Public Funding for Metallobio Limited

Antimicrobial resistance, AMR, is globally responsible for 1.2 million annual fatalities. Failure to address the issue by 2050 could result in 10 million deaths per year, costing the global economy £66 trillion. To put this in to context, the predicted death rate for cancer is 8.2 million by the same year. As current antibiotics fail minor injuries, like a scratch on the knee, could soon become fatal. To address this emergency, the World Health Organisation, WHO, has called for novel methods to treat antibiotic resistant infections. Our team are directly answering this call, in line with the UK Government's 20-year vision to control and contain AMR by 2040\. As part of a highly skilled team, MetalloBio has developed two novel antimicrobial compounds to treat these extensively-drug resistant infections where other antibiotics are failing. The compounds exhibit comparable activities to clinical antibiotics but, crucially retain this high activity against drug-resistant bacteria, including bacterial strains the WHO has declared as critical priorities for new treatments. The complexes themselves have a modular synthesis. Like Lego, we can exchange the "building blocks" of our current leads to make a whole series of potential drugs. Both compounds have been found to be non-toxic to human cell lines in wax moth larvae and rodents. In addition, both compounds cleared a fatal infection from the larvae using a single dose and significantly reduced bacterial burden in a mouse infection model at an ultra-low dose <0.02 mg/kg. This project will directly build upon our preclinical data, including already determined toxicology and pharmacokinetic profiles in mice, accelerating the technology's development, reducing our time to market. This will increase the probability of the compounds successfully reaching the clinic. The full _in vitro_ toxicology profiles of the compounds will be studied including genotoxicity and off-target toxicities. The microbiology data package will be built up for IND-filing, including increasing the antimicrobial efficacy studies to 200 relevant hospital-acquired pneumonia strains and the excretion of the compounds will be studied in a mouse model over 72-hours. Our compounds explore a new area of antimicrobial chemistry, their structures are radically different to any antibiotics in the clinic. This will reduce the likelihood of resistance emerging, increasing the capability to treat infections and improve patient quality of life.

Antimicrobial resistance, AMR, is globally responsible for 1.2 million annual fatalities. Failure to address the issue by 2050 could result in 10 million deaths per year, costing the global economy £66 trillion. To put this in to context, the predicted death rate for cancer is 8.2 million by the same year. As current antibiotics fail minor injuries, like a scratch on the knee, could soon become fatal. To address this emergency, the World Health Organisation, WHO, has called for novel methods to treat antibiotic resistant infections. Our team are directly answering this call, in line with the UK Government's 20-year vision to control and contain AMR by 2040\. As part of a highly skilled team, MetalloBio have developed two novel antimicrobial compounds to treat these extensively-drug resistant infections where other antibiotics are failing. The compounds exhibit comparable activities to clinical antibiotics but, crucially retain this high activity against drug-resistant bacteria, including bacterial strains the WHO has declared as critical priorities for new treatments. The complexes themselves have a modular synthesis. Like Lego, we can exchange the "building blocks" of our current leads to make a whole series of potential drugs. Both compounds have been found to be non-toxic to human cell lines in wax moth larvae and rodents. In addition, both compounds cleared a fatal infection from the larvae using a single dose. This project will directly build upon our preclinical data, including already determined toxicology and pharmacokinetic profiles in mice, accelerating the technology's development, reducing our time to market. This will increase the probability of the compounds successfully reaching the clinic. The full mechanism of action of both compounds will be studied and the efficacy of both compounds against a P. aeruginosa efficacy model determined. These experiments will de-risk the technology, allowing its progression onto medium animal models. Our compounds explore a new area of antimicrobial chemistry, their structures are radically different to any antibiotics in the clinic. This will reduce the likelihood of resistance emerging, increasing the capability to treat infections and improve patient quality of life.

MetalloBio is a University of Sheffield spin-out company co-founded by Dr Kirsty Smitten and Professor Jim Thomas. MetalloBio are developing a new series of antimicrobial compounds. The compounds are being developed as drugs to treat respiratory bacterial infections and as medical device coatings to prevent infections from developing at the medical device site. The compounds that underpin the platform are more active than current antibiotics, have a novel mechanism of action, little-to-no emergence of resistance and represent a new antimicrobial class. To put this into perspective a new antimicrobial class has not reached the clinic in over 30-years. The antimicrobial is in the preclinical stage of development and the coating technology prototype has been developed. This award accelerate MetalloBio's technology's development and reduce the time to the market, where maximum impact through improved patient quality of life and reduced death rates will be achieved. The project will allow MetalloBio to complete key preclinical experiments outlined by potential customers as essential, including a wide antimicrobial screen of 90 bacterial strains relevant to respiratory infections. Additionally, it will allow the team to scale the synthesis of the antimicrobials to a level that will allow incorporation into polymers for commercial applications. Finally, commercial validity will be studied with a top 10 medical device company, to determine if the polymer can be used to coat their medical device technology's.

