Inside the dream factory

Professors Alan and Susan Kingsman left the labs of academia to pursue their goal of developing a vaccine to fight and prevent cancer. Now, with with a team of graduates and 26 PhDs, they are ready to begin human trials that could turn Oxford Bio Medica into the giant of biotech companies
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The Independent Online

Imagine a vaccine that works against cancer. Suppose that just one jab with this vaccine would not only zap any cancerous tumours around, but could eventually prevent them from forming elsewhere. Professor Alan Kingsman and his team not only dared to imagine such a bold concept, they have made it work, at least in animals, and now they are ready to hold human clinical trials.

Imagine a vaccine that works against cancer. Suppose that just one jab with this vaccine would not only zap any cancerous tumours around, but could eventually prevent them from forming elsewhere. Professor Alan Kingsman and his team not only dared to imagine such a bold concept, they have made it work, at least in animals, and now they are ready to hold human clinical trials.

The vaccination is one of the jewels in the crown of Oxford BioMedica, a five-year- old biotech company spun out of Oxford university by two of its leading and most successful scientists, Professor Kingsman, now CEO and his professor wife Susan, as research director.

For 17 years the couple had run one of the largest molecular biology groups at Oxford, and swapping the ivory towers of academia for commerce was more of an evolution than a revolution for the couple. Physically, it may have meant a move across town, but the work remained much the same, though more focused on the end game, taking products to market.

"While we were working in the lab, we had had a lot to do with the biotech industry,'' says Professor Kingsman. "We worked for many years with Glaxo, Amersham and so on, and so we had built up a lot of exposure to industry and intellectual property management.

"Over the years we also transferred a lot of technology to other companies, but then around 1995 we had assembled a number of patents that were very exciting for gene therapy and which affected issues that were holding the field up. We had two choices, we could license it to others as we had done before, or we could do it ourselves. It seemed a rather exciting opportunity so we decided to do it ourselves.''

He and his wife set up Oxford BioMedica, armed with six patents from their work in the university lab. The university agreed to assign them the patents in return for an equity stake in the company worth 6 per cent. "We moved over with just a couple of people," says the professor. "We took the view that we needed a different sort of person. Universities are very good at basic research, but we also wanted to develop products and we needed a slightly different kind of person."

At the last count, the staff of 50 at its base on the Oxford Science Park included 41 graduates and 26 PhDs. There are about 20 other staff, who are out-workers in various labs around the world. The company was formally set up in 1996, went onto AIM in December 1996 with a capitalisation of £50m, and by January the following year was fully functioning in the field of gene therapy products, where it has focussed on treatments for cancer, as well as AIDS and neuro-degenerative diseases.

Gene therapy is seen by many as the medicine of the future. Genes are the masterplan for life carrying the coded instructions for each individual. Using the genes to treat the disease is seen as the way forward in medicine.

With very few exceptions, every cell in the body has a set of around 100,000 genes packed into 46 chromosomes, half inherited maternally and half from the father. These genes are the blueprint for manufacturing proteins that make the cells which are the basic building blocks of the body. Problems can be inherited, such as cystic fibrosis, and in other diseases, including many cancers, several genes are thought to be involved in tandem with environmental triggers, including smoking with lung cancer, diet and colon cancer, and the sun and skin cancers.

Researchers are also reporting increasing evidence that behaviour also has genetic links. So far, shyness, IQ, extroversion, creativity, bullying, depression, obesity, alcoholism, criminality, and a vulnerability to stress, have all been linked to genes.

Gene therapy was thought of primarily as a way of treating inherited disorders, but the market for that technology is small. The biggest area of gene therapy, and the sector in which Oxford Biomedica is deeply involved, is the process of genetically triggering the patient's cells to make their own medicine.

Having accepted that gene therapy is the way forward, the first hurdle which had to be surmounted was how to actually penetrate cells to get at the genetic material.

The answer turned out to be simple. The one thing that gets into cells rapidly is a virus. The common cold virus, for example, works by invading the cells of the body, dumping its genes into those cells and turning them into mini-factories churning out more and more of its virus.

What gene therapy scientists have done is the Trojan Horse approach. They take a virus cell, remove its own genetic material, making it harmless, and replace it with the therapeutic gene. In this way, the virus is used as a vehicle to invade the cells of the body, but instead of depositing its own harmful genetic material releases its therapeutic agents.

Oxford BioMedica's two lead products show two ways gene therapy can be used. MetXia-P450, which is already in human clinical trials in patients with breast cancer, works by converting an existing tumour into an anti-cancer drug factory. It used a virus to take in a gene that carries the genetic instructions for cells in the tumour to activate an anti-cancer drug.

The second lead product is Trovax, a gene-based cancer vaccine. Professor Kingsman says: "There is a debate that we develop tumours throughout our lives but the immune system clears them up, and only when the immune system, for whatever reason fails to do that, we end up going to the GP with a lump or whatever. What you then need is to wake the immune system and that's what our vaccine is designed to do."

The group is unlikely to be able to file a product with drugs regulators before 2007. The vaccine works on the basis that the cells of cancer tumours have different proteins on their surfaces which single them out from normal, healthy tissue. It uses a pox virus containing a gene that has the instructions for the producing those proteins. By exposing it to the virus-delivered gene, the immune system is taught to recognise cancer cells as an enemy and destroy the tumour.

"You would then have killer cells and antibodies cruising around the body looking for cells carrying this protein," says the professor. "We are very excited about it and it has worked stunningly well in lots of work we have done on animal models. We are now going through the regulatory approval process and we hope to be in human trials by the end of the year.''

Initially, the treatment will be tried on patients who have cancer to see if it can prevent spread of the disease to other areas of the body. "This will be the first therapeutic vaccine of this type, and we have a strong intellectual property position on it. If it proved to be very safe one could imagine a time when we had a preventive vaccine, but that is some time off.'' Once the vaccine is in clinical trials, he says the company will look at an official Stock Exchange listing, possibly next year.

"We are still on AIM but we're hoping to move early next year and the key to that is that we need to get our second product in clinical trials. When that happens, I imagine moving to the official list in the first quarter of next year subject to market conditions." Professor Kingsman, who, like his wife, has 5.5 per cent of the equity, which makes both millionaires.

As well as pushing ahead with the development of a range of gene therapy products, the company also works with major pharmaceutical partners on joint product development. Last week it also completed a fund-raising project among major institutions to raise £8.5m for a gene discovery division. Using their own technology, the company will be trying to discover new genes involved in diseases.

For Professor Kingsman, it's another challenge, but one he is looking forward to, just like the move from academia. "I have never regretted moving for one second," he says. "It is fascinating, absorbing and very exciting work. We do first-class science here and some of it is stunning.

"Running an organisation, and making exciting discoveries that are going to have a major impact on people who are ill ... I love it. Stepping down from the ivory tower to commercial work was relatively easy for me. We used to run our university lab on the American lines, performance-related, and goal-oriented.

"We weren't coasting, we used to drive the group very hard and we were successful and known throughout the world. When we set up the company we just changed the focus. We have never made a distinction between work and non-work, and I am available 24 hours a day, seven days a week. That's the way I function and the way I have always functioned.'' He is also confident that in a decade, Oxford Biomedica will be there, at the forefront of gene therapy.

"In 10 years, I hope we are still be a research-based company, but we should be well and truly in profit by then, and running the world's top tier gene-therapy, gene-discovery, gene-manipulation company," says Professor Kingsman. "I don't think that we will grow into a pharmaceutical-size company but I would envisage at that time that our market capitalisation will run into billions of pounds.''