In less than two years, Orchard Therapeutics has changed from a small, relatively unknown UK biotech specializing in gene therapy into a billion euro company listed on the Nasdaq. This is in no small part due to the skills and experience of Mark Rothera, its CEO and President, who joined the company in 2017.
Orchard Therapeutics is the sixth biotech company that Rothera has helped build up into a successful business, although his first as CEO. He has specialized in the rare disease space, and has helped get several therapies to market including the first treatment for Duchenne muscular dystrophy, a rare degenerative muscular disease, at his last company PTC Therapeutics.
After spending several years working in big pharma at GlaxoWellcome, he made the jump to biotech because he felt the draw of the more entrepreneurial atmosphere in this field. Like a lot of people working in the space he has experienced the highs and the lows of the business, but he believes it gives him the opportunity to make a bigger impact than if he had stayed in pharma.
What inspired you to get into biotech in the first place?
I think the first six-seven years of my career with Glaxo were very formative, but there was something in me that I think was very much about making a bigger impact and building something in a more entrepreneurial way. In 1996, I chose to leave what would have been a very nice career, but a very much safer career in a bigger company, to go into a more entrepreneurial, science-driven biotech company.
Orchard is my sixth build that I’ve been involved in. In 1998, I joined a rare disease-focused, emerging company called PathoGenesis to launch the world’s first inhaled antibiotic for cystic fibrosis. This was the first experience of serving patient communities with rare diseases that have significant need that certainly wasn’t being addressed well at that time… I found that particularly rewarding.
I’ve kept that focus since 1998, so 20 years now, involved in building five different companies to bring treatment to patients with rare diseases. These are some of the most important unmet needs and generally, these are very severe, life-threatening and life-limiting conditions.
What’s different about Orchard is we’re talking about one-off, disease-correcting, potentially curative treatments for the rest of their life.
What attracted you to coming to work at Orchard Therapeutics?
I had never heard of Orchard before I was approached by somebody, an intermediary, to come and meet with the investors and some of the top leadership. At that time, it was a company of about 20 people. I was blown away by the extraordinary data that was being generated using ex-vivo hematopoietic stem-cell gene therapy. It was something I hadn’t seen before and I was very excited about the possibility of building a company, a unique company, at the forefront of gene therapy and focused on rare diseases.
There are 7,000 rare diseases that affect 60 million people in Europe and the United States, but only 5% have treatments today. These often affect children and they are often devastating and very life-limiting… Gene therapy is, I think, the new way of medicine that will replace chronic treatments in many, many indications by one-off interventions.
I am very attracted to staying and being in the rare-disease field because you’re not talking about marginal needs here. You’re talking about very serious conditions. If you can bring science to the world that can help patients with these really debilitating, life-limiting conditions, that’s fantastic for those patient communities. But, I think it’s also bringing a new scientific platform that, who knows, could go into other areas in time.
It was shortly after you began in 2017 that Orchard bought the gene therapy Strimvelis from GSK, after it failed to make any money. Why did you make that decision?
When I joined, we had two programs in the clinic for two indications… Emma Walmsley, the new GSK CEO, had decided to prioritize R&D investment in large indication areas and decided to close the rare disease unit. Within that unit, they had four gene therapy programs using exactly the same gene therapy platform that we had.
This was like a starting gun. Almost from day one when that announcement came out, we bid for those four gene therapy assets in rare diseases, including Strimvelis. Over a nine-month period, it was extremely competitive. We won because of our expertise in the field, our great focus and the desire to put these assets in the hands of a company that would fulfill the mission that they began. They also took an equity stake in Orchard, as well as a board position.
I think it was a great outcome because – having joined in September 2017 – by April 2018, we had five programs in the clinic and one on the market, Strimvelis. I think it was a transformative business development transaction that put us in a very different place. Today, I would say we have one of the world-leading gene therapy pipelines. We have now six programs in the clinic and the seventh one in the clinic by the end of this year.
In three of our programs, we’re looking to get regulatory approval in the next two and a half years. It’s been really transformative. The good thing about Strimvelis is that, not only is it a very effective medicine, but it’s also been a useful training ground for us, from a commercial platform point of view. This is because we’re already managing a commercial asset and we’re preparing the ground for three launches within the next three years or so. It’s helpful to accelerate our thinking.
I know pricing is an issue for gene therapies. How are you going to make that balance of providing very important treatments for patients, but also making sure that the company is successful from a financial point of view?
I want to illustrate an example of one of our programs targeting a condition called metachromatic leukodystrophy, which we will be filing with the EMA in the first half of next year. It’s a rare disease that affects the brain. In the fastest progressing form, life expectancy is about five or six years. We have developed a gene therapy medicine and have shown that it has curative potential.
You’re collapsing a lifetime of value into one single intervention. It’s not a chronic treatment for the rest of their life. I think it is intrinsically a very valuable proposition for the healthcare system, for patients, for society. We’re looking to find that balance with peers in the healthcare system to build a sustainable business which brings these extraordinary medicines to the world.
I don’t think there’s a ‘one size fits all’ approach. I think we’re very open to different possible payment approaches, whether it includes risk sharing, whether it’s about dividing payments over a period of time, or possibly, because you’re dealing with rare conditions, they might just say, “Look, we’re willing to pay up front because we’ve seen your data and we don’t think that the uncertainty warrants a risk-sharing approach.”
