Spinning out the science

Basic, or fundamental, research aims to better understand the world, be that the processes that cause a disease, or the role of a specific gene in our genome. Basic research generates deep knowledge of previously unexplored natural processes and phenomena – usually without prior expectations of how that knowledge might be used.

In this post, Alexandra Canet-Font, Marketing Manager at the Wellcome Genome Campus, explores some of the ways scientists at the Sanger Institute are taking the next steps. She discusses how they are applying their research to health, and moving science from bench to bedside.

By Alexandra Canet-Font, Marketing Manager at the Wellcome Genome Campus

Scientific papers advance understanding but to have a direct impact on a person’s life, that science needs translating into a tangible output. That might be a monitoring tool to track parasitic infections in Bolivia, a novel drug to treat inflammatory bowel diseases or surveillance software to monitor a global pandemic. And who is best equipped to do this but the scientists working on it? Taking a research idea to market isn’t a straightforward process, but it’s definitely a rewarding one. There also isn’t one way of doing it; there are hundreds.

At the Wellcome Sanger Institute, most programme leads are actively engaged in translating their work, and over 50 per cent of Faculty are developing research that will impact society directly. We are not alone, the Cambridge life sciences ecosystem is vibrant, with more than 450 companies based in the area, employing more than 50,000 people in highly qualified roles.

Back to Sanger, four out of five spin-out companies have a trajectory of more than five years, developing ground-breaking solutions in areas such as drug development, bacteriotherapy such as Microbiotica, or the therapeutic exploitation of vulnerabilities in cancer cells, a service delivered by COSMIC. Some, like Congenica, have been developing for over 10 years, giving use to a pipeline that had exhausted its research potential but could provide a valuable service to pharmaceutical companies, universities, research institutions and patients.

However, not all research necessarily translates into a commercial solution. Some of Sanger’s research outputs can be licensed to external companies, they can be used by charities or non-governmental organisations, or public health bodies in low- and middle-income countries. At Sanger, in the words of Adrian Ibrahim, Head of the Technology Translation Office, what matters is ‘health above wealth’. Translation is all about getting treatments out there quicker; applying our brilliant science to real-life challenges, creating a product or service that will improve the health of patients, carers and communities across the globe.

Learning to be an entrepreneur

How does it all start? Can entrepreneurship be learnt? It can, and with this in mind, the entrepreneurship team based at the Biodata Innovation Centre on the Wellcome Genome Campus, which is also home to the Sanger Institute, launched Start-up School in 2020. Joanna Mills, Head of Entrepreneurship, and her team have spearheaded an immersive entrepreneurial learning experience for genomics and biodata scientists. Its aim is to give them the tools and skills to explore the scope and value of ideas stemming from their world-leading research on genomics and biological data.

Start-up School kicked off in November 2020 with a cohort of 24 scientists from the Sanger Institute and EMBL’s European Bioinformatics Institute. Of those 24 participants, a mix of PhD students, Postdocs and technical experts; six are now progressing their idea with the aim of ultimately bringing it to market. They have the continued support of the course mentors, using the tools, skills and contacts gained throughout the programme.

Alex Cagan, a Postdoctoral Fellow at the Sanger Institute, is one of them. He had always been interested in alternatives to academia and how the research he was carrying out within his team in the Cancer, Aging and Somatic Mutation programme had potential relevance to patients. “It’s great to contribute to the development of science, but sometimes you realise you have something that could really impact people. Why not try and develop it into something that can be used?”, he says.

Alex went through the eight modules of the programme, learning with peers and creating a valuable relationship with his mentor, Nick Lench, co-founder and CSO of one of Sanger’s spin-out companies, Congenica. “Start-up School gave me a really good, comprehensive overview of all of the stages in terms of putting together a team, figuring out if your idea has commercial viability or how to develop a business plan”, Alex says.

From idea to business

Start-up School can be seen as the very first stepping stone in this long but exciting journey of building a spin-out company. It’s a journey in which steps are not defined but follow the same direction. Mariya Chhatriwala, Business Development Manager in Sanger’s Technology Translation team, gives an initial piece of advice: “Always write down your ideas. Ideas in one’s mind don’t progress, they need to be identified and fleshed out.”

Let’s take Trevor Lawley, co-founder and Chief Scientific Officer of Microbiotica and Sanger senior group leader, as an example. Microbiotica was created in 2016 as a Sanger spin-out company with the aim of designing and developing novel therapies that use bacteria as medicine. Trevor had been thinking about this idea since his undergraduate degree studying microbial ecology, back in Nova Scotia, Canada. He kept a record of his thoughts, jotting down notes and drawing figures about his research and how he envisioned using the human microbiome and the deep understanding of our digestive system to develop live bacterial solutions to treat diseases and enhance clinical responses to life-saving drugs.

Trevor’s is the story of turning basic, fundamental research into innovative science with potential to treat a broad range of human diseases. He could see the scope of his research work beyond academia. But it’s also the story of someone who knew he couldn’t fly solo. He was in this along with Gordon Dougan, his mentor and a former Sanger senior group leader. They both knew about their own research and potentials extremely well, being widely recognised as the experts in the field globally. But they didn’t have all the key pieces to start a biotech company – how to raise funds from investors to develop a product, develop a commercial patent portfolio, grow and manage a company and go through the regulatory authorities’ approval process. That’s when Mike Romanos came in as CEO of Microbiotica, bringing that knowledge with him. Mike had ample experience in the biotech and pharmaceutical industry, and helped scope out and focus the spinout’s mission, objectives and milestones.

