have arisen recently (as a result of exciting new findings) that mean an increase in the range of information will be required in support of a **F**irst-**I**n-human clinical **T**rial of **SMRT** formulations. The project will involve collaboration with the UK National Measurement Laboratory (NML) that brings world-class analytical methods and experience to provide deep characterisation of the formulations with findings presented in a format that meets the needs of regulators (such as MHRA). RNA is the medicine platform of the future with many application-types in clinical trial. RNA therapeutics are suitable for manufacture without using cell-based processes, so it is possible to take an RNA sequence to a candidate vaccine or therapeutic in weeks. A particular advantage is that same manufacturing plant can be used to produce an extraordinary array of drugs from personalised medicines to vaccines. In the Innovate-UK Sustainable-Medicines-Manufacturing Project "SUMMIT", the SMRT delivery technology is being developed alongside Centillion Technology's Biofoundry-in-a-Box (BiaB), a small-footprint, continuous-flow-based manufacturing technology that will synthesize target RNA and formulate it into SMRTs in-line. Both BiaB and SMRTs are UK innovations. The supramolecular delivery system requires no ethanol in formulation, has potential to avoid cold-chain storage and to be tuned to different applications. Combined, these technologies are suitable for global manufacture of RNA therapies. Whilst we anticipate that RNA can be used for a wide range of indications, SUMMIT's immediate use case is as a vaccine. Vaccines are used for healthy people, consequently regulatory requirements are extremely demanding, so very full characterisation will be required. Humanity has never been at greater risk of zoonotic-pathogen outbreaks, recent high-profile examples include zoonotic viral pathogens (SARS/MERS/Ebola/Influenza/monkeypox). The COVID-19 pandemic demonstrated the capacity for rapid development, high efficacy and positive safety profile of mRNA vaccines as needs arise. The focus of this A4I-CEP application is to generate methods and data towards meeting the regulatory requirements that would facilitate commissioning of first-in-human clinical trial of SMRTs. If approved, this UKRI-funded work will have facilitated a significantly more sustainable RNA delivery technology that has been developed in and commercialised from the UK.

Aqdot is advancing AqFresh, a drop-in materials technology that reduces odour and volatile organic compound (VOC) emissions in post-consumer recycled (PCR) plastics, enabling higher recycled content in vehicle components. Odour/VOC issues currently constrain post-consumer recycled plastics in sensitive automotive applications; this project demonstrates a practical route to overcome that barrier. Over five months we will: (1) formulate and pilot a masterbatch compatible with standard compounding and moulding; (2) produce representative demonstrator parts with a UK manufacturing partner; and (3) validate performance using recognised automotive tests for odour and VOCs. Operational results will feed a comparative life-cycle assessment and an Impact Validation Report aligned with Department for Energy Security and Net Zero guidance, providing transparent evidence of environmental benefit. The aim is to show that AqFresh enables greater recycled plastic use without compromising performance, in-cabin air quality, or recyclability, helping UK manufacturers increase circularity and reduce reliance on virgin polymers. By unlocking demand for higher-quality recycled plastics across UK supply chains, the project supports domestic resource efficiency and measurable greenhouse-gas reductions. The approach is designed for rapid scale-up across interior trim parts using existing production equipment, with future potential beyond automotive in consumer goods and packaging. The project will generate demonstrator data, impact evidence, and a clear route to adoption for UK industry.

