Written for and originally published on BioSpace
BioSpace spoke with Paula Ragan, CEO and President of X4 Pharmaceuticals, a company focused on restoring healthy immune system function in people with rare diseases. X4’s lead product candidate, mavorixafor (X4P-001), is a potential first-in-class inhibitor of CXCR4.
Q: What are your daily activities as CEO and President of X4 Pharmaceuticals?
A: My role is to be captain of the ship: picking a destination, getting people on board and then hopefully getting some wind in the sails. On a day-to-day basis, I have the great opportunity of communicating our vision to do something meaningful for patients, even if in casual conversations or, obviously, in a more visionary form in town halls. Getting on board and getting people on board, is a constant interaction. It's a constant team effort. It's a constant way of communicating, inspiring, aligning, arguing and presenting different sides. The wind in your sails? That's our investors, our patients, our external constituents like regulators and key opinion leaders (KOLs). Every day I have some form of interaction with those parts of our world. I try to keep people interested and wanting to spend time with us because time is the most precious thing for all of us. So, getting people engaged and keeping that wind in our sails so we can keep moving forward is part of my job, too.
Q: How did you choose to work in biotech?
A: I've always, even since I was young, really liked building things to help people. I was always trying to build something that could help my parents out with a particular project or problem that they were having. And then as I emerged in my own appreciation for academics, I really liked science and engineering and kind of married those two through my academic career. When I started to learn about biotech and drugs, I thought wouldn't it be perfect if you could regrow a limb instead of rebuilding one? So I really got excited about drug development and went down my career path there. When I think about biotech, I actually don't particularly think about biotech as a modality like a gene or a cell therapy. I just think about it as innovation.
Q: What experience do you have in the field?
A: I came from Genzyme, when Henry Termeer, the godfather of all things rare disease was there. I had the privilege of working with him. I have a great appreciation for Genzyme and work in rare diseases. That's where I really had my sort of baptism into what rare disease really means. And the company was so good about having the patient first, in my mind, in working on amazing drugs that really changed the lives of so many people.
Q: Tell me about what’s happening at X4 right now.
A: The particular diseases that we're most advanced in are WHIM syndrome and a rare blood cancer called Waldenstrom's macroglobulinemia. Both of those diseases arise from a genetic dysfunction from a genetic mutation in the CXCR4 receptor. And so, they've almost presented themselves to us. We had a drug that we knew could act and turn down the receptor. These diseases are diseases caused by the receptor turning on too much. It was almost as if there is a marriage of the mechanism of the disease, and we have the one solution. So that's really how we started these initial studies. As we're learning more about the drug in patients, there are also some broader opportunities to go with. But we're going with the most targeted approach first, and then as we learn about the drug, we'll consider broadening out.
Q: When you speak of broadening out, do you have anything in mind?
A: There are some other types of diseases of the immune system that cause very low white-blood-cell counts, and our drug absolutely increases white-blood-cell count. We think we have some other opportunities. Severe congenital neutropenia is a disease patients are born with, with very low neutrophil counts. We think our oral once-a-day therapy has the potential to help those patients as well. It can go much, much beyond that. People are very interested in boosting the immune system in oncology if you check on all the checkpoint inhibitors. There's been some early work where our drug could help there as well. So there are some early-stage studies that could open up that door which could be obviously an easy door to go through as the data emerges.
Q: What’s the best part of your work?
A: I think it's a little bit of the unsung hero aspects of these patients. I don't like people defining the importance of a disease based on the number of patients. Everyone's individual disease is hard on that individual person. And so, I really look at it at an individual level. I want people to feel like they have a champion. I think it's got to be even worse to have some of these diseases that people dismiss like it doesn't matter just because there aren't more of you. I just can't even imagine that. One of our patients that we've had the good fortune to meet, sent us a video to say thank you for what we're doing. I kind of just like championing maybe the underdog or the giving of a louder voice, because the disease is important. It's important science regardless of how many are there - I'm excited about what we're doing because it's not only about WHIM syndrome or even WHIM and these other diseases, but we're learning about the immune system. Everything that we learn from these trials might open up a door for somebody else's treatment. I feel like it's a really good lens for delivering something meaningful shorter term, and then longer term, it can open up doors in ways we don't even know yet. So it really resonates a lot with me.