IIn a science park lab next to the University of York, two groups of robots are busy moving transparent plates with mechanical arms as they sift through several million molecules. The machines only need 24 hours to complete work that would typically take teams of human scientists days to complete.
The lab is run by Aptamer Group, a small biotech company that has quietly carved out a leadership position in the development of a highly sought-after technology. Its scientists create aptamers – fragments of DNA, also known as synthetic antibodies, which are used to diagnose diseases or deliver drugs to their target to fight various 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,” says Dr. David Bunka, the company’s CTO, during our tour of the lab. The word comes from the Latin “aptus”, to adapt.
As aptamers, or nucleic acid molecules, pass through a series of high-tech laboratories, they are tested for their ability to bind to proteins or other cellular targets. The best binders are then cut and checked by the quality control team before the final product is manufactured on a larger scale, purified and put into tubes for packaging and shipping.
The company’s customers include three-quarters of the world’s 20 largest pharmaceutical companies, including Japan’s largest drugmaker, Takeda. He works with the UK’s largest pharmaceutical company, AstraZeneca, on treatments for kidney disease; 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 United States to create gene therapies.
Aptamer Group’s £81million IPO on London’s Aim Junior Market last year turned its two founders into paper millionaires with a combined fortune of £33million. The company is growing rapidly. It has just moved into new headquarters in York Science Park which has doubled its lab space – but is struggling to recruit more scientists, in part due to a lack of affordable housing in York and the difficulty in hiring Europeans after Brexit.
The group has developed a test capable of detecting Covid-19 in wastewater with environmental technology group Deepverge and is currently pursuing tests for other contaminants. It dropped a partnership with Mologic to develop a rapid lateral flow Covid test last year because it realized the market was “saturated”.
The company was founded in 2008 by Bunka, a molecular biologist, and Dr. Arron Tolley, an ADHD high school dropout who became a bricklayer and later earned a doctorate in biophysics and molecular biology. They met at Leeds University and formed a “bromance”, Tolley says.
Aptamers, like antibodies, bind specifically to a target molecule and can be used to deliver drugs to tumor cells as precision chemotherapy, for example, or to identify cancer cells in samples for diagnostic purposes, without binding to healthy cells.
However, antibodies must be generated inside living things such as rabbits, mice, goats or sheep, by injecting an animal with a target of interest such as a virus, which will trigger a response immune. In contrast, aptamers are produced using state-of-the-art synthetic DNA technology.
Bunka states, “The key principles of aptamer selection are to take a library of aptamers, incubate them with the target molecules, separate aptamers that stick from those that don’t, and amplify those that stick, creating a new generation of binders. ”
Aptamers are also more stable than antibodies and have a longer shelf life; they can be stored in the refrigerator while antibodies require storage in the freezer.
Nick Turner, Professor of 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’re artificially synthesized, you don’t have 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 to make them easy to detect.
Aptamers are also much more effective. Antibodies fail 50% of the time, according to research from several journals, including Nature, while synthetic antibodies from the Aptamer group have a 70% success rate, according to internal data.
The company is able to develop aptamers in 15 days if needed, although it typically takes 10-12 weeks, while antibodies take between four and 18 months to generate.
The global aptamers market was worth $2.4 billion (£2.0 billion) last year and is expected to generate annual revenues of $11.5 billion by 2030, according to research firm Market Fact.MR.
“Nucleic acid technology as a whole is a growing field, and aptamers are one of the key players in this field,” says Turner. “The UK has always been a strong science leader. In the field of molecular recognition, including aptamers… we are one of the world leaders.
The Aptamer group – which moved into the basement of Tolley’s former home in Leeds – now employs nearly 60 people, including 35 scientists. Its new three-story building can accommodate up to 100 people, but the company is struggling to find staff, including chemists, quality control scientists and project managers.
“Our biggest challenge is recruiting,” explains Alastair Fleming, Director of Operations. “Hiring is difficult, even bringing in basic scientists. Brexit has also affected us. We normally expect more Europeans. Britain’s departure from the EU has created more paperwork and wait times of around six months for a work visa.
Fleming says it’s hard to ‘attract the right caliber graduate’, with a shortage of affordable housing in York, where house prices have risen 9% in the past year while rents have risen. jumped 21%. The average asking price in York has risen to £368,878 while the average asking rent has risen to £1,378 per month, according to property website Rightmove. Many Aptamer Group scientists come from local universities – York, Leeds, Huddersfield or Edinburgh.
Described by Tolley as a “genuine seed company”, it managed to grow with £5million in funding until its stock market debut last year, including from a local angel investor, government money and £14,000 each from Tolley’s and Bunka’s parents.
For a company of its size, London’s Aim junior market was the only option, but Tolley isn’t ruling out one day moving to the Nasdaq in the US. “You see a lot of companies going to the United States because there are more funding opportunities. It’s not a cheap industry,” he says.
A report by the House of Commons Science and Technology Committee in 2013 spoke of the “valley of death” that prevents the progress of science from the lab bench to a commercially successful product, and despite the stated ambition from Rishi Sunak to turn the UK into a “science and technology superpower”, this lack of venture capital for companies as they grow is still a big problem, says Tolley.
The shares have fallen around 50% since the IPO, along with other biotech stocks, “affected by the macro backdrop and weak growth sentiment,” says Liberum analyst Edward Thomason. “However, Aptamer continues to meet 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 into their holdings for a year, and Tolley says they have no plans to sell them.