Public Funding for Vector Bioscience Cambridge Ltd

Nanoparticle drug delivery systems (DDS) are seeing growing attention for their potential to drastically improve the efficacy and safety of many cancer therapeutics. Key challenges DDSs address include cargos that are insoluble, have poor stability or have significant off-target effects. With current DDS technologies, only a small fraction of the administered dose ends up reaching the target site to have its intended effect. In addition, these provide non-complementary and highly fragmented solutions, with individual approaches that are only able to address a subset of these challenges with a subset of potential cargos. Developed for the first time 20 years ago, metal-organic frameworks (MOFs) are one of the most exciting areas in recent materials science. These porous hybrid solids are largely payload-agnostic, and the modifications used to control the carrier’s behaviour transfer well between different MOFs. This enables them to house virtually any therapeutic payload and use industry-standard technologies to modify the delivery profile, offering a technology platform with the potential to ultimately become the almost universal solution highly needed in the drug delivery industry. Vector Bioscience Cambridge was founded in 2021 based on +15 years of research at the University of Cambridge with the objective to become the first company to take this highly promising DSS platform to the market, focusing on macromolecule delivery. Macromolecules such as siRNA are potentially the most powerful anti-cancer drugs that exist, but there is currently no efficient way to deliver them specifically to the tumour. GENERA answers the Pathfinder Challenge call for novel RNA delivery methods and therapies through the validation of a new delivery method with enormous potential to improve the safety and effectiveness of RNA-based therapies. Our first use case consists of the deployment of siRNA for the treatment of hard-to-treat cancer types, starting with pancreatic cancer.

Nanoparticle drug delivery systems (DDS) are seeing growing attention for their potential to drastically improve the safety and efficacy of many therapeutics. Key challenges these systems address include active pharmaceutical ingredients (APIs) that are insoluble, have poor stability or have significant off-target effects. These are particularly important for cancer therapies, which are often highly toxic, and novel gene therapies, which are unstable and cannot cross biological barriers. By encapsulating or otherwise holding API molecules within a nanocarrier, therapeutics can be given a wide range of beneficial pharmacokinetic properties, including slow and targeted release. Current technologies, however, provide a non-complementary and highly fragmented toolbox, with individual approaches that are only able to address a subset of these challenges with a subset of potential APIs. The result is that carriers require painstaking optimisation and characterisation for each application. The field would be considerably streamlined by a "plug-and-play" system, in which a new API -- regardless of its size or chemistry -- could be loaded into a universal carrier, which is then altered to suit its function. This project will develop a novel DDS based on metal-organic frameworks (MOFs), a class of materials with exceptionally broad functionality and a modular approach to vehicle design. They can accept virtually any API and be modified as required using industry-standard techniques. This means that a MOF carrier, once proven with a particular drug, might be expected to behave similarly with a new drug; and a surface modification -- once its impact has been characterised -- might be expected to behave similarly when applied to a new carrier. MOFs may therefore offer a "modular toolbox" approach to carrier design and potentially the closest technology yet to a true plug-and-play system. Vector Bioscience, together with the Medicines Discovery Catapult, is working to accelerate the transition of this technology to the clinic. This 2-year project will seek to demonstrate the functionality of the platform across conventional small-molecule therapeutics, antibody-targeted delivery, and delivery of novel siRNA gene therapies. It will target clinically relevant _in vivo_ milestones covering the technology's efficacy, biocompatibility, and pharmacokinetics. In doing so, it will validate and de-risk the technology to the pharmaceutical industry, enabling collaborations to be structured and the development of the platform to continue once the project is complete. The focus of this project is pancreatic cancer. However, the platform has broad applicability and adjacent areas will be explored post-project.

Nanoparticle drug delivery systems (DDS) are seeing growing attention for their potential to drastically improve the safety and efficacy of many therapeutics. Key challenges these systems address include active pharmaceutical ingredients (APIs) that are insoluble, have poor stability or have significant off-target effects. These are particularly important for cancer therapies, which are often highly toxic, and novel gene therapies, which are unstable and cannot cross biological barriers. By encapsulating or otherwise holding API molecules within a nanocarrier, therapeutics can be given a wide range of beneficial properties, including slow and targeted release. Current technologies, however, provide non-complementary and highly fragmented solutions. For macromolecules, in particular, these technologies require cryogenic temperatures: this is, their storage at -80 or -20C to avoid degradation. This limits the usage of such molecules in remote locations but also increases their carbon footprint and the transition to net-zero, decentralised healthcare. This project will develop a novel DDS based on metal-organic frameworks (MOFs), a class of materials with exceptionally broad functionality and a modular approach to vehicle design. They can accept virtually any API and be modified as required using industry-standard techniques. This means that a MOF carrier, once proven with a particular macromolecule, will behave similarly with a new one; and a surface modification -- once its impact has been characterised -- is expected to behave similarly when applied to a new carrier. MOFs may therefore offer a "modular toolbox" approach to carrier design and potentially the closest technology yet to a true plug-and-play system. Vector Bioscience Cambridge is working to accelerate the transition of this technology to the clinic. This 6-month project will seek to demonstrate the functionality of the platform across novel siRNA gene therapies by improving their stability at room temperature. It will target clinically relevant milestones covering the technology's efficacy and biocompatibility. In doing so, it will validate and de-risk the technology to the pharmaceutical industry, enabling collaborations to be structured and the development of the platform to continue once the project is complete. The focus of this project is de-centralised healthcare in pancreatic cancer. However, the platform has broad applicability and adjacent, self-driven healthcare areas will be developed post-project.