This project will develop a flexible and scalable RNA-manufacturing process and delivery system for the sustainable manufacture of biologic drugs, with considerably reduced material-use/energy-costs and the need for repurposing or rebuilding facilities. RNA is the medicine platform of the future with many application-types in clinical trial. RNA therapeutics are suitable for manufacture without using cell-based processes, so it is possible to take an RNA sequence to a candidate vaccine or therapeutic in weeks. A particular advantage is that same manufacturing plant can be used to produce an extraordinary array of drugs from personalised medicines to vaccines. The aim of this application is to further enhance the RNA-manufacturing process to reduce waste and improve sustainability. We will achieve this through several RNA-manufacturing innovations. We will optimise a scalable RNA Biofoundry (that we call Biofoundry in a box --BiaB). This will enable globally distributed-manufacturing via continuous-flow processes, to improve RNA purity and reduce waste. We will also develop tunable and thermostable formulations; these reduce cold-chain requirements and the need for energy-consuming ultralow temperature freezers. Alongside the equipment, novel excipients will be developed for a supramolecular _delivery system_ _that does not require organic solvents_ for sustainable manufacture of local, disease-strain-specific therapeutic/vaccine applications. We will also develop a low-loss fill-finish line so that all of the process intensification advantages of the RNA Biofoundary to produce a minimum viable product size for early clinical development are not wasted through the traditional approaches to demonstrating quality and sterility assurance. Whilst we anticipate that RNA can be used for a wide range of indications, the immediate use case is as a vaccine. Humanity has never been at greater risk of zoonotic-pathogen outbreaks, recent high-profile examples include zoonotic viral pathogens (SARS/MERS/Ebola/Influenza/monkeypox). The COVID-19 pandemic demonstrated the capacity for rapid development, high efficacy and positive safety profile of mRNA vaccines as needs arise. The focus of this application therefore will be to optimise the sustainability of facility capable of manufacturing a pipeline of RNA vaccines to prevent a potential avian-influenza crossover-event before it becomes a pandemic. Improved pathogen surveillance and sequencing will enable infectious diseases to be identified and therapeutics designed earlier (e.g. the CEPI 100-day mission). The scale of the manufacture we are proposing, combined with the thermostability makes our approach highly suitable for use in low-and-middle-income countries (LMICs), where there is a vaccination backlog.

**Aqdot**, a young **UK-based** Chemtech company, has completed relevant regulatory approvals and is now accelerating scaling of a novel macrocyclic chemical, **cucurbit\[n\]uril**, "**CB\[n**\]". Cucurbit\[n\]urils are extremely effective "supramolecular hosts": they non-covalently bind a wide range of chemical "guests". Cucurbit\[n\]urils have potential to provide significant societal benefits by reducing levels of volatile organic compounds (VOCs), and in particular unpleasant odours, for which it is marketed as "AqFresh(TM)". Commercial application areas for AqFresh in powder or suspension form include: home and personal care products, automotive plastics and nonwovens. Aqdot has identified and grown potential markets for AqFresh, developed the manufacturing process to increasing scale and undertaken the extensive health and environmental regulatory processes required for large-scale manufacture and sale. The **current product** is manufactured at multi-tonne scale. Early in 2024, Aqdot will complete commissioning of its first CB\[n\]-manufacturing facility, building on the experience with several contract manufacturers. The small-footprint plant and make-to-demand capability is suited for globally-distributed manufacturing (potentially adjacent-to-customer, thus reducing environmental footprint, and with potential for bespoke composition) facilitating Aqdot's global growth in an agile manner without requiring the £100M+ investments needed to construct a "mega" manufacturing plant. This project aims to enhance AqFresh product quality such that it can be even more widely applied as a white powder or colourless solution, particularly for the nonwoven-hygiene market (baby and adult diapers, feminine hygiene). This market is very large (~£30B, 2023) and inclusion of AqFresh would bring significant cost-effective benefits, by enhancing the user experience/confidence. According to a survey by Euromonitor International, the greatest _unmet_ _need_ and, slightly behind absorbency, the biggest _consumer demand_ for adult-incontinence products is odour control. AqFresh in nonwoven-hygiene products reduces urine-odours significantly. The reduction occurs within seconds and lasts far beyond typical product-wear times. This A4I project would enable Aqdot scientists and engineers to work with world-leading scientists at the UK National Measurement Laboratory who will apply world-leading analytical techniques to the challenge of identifying then eliminating a yellow/brown colourant from AqFresh. They will work with Aqdot to identify the process and/or material causes thereby enabling **enhanced product quality and increasing the speed of this UK company to profitable global growth**.