“You’ll normally develop a business plan in partnership with a CEO elect or entrepreneur in residence,” Gary Dillon, Business Development Manager at Sanger says. Their aim is to sketch out the company’s pathway enough so it makes sense to investors to come in, put money into the company and take equity. They know their ecosystems inside out and can draw on a wide network to build a robust business plan. They understand which collaborations will flourish and, very importantly, build a portfolio – a catalogue of services or capabilities of a product that will form the basis of a new company.

In 2016 the founders of Microbiotica licensed a portfolio that covered software, data, materials and therapeutic patents into the company.  They knew that their company’s assets needed to be founded on a well-rounded portfolio of Intellectual Property (IP). “This is one of the first steps towards building your company. It not only comes in the form of a patent of a scientific system or technology but softer IP elements, such as software or different intangible assets, like your know-how,” Gary explains.

A year and a half later, Microbiotica had partnered with a strong collaborator from the pharmaceutical industry, giving them third party validation of the company’s microbiome analysis platform. Today, Microbiotica is a company with 45 employees, investment from Cambridge Innovation Capital, IP Group plc and Seventure Partners, and a partnership with Cancer Research UK. It’s an invigorating time for Microbiotica, as they enter one of the last phases of the long road to market – the clinical phase.

“It’s an exciting time for us, as we are starting clinical trials to test our live bacterial therapeutics in IBD (Inflammatory bowel disease) and melanoma patients, but it hasn’t been easy. It was challenging to understand how the commercial, clinical and regulatory landscapes work for this completely new area, and we’ve also had to learn from so many different areas of science at once. Having navigated many of these areas, we are truly pioneering the live bacterial therapeutics industry and are one step closer to becoming a transformational company. I believe we are in this position because the Technology Translation Office was there helping us shape our idea from the outset, from 2012 all the way until we spun out, and even after, during the incubation period.”- Dr Trevor Lawley

Dr. Trevor Lawley. Credit: Microbiotica

Not all translation becomes business

Spin-out companies are not the only way of taking research to those who need it, and Sanger’s extensive work on malaria is a great example. Professor Dominic Kwiatkowski’s group has developed a framework to track the spread of drug resistance in the parasites that cause malaria, the Malaria Genomic Epidemiology Network (MalariaGEN).

The team created a genomic surveillance tool that allowed field samples to follow a complex but clear pathway in order to monitor what was happening with malaria parasites in specific areas of the globe, feeding that information back to national public health bodies so that they’d be able to make informed decisions about disease control. It all started in Vietnam’s Mekong Delta, when alarming reports showed that Plasmodium falciparum, the most deadly malaria parasite, had started developing resistance to front-line treatments. The trend was growing, and if resistance spread to Africa it would be a disaster. The team secured financing from the Sanger’s Technology Translation Office to drive a pilot in Northern Ghana. With this, they redoubled their efforts to be able to generate more data from fewer samples. They developed a method which changed the whole ball game –  the ability to sequence parasites from a dried blood spot. This made the process simpler, moving from the need to collect blood with a syringe, to just a drop of blood on a filter paper from a finger prick. With this in hand, they could begin to move away from high cost and difficult to deploy whole-genome sequencing to a more targeted approach, focusing directly on the areas of the parasite genome that would tell them whether it was resistant to frontline drug treatments.

This technology developed by Dominic’s team was a feat for the Institute and they have now created SpotMalaria, which connects local and national partners to support malaria control interventions. This experience was invaluable when Sanger was invited to join a major effort against COVID-19, the Covid19 Genomics UK Consortium. “When COVID appeared, we already had a system in place to receive samples from partners, definitely not at the scale of COVID, but we were used to doing that mapping and tracking. We knew it was hard and understood what needed to be put in place upfront to make sure all the information we were gathering was as accurate as possible,” says Vikki Simpson, Head of Strategic Partnership and Engagement Parasites and Microbes Programme at Sanger.

With an experienced team and considerable know-how, pivoting from malaria surveillance to COVID-19 surveillance was possible in record time, enabling Sanger to become one of the main sequencing hubs for COVID-19 in the UK. As Vikki sums it up, “It is the consistent and repeated sustained investment that brings change. It’s taking the time and resources to invest in this technology before there is an urgent need for it”. It is in this way that the Sanger has been able to provide a rapid response in times of need.

“This is the way in which the Institute funds work to test out if capabilities can be effectively translated, and start to build a portfolio for the future company or service,” Adrian Ibrahim says. The job of the translation team is to embrace risk in order to bring technologies to market that wouldn’t be funded otherwise. Not because they’re not promising, but because they’re either in a too early stage to show robust results, or because the solutions seem uncertain and need further development.

Alex Cagan, who is now developing his own idea, is in the initial stage of this long process, but his enthusiasm and passion are contagious. He has gained significant knowledge and confidence through Start-up School which have given him two key things: firstly, a mentorship experience that has facilitated an important collaboration with a clinic from Addenbrookes Hospital. With them, he is gathering the necessary data to create a proof of concept that will show if the product is viable. Secondly, the knowledge from those who have already been through this. He says: “I understand there are going to be many challenges, but they will not come by surprise. We have been taught where they’ll be coming from, so I’ll certainly be alert”.

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