Welcome to Partnology’s Biotech Leader Spotlight Series, where we highlight the remarkable accomplishments and visionary leadership of biotech industry pioneers. This series is about showcasing the groundbreaking strides made by exceptional leaders who have transformed scientific possibilities into tangible realities. Through insightful interviews, we invite you to join us in following the inspiring journeys of these executives who continue to shape the landscape of the biotech industry.
Javier San Martin is the CMO of LeonaBio, a late clinical-stage biopharmaceutical company dedicated to the development of novel therapeutics for diseases with high unmet medical needs, including treatment-resistant metastatic breast cancer and amyotrophic lateral sclerosis (ALS). Dr. San Martin joined LeonaBio from Arrowhead Pharmaceuticals, where he served as Chief Medical Officer and guided development teams to advance that company’s RNAi-based therapeutics in the metabolic and liver disease area. Prior to Arrowhead, he served as Senior Vice President and Head of Global Clinical Development at Ultragenyx Pharmaceutical, where he led the development of Crysvita® (burosumab-twza), the first drug approved to treat the rare, inherited disease of x-linked hypophosphatemia. Before that, Dr. San Martin served as Senior Vice President of Clinical Development at Alder Biopharmaceuticals, where he managed medical, regulatory, and clinical operations. Earlier, he led two major development programs as Global Development Leader for Amgen’s Bone Therapeutic Area and directed the anti-sclerostin antibody clinical program Eventiy® (romosozumab-aqqg) through the end of Phase 2 and was responsible for development and approval of Prolia® (denosumab) for the treatment of postmenopausal osteoporosis. Prior to Amgen, Dr. San Martin spent seven years at Eli Lilly working on Phase 3b and Phase 4 clinical trials to support the successful launch and medical affairs activities for Evista® and Forteo®.
Your career spans practicing medicine, global clinical development, blockbuster product launches (Prolia, Evenity, Forteo, Evista), rare diseases, RNAi, and now oncology and neurodegeneration. Looking across those experiences, what do you believe truly separates development programs that change patients’ lives from those that never reach their potential?
I started as a clinician in Argentina, where I’m from, and practiced very intensively for about eight years—first as a resident and chief resident, and then for four years as a full-time attending physician. I loved it. I thought that was what I was born to do, and I think I was very good at it.
Then I had the opportunity to join Lilly. I initially worked part-time while still practicing in Argentina before eventually moving to Indianapolis, where I spent most of my time in the bone therapeutic area. From there, I went to Amgen, another large company, where I took on my first major leadership role.
Eventually, I joined Ultragenyx, a small biotech in the Bay Area focused on rare diseases. At that point in my career, I was really looking for a project that would give me a stronger sense of purpose—something that would bring me closer to patients and allow me to see more directly what happens when a drug is approved and the impact it can have on people living with a disease. That was the breakthrough for me.
At Ultragenyx, I led the development of burosumab, or Crysvita, for a rare disease called X-linked hypophosphatemia, or XLH. The drug addresses the underlying mechanism of the disease and translates that into meaningful clinical outcomes. Children with XLH develop rickets: they don’t grow properly, their legs can become bowed, and they can experience lifelong pain, disability, and other limitations. Because it’s hereditary, you often see parents and children within the same family living with the disease.
Burosumab is an antibody that blocks FGF23, a protein that is present in excess in XLH. By blocking FGF23, the kidneys can properly reabsorb phosphate, normalizing phosphate levels and allowing the rickets to heal.
That was the first time in my career that I used the word “healing,” which is very different from simply treating a disease. These children began growing at a normal pace, and their legs started to straighten.
It has now been more than 10 years, and next week I’m actually attending an advisory board and an XLH Patient Day with the company that now owns the drug. I’ll have the opportunity to meet some of the children who participated in those original studies when they were four, five, or seven years old. Now they’re 15 or 16. I’ve been told they’re doing incredibly well—they’ve achieved their expected height, many are significantly taller than their parents, and their legs are straight.
That project gave me back the feeling I had as a clinician—the sense that the work we’re doing can genuinely heal someone or fundamentally improve their life. It took me probably 12 or 14 years in industry to arrive at that realization, but I also needed everything I had learned along the way.
