Inside a science park lab next to the University of York, two clusters of robots are busy moving clear plates with mechanical arms as they screen many millions of molecules. The machines need only 24 hours to complete work that would usually take teams of human scientists several days.
The lab is run by Aptamer Group, a small biotech firm that has quietly carved out a leading position in the development of a highly sought after technology. Its scientists create aptamers – fragments of DNA, also known as synthetic antibodies, that are used to diagnose illnesses, or to deliver drugs to their target to fight a range of diseases including cancer.
“An aptamer is a short synthetic piece of DNA or RNA that folds into three-dimensional shapes and sticks to targets of interest,” Dr David Bunka, the company’s chief technical officer, explains on our lab tour. The word comes from the Latin “aptus”, to fit.
As the aptamers, or nucleic acid molecules, pass through a suite of hi-tech labs, they are tested according to how well they bind to proteins or other cellular targets. The best binders are then trimmed and checked by the quality control team before the final product is made on a larger scale, purified, and put into tubes for packing and shipping.
The business counts three-quarters of the world’s top 20 pharmaceutical companies among its clients, including Japan’s largest drugmaker, Takeda. It is working with the UK’s top drugs firm, AstraZeneca, on kidney disease treatments; with Cancer Research UK to develop aptamers as targeted treatments for chronic myelomonocytic leukaemia, a rare type of blood cancer; with South Korea’s PinotBio to develop precision chemotherapy treatments; and with Gene Therapeutics in the US to create gene therapies.
Aptamer Group’s £81m flotation on London’s junior Aim market last year turned its two founders into paper millionaires with a combined fortune of £33m. The company is rapidly expanding. It has just moved into a new headquarters in the York science park that has doubled its lab space – but is struggling to recruit more scientists, in part because of a lack of affordable housing in York, and the difficulty of hiring Europeans following Brexit.
The group has developed a test that can detect Covid-19 in wastewater with the environmental technology group Deepverge and are now pursuing tests for other contaminants. It dropped a partnership with Mologic to develop a rapid lateral flow Covid test last year because it realised the market was “saturated”.
The business was founded in 2008 by Bunka, a molecular biologist, and Dr Arron Tolley, an early school leaver with ADHD, who became a bricklayer and later completed a doctorate in biophysics and molecular biology. They met at Leeds university and formed a “bromance”, says Tolley.
Aptamers, like antibodies, bind specifically to a target molecule and can be used to deliver drugs to tumour cells as precision chemotherapy, for example, or to identify cancer cells in samples for diagnostic purposes, with no binding to healthy cells.
However, antibodies have to be generated inside living beings such as rabbits, mice, goats or sheep, by injecting an animal with a target of interest such as a virus, which will trigger an immune response. By contrast aptamers are produced using cutting-edge synthetic DNA technology.
Bunka says: “The key principles of aptamer selection are taking a library of aptamers, incubating them with the target molecules, separating the aptamers that stick from those that don’t, and amplifying the ones that stick, creating a new generation of binders.”
Aptamers are also more stable than antibodies and have a longer shelf life; they can be kept in the fridge while antibodies require freezer storage.
Nick Turner, professor in bioanalytical chemistry at De Montfort University in Leicester, who works with aptamers, says: “They are faster to produce than antibodies, but one of the key things is the ethical advantages: because they are synthesised artificially, you haven’t got to go through the process of using animal models.
“They are environmentally stable, more robust, and so much easier to handle than antibodies. They are also relatively easy to label. You can add fluorescent tags to them so they are easy to detect.”
Aptamers are also far more effective. Antibodies fail 50% of the time, research from several journals including Nature has shown, while Aptamer Group’s synthetic antibodies have a 70% success rate, according to internal data.
The firm is able to develop aptamers within 15 days if needed, although it typically takes 10 to 12 weeks, while antibodies take anywhere from four to 18 months to generate.
The global aptamer market was worth $2.4bn (£2.0bn) last year and is forecast to rake in annual revenues of $11.5bn by 2030, according to the market research firm Fact.MR.
“Nucleic acid technology as a whole is a massively growing area, and aptamers are one of the key players in that field,” Turner says. “The UK has always been a strong science leader. In the area of molecular recognition including aptamers … we are one of the world leaders.”
Aptamer Group – which was set up in the basement of Tolley’s former home in Leeds – employs almost 60 people today, including 35 scientists. Its new, three-storey building can accommodate up to 100 people but the company is struggling to find staff – in particular, chemists, quality control scientists and project managers.
“The biggest challenge we’ve got is recruitment,” says Alastair Fleming, the chief operations officer. “Hiring is difficult, even bringing in basic scientists. Brexit has affected us as well. We normally expect more Europeans.” Britain’s departure from the EU has created more paperwork, and waiting times of about six months for a work visa.
Fleming says it’s hard “to get the right-calibre graduate in”, with a shortage of affordable housing in York, where property prices have risen 9% in the past year while rents surged 21%. The average asking price in York has reached £368,878 while the average asking rent has risen to £1,378 a month, according to the property website Rightmove. Many of Aptamer Group’s scientists come from local universities – York, Leedsor Huddersfield.
Described by Tolley as a “true bootstrap company”, it managed to grow on £5m of funding until its stock market debut last year, including from a local angel investor, some government money and £14,000 each from Tolley’s and Bunka’s parents.
For a company of its size, London’s junior market Aim was the only option, but Tolley does not rule out shifting to Nasdaq in the US one day. “You see a lot of companies go to the US because there are more funding opportunities. It’s not a cheap industry to be in,” he says.
A House of Commons science and technology committee report in 2013 talked of the “valley of death” that prevents the progress of science from the lab bench to a commercially successful product, and despite Rishi Sunak’s declared ambition to turn the UK into a “science and technology superpower”, this lack of venture funding for companies as they grow is still a big problem, Tolley says.
The shares have fallen about 50% since the IPO, similar to other biotech stocks, “impacted by the macro backdrop and poor sentiment for growth”, says Liberum analyst Edward Thomason. “However, Aptamer continues to deliver against its IPO mandate to scale the business and grow its business development pipeline.”
Tolley, Bunka and the rest of the management team have been locked in to their shareholdings for a year, and Tolley says they have no intention of selling them.