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Antimicrobial resistance, AMR, is globally responsible for 1.2 million annual fatalities. Antimicrobial resistance, AMR, is already responsible for 1.2 million annual fatalities. Failure to address the issue by 2050 could result in 10 million deaths per year, costing the global economy £66 trillion. To put this into context, the predicted death rates for cancer will be 8.2 million by the same year. As current treatment and preventative antimicrobial technologies fail, minor injuries and simple surgeries, such as a scratch on the knee, could soon become fatal. To address this global healthcare emergency the World Health Organisation, WHO, have highlighted there is a clinical unmet need for novel technologies that can treat and prevent such pathogenic diseases. At MetalloBio we are directly answering this unmet need, in line with the UK Government's 20-year vision to control and contain AMR by 2040\. As part of highly skilled team, MetalloBio have developed two lead antimicrobial additives, that can be incorporated into different materials and coatings. These materials can be applied to medical and non-medical applications such as catheter coatings, orthopedics, wound care, paints, textiles and food packaging. MetalloBio's antimicrobial functionalised materials will be able to prevent infection, transmission and spread of harmful pathogens, improving human health and patient quality of life. The antimicrobial additives have higher activities than clinical antibiotics and current antimicrobial additives, but crucially this activity is retained against drug-resistant bacteria, including those highlighted by the WHO as a critical priority. The complexes have a modular synthesis, like Lego, we can exchange the "building blocks" of our additives to make a whole series of these complexes. Additionally, they are non-toxic and highly active when incorporated into different polymeric materials. As these complexes are highly innovative, and radically different from anything on the market, the likelihood of emergence of resistance is highly reduced. This project will directly build upon preclinical data on the additives, and proof-of-concept coating studies, to optimise our antimicrobial materials. Antimicrobial and antibiofilm efficacy studies will be completed on a broad-spectrum of pathogens and the coatings will be applied to a number of different materials to broaden the application potential. The recent COVID-19 pandemic highlighted the catastrophic effects of a global pandemic, increasing MetalloBio's technology's application potential will help in the fight to prevent AMR causing the next pandemic. MetalloBio will work closely with commercial partners to ensure the technology will be applicable in commercial environments.

Antimicrobial resistance (AMR) is globally responsible for 700,000 annual fatalities. Failure to address this issue by 2050 could result in 10 million deaths per year, costing the global economy £66 trillion. To put this into context, the predicted death rate for cancer will be 8.2 million by the same year. As current antibiotics fail minor injuries, like a scratch on the knee, could soon become fatal. To address this emergency, the World Health Organisation (WHO) has called for novel methods to treat antibiotic resistant infections. Our team are directly answering this call, in line with the UK Government's 20-year vision to control and contain AMR by 2040\. As part of a highly skilled team, we have developed two novel antimicrobial compounds to treat these extensively-drug resistant infections where other antibiotics are failing. The compounds exhibit comparable activities to clinical antibiotics but, crucially they retain this high activity against drug-resistant bacteria, including bacterial strains The WHO has declared as critical priorities for new treatments. The complexes themselves have a modular synthesis. Like Lego, we can exchange the " building blocks" of our current leads to make a whole series of potential drugs. Both compounds have been found to be non-toxic to human cell lines and in living wax moth larvae. In addition, both compounds cleared a fatal infection from the larvae using a single dose. This project will directly build upon our preclinical data, accelerating the technology's development, reducing our time to market. This will increase the probability of the compounds successfully reaching the clinic. Final activity and toxicity studies will be carried out in cell lines (in a test tube/culture dish) and data from these studies will be used to facilitate co-development discussions. To build upon the previous living model data, the adsorption, distribution, metabolism and excretion properties of the drugs will be studied in a mouse model. In addition, the compounds toxicity levels, and their ability to clear a pathogenic _E. coli_ thigh infection will be studied. The mice will be closely monitored in the studies to record any effects of the compounds. These experiments will de-risk the technology, allowing its progression onto a medium animal pre-clinical model. Our compounds explore a new area of antimicrobial chemistry, their structures are radically different to any antibiotics in the clinic. This will reduce the likelihood of resistance emerging, increasing the capability to treat infections and improve patient quality of life.