Early introduction to medical research

Deborah grew up in a family that ran its own businesses. When at school Deborah always found humanities subjects easier and ‘absolutely loved history’. But early on she got drawn to science. As she recalls ‘there was something about science that fascinated me in a different way’ and ‘innately I just knew, even though it wasn’t the easiest, it was something that I wanted to stick with for the longer term.’ What she particularly liked about science was its potential to open up new understandings about disease and develop new treatments for them.

Deborah’s interest in the application of science to medicine was also galvanised by some of the health issues she experienced at a young age. As a teenager she developed Crohn’s disease, a life-long condition in which parts of the gut get attacked by the immune system. This can cause painful ulcers and inflammation anywhere in the gastrointestinal gut, all the way from the mouth through to the bottom. Everyone experiences the disease differently but the most common symptoms are abdominal pain, diarrhoea, weight loss and tiredness. It can also cause anaemia, skin rashes, arthritis and inflammation of the eye.

As a result of her disease, her family got closely involved in fundraising for the Crohn’s in Childhood Research Association, a charity dedicated to supporting research into better treatments to support children with inflammatory bowel diseases like Crohn’s. At this point there was no really satisfactory method to diagnose the condition, or way to prevent or treat it. For Deborah one of the benefits of family’s helping the charity was it opened up to her the world of medical research at an early age. Importantly the charity enabled her to go into research laboratories to see upfront how their funds were being used to advance the understanding and treatments for unmet disease conditions like Crohn’s. This coincided with the time when Deborah was just beginning to decide what subjects she wanted to do for her final school exams. With neither of her parents having any experience of science, let alone university, Deborah found the contact with the different laboratories enormously helpful.

>h2>Falling in love with immunology and putting ‘lots of miles on the science tyres’

By the time Deborah finished school she had developed an interest in microbes and infection but was unsure exactly what she should study at university. In the end she opted to do a very broad degree in biochemistry. One of the components of her course turned out to be immunology, a branch of biomedical science that studies how the body’s defence system works. Prior to university Deborah had never heard about immunology and says ‘I absolutely fell in love with [it]’. She recalls, ‘I fell in love with immunology from my first university lecture’ because of ‘the fascinating complexity and criticality of the immune system to our health’.

From then on Deborah became hooked on immunology. After completing her biochemistry degree, she did a doctorate in immunology at University College London which she finished in 1997. Once she was armed with a doctorate, Deborah took advantage of the opportunity it opened up for her to live abroad. As she comments, ‘I put lots of miles on the science tyres’ working as a postdoctoral researcher looking at different aspects of immunology. Among the places she landed up going to were the University of California San Diego, in the United States, and then the University of Ghent, in Belgium.

The journey to creating a new therapeutic platform and company

After spending nearly five years abroad, in 2001 Deborah was offered a job as a senior immunologist at the Rowett Research Institute which is now part of the University of Aberdeen. Taking up the position required her leaving Belgium one year earlier than she intended, but the move was attractive because it offered a secure academic job which can be hard to get.

Established in the early twentieth century, the Institute had a strong track record for examining health and nutrition. Since it was founded its research has shifted away from looking at health and nutrition in animals towards more of a focus on the human diet and health.

A year after Deborah arrived in Aberdeen the Scottish government and Scottish Enterprise were launching initiatives to provide financial support for academic researchers to explore the potential commercial applications of their work. At the same time, Deborah actually heard about the RSE’s Enterprise Fellowships and was more intrigued about the possibility of life beyond academia. The support Deborah successfully leveraged from Scottish Enterprise provided an ideal opportunity to get funding to test out whether it was possible to develop new therapeutics out of antimicrobial peptides (AMPs), one of the body’s first lines of defence when responding to infection. She had been studying these molecules for a number of years and when in San Diego she realised that they could potentially be harnessed to create new therapies for fighting difficult to treat infections caused by fungi and bacteria. Since then, Deborah has developed a second, small molecule (aminothiol) technology platform, also based on the innate immune response to infection, which also has potential against respiratory disease, viruses and helping with inflammatory disease.

If proven effective, Deborah realised these technologies could provide a powerful tool in the fight against antimicrobial resistance, also known as AMR. AMR occurs when pathogens no longer respond to medicines like antibiotics. This makes infections harder to treat and increases the risk of spread to others thereby raising its potential to cause more severe disease and mortality. In 2001 the European Antimicrobial Surveillance System, a network of 700 laboratories from 28 countries, flagged AMR up to be one of the most pressing challenges to global health and threatened to wipe out many of the recent advances in medicine. Three years later the US Centers for Disease Control and Prevention put out a report called ‘Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, A Public Health Crisis Brews’ in which it estimated that over 35,000 Americans were dying from AMR each year and raised the alarm about the stagnation in development of drugs for dealing with resistant infections.

