Written by Aonghus Topham, Edited by: Ana Ivanus and Caroline Babisz.

Introduction

The rising tide of antimicrobial resistance (AMR) is recognised as one of the major hurdles of the 21st century, being predicted to cause more deaths worldwide than cancer within the next 25 years [5]. Our overuse of antibiotic agents is driving the evolution of novel antimicrobial-resistant bacterial strains across both agricultural and healthcare sectors. Humanity is fighting a losing battle against billions of years of bacterial evolution. To keep in this fight, we need to come up with more innovative solutions within the field of antimicrobial biotechnology. 

Zonova Animal Health, use proprietary antimicrobial technology, aiming to revolutionize the veterinary medical device industry. We caught up with Dr. Georgia Fleet, CEO and founder of Zonova Animal Health, to discuss directions and the future of the company.

Zonova’s origins

During an undergraduate placement at a BTG Biocompatibles, Georgia was introduced to the medical devices industry and was engrossed with the fast-paced nature of the industry. 

Fast forward to her PhD, which involved studying materials science, Georgia started looking into hospital-acquired infections. After speaking with a critical care consultant, she learned that the highest cause of death in critical care units was ventilator-associated pneumonia, which occurs via bacterial biofilms growing on endotracheal tubes used for intubation. Most emergency procedures are equally invasive and leave patients at high risk of fatal infections. As a result, these procedures are often accompanied by multiple rounds of antibiotic treatments to prevent infections (known as prophylaxis), which upregulate the evolution of resistant strains such as Methicilin-Resistant S. aureus (MRSA), in turn leading to more rounds of antibiotics. The inherent problem posed by prophylactic antibiotics is not to be understated and is guaranteed to lead to the evolution of more resistant strains of bacteria, narrowing our ability to defend against hospital acquired infections.  

It became clear that the same medical devices and antibiotics are used for both humans and animals. Often, human-focused pharmaceutical companies siphon off a spin-out department/company, for example Pfizer spinning out their animal health department Zoetis. Many of these spin-outs operate with with a much tighter R&D budget, Pfizer operated with an R&D budget of $11.4Bn in 2022 [6] in comparison to Zoetis’ 2022 R&D budget of $539M [7]. As a result, the veterinary sector is largely overlooked, partially due to the comparatively smaller funding landscape and predicted returns on investment compared to human-centred medical devices. 

This leaves a huge gap within the market, therefore representing an untapped industry within biotechnology.

The impact of infectious diseases on the global livestock industry highlights the importance of animal healthcare from an economic perspective. In 2019 African Swine Fever (ASF) cost the Chinese economy an estimated $111.2Bn [9], whereas the impact of Foot and Mouth Disease (FMD) annually  costs an estimated $21.1Bn worldwide [8]. These figures really show the huge need for innovative animal-focused biotechs to prevent catastrophic economic impact worldwide, enter Zonova Animal Health…

By making the medical device itself antimicrobial, Zonova Animal Health are simultaneously solving two major issues. First and foremost, it avoids infection-related deaths in livestock and our pets. The regulatory landscape surrounding antibiotics use is changing rapidly, with governments around the world realising the critical impact of reinforcing the need of a “one-health” approach to combating the AMR crisis. This approach views the AMR crisis from a more holistic standpoint, considering the circular nature and interplay between human health, animal health and the environment (Figure 1). Since resistant strains are transmitted to humans through animal-based products, pets, and through the environment, tackling this problem at the source has never been more important. Innovative solutions to avoid unnecessary overuse of our finite antibiotics are desperately needed as we approach a bottleneck in our ability to fight microbial infections. Zonova’s proprietary antimicrobial technology offers an elegant solution for both issues. 

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Figure 1: One Health approach to tackling Antimicrobial Resistance. (Taken from: file:///C:/Users/aongh/Downloads/bracing-superbugs-strengthening-environmental-action.pdf

Current Antimicrobial materials on the market

As with all antimicrobial agents, a major hurdle of current antibacterial biomaterials is selective toxicity, which often inhibits translation into the clinic. Current antimicrobial materials involve coatings applied directly to the surface of medical devices. These primarily work through eluting either silver (Ag+) or honey which kill bacteria at the site of infection.