People sometimes say when they’re interviewing at a small biotech, “I don’t like large companies; I only want to work at small companies.” I always say, “Time out.” You can learn an enormous amount at companies like Lilly and Amgen and then bring those lessons into a smaller organization. Small companies can certainly be more dynamic and nimble. You have access to more information, there are fewer layers, and there are many things I love about that environment. But I learned tremendously from my experiences at those two large companies before moving into biotech.
Because of the experience with burosumab, I made the decision that I wanted to focus on programs where the medical need is significant and the intervention has the potential to truly address the disease—to heal a patient, restore quality of life, or prolong life when that is the ultimate goal of therapy.
From there, I spent four years at Arrowhead, an RNAi company, which was an incredible experience for different reasons. It taught me a tremendous amount about science and about building a high-performing team from the ground up. But ultimately, I wanted to return to diseases where there is an enormous unmet need and the potential to have that kind of profound impact on patients. The opportunity to contribute to developing treatments in indications such as treatment-resistant metastatic breast cancer and ALS, and to thereby meaningfully improve patients’ lives, would represent a significant personal milestone in my career.
You’ve led development programs ranging from early clinical proof-of-concept to global Phase 3 studies involving more than 14,000 patients. At what point does scaling a clinical program become less about science and more about operational excellence?
Operational excellence should always be present, but its importance evolves as a program progresses. When you’re launching a Phase 3 study, you should already have a clear vision for what that drug needs to look like. You need to understand what you want the label to say, what the target product profile should be, and what the value proposition will be. Phase 3 is ultimately the study that defines what that drug will become.
At the same time, it’s typically the longest and largest study you’ll execute. At that stage, execution excellence becomes absolutely critical. Your clinical and regulatory strategy needs to be well defined because once you start, your ability to change course becomes much more limited. Earlier in development, you can make mistakes, learn from them, and adjust. By the time you reach Phase 3, mistakes become much more costly.
So operational excellence is particularly important in the late stages of a program. But you have to define what you want that drug to look like before you ever start Phase 3—and, ideally, you begin thinking about that at the very beginning of development.
One of the first things I learned at Lilly, and something I’ve carried with me throughout my career, is that you need to start with the end in mind.
It’s an incredibly valuable exercise early in a program to ask: What is the disease? What is the drug? How do the two connect? How will that interaction translate into an improvement in the underlying disease biology? How will that biological effect translate into a meaningful clinical benefit? And ultimately, how will that clinical benefit create value for patients and for the healthcare system?
If you can start answering those questions from the beginning, you have a much clearer framework for every development decision that follows.
You’ve worked closely with regulators around the world throughout your career. How has your philosophy on regulatory engagement changed over the last two decades, and what do younger clinical leaders often misunderstand about those interactions?
The number one thing I’ve learned—and that I teach my teams—about regulatory interactions is that you have to put yourself on the other side of the table.
Picture yourself as the regulatory reviewer at the FDA, EMA, or another agency. When you’re writing a briefing document, your message needs to be clear, but you should also think about the person who has to read it. These are people just like you who may have to work through a 120-page document. Make it easy for them. Think carefully about how you deliver the message, how you use figures, how you connect ideas, and how you structure the document. Put yourself in their place.
The second thing is that you need to know what you want, and you need to ask for it. Then you need to put the evidence behind that request. That doesn’t mean manipulating the data to make it look a certain way. You have the data, you believe in your interpretation of it, and your job is to present that evidence clearly in support of the position you’re asking the agency to agree with.
I’ve seen very different approaches to regulatory relationships over the years. At some large companies, I’ve seen a very adversarial relationship develop, with even senior clinical and regulatory leaders openly criticizing the FDA. I take the opposite approach.
I tell my teams: We work with the FDA, not against the FDA.
Even if we don’t like what the agency tells us, criticizing them doesn’t accomplish anything. My role is to understand their perspective and determine whether we can shift their thinking through the strength of our data and the way we communicate the story. How can we present the evidence in a way that helps the reviewers, the division, or the agency understand our position and potentially agree with us?
I see regulators as partners. I try to put myself on their side of the table, and I care tremendously about the quality of the briefing document and every other communication that goes to the agency. Everything should go through the same filter: If you were the person on the other side reading this, would the message be clear and compelling?
