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.
Dr. Harold Bernstein is the President of Research & Development and Chief Medical Officer at Maze Therapeutics. Before joining Maze, Dr. Bernstein was Senior Vice President, Chief Medical Officer and Head of Global Clinical Development at BioMarin. Prior to that, he served as Head of Translational Medicine and Vice President of Global Medicines Development and Medical Affairs at Vertex, and held roles of increasing responsibility at Merck and Co, including Head of Early Development for Cardiometabolic Diseases. He was Professor of Pediatrics and a senior investigator at the Cardiovascular Research Institute and the Broad Center of Regeneration Medicine and Stem Cell Research at the University of California, San Francisco (UCSF). He also served as attending physician at UCSF Benioff Children’s Hospital in Pediatric Cardiology, and at the Mount Sinai Kravis Children’s Hospital in Pediatrics and Cardiovascular Genetics.
Currently, Dr. Bernstein holds an appointment as Adjunct Professor of Pediatrics and the Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai. He studied biomedical science, human genetics, and medicine at the Mount Sinai School of Medicine, earning MPhil, PhD, and MD degrees. He completed a pediatric residency, cardiology fellowship, and postdoctoral fellowship at UCSF and earned an undergraduate degree in biological sciences from Harvard College.
Walk me through your career, highlighting the most pivotal moments or decisions throughout:
My career started in academic medicine, where I was caring for patients, running a research lab, teaching medical and graduate students, and mentoring postdoctoral fellows. I still strongly believe in that mission and have tremendous respect for my colleagues who have dedicated their careers to it.
But there came a time when I started to wonder whether the basic scientific discoveries we were making in the lab would ever truly benefit the patients we were caring for. I had an opportunity to join some former academic colleagues in Big Pharma, and—somewhat as a leap of faith—I made the decision to turn over my grants and my patients and make the move.
Looking back, I’m especially proud that I was willing to take that risk. Because honestly, my time in industry has been some of the most exciting and gratifying of my career. I’ve had the chance to work on dozens of programs, and I’ve collaborated with some of the smartest, most thoughtful scientists and clinicians I’ve ever encountered. I’ve also had the privilege of seeing more than a handful of medicines make their way to patients.
And along the way—really throughout my career—I’ve taken a lot of pride in helping others reach their goals, developing their own careers, and making a difference for patients.
What inspired your transition from academia and pediatric cardiology to leading translational medicine and R&D strategy in industry?
I started as a graduate student in human genetics, driven by a desire to understand how, in part, our genes make us who we are. As I was finishing up, and on the advice of my PhD advisor, I went to medical school—initially to gain a deeper understanding of human biology and disease. But I quickly discovered that I really enjoyed the interactions with patients and their families.
As I progressed in academic medicine, my research focused on the basic mechanisms of tissue development and repair. Over time, though, I became increasingly interested in how we could translate that science into real treatments for patients. That drive ultimately led me to make the move to industry more than 12 years ago.
In industry, I began to see how that foundational understanding of human genetics could be applied. At the time, while we knew how to gather genetic information, the impact of that information on how patients respond to disease was only just beginning to be appreciated.
Over the years, I’ve worked at several companies—all deeply committed to translating good science into medicine and to serving people. Along the way, I learned a great deal about the operational side of drug development. And although I can trace my contributions to at least seven or eight approved medicines that are now helping patients, I think I’m most proud of what we’re doing now at Maze.
At Maze, we’re building a company that’s truly leveraging our growing understanding of human genetic variation to develop new therapies for patients with some truly devastating diseases.
Tell me more about Maze Therapeutics, what are you currently working on?
Maze was conceived to harness the power of human genetics to transform the lives of patients – by analyzing large datasets of matched genetic and clinical information to understand not only how genetic variation increases disease risk, but also how it can be protective. For example, why do two people with the same disease have such different outcomes? One may progress rapidly to severe illness, while the other experiences a slower course. And why do some people never develop the disease at all with some of the same risk factors?
We’ve used this approach—what we call our Compass Platform—to develop potential medicines for chronic kidney disease, as with our MZE829 and MZE782 programs, as well as rare metabolic disorders like Pompe disease and phenylketonuria (PKU). In addition, we have several early-stage programs focused on metabolic diseases that affect large segments of the population and often include obesity as a key component.
How do you view the evolving role of human genetics and functional genomics in shaping the next decade of drug development?
Over the past few decades, our understanding of the genome has led to the development of new therapies—but primarily for single-gene disorders that affect relatively rare patient populations. This progress has been incredibly important, especially for patients who had previously been overlooked.
However, very few of these gene-disease associations have guided the development of new medicines for more common, complex diseases like chronic kidney disease, metabolic syndrome, or cardiovascular disease. At Maze, we believe the real opportunity lies in learning from genetic variation—specifically, how it influences disease progression and patient response. That’s what will drive the next generation of impactful medicines for the broader, more prevalent diseases that significantly affect public health and the patients we aim to serve.
How is the biotech sector adapting to today’s tighter capital markets, and what role does clinical differentiation play in building investor confidence?
It’s difficult to predict where financial markets will be in the short term, but investors have always sought assurance in the potential value of drug development programs. As we know, the further along a program is in clinical development, the higher the probability it will ultimately reach patients. What we’re seeing today is that clinical data has become essential for building that confidence—and high-quality, well-understood data continues to be well received and supported.
What are your thoughts on the convergence of AI, multi-omics, and human biology in accelerating precision medicine? Are we seeing hype or true value creation?
I don’t believe it’s all hype but rather hope for the kind of breakthroughs that come with any transformational technology. I think we’re still exploring the many ways these tools can help us, whether that’s validating new therapeutic targets, designing new drugs, or gaining an edge in clinical trial design, all of which we’re doing at Maze.
For example, we’ve been using machine learning for several years to simulate aspects of drug design and accelerate the work of our medicinal chemists. But it still takes human insight to build those algorithms—and astute chemists to understand how best to apply these emerging technologies.
Now that we’re a clinical-stage company, we’re also working with partners to use AI to identify where potential participants may be for our trials, and to improve their experience based on how they typically access care. So yes, I do think there’s a lot of promise—and we’re now at the stage of learning how to apply AI in the most impactful ways.
