Public Funding for Micropore Technologies Ltd

The RAP-IDD project (Rapid Development of Intracellular Drug Delivery Innovations), led by the UK SME Micropore Technologies (Micropore), supported by SME Labman Automation (Labman) and CPI, aims to develop and validate a new technology platform to encapsulate genomic material (RNA and DNA) in protective nanoparticles and integrate this with high-throughput characterisation. In a game-changing advance over current methods, the platform will be upgraded to continuous production to make it applicable to both high-throughput formulation development and continuous manufacturing - compliant with Good Manufacturing Practice (GMP). If successful, this new platform will make a step-change improvement in the efficiency with which new genomic medicines progress from discovery to real application in disease prevention and treatment. The success of mRNA-based vaccines during the COVID-19 pandemic has resulted in a large increase in interest in other nucleic acid medicines that are delivered to cells via nanoparticle delivery systems. Similar technologies are being researched to enable breakthrough vaccines for other diseases, as well as targeted treatments for cancer, rare diseases and more. However, there remain barriers to successful development and manufacture of nanodelivered intracellular drugs. The encapsulation of the nucleic acids within protective nanoparticles (NPs), such as lipid nanoparticles (LNPs), is perhaps the most critical stage in the manufacturing process. Currently there are two major encapsulation technology approaches used: In research, microfluidic mixing devices are commonly used as they can quickly produce large formulation libraries while minimizing waste. However, these mixers cannot accommodate commercial-scale production volumes. Impingement jet mixing (IJM) technology was chosen as an available means to achieve large scale commercial production during the COVID pandemic, by stacking many units in parallel. However, this approach is less controllable and is wasteful and inefficient for discovery. Micropore is pioneering an alternative and patented micromixing/encapsulation technology called Advanced Crossflow (AXF) that combines the size-control and uniformity advantages of microfluidic approaches with an ability to scale up to commercial volumes, simply by increasing instrument size and material flow. The RAP-IDD project will build on this AXF technology with the aim of achieving the 'holy grail' of intracellular drug production: A single, highly-efficient, but flexible, multi-product technology platform that can span multiple phases of the drug development and production pathway -- from lab scale to commercial scale -- without the need to redevelop and re-optimise processes at different stages. The project will undertake research to de-risk and validate this approach.

**Need** The UK is currently undergoing a **cost of living crisis**. **Soaring energy prices** and the war in Ukraine are highlighting both **energy security** and **fuel poverty** issues, with **3.16m** UK households (13.2%) **living in fuel poverty** (BEIS, 2020) choosing between eating and heating. This was estimated to increase to 5m fuel poor homes with Ofgem's April 2022 price-cap increase, and is expected to increase further with October's price rise; further fuelling the crisis. Additionally, UK Greenhouse gas buildings emissions (GHGs) were 87 MtCO2 equivalent in 2019, accounting for 17% of GHGs. The UK has enforceable emissions reduction targets to hit net-zero by 2050\. The UK _can_ deliver affordable and sustainable house heating with air-source heat pumps, but **80% of UK homes aren't heat pump ready** due to **poor insulation** (BEIS, 2021). **Insulating homes is paramount to reaching net zero and reducing fuel poverty.** To do this, building retrofit rates need to increase from 26,000/year to 250,000/year (CfCC, 2020). Current materials failed to insulate the UK's buildings, with 90% of 8m solid wall buildings completely uninsulated (7m; 26% of housing). **Solution** Thermulon has developed a **cost-effective** and **easy solution to insulate these houses** by developing **novel chemical process** (Thermulon-process) to **reduce the cost of insulating aerogel**. Aerogels are the most insulating materials in existence, with superior fire-safety properties (when made of silica), but have been limited in their use due to their high cost which is a product of their complex manufacture. Thermulon has developed a continuous chemical process than **de-bottlenecks current production** issues and makes use of economies of scale to **drastically reduce aerogel price**; enabling the use of aerogels in products such as insulating plasters, blankets and cladding to bring the housing stock up to a standard in which houses can be easily retrofitted and affordably heated.