Arriving in Aberdeen just at the right moment, Deborah managed to secure a small grant to determine if she could create a viable peptide anti-infective platform. Encouraged by the initial data, she quickly grasped that she would not be able to fully advance the platform if

she did not dedicate all of her time and energy into it. This spurred her on to leave her academic post at Rowett Institute in 2004 and set up a company called Novabiotics.

Deborah’s founding vision for NovaBiotics was to approach the challenge of infection (including AMR), inflammation and respiratory disease by harnessing the natural components of the immune system, particularly AMPS and aminothiols. Her idea was to develop therapies to fight common pathogens like Staphylococcus aureus and Candida. Staphylococcus aureus which is a type of bacteria frequently found in the respiratory tract and skin which can cause a variety of diseases including life-threatening illnesses like pneumonia and sepsis. It is one of the leading causes of death associated with AMR and resistant to multiple antibiotics. One of the most well-spread forms is methicillin-resistant S. aureus (MRSA), often called a superbug. Candida is a type of yeast that is one of the most common causes of fungal infections. It can be found on the skin and inside the body, such as the mouth, throat, gut and vagina. Usually harmless, Candida can cause serious infections if it grows out of control.

Leaving academia to set up a new company took a lot of courage, but Deborah was of the view that if the venture did not work out, it would still look good on her CV and she could always return to academic science. As she points out ‘great science is great science and that doesn’t change whether it's in academia or the commercial world.’ Deciding to take the plunge was also made easier by the fact that she had grown up in a family that ran its own businesses which gave her an innate sense of entrepreneurship. She recalls ‘when I was faced with a choice - of the early science that became Novabiotics being a side-project, or spinning it out and doing it properly - it wasn’t even a question. I just did it.’

Building out NovaBiotics and its platforms

For a long time Deborah felt like she was swimming against the tide to get NovaBiotics up and running. One of her challenges was raising enough funds, which she often felt was ‘like being on a treadmill’. Part of the problem was that very few investors could see how a company focused on developing drugs for infection and inflammatory diseases could survive and turn a profit. Indeed many companies originally set up to develop antimicrobial drugs subsequently moved over into oncology because this had the potential to generate more money. The pull away from the development of antimicrobial drugs was reinforced by the fact that global revenues for antibiotics had begun to decline. At this point MRSA and other types of superbug were only just beginning to get on what Deborah calls the ‘public radar’.

What helped Deborah move NovaBiotics forward, was that John Pool, one of her co-founders and an advisor from Scottish Enterprise, realised there could be a huge market demand for a product that could tackle onychomycosis. This is a type of fungus that commonly infects nails, causing them to become discoloured, thickened and distorted. In 2009 the condition was estimated to affect more than 12% of the world’s population, which equated to a global market of US$5 billion. The fungal infection is especially prevalent in the elderly and individuals who have circulatory problems. It is very difficult to treat and frequently fails to respond to the limited treatments on the market. Additionally fungal infections have become increasingly becoming resistant to the available treatments.

As a result, Deborah decided to begin developing a brush-on nail treatment using her peptide anti-infective platform which Novabiotics first patented in 2005. If this proved successful, it would give the company a strong foundation to build out other products. By 2010 the nail treatment had been shown to be safe and rapidly clear fungal nail infection in Phase II clinical trials and in 2013 Novabiotics entered an exclusive agreement with a leading dermatology company in the United States to licence the treatment and support its further development. This gave Novabiotics not only the necessary injection of funding to continue developing the nail treatment but also to advance other therapies in its pipeline.

By this time NovaBiotics had two technology platforms for creating drugs. The first was built around AMPs and the second was devised with cysteamine, a type of aminothiol produced in mammalian cells that is an important component of the innate immune system. Cysteamine had been successfully used as a drug for over twenty years to treat cystinosis, a rare and multi-system genetic disorder characterised by the accumulation of an amino acid called cystine. One of the reasons Novabiotics incorporated cysteamine into its second platform was because its team discovered it to have improved the efficacy of antibiotics and reverse multidrug resistant infections. They also believed it had potential to resolve inflammation elevated by infections.

Drug development

In the early years, Deborah and her company team decided to focus much of their attention on developing treatments for niche indications. This included one for treating the complex chest infections and inflammation that commonly plague patients with cystic fibrosis (CF), an inherited, chronic, debilitating and life-limiting disease. Caused by a single gene mutation, one the main issues with CF is the overproduction of mucus by cells that line the airways and digestive tract. This can severely impair lung function and ability to eat food. It can also cause issues in other organs of the body. People with CF are also highly prone to recurrent or chronic respiratory infections and inflammation.

One of the advantages of developing treatments for CF was that such drugs were more likely to be granted orphan status. This category is assigned by regulatory authorities to medicines intended for use against a rare condition which are unlikely to make a profit. The category makes it easier for companies to get government assistance and certain tax breaks as well as get fast-track approval. By 2016 Novabiotics had made sufficient progress to outlicense its CF drug to a French pharmaceutical company specialising in the development of orphan drugs for rare diseases. What was promising about the drug was that it managed to break down the sticky mucus that builds up in the airways and digestive tract as a result of CF and reduce the amount of inflammation. In some cases the drug had been found to improve the efficacy of antibiotics and be effective against multi-drug resistant infections.

