Sharlini Sankaran spoke with Dr. Jeff Lawson, who is on sabbatical from Duke University to serve as Chief Medical Officer (CMO) for Humacyte, about his work with engineered blood vessels. Humacyte’s investigative human acellular vessel recently received one of the US Food and Drug Administration (FDA)’s first Regenerative Medicine Advanced Therapy (RMAT) designations.
What excites you about your work?
What excites me is the potential to regenerate something as simple as a blood vessel; that may be a platform which we can use to regenerate a litany of organs in the future. I’m reminded that the first barrier to transplantation wasn’t the immunosuppression, but the vascularization. When Alexis Carrel won the Nobel prize it wasn’t for transplantation, but for vascular anastomosis – which lay the groundwork for him to one day do the first kidney transplant. So, I think we have to get the blood vessel right first before you can do any more complex organ, because they are all absolutely dependent on the blood vessels. In fact, the blood vessel isn’t just a tube – the vasculature functions as its own organ with its own physiology. So, to create a functioning blood vessel from a manufacturing standpoint is a very exciting opportunity and reflects a very do-able state of science in 2017. Some day, we may 3D print an organ which we can then pre-incubate with stem cells, which may then differentiate into a kidney. And I think we should try! In the 90s, when we first started doing this, we didn’t know that it would take twenty-some years to get it right and to be in Phase III clinical trials.
So that’s where Humacyte is now, right? Tell me more about your role at Humacyte and what drives you.
Yes, we are in global clinical trials right now. We just enrolled our 190th patient in our global clinical Phase II trial. It’s so exciting. The other exciting thing is, that I get to participate in something which may impact the lives of patients whom I’ve cared for. You can’t save humanity as one surgeon – you can only do one surgery at a time and there are more to be cared for. And you get to a phase in your career where you think, maybe I can impact 10,000 patients, maybe I can work on something that changes the way care is done for the better. So for me, the opportunity to change the vascular platform which surgeons can use to treat patients is very unique and very impactful. You only get one shot at this kind of chance – that is part of what drove my decision to uncouple my day job as an academic vascular surgeon for a period of time to get the clinical execution of the trial done by taking the position at Humacyte.
Describe why your research, and Humacyte’s products, are so important to human health.
What we’re doing is making the blood vessels that can be used in the initial trial. We have a number of products in clinical trials and the one that’s furthest along the regulatory path is in dialysis care. There’s a huge unmet need for patients to have blood vessels working in their arm that they can then use to get dialysis. We have also already initiated a number of Phase II clinical studies that are more arterial reconstruction based. These fall into two domains: one for patients with peripheral arterial disease, and the possibly more intriguing one is for emergency vascular trauma, when someone is injured and you have no synthetic material to reconstruct their blood vessels with today – we think we can provide a human tissue that is safe and potentially infection resistant.
We have support from the Department of Defense to develop a blood vessel that could be deployed to far forward military facilities, civilian trauma centers, and can also be used to reconstruct failing arteries from conventional atherosclerosis in an aging population. Where we started this story a long time ago, was to be a conduit for coronary heart surgery and we have every intent of having the vessels available in a smaller size. We currently make it in one size for clinical application but we have the capacity to manufacture the blood vessel in different sizes and shapes.
We’re also looking at extending the manufacturing of tubes to other organs outside the vascular system. We are looking at things like urinary conduit, and the esophagus, and the trachea. We would first like to be able to make different types of tubes that are necessary and can be replacement human tissue, and at that point we can look at transitioning to more complicated regenerative medicine. We’ve actually done some preclinical work already with urinary conduit, we know we can make the constructs for things like trachea and esophagus. It takes the same conceptual platform of taking human cells, and making the relevant shape and structure. The other questions are, do you have to have unique attributes to the matrix that’s made? If it’s placed in a different anatomic location, will it remodel and repopulate with the host cells in similar fashion? Those are questions that will be answered in the next 20 years – certainly through the rest of my career!
What has been your biggest challenge in transitioning from the university environment to chief medical officer in a startup, recognizing you’re still doing both?
I love being a physician-scientist, it’s what I’m emotionally suited to do. I never intended to become an expert in certain regulatory, or business-oriented, or administrative things. It’s interesting where your career takes you – I’m doing things that I never trained to do. The hardest thing for me, has been giving up the things I know how to do well, like operating. The operating room is such a comfortable environment for me, and I’ve been doing it for 20 years – being out of that environment has really given an appreciation for doing the things that are part of a conventional clinical practice.
One thing I’ve learned: as a CMO, you have to be committed to working as a team. As a surgeon, you are of course working with your surgical team, but a lot of the final decision-making is the surgeon’s call. In the corporate world, there are a lot of different people that you have to negotiate with as you make decisions that impact the company. So that has been a different skillset than saying “I’m the surgeon, I’m making this decision.” It’s a skillset that says: “all right we’ve got to sit down and negotiate and talk about how we are going to solve this problem.” So that’s been a transition that’s been a good one, but a challenge. Many of these decisions are made at an organizational level where the CEO, CMO, COO and a few other people all have to concur if we are going to proceed with a decision.
One of the things that’s really challenging from a company standpoint, is that we have all of this exciting stuff that’s happening and we are growing so fast. You raise enough money to do these three clinical trials, you got to jump all in: you got to finish the studies, you gotta be able to manufacture the vessels, you gotta scale up the workforce. But that means you gotta burn a lot of money over a short period of time. The analogy that often gets used is: you are building the plane as you are flying it. Even though we haven’t figured out everything yet, we have to make it work as we go. It’s an incredible pace for the entire company.
How do you do maintain the different professional roles? What advice do you have for people who are at the beginning of their careers and looking to follow a similar path?
I operate one day a month and I have clinic one day a month, but the rest of my time is primarily dedicated to Humacyte activities while we are in this clinical trial. When I spoke with Duke’s leadership about taking the Humacyte CMO position as a sabbatical, they were fully supportive. They appreciated that we had the ability to translate something from its inception as a research project, to something that could eventually help save so many lives. Duke’s leadership understands the need for faculty to have time to innovate.
In terms of advice, there are three things I would say: First, when an opportunity comes around the corner and smacks you upside the head, don’t pass it up. For example, Laura (Niklason, co-founder of Humacyte) and I met by accident in the operating room and realized our research had a lot in common. She was trying to make a vascular tube and I was looking at endothelial function, and she was looking for someone to put cells in the tube, and we realized, we have a collaboration!
Secondly, I emphasize the importance of building teams with different domains – clinicians, researchers, engineers, regulatory specialists, et cetera. The whole really is stronger than the parts. By building a complementary team, we were able to successfully compete for one grant, followed by another, and another, to where we are now. Finally, never let your ego get in the way of a successful collaboration. We have had a longitudinal collaboration for 20 years that has transcended a lot of things – the concept of keeping your collaborators and your team, really goes a long way. It isn’t always about who’s last author, or who’s main PI on a grant, it’s about what the team can achieve.
The first human engineered blood vessel transplant was performed in 2013 – watch a short video featuring Dr. Lawson, Humacyte co-founder Dr. Laura Niklason, and the patient here (contains brief footage of surgical procedure). Interested in learning more about Dr. Lawson’s work? Check out this TedX talk: Engineered human-tissue blood vessels .