Alongside its applications as a food product, honey’s antimicrobial properties have been well studied. Honey contains mostly sugars, water, and other small molecules (enzymes, vitamins, minerals, phenols, organic acids, etc). The main sugars in honey are fructose and glucose, along with other small amounts of mono- and disaccharides. Honey’s main antimicrobial activity stems from the release of H2O2 (hydrogen peroxide), but other constituents of honey also contribute to this (low pH, defensin enzymes from bees, methylglyoxal (MGO) in non-peroxide honeys)[2]

In contrast, Ag+ eluting materials describe another class of antimicrobial materials. Ag+ ions essentially work by disrupting the permeability of the bacterial membrane through chemical modifications of phosphorus-containing compounds. In addition, they can bind and disrupt activity of bacterial enzymes and interfering with the electron transport chain thereby inhibiting ATP production [1]

A major limitation of the types of materials described above is their range of antimicrobial activity. These materials are often ineffective against gram-positive bacteria such as MRSA. Comparatively, Zonova’s material has >99.99% antimicrobial activity against MRSA, ESBL-producing P. aeruginosas, E. coli, and SARS-CoV-2. (Figure 2)

“The extra 0.09% makes a huge difference in reality! If a product claims to be 99% effective, from a starting number of 1,000,000 bacteria, the number of bacteria remaining after treatment is still over 10,000. For products that are 99.9% effective, this reduces to 1,000. For Zonova® products which are over 99.99% effective this is reduced to under 100 bacteria remaining from that initial 1,000,000.” – Dr Georgia Fleet.

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Figure 2: Comparison of range of antimicrobial materials in medical devices [3].

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Figure 3: Zonova Animal Health products demonstrated in a skin pad [3].

What do the next few months look like for Zonova Animal Health?

Zonova aims to launch their first product by 2025, leading with the Zonova® Suture Kit (Figure 3). The suture will kill bacteria at the source, preventing surgical site infections and aid wound healing, removing the need for prophylactic antibiotics over the course of treatment.

Traditionally, devices like this are made from polymers and are accompanied by aggressive prophylactic antibiotic courses to combat infections. The next step is to gain clinical data via a pilot study starting in 2024. If any of our readers would like to be involved in this study or learn more about the technology, please feel free to reach out to Georgia at georgia@zonovaanimalhealth.com. 

After entering the SEC’s accelerator programme, The Innovators Club in 2023 Georgia was able to show off her expertise and build new skills and networks within our community and go on to win our pitching competition to a room of 50+ biotech investors. Georgia received a brilliant prize package including three months rent-free lab space at Co-Laboratories incubator in King’s Cross, a grant support package from PNO Consultants Ltd (UK) and a Kick-StartIP package from Potter Clarkson.

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Zonova Animal Health is currently fundraising to allow them to launch their lead product, the Zonova® Suture kit. The scope of areas within veterinary devices Zonova Animal Health could address in the future is vast, with their sights set firmly on other medical devices within the next 12-18 months. This places Zonova Animal Health at the forefront of innovation in this explosive area of biotechnology, so watch this space! 

References

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037843/ 

[2] https://www.mdpi.com/2079-6382/11/7/975#:~:text=The%20antibacterial%20activity%20of%20honey%20has%20been%20associated,enzymes%20alongside%20high%20osmolarity%20and%20a%20low%20pH

[3] https://zonovaanimalhealth.com/how-it-works 

[4] https://www.nature.com/articles/s41578-021-00362-4  

[5] O'Neil, J. (2016). TACKLING DRUG-RESISTANT INFECTIONS GLOBALLY: FINAL REPORT AND RECOMMENDATIONS. [online] Available at: https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf [Accessed 18 Nov. 2019]. 

[6] https://s28.q4cdn.com/781576035/files/doc_financials/2022/q4/Q4-2022-Earnings-Infographic-FINAL.pdf 

[7] https://www.zoetis.com/_assets/pdf/corporate/zoetis-2022-annual-report.pdf 

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989032/ 

[9] https://www.nature.com/articles/s43016-021-00362-1 

[10] https://healthforanimals.org/pages/global-trends-in-the-animal-health-sector/ 

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