Having demonstrated the potential of the company’s products for rare diseases, Deborah and her team now had scope to develop antimicrobial drugs for more mainstream conditions. One of the areas they decided to target was Community Acquired Pneumonia (CAP), which is a common illness that affects the lungs and makes breathing difficult. It can be caused by bacteria, viruses and fungi. The condition is highly infectious and is a leading cause of death in developing countries and the fourth most common cause of death worldwide. It is also very expensive as many patients who get it require admission to intensive care units. In December 2021 Novabiotics was able to put forward a late-stage clinical product for testing in an international, adaptive Phase III trial simultaneously evaluating multiple treatment options for CAP at more than 300 clinical sites across more than 20 countries worldwide. Government agencies from participating countries are funding the trial. NovaBiotics undertook to provide its drug for the initial UK phase of the trial for which it had developed a scalable manufacturing process.

In addition to CAP, NovaBiotics has been investing in the development of antibacterial peptide therapy candidates for multiple-drug resistant bacterial infections, including Pseudomonas aeruginosa, Clostridium difficile, Acinetobacter baumannii and Klebsiella pnuemoniae. These bacteria have been identified by the World Health Organisation (WHO) as posing the greatest threat to human health.

Life threatening fungal infections in immunosuppressed individuals, for example post-chemotherapy or post-transplant, is another area NovaBiotics is focused on developing its technology for. Fungal infections and drug resistance in fungi is a growing problem and a massively unmet clinical need. Fungal cells are more closely related to human cells than they are to bacteria and so developing new therapies that are safe and will not be toxic to the host is a greater challenge than when developing antibacterial therapies. NovaBiotics' strategy of harnessing how a fully functioning immune system would tackle the problem of fungal infection is what makes NovaBiotics’ approach so different to traditional antifungal treatments.

The challenges of leading a fast-growing company

In 2017 Deborah was named by Labiotech.eu as one of the 15 leading women in European biotech marking her success in turning Novabiotics into a leading global biotechnology company. By then NovaBiotics had raised €22 million and progressed four treatments into clinical development. Over the course of 13 years Deborah had gained experience in taking drug candidates for challenging conditions from early laboratory discovery through to clinical development and commercialisation.

Looking back. Deborah attributes a lot of her success to having a good support network around her. What also helped was her scientific grounding. As she comments ‘scientists are always setting out to discover new things and push new boundaries’. From her perspective this means scientists are inherently entrepreneurial. Running a laboratory can also be very similar to running a business in that it requires knowing how to manage a group of people.

Deborah really enjoys what she does even if at times she says ‘it feels like the hardest job’. What has carried her forward is her vision that her company has the potential to make a real difference to patients’ lives. As she says ‘that is absolutely the fuel that you need’ and is really important for getting her out of bed in the morning, particularly when raising funds is tough.

Fortunately Deborah says the landscape for antimicrobial drugs is beginning to change due to the introduction of the NHS subscription model in 2019. This scheme provides a fixed fee to companies to develop treatments to tackle drug-resistant infections. Such payments are intended to incentivise companies to invest in the research and development of new antimicrobial drugs. The model was devised so that the NHS would have new drugs to call on when needed at the same time as guaranteeing companies to return on their investment.

Diverse skills needed for a career in the biomedical sector

Deborah has found her scientific background enormously helpful to getting to where she is today. But she points out that some of her best team members are people who do not have this training. She emphasises that the biomedical industry requires people with a diverse range of skills. In her case she has found that ‘some of the best pairs at hands at the bench’ in the laboratory have been people who came straight from school.

Nor does Deborah advocate that one type of university degree is better than another. This is because biomedical science relies on many different skills, ranging from those who are good at coming up with big concepts to others who are more practical and good at thinking through the ins and outs of planning experiments. The industry requires people who enjoy bench work, but it also needs those who like writing. Deborah says there are so many options across the biomedical industry. These can be found not just in academic research laboratories or drug discovery laboratories in companies like Novabiotics, but also on the service side of the industry such as contract research organisations (CROS) which help in formulation development, manufacturing and clinical testing.

In terms of women considering a career in the area, Deborah says that biotechnology start-up companies tend to be much more welcoming to women than large established pharmaceutical companies. This is partly because biotechnology companies tend to be smaller so it is easier to have a voice and get noticed. Many of these companies are also often headed by women. Overall Deborah is very positive about the prospects for women in the biotechnology space, which she says in her experience has no real gender barriers.

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This article was written by Dr Lara Marks based on an interview conducted with Dr Deborah O’Neil on 17th July 2023.