This project aims to transform a batch process for the manufacture of controlled release injectable drugs into a continuous process with appropriate control mechanisms to ensure robust, consistent product using methods that comply with FDA and other regulators' requirements. This has never been achieved before. It is particularly important for patient care and their treatments that sustained release drug therapies deliver their active components at a controlled and predictable release rate. Achieving this precise control of drug microspheres requires good control over particle size and size distribution during the manufacturing process. Micropore will partner with G2GBIO INC of South Korea in the project. The two companies have a history of collaboration since 2019\. During this time G2G BIO has repurposed an existing Alzheimer's drug as a long acting injectable to improve patient compliance. Micropore has supported G2GBIO with its advanced crossflow technology. G2GBIO has achieved Phase 1 clinical trial approval in Canada for their product. The next step in development is to convert the manufacturing process into a high volume continuous process that will pass regulatory scrutiny. Historically, it has been difficult to achieve economies of scale in the emulsification production supply chain. Standard manufacturing technology uses brute force rotor/stator homogenisation techniques, which provide localised high shear forces, damaging product quality, and resulting in a broad emulsion droplet size distribution. This requires costly separation processes to produce a narrower size range final product and creates significant wastage (Typically 30%+ but Micropore has a few examples of up to 90% wastage) of out-of-specification material. More recently Micropore's technology has demonstrated a near-zero waste capability arising from its gentle process technology. In this 3 year Micropore Technologies and G2GBio propose to scale up Micropore's crossflow technology from a single-membrane unit to multiple-membrane units to provide a significantly more cost-effective robust manufacturing route, meeting G2GBio's known requirements for multi-kilogramme manufacturing. In addition to this Micropore and G2GBio will collaborate to identify inline process analytics to enable the principles of the FDA, and other regulators, of Quality by Design (QbD) and Process Analytical Technology (PAT) to deliver an integrated process with robust process control. Micropore has won a number of global awards for its core technology and has gained market traction across the world.

This project aims to transform a batch process for the manufacture of controlled release injectable drugs into a continuous process with appropriate control mechanisms to ensure robust, consistent product using methods that comply with FDA and other regulators' requirements. This has never been achieved before. It is particularly important for patient care and their treatments that sustained release drug therapies deliver their active components at a controlled and predictable release rate. Achieving this precise control of drug microspheres requires good control over particle size and size distribution during the manufacturing process. Micropore will partner with G2GBIO INC of South Korea in the project. The two companies have a history of collaboration since 2019\. During this time G2G BIO has repurposed an existing Alzheimer's drug as a long acting injectable to improve patient compliance. Micropore has supported G2GBIO with its advanced crossflow technology. G2GBIO has achieved Phase 1 clinical trial approval in Canada for their product. The next step in development is to convert the manufacturing process into a high volume continuous process that will pass regulatory scrutiny. Historically, it has been difficult to achieve economies of scale in the emulsification production supply chain. Standard manufacturing technology uses brute force rotor/stator homogenisation techniques, which provide localised high shear forces, damaging product quality, and resulting in a broad emulsion droplet size distribution. This requires costly separation processes to produce a narrower size range final product and creates significant wastage (Typically 30%+ but Micropore has a few examples of up to 90% wastage) of out-of-specification material. More recently Micropore's technology has demonstrated a near-zero waste capability arising from its gentle process technology. In this 3 year Micropore Technologies and G2GBio propose to scale up Micropore's crossflow technology from a single-membrane unit to multiple-membrane units to provide a significantly more cost-effective robust manufacturing route, meeting G2GBio's known requirements for multi-kilogramme manufacturing. In addition to this Micropore and G2GBio will collaborate to identify inline process analytics to enable the principles of the FDA, and other regulators, of Quality by Design (QbD) and Process Analytical Technology (PAT) to deliver an integrated process with robust process control. Micropore has won a number of global awards for its core technology and has gained market traction across the world.

Microcapsules are ubiquitous in everyday life and are found in products used in crop protection, drug delivery, personal care, cosmetics etc. All microcapsules contain an active ingredient protected by the capsule shell for a multitude of purposes including safety, taste masking, stability and targeted delivery. To improve the performance of the capsule (in terms of stability and delivery behaviour) the capsule size distribution needs to be as narrow as possible, which is currently very difficult to achieve on industrial scales using existing manufacturing processes. Adapting microfiltration technologies to create membrane emulsification is a currently under-exploited manufacturing route that will enable the large-scale production of capsules with tightly controlled size distributions, leading to products with improved release properties at a cost that industry can afford. The technology will be tested on a specific high-value coatings application. The project is led by a small dynamic company, escubed limited who will work closely with researchers at the University of Leeds to develop the membrane technology for industrial use and will demonstrate its applicability to pilot plant scale at International Paint, a global leader in coatings technologies.

A research-based feasibilty study using a new manufacturing process to investigate production of specialist formulated particles in a cost-effective and high throughput process with highly defined particle properties. The innovative aim of the project is to use continuous membrane emsulsification as a means to formulate particles using physical as well as chemical formulation control, on a large enough scale to meet disclosed industry needs. Specialist particles have been shown to have unique properties for a number of commercial applications. The proposed research is preparatory to 'industrial research' which would build on the results from this initial feasibility study, investigating the behaviour of specific particle formulations in different commercial applications.

Awaiting Public Project Summary

Awaiting Public Summary