**Aqdot**, a young **UK-based company**, has completed all relevant regulatory and environmental hurdles and is now accelerating production and commercialisation of a novel macrocyclic chemical, **cucurbit\[n\]uril**, "**CB\[n**\]". Cucurbit\[n\]urils are extremely effective "supramolecular hosts": they non-covalently bind a wide range of chemical "guests" and thereby have potential to provide significant societal benefits in many application areas, with commercial sales in powder or suspension form for use in deodorants, air-fresheners, and general home and personal care. The immediate application for CB\[n\] is as an odour- and VOC-capture ingredient, for which it is marketed as "**AqFresh**". Aqdot has identified and grown the potential markets for CB\[n\], developed the manufacturing process to increasing scale and undertaken the health/safety/environment regulatory processes required for large-scale manufacture and application. REACH approval is currently 100tonne/annum with similar situations in USA, Canada and China. Investment is ongoing to complete the tests required to secure regulatory approval to manufacture and sell CB\[n\] at very much larger scales. The **current product** is manufactured in multi-tonne batches. Early in 2024, Aqdot will complete the commissioning of its first CB\[n\]-manufacturing facility, building on the experience with several contract manufacturers. The small-footprint plant and make-to-demand capability is suited for globally distributed manufacturing (potentially adjacent-to-customer, reducing environmental footprint and with potential for bespoke composition) and will facilitate Aqdot's global growth in an agile manner without requiring the £100M+ investments required to construct "mega" manufacturing plants. To date, Aqdot has had more than 100 product batches contract-manufactured, each characterised by many analytical techniques, including: proton-NMR, water-content, elemental-analysis, GC, Karl-Fischer titration, pH, UV-visible spectroscopy, conductivity, laser-diffraction, and packing-density. All batches investigated fall within the specifications. However, in one or two potential new formulation formats, for which there is very significant market "pull", there are "show-stopping" differences in batch-to-batch performance that prevents Aqdot from entering those markets with confidence, if at all. This A4I project allows Aqdot scientists and engineers to work with world-leading scientists at key UK laboratories who will apply advanced analytical techniques to identify differences between AqFresh batches, thereby enabling **identification and elimination of the batch-to-batch variation and increasing the speed of this UK company to profitable global growth**.

RNA-based medicines and vaccines are of increasing importance to UK national health and wealth. These therapeutics are effective at low dose levels. Different diseases can be treated with different RNAs; but Different RNAs, however, may be made by the same process. The RNA performs its therapeutic task inside a patient's cells: intracellular delivery is currently achieved by incorporating RNA into Lipid Nanoparticles (LNPs). However, LNP use is challenging because of high lipid cost and patent constraints: solvent use (then removal) in LNP manufacture; and expensive cold chain between LNP manufacture and patient. We have developed a new delivery system that uses safe and accessible small-molecule components which, with CB\[8\] and RNA, spontaneously self-assemble. These supramolecular RNA therapeutics (SMRTs) efficiently encapsulate and deliver RNA into cells, do not require organic solvents, have low material costs (<£2/dose), good room-temperature stability, and avoid the toxicity of polymer-based RNA-delivery systems. SMRTs are adaptable to different RNA types and may be formulated to include special stabilising or cell-targeting components, giving potential to address diseases in different parts of the body. Our innovation will combine SMRT formulations with development of a miniaturised flow-based manufacture unit to a scale suitable for in-hospital applications. The facility (currently aimed at producing millions of doses of RNA-vaccine/day) uses modular continuous-flow processes, which permits scale independence (down to individual RNA-therapeutic doses). The processes have already demonstrated in-situ in a single unit manufacture of high-purity mRNA at high concentration _and_ formulation into a delivery system. Integrating multi-RNA synthesis with SMRT formulation enables streamlined production of multiple drug products from the same facility. Ease in scaling enables longer running with minimal adjustments, while continuous process-verification-in-flow reduces validation complexity and simplifies regulatory reporting, yielding shorter approval schedules and time-to-market. Small-footprint units can be sited in individual hospitals, enabling local production of RNA-medicine for individual patients or stratified patient groups, eliminating cold- and supply-chain hurdles. The delivery-system/manufacturing-unit combination will be developed for the clinical example of triple negative breast cancer (TNBC). In the UK, 51% of cancer diagnoses are for breast cancer (BC), which has 7% mortality. Compared to other BCs, TNBC tends to grow and spread faster, have fewer treatment options, more recurrences, and worse outcomes.so needs new therapeutic options. BC is an NHS (and global) priority. Project partners UK SMEs Aqdot and Centillion Technology and Nottingham University's research groups in Pharmacy and Medicine combine expertise in supramolecular-assembly, flow-based manufacture, and cancer therapy delivery/design/testing.

