Searching for a cure for cancer and a healthy bottom line

GENE EDITING, OR THE PROCESS OF MANIPULATING DNA AT SPECIFIC SITES IN A CELL, HAS SPURRED A WAVE OF BIOTECH ACTIVITY

ourteen years ago the first human genome was sequenced. It cost somewhere in the region of $2.7 billion (Dh9.9 billion). It was a collaborative effort across the globe that started in 1990 and took 13 years to complete. Fast forward to today, and companies are offering genome sequencing at a mere $1,000 a pop, taking hours or days, not years, and the price continues to fall.

This revolution in human genomics has transformed the way we think about disease and our understanding of what causes it, paving the way for the development of treatments that are much more targeted at both the illness and the patient, such as cancer sufferers with a particular genetic mutation.

It has also led to the rise of gene editing, a pioneering field in biotechnology whereby scientists can chop and change DNA at specific sites in an organism or cell using special molecular scissors. It’s becoming increasingly crucial in the discovery, testing and manufacture of new drugs.

“Gene editing has been something of a revolution. It has transformed from something that is fantastically difficult to carry out into a day-today laboratory technology,” says Dr Mike Mitchell, an analyst at Panmure Gordon. “It is now vital in both drug discovery and diagnostics, and it’s oncology and precision medicine that are driving this.” The technique has taken off over the past decade. New editing tools to create genetically defined human cell lines have come to the fore, some open-access, others privately owned. The most popular is called Crispr and is accessible to all researchers. This has spurred a wave of activity in the biotech sector, with several companies now offering a suite of complex gene editing services that big pharmaceutical companies are more than happy to pay for. “We’ve had new companies with multibillion dollar valuations coming to the market. I’m sure we will see many more active in this space, creating their own niches and applications and IP spurring further advances,” says Dr Mitchell.

One such company is Horizon Discovery. Founded in 2007, it was established after two Cambridge academics, fed up with the time it was taking to identify the genetic variations in colon cancer tissue, sourced a super-efficient gene editing tool from the University of Washington in the US called rAAV. They brought it back to Cambridge, hired Horizon’s current chief executive, Darrin Disley, and others, secured £25,000 (Dh114,560) in grant funding from the university and bought the intellectual property rights to the tool for just $10,000. Today, Horizon is a £162 million publicly listed company. “It looked really quite good. I knew sequencing costs were definitely going to come down, so I put money in along with other investors and that is how Horizon got commercially started,” explains Disley.

Still, it wasn’t all plain sailing. It was 2007, the recession was about to hit, and nobody understood the importance of gene therapy. Horizon could not even secure office space because no one would rent to the company. It set up its first six employees in Italy and occupied a little pig shed and former toilet at the Babraham Institute outside Cambridge. “It really was a dump,” Disley recalls. “Sequencing was still costing $10 million and no one envisioned you could get it done for as little as it costs now.” But the 49-yearold, who had pursued a career in football before joining the world of science, was not one to be deterred. Born in London’s East End into a singleparent, working-class family, his journey into the fields of science, academia and business has been anything but conventional.

A different route

“When my mother fell pregnant with me my father was on the run from prison,” he says. “There had been 10 years of investment in this editing tool we bought and when we got the IP we went around to all the universities who had used it over the past decade and made models and offered them a route to selling those models, in return for a nice royalty payment,” he says.

Within weeks, Horizon started selling these genetically engineered cell lines and in the first year made $500,000 in revenue and turned a profit. In 2009, sales rose to $1.2 million. “At that point we started getting real interest because sequencing costs had come down even more and we were doing well in a recession,” Disley recalls. That led to further investment.

Companies such as Genentech, later acquired by Roche, put in £1 million, existing investors stumped up more cash, and venture capital flowed in. Today, after several acquisitions and a stock market listing, Horizon sells extremely complex genetically engineered cell lines to researchers around the world, helping them find cures for diseases like cancer. These cells can either be made bespoke or bought off the shelf from Horizon’s portfolio. They are effectively “patients in a test tube” explains Disley.

They can be engineered to have certain characteristics, like mutations, to represent healthy or diseased patients. This allows scientists to use the cell lines to prove a hypothesis or to test a drug to see what happens. They are also being used in diagnostic tools and genetic screening, to determine which subset of patients might benefit from a particular treatment. “Diseases happen in functional units called cells, not isolated in a test tube, and so you need to test a drug in a situation that is relevant to the patient that it is ultimately going to end up in,” Disley explains. At the turn of the millennium, however, this sort of thinking was “heresy” in scientific circles, despite consistently high failure rates in oncology drugs in clinical trials.

“Everyone thought that you shouldn’t be narrowing down the question so much, but in fact, that is what you should be doing. In personalised medicine now, we are narrowing it down to the genetics of small patient groups because your body is the most complex non-linear organism there is.” In the first few years in business, Horizon would sell its cell lines from anywhere from $15,000 to $150,000. Today they can cost just $500. Thanks to this and further advances in gene editing, pharmaceutical companies and scientists have been able to speed up research and development. That is good news for oncologists, because the advent of precision medicine means the days of the blockbuster one-size-fits-all cancer drug are gone. Moreover, health authorities around the globe are facing tighter budgets and cracking down on pricing, so getting a drug