Memories From the Start of the Gene Therapy Wave: Lessons Learned with Alan Boyd
The remarkable story of gene therapy drug development during the 1990s and early 2000s
Stephanie Sutton | | 10 min read | Career
Featuring Alan Boyd, CEO of Boyds
Don’t be limited by your origins
When adults asked what I wanted to be, I would reply: “A doctor.” In the post-war council estate in Blackpool where I grew up, this type of aspiration was unheard of – and I think my parents were horrified! People would say to my parents, “Don’t worry, he’ll grow out of it.”
But I did not! I worked hard and I attended the local grammar school. The school bus had to change its route to pick me up because I was the only one from my area who attended. It was known as a “rugby school” in England, which means that everybody played rugby rather than soccer, and nearly everybody was good at it. Except me. I was absolutely hopeless at rugby, but it didn’t stop me from becoming head boy. In fact, I was the first head boy who wasn’t also captain of the rugby team in over 100 years. After that, I moved from Blackpool to Birmingham to study medicine and biochemistry, waving goodbye to a dad who worked in a factory and a mother who worked as a cleaner. I like to think their horror had subsided at that point.
Mergers and acquisitions can change companies – and jobs – fast
For five years, I worked in hospital medicine, looking after patients with heart attacks, kidney failure, diabetes, strokes, and so on. I was on track to become an academic clinical pharmacologist, but in the mid-1980s I was recruited by Glaxo. Back then, it was a very different company to what it is today – they were nowhere near the top ten of big pharma. They made more money in baby food and other commodities than from their small range of medicines. As part of my new job, I set up their first phase I unit in Greenford, West London, on the floor of an old milk packing factory. Regulations regarding clinical trial approvals were less extensive than they are today. I managed many trials in human volunteers for products that brought Glaxo to where they are today, including fluticasone, cefuroxime, and ceftazidime, among others.
Then I moved to ICI where I developed their heart failure drug, lisinopril, before being promoted to head of cardiovascular research. In the early 1990s, they sent me to Toronto with the mission of setting up a research and development centre for their products. After a few (very fun) years, I returned to the UK and was promoted to global head of medical research for Zeneca, which by then had spun out from ICI. It was a huge job! Sitting one level below the board, I had over a thousand people reporting to me from all over the world.
Under my leadership at Zeneca, we got six major products approved, many in oncology. But then Zeneca merged with Astra, creating AstraZeneca. Being one level below the board and with not enough seats at the table, I was made – to put it gently – redundant. Most of the R&D jobs went to Astra people, and most of the commercial jobs went to Zeneca people.
Some setbacks lead to new opportunities
In retrospect, the redundancy was probably one of the best things that ever happened to me. I wasn’t short of job offers and I ended up taking the opportunity to help set up one of the world’s first gene therapy companies: Ark Therapeutics.
Ark Therapeutics was a spinout from University College London and the University of Kuopio in Finland. The UCL scientist was John Martin, a professor of cardiology, and his Kuopio counterpart was Seppo Ylä-Herttuala. The two had previously worked together on research into gene therapies, eating up a €250,000 EU grant in the process. For their spinoff, they went to a prominent UK investor who was quite happy to back their startup – provided they could install proper leadership.
And that’s where I came in. We took on a CEO and a CFO, and I became the R&D director. This all happened only four or five years after the very first clinical study of a gene therapy, so it was terra incognita for everybody.
Embracing craziness? It’s not always a bad thing – but it can be a gamble
As an interesting sidenote: Two years prior to Ark, Zeneca had asked me if it was worth getting into gene therapy – my reply: “Don’t touch it with a bargepole!”
When I joined Ark, people in the industry told me that I was crazy. There were no precedents and no regulations, after all.
But I was excited by the science and what we could achieve. I was willing to take the risk, and gamble a portion of my reputation on it. My thinking was that, no matter the nature of the product, the four criteria you must satisfy for the regulators always remain the same:
- You must be able to make the product, and make it consistently
- It must be safe in the patient population
- It must be efficacious
- It must have the right risk/benefit ratio
Those four targets are the constant, and so we set about our task by trying to meet them.
Money talks. But that’s not always enough
We raised millions in venture capital and came to float the company on the main London stock market in 2004, which raised another £55 million – taking the record for the biggest ever biotech float (and holding it for many years). Next, we built a manufacturing facility in Finland, with the assistance of the Finnish government. The gene therapy we developed was for the treatment of malignant glioma which included a large phase III study across 36 European sites, we also received a commercial licence from the Finnish authorities for the manufacturing facility – the first ever in the world for gene therapy production. We achieved a great deal.