The Covid-19 pandemic has caused extensive health, economic and social damage in the UK and worldwide. As countries reactivate economies, it is essential to reduce transmission risks of bioaerosols in enclosed places (e.g. public transport, workplaces, health, education, and leisure settings) and contaminated soft surfaces (textiles/face masks) using safe disinfection technologies. In response to the Covid-19 crisis, Aqdot (Cambridge-based SME), in collaboration with University of Cambridge has recently demonstrated that its platform technology, AqBit (cucurbit\[n\]urils, CBs), is a unique virucide that inhibits SARS-CoV-2-pseudovirus without harming human cells. The technology, available at multi-tonne scale, is safe for humans and the environment as evidenced in the REACH (100 tonne/annum) registration dossier. The project will be completed in the UK between Aqdot, Dr Sam Jones (cucurbit\[n\]uril understanding and virology expertise) at the Henry Royce Institute, University of Manchester, and Professors Andrew Bayly and Nik Kapur (spray generation, characterisation and development) at the School of Chemical and Process Engineering, University of Leeds. The project will focus on the development of safe and efficacious antiviral spray formulations based on Aqdot's technology to inactivate SARS-CoV-2 in soft surfaces (fabrics) and bioaerosols. The project will deliver comprehensive technical, safety data packages, including AqBit-based formulations, delivery devices specification and virucidal performance validation against SARS-CoV-2\. Scalable product demonstrators will be generated for each application (fabric and airborne virus) using hand-held spray devices for small spaces, and a regulatory strategy will be put in place to ensure quick biocidal registration. Also, the concept of automatic spray devices will be validated for use in larger enclosed spaces. The demonstrator formulation/device combinations will be designed for rapid commercialisation, upon success, as low-cost products providing readily available, affordable solutions to reduce the transmission rates of Covid-19, benefitting individuals and businesses. These products will build societal confidence to "return to normal" in the UK and beyond.

The transport industry has been significantly impacted by the Covid-19 pandemic. People fear that virus-containing bioaerosols cause infection on board which has contributed to the spread of the pandemic. This is also compounded by reports of air-quality issues arising from the often-unpleasant odorous volatile organic compounds (VOCs) and airborne particles. This problem is global, affecting all types of transport including airplanes, trains, buses, cars and even passenger ships. Air quality could be greatly improved by introducing filters that not only kill viruses but also capture VOCs and odours, thereby reducing risks of infection and health concerns while boosting the confidence of passengers and crew in post-pandemic travel. Unfortunately, existing air-filtration technologies are unable to deliver the performance required even when used in combination (i.e. HEPA with charcoal filters). Therefore, alternative and novel solutions are required. Aqdot (a Cambridge-based SME) has a unique, proprietary VOC/malodour-capture technology (AqFresh) that is effective against a wide range of molecules that are unpleasant and/or harmful. The innovation is currently commercially available in home care, pet care and industrial cleaning products. This project aims to adapt the technology to meet the needs of the transport industry by developing scalable, ready-to-adopt air filters that bring together novel VOC/odour capture technology with antiviral capabilities, significantly improving air safety and quality in transport. The innovative filters, generated by impregnating appropriate polyurethane foam substrates with a unique coating formulation, will be designed to fit into existing systems of global filter manufacturers. The filters will be formulated and tested for anti-viral and VOC-reduction capabilities. These filter prototypes will then be incorporated and tested in operational environments by commercial manufacturers with a view for global roll out. Aqdot will partner with customers to allow rapid adoption of this innovation in their filtration frameworks in aerospace, automotive and public transport. Upon success, Aqdot's innovative air filters will bring major improvements in air quality for the transport industry worldwide to be free from viruses, VOCs and odours, minimising the risk of infections and health concerns onboard, helping to combat the immediate Covid-19 pandemic while reducing the impact of future potential pandemics. It will also assure safety and build confidence among passengers and crew to resume travelling following the pandemic, reinvigorating the transport industry and giving a much-needed boost to the economy. The project will demonstrate support for innovative UK-based SMEs, strengthen the UK technology portfolio and has significant export potential. After successful demonstration of the technical feasibility and potential of the innovative filtration technology combining VOCs/malodour capture and antiviral performance, the extension for impact will focus on speeding the market uptake of the technology. Key partners will be engaged in collaboration programs to assess the filters performance under operational conditions. A clear and detailed commercialization strategy will be put in place as well as key engagements will be established for definition of the supply chain for large scale production of the materials. In overall, the new filters will be ready for market adoption in a suitable format for large scale production and their market potential will be realised, strengthening the UK technology portfolio, minimizing the impact of Covid-19 and delivering extra benefits to society.