One of the unique features of our hematopoietic stem-cell gene therapy platform is durability of response… We’re showing that so far, for eight years or even more, once you’ve had that one treatment, we’re delivering that benefit. When there’s less uncertainty, payers might be willing to pay more upfront.
You had a very successful NASDAQ IPO last year. How did you decide it was the right time to do it?
We began in September 2017 with two clinical-stage programs and post GSK, we went to having five in the clinic plus one commercial product. It was clear that we would need to raise more capital. We knew not only would we need more funds to continue to parallel process so many programs in our portfolio, but we also wanted to build our own manufacturing capability for the longer term.
One of the keys to success is owning your destiny as far as manufacturing is concerned. It really provided us with the capital to be able to build, as we felt we needed to to be successful for the future.
Having made that decision to become a public company, you take on board all that represents as well, which is more reporting, quarterly earning calls, a lot more engagement with the investor community. We felt that this trade off was appropriate given our strategic intention.
Going public is a tricky decision for anyone leading a biotech. What advice would you give other companies considering this option?
It may not be the best decision for everybody. You could argue in earlier stages, when there’s more uncertainty and you have quite a lot of ‘sausage making’ to go through, it might be easier to do so without being in the public domain. To go through those really tough moments, early stage, as a company, might be better done under a private-company umbrella.
I would say that in our case, and maybe in others when the science is more developed and you have strong demonstration of your principles, of your platform, of your approach, it may be a very good route to raise capital. You’re certainly more visible, you have lots of reporting obligations, but for the right-stage company I think it can be a really good step.
What are your biggest management lessons from being a CEO?
It’s been an exciting move to take on this role as CEO of Orchard. One of the things that I have felt strongly about right from the beginning is building a cohesive leadership team, highly aligned on where we want to go as a company.
In my first week, we started to talk about the culture. We were about 25-30 people at the time. We’re now over 200 people. We’ll be 300 by the end of this year. It’s really important to have the right type of culture right from the beginning. You know the expression “culture eats strategy for breakfast”? I’m a big believer in that because I think if you have the right spirit in the organization, you can do extraordinary things.
I think the areas that were new for me, that I haven’t previously worked on, were things like having to establish a board, moving from a privately-owned company to a public one, and having the right board with you to share the vision of the company. Also, spending a lot of time with the investor community… I had done quite a bit of that before, but this is even more important in my role as CEO.
I am proud of the fact that we’ve established an extraordinary culture. People really go the extra mile — extraordinary efforts for patients in that community, great teamwork, tremendous positive intent and a real desire to embrace diversity because we’re building a global company.
How are you working to build a good culture at Orchard?
We’ve laid out some of the values that we feel are important. Time matters to patients with these fast-developing rare diseases. The time we take to make decisions and to move things forward is important. That’s why we make extraordinary efforts and try to move things forward as quickly as we can.
I think teamwork is such an important element. There are always challenges, but it’s how you face them. I think assuming positive intent in other people is a key attribute that we look for. They aren’t always right, but it doesn’t mean that the intention was wrong.
How you deal with challenges, as colleagues, is important. Respecting people’s contributions and their insights and not being afraid of conflicts of ideas or sharing ideas that are different.
How important are role models to you?
I had had mentors in the past. For example, I was hired into Glaxo by Franz Humer who then went on to run Roche. He was a mentor to me in my early career. Matt Emmens at Shire was a mentor in some ways to me in the rare disease area.
But, I think it’s also about being inspired by people to do what you do. Some of the most inspiring people I’ve met have been from the patient communities because they’re just extraordinary brave people.
In the field of metachromatic leukodystrophy, I had the privilege to meet Amy Price from Nebraska who had three children with the disease. She sadly lost her first child, but as a result, diagnosed two of her other children that were able to participate in gene therapy programs. She’s a huge supporter and advocate of helping this community find solutions for patients. I think you can draw extraordinary inspiration from the courage and leadership of people who’ve had to deal with extremely difficult circumstances.
What advice would you give yourself if you could go back in time to when you started in biotech?
Firstly, I would say to myself, “Make the same decision to join the entrepreneurial, innovative biotech sector. It’s a great way to spend your career.” I do not in any way regret that decision. It was a great decision and I would encourage others to take on that journey.
I think there’s something about being geographically mobile, which is useful if you want to progress in the sectors, because ultimately, you’re bringing medicines not just to patients from one country, but you want to be doing that with a worldwide view.
One thing I would encourage my younger self to do even more is to never be afraid to take a bit of a step into roles that you really don’t know a great deal about. It’s an extraordinary learning opportunity and I would say I’ve definitely been able to step through many roles in my career.
It is scary to go into a small entrepreneurial biotech to some extent if you’ve come from a big pharma background. I learnt that the hard way when I moved from Glaxo to Amylin Pharmaceuticals. It was my first biotech. Two and a half years later, its phase III failed and I found myself without a job, six months of cash left, four children, a fee-paying school and a mortgage.
It was very scary, but when I look back, having got my next job, I had learnt so much from that experience that I would encourage people not to be so worried about risk, but think about the opportunity to learn.
Design via E. Resko