That mindset changes the relationship. It puts you in a much more productive place when working with regulators.
You’ve led organizations through both success and disappointment. When a study doesn’t deliver the outcome you hoped for, what have you learned about maintaining team confidence while still making objective decisions about the program?
I went through that with our Alzheimer’s program. I had only been at the company for about six months when the study came back negative. One thing that was new for me was becoming the voice of the company, both externally and internally. I remember the day of the press release, the 6 a.m. call with investors and analysts, and all the preparation in the days leading up to it. It was incredibly challenging.
Like many studies that fail, there were still things in the data that looked potentially interesting. The difficult part was finding the right balance in the message: Yes, the study failed. The p-value was not significant, the effect size was small, and this program was over. At the same time, there were observations in the data that could still teach us something. You have to communicate those nuances without losing sight of the fundamental conclusion that the drug did not work.
Communicating that to investors and analysts was challenging, but internally it was difficult in a completely different way.
This was a homegrown molecule that people at the company had spent more than 10 years developing. They were incredibly attached to it, and I was the newcomer. Some people had spent seven years of their lives working on this one program. In a small company, when that molecule is the company, a negative study becomes very personal. You also know what that outcome may ultimately mean for people and their jobs because the company may no longer have the resources to keep everyone.
My message to the team was to focus on the quality of the work they had done. They had done a fantastic job. There wasn’t some obvious error or mistake that caused the study to fail. This is drug development, and in Alzheimer’s disease, it’s particularly difficult.
We did good work. We learned things that could be valuable the next time—or valuable to someone else pursuing a similar approach. There was no clear way we could have predicted that the drug wouldn’t work. There wasn’t a major flaw in the study where we could point to geography, randomization, execution, or some other issue and say, “That’s why it failed.” The study was well executed, and the result was still negative.
I think that situation can be somewhat easier to absorb in a large company because there are so many other programs and priorities. In a small company, the consequences are much more immediate. I knew that within a few weeks, the message about the failed study would be followed by another difficult message: We couldn’t keep everyone because we no longer had the resources, and we needed to reinvent the company.
And we did reinvent ourselves. We still had our ALS program, and we went out and identified another drug that we could license with the support of our investors. We found a path forward and kept as many people as we could. But it was a very difficult period.
The opposite experience, of course, is an incredible place to be. I remember seeing the data from the Crysvita programs in both pediatric and adult patients. Those are the results you dream about. You look at the data and think, “This is going to be great.” Then you get to give the presentations, share the results, and take the victory lap—and that feels very good. But in this business, you have to be able to lead through both.
Early in your career you helped build clinical research infrastructure in Argentina, and you’ve also led large multidisciplinary global organizations. How did those early experiences shape the way you think about patients, leadership, and developing medicines today?
Well, I may need to go back a few years, even before I joined Lilly Argentina and helped build the medical and clinical operations function there. What taught me many of those lessons wasn’t industry—it was the hospital.
I was fortunate to serve as chief resident at a very good, small academic institution, and I still remember that as one of the best professional years of my life. You suddenly have responsibility for the unit, the residents, and the students. The environment is incredibly dynamic and intense, and every day you learn something new.
I didn’t have any formal background in how to lead people. I learned by being in that role. I discovered that I could get people’s attention and create a sense of purpose and responsibility around the work. What does it mean to be a clinician and take care of a patient? What does it mean to talk with that patient’s family? What does it mean to teach a younger resident who has made a mistake and help them learn from it?
Even today, I think those experiences are the foundation of my ability to rally people around an idea and lead a team toward a common goal.
My medical training also shaped the way I think about clinical development. I naturally come back to the question: What are you trying to offer the patient? What would be a meaningful outcome—something that a patient would actually feel or perceive as relevant to their life?
So I think it was that early part of my professional career that created the foundation, and I carried those lessons into everything that followed.
But as I reflect on my career, every step along the way has added something. Every job, every type of company, every disease and therapeutic area, and every group of people I’ve worked with has continued to shape the way I think and the way I lead. I think it’s really the totality of those experiences.
When it comes specifically to keeping patients at the center of clinical development, though, it’s very easy for me to go back to that original physician-patient relationship—the patient, their family, the hospital, and everything that comes with caring for a person directly. That experience has never really left me.