"Aqdot has developed a proprietary technology to bring innovation to the performance chemistry industry with applications in agrichemicals, household and personal care. CORE is a game-changing project which will bring the new chemical compounds, cucurbit\[n\]urils (Aq(tm)Bit) to the global market via a disruptive manufacturing process based on continuous-flow chemistry that will increase production capacity and cost-efficiency, as well as reduce environmental impact. AqBit has commercially relevant characteristics enabling unique properties in chemical formulations for consumer and industrial products. However, due to difficulties in its manufacture, it has never been available in commercial quantities. By building upon successes achieved at Aqdot's initial scale-up work, AqBit will become available in multi-tonne quantities (up to 200 tonne/annum), ready to be incorporated into products that will be supplied to some of the world's largest chemical manufacturers, formulators, and fast-moving consumer goods companies. This availability will lead to a multi-million-pound added value export market to UK's industrial chemicals sector, long term job growth and uptake of the cutting-edge technology in materials chemistry."

Aqdot has developed proprietary technology to bring innovation in micro-encapsulation technologies relevant to agriculture and consumer products. AqCooper is a highly disruptive project which will bring the new chemical compound, cucurbit[n]urils (CBs), to the global market. The chemical and its derivatives have commercially relevant characteristics enabling enhanced properties in chemical formulations and consumer & industrial products, but due to difficulties in its manufacture, has never been available at commercial quantities. By building upon successes achieved at Aqdot’s pilot production facility, CBs will become available at multi-tonne quantities and available for supply to established buyers from some of the world’s largest chemicals manufacturers and formulators. This will lead to a multi-million-pound export market, added value to UK’s industrial chemicals sector, long term job growth and uptake of the leading-edge technology in materials chemistry.

The AqBusDUE project will see Aqdot Limited conduct business development activities to engage major market actors in Europe and the United States. It will focus on accelerating the commercialisation of Aqdot Limited technology in microencapsulation in the consumer air care and household care industry. We will conduct intercontinental multi-stage visits to the headquarters and research development facilities of some of the world's leading chemical and consumer products manufacturing companies with an aim to establishing formal collaboration towards including our technology in new and existing products available to consumers throughout the UK, EU and US.

Epoxy resins are robust, light-weight plastics that are used in the manufacture of composite materials used throughout commercial aircraft. Using epoxy composites to construct aircraft makes them lighter and more fuel efficient. Developing new kinds of epoxy resin could make manufacturing of composite materials simpler, more energy efficient and less expensive. Aqdot has developed epoxy curing catalysts that could simplify the manufacture of epoxy composites by making them stable at room temperature. In this feasibility study, Aqdot and the University of Manchester seek to investigate whether the new catalysts can be successfully applied to aerospace composites.

AQDOT is a spin-out company from the Department of Chemistry, University of Cambridge. The company has developed a platform technology that exploits the dynamic and orthogonal supramolecular chemistry to encapsulate a wide variety of materials in one step in aqueous solutions. AQDOT’s microcapsules can protect active agrochemical ingredients and ensure that they get to where they’re needed, when they’re needed – leading to a dramatic reduction in the wastage of valuable cargo. Furthermore, production is inexpensive and potentially uses less energy and less material than current routes. AQDOT provides a unique, innovative solution to the formulation challenges of the agrochemicals, and other markets.