But when we took all this to the EMA, they didn’t approve it. They were happy with the manufacturing and the toxicology work, but the medical reviewer was unsure about the endpoint we’d used. We had agreed upfront to go for progression-free survival, but the medical reviewer insisted upon us having overall survival. We went back for an appeal, but were denied.
It was a shame. We had raised about £150 million pounds to develop this project, but couldn’t raise any further funds. By now, it was 2008, and we were in the start of the recession. Who would give any more money to a gene therapy company that just had a product rejected?
Companies in cell and gene need to prepare for a funding fight
Even today, where there is so much excitement around cell and gene therapy, funding is still difficult to access. In the US alone, there are over 500 budding cell and gene therapy companies. There are so many great ideas out there – but they need money.
There have been several cell and gene therapy companies that have raised a lot of money and floated on the New York Stock Exchange in recent years, but share prices have tanked over the last 12 months or so, and this is creating problems. It seems that the market is not particularly interested in new cell and gene therapy products right now. But we have to remember that things are cyclical.
When I was at Ark, big pharma was starting to show interest in gene therapies and I predicted they would get more involved, but then, in 1999, Jesse Gelsinger died after taking part in a clinical trial for a gene therapy. There were also a few other issues in studies – and big pharma left the sinking ship.
Many of us knew that big pharma would be back, which is exactly what happened. In recent years there have been a lot of deals and acquisitions, with big pharma snapping up cell and gene therapy specialists. However, many cell and gene therapy companies today will probably go to the wall because of the lack of funding. I think it will be survival of the fittest.
Every cloud really does have a silver lining
They say every cloud has a silver lining and it is true. At Ark Therapeutics, we had proven that something new was possible. We were able to take a DNA gene therapy product all the way through the development process and make a submission to the EMA – all by the book. We didn’t get the product approved, but we’d still achieved something meaningful.
Prompted by encouragement from my investors, I then set up my consulting business, Boyd Consultants. My experience in both senior pharma roles and a biotech startup made me somewhat unusual at that time – in the best possible way.
The investors told me that I could offer them due diligence on their potential investments, and that they may well come to me seeking help with their developments at the board level. So I formed my consultancy solo but soon realized that I needed help. I started hiring, and after 17 years we now have almost 40 employees, just under half of whom make up the regulatory group. We have a global client base, and we’ve got two offices in England, one in Philadelphia, and – prompted by Brexit – one in Dublin, to keep us in contact with the EMA.
We do a lot of cell and gene therapy work because of my background – in fact, I’m proud to say that we have contributed at some time to eight advanced therapy products approved on either side of the Atlantic.
Looking back on this I know that to some extent I was lucky. My career is not one you could replicate starting today, because I was placed and working at a particular place and at a particular time. The moment has passed.
Science takes time – be patient
Consider this. Watson, Crick, and Franklin identified the structure of DNA in 1953. Twenty one years later, I started medical school. Across six years of studying biochemistry, I received one lecture on DNA. I remember it very clearly. It was mainly limited to the topic of structure, but at the end of the lecture the professor said, “Look, one day, this DNA structure might be useful.” Twenty years later, I formed a company based on DNA gene therapy, and fell one hair short of bringing it to market. Now, in 2022, with some help from my consultancy, ten approved gene therapies exist. So my professor was right – that DNA stuff did prove useful. It just needed time – albeit forty years’ worth!
Key career advice and anecdotes
Experience is something you often gain 10 minutes after you needed it:
“In the early days of gene therapy, I’d spend the afternoon on the phone to the toxicology people at the FDA where we would design toxicology studies together. All of us were in the dark at these early stages of the gene therapy era. You have to accept the challenges as they come.”
“Establish a good network of people and keep in contact with them. I have a great team and we can help most clients with whatever problems they come to us with. But occasionally we can’t, but we will know someone who can help, so we can refer the client to them; this is a great way to do business and collaborate with others. Most of our business comes from referrals – and reputation is key.”
Put patients first:
“There are bad apples in any industry, but the pharma industry does have a reputation as the ‘dark side.’ Back when I joined the industry, it was considered an unusual move for a doctor and people even accused me of leaving medicine. When people tell me they don’t like the pharma industry, I remind them that someone has to pay for drug development. And I tell them that I am a doctor first. I put patients first. I like developing medicines for patients, and it’s good